[Cost-effectiveness of HCV testing strategies for hepatitis C elimination in general population in China].

Objective: To evaluate the cost-effectiveness of hepatitis C screening in general population in China, and find the age group in which hepatitis C screening can achieve the best cost-effectiveness. Methods: A decision-Markov model was constructed by using software TreeAge pro 2019 to simulate the outcomes of hepatitis C disease pregression of 100 000 persons aged 20-59 years. The cost-effectiveness of the strategies were evaluated from societal perspectives by using incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB). One-way sensitivity analysis and probability sensitivity analysis were used to evaluate the uncertainty of parameters and model. Results: Hepatitis C screening was cost-effective in people aged 20- 59 years and the cost effectiveness was best in age group 40-49 years. Compared with non-screening strategy of hepatitis C in people aged 20-59 years, the incremental cost was 161.24 yuan, the incremental utility was 0.003 6 quality adjusted life years (QALYs)/per person, ICER was 45 197.26 yuan/QALY, ICER was less than the willing payment threshold. The ICER and NMB in all age groups were 42 055.06-53 249.43 yuan/QALY and 96.52-169.86 yuan/per person. Hepatitis C screening in people aged 40-49 years had the best cost-effectiveness. The results of one-way sensitivity analysis showed that the discount rate, anti-HCV detection cost, anti-HCV infection rate and the cost of direct antiviral agents were the main factors influencing economic evaluation. The results of the probability sensitivity analysis indicated that the model analysis was stable. Conclusions: Implementing hepatitis C screening based on medical institutions is cost-effective in people aged 20- 59 years, especially in those aged 40-49 years. Implementing the HCV screening strategy of be willing to test as far as possible in general population can reduce hepatitis C disease burden in China.

Epidemiology and molecular characterization of chicken anaemia virus from commercial and native chickens in Taiwan.

Chicken infectious anaemia (CIA) is a disease with a highly economic impact in the poultry industry. The infected chickens are characterized by aplastic anaemia and extreme immunosuppression, followed by the increased susceptibility to secondary infectious pathogens and suboptimal immune responses for vaccination. Commercially available CIA vaccines are routinely used in the breeders in Taiwan to protect their progeny with maternal-derived antibodies. However, CIA cases still occur in the field and little is known about the genetic characteristics of Taiwanese chicken anaemia viruses (CAVs). In this study, CAV DNA was detected in 72 of 137 flocks collected during 2010-2015. Among the PCR-positive samples, the coding regions of 51 CAVs were sequenced. Phylogenetic analysis of the VP1 gene revealed that, although most of Taiwanese CAVs belonged to genotypes II and III, some isolates were clustered into a novel genotype (genotype IV). Moreover, a Taiwanese isolate in this novel genotype IV appeared to be derived from a recombination event between genotypes II and III viruses. Five Taiwanese CAV isolates were highly similar to the vaccine strains, 26P4 or Del-Ros. Taken together, these results indicate that the sequences of CAVs in Taiwan are variable, and inter-genotypic recombination had occurred between viruses of different genotypes. Moreover, vaccine-like strains might induce clinical signs of CIA in chickens. Our findings could be useful for understanding the evolution of CAVs and development of a better control strategy for CIA.

Application of xenogeneic anti-canine distemper virus antibodies in treatment of canine distemper puppies.

OBJECTIVE: The clinical feasibility of passive immunotherapy has not been demonstrated in dogs naturally infected with canine distemper. In this study, porcine anti-canine distemper virus IgG and F(ab')2 antibody fragments were used to treat infected puppies. METHODS: A total of 41 naturally infected puppies (age Äsix months) exhibiting severe respiratory signs, but lacking neurological signs, were enrolled in the study. Twenty-five puppies were treated with a combination of IgG or F(ab')2 antibody fragments (Group 1) and supportive therapy and 16 puppies received routine supportive care only (Group 2). RESULTS: The survival rate of dogs in Group 1 (19/25; 76%) was significantly higher than that in Group 2 (5/16; 31·3%) (P<0·05). During the therapy, 8 of the 25 dogs (32%) in Group 1 developed neurological signs versus 12 of the 16 dogs (75%) in Group 2 (P<0·05). Adverse reactions were limited to elevated body temperature in dogs that received IgG antibodies. CLINICAL SIGNIFICANCE: Porcine anti-canine distemper virus antibodies improved survival in puppies affected with canine distemper with minimal adverse effects. Therefore, this therapy could be considered for treatment of endangered animal species infected with canine distemper virus.

Isolation of a novel polyomavirus, related to Japanese eel endothelial cell-infecting virus, from marbled eels, Anguilla marmorata (Quoy & Gaimard).

Marbled eels, Anguilla marmorata (Quoy & Gaimard), cultured in Taiwan exhibited haemorrhage and mortality in January 2012. The severely diseased eels bled from the gills and showed congestion of the central venous sinus of the gill filaments and haemorrhage throughout the body similar to viral endothelial cell necrosis of eel. In this study, a novel polyomavirus (AmPyV) was isolated from the diseased eels using the AMPF cell line established from the pectoral fin of healthy marbled eels. AmPyV was found to encode a long T-antigen orthologous gene. Phylogenetic analysis showed that AmPyV was closely related to Japanese eel endothelial cell-infecting virus. PCR assays revealed AmPyV infection throughout the systemic organs. AmPyV proliferated in the AMPF, EK-1 and EO-2 cells at temperatures 25-30 °C, and the progeny virus yields were 10(7.0) , 10(7.4) and 10(7.7) TCID50  mL(-1) , respectively. The purified virions were icosahedral particles, 70-80 nm in diameter. No clinical signs or mortality was observed among the eels injected with the virus; however, the virus was reisolated from the brain, eyes, kidneys, fins and gills of infected eels 2 month after injection. Our results suggest that AmPyV exhibits a latent infection. Pathogen of the disease needs to study further.

A novel loop-mediated isothermal amplification approach for sex identification of Columbidae birds.

Because it is difficult to differentiate male and female Columbidae birds (e.g., Columba livia) on the basis of morphology, detection of DNA fragments associated with Chromobox-Helicase-DNA binding genes or female-specific genes have been widely used. The objective was to establish a loop-mediated isothermal amplification system involving the 18S ribosomal RNA gene and a female-specific gene for sex identification of Columba livia birds. Unlike polymerase chain reaction (PCR), random amplification polymorphic DNA-PCR and amplified fragment length polymorphism-PCR, target DNA was amplified under isothermal conditions (the entire process was completed in <60 min). By modulating various parameters involved in amplification, e.g., concentrations of MgSO(4), betaine, Bst polymerase, and deoxynucleotide triphosphates, as well as the relative ratio of outer/inner primers and temperatures, optimal conditions for both targets were established that had equal detection limits (62.5 ng). To simplify sex determination, direct observations of the presence of white precipitate (derived from magnesium pyrophosphates) were used for positive samples, which was compared with the whitish ring which formed in a negative sample after addition of CuSO(4). This approach was a rapid alternative to electrophoresis or turbidimetry. DNA extracted from the blood and feathers of various birds were tested using loop-mediated isothermal amplification; results were consistent with a standard PCR. Thus, the assay was a simple, accurate, fast, and economical alternative suitable for veterinary practice.

Termination of two-dimensional metallic conduction near the metal-insulator transition in a Si/SiGe quantum well.

We report in this Letter our recent low-temperature transport results in a Si/SiGe quantum well with moderate peak mobility. An apparent metal-insulating transition is observed. Within a small range of densities near the transition, the conductivity σ displays a nonmonotonic temperature dependence. After an initial decrease at high temperatures, σ first increases with decreasing temperature T, showing a metallic behavior. As T continues decreasing, a downturn in σ is observed. This downturn shifts to a lower T at higher densities. More interestingly, the downturn temperature shows a power-law dependence on the mobility at the downturn position, suggesting that a similar downturn is also expected to occur deep in the apparent metallic regime at albeit experimentally inaccessible temperatures. This thus hints that the observed metallic phase in 2D systems might be a finite temperature effect.

Malignancies associated with dermatomyositis and polymyositis in Taiwan: a nationwide population-based study.

BACKGROUND: Previous studies showed that idiopathic inflammatory myopathies (IIM) carried an increased risk of cancers. However, no large-scale study of IIM has been conducted in the Chinese population. OBJECTIVES: We sought to delineate the association of IIM and various cancer types from a nationwide database in Taiwan. METHODS: We analysed the published national data from records of National Health Insurance claims. Cases of dermatomyositis (DM) and polymyositis (PM) from 2000 to 2005 and cancers registered in the catastrophic illness profile from 1997 to 2006 were collected. A nationally representative cohort of 1,000,000 enrollees was included for comparison. RESULTS: In total, 136 patients (12.8%) among 1059 cases of DM and 46 persons (7.0%) among 661 cases of PM carried internal malignancies. Patients with DM tended to have cancers of nasopharynx, lung and breast. On the other hand, patients with PM tended to have breast, uterine cervix and lung cancers. Compared with the general population, DM gave a 10-fold increased risk for cancers, in which a 66-fold increased risk for nasopharyngeal carcinoma and a 31-fold increased risk for lung cancer were the two most significant. For patients with PM, a 6-fold increased risk for cancer was observed. Juvenile DM had a 16-fold increased risk for haematopoietic or lymphoid malignancy. Two thirds of comorbid malignancies were detected shortly after the diagnoses of IIM, within a mean of 1-2 years. Overall, younger patients with IIM carried the highest risk for malignancies, especially those in their twenties and thirties. CONCLUSIONS: This is the first large-scale study to report the associated malignancies and the cancer risk of IIM in Taiwan.

Pathogenesis of gastroenteritis caused by Vibrio carchariae in cultured marine fish.

Serious mortality among the cultured grouper Epinephelus coioides, characterized by a swollen intestine containing yellow fluid (gastroenteritis), occurred in 1993 in Taiwan. A bacterium isolated from the intestinal fluid and head kidney of moribund groupers was identified as Vibrio carchariae. Since then, the same Vibrio species has also been isolated from moribund black sea bream Acanthopagrus schlegeli, yellowfin sea bream A. latus, Japanese sea bass Lateolabrax japonicus, and red drum Sciaenops ocellatus suffering from the same syndrome. Each isolate was virulent to the respective fish. Recently, a similar syndrome, flounder infectious necrotizing enteritis, also caused by V. carchariae in summer flounder Paralichthys dentatus, was reported in Rhode Island. The extracellular products (ECPs) of V. carchariae strains EmI82KL (from grouper), Rd (from red drum), and SfUSA (from summer flounder, U.S.A.) were virulent to the grouper or red drum. A 33-kDa serine protease partially purified from the ECP of strain EmI82KL was lethal to the fish. All the moribund or killed fish exhibited gastroenteritis except those killed within 12 hours. This report is the first to show that intraperitoneal injection of the ECP or protease in the fish is virulent and can reproduce gastroenteritis. The serine protease was suggested as a major toxin in the grouper or red drum secreted by V. carchariae.

Novel stress-responsive genes EMG1 and NOP14 encode conserved, interacting proteins required for 40S ribosome biogenesis.

Under stressful conditions organisms adjust the synthesis, processing, and trafficking of molecules to allow survival from and recovery after stress. In baker's yeast Saccharomyces cerevisiae, the cellular production of ribosomes is tightly matched with environmental conditions and nutrient availability through coordinate transcriptional regulation of genes involved in ribosome biogenesis. On the basis of stress-responsive gene expression and functional studies, we have identified a novel, evolutionarily conserved gene, EMG1, that has similar stress-responsive gene expression patterns as ribosomal protein genes and is required for the biogenesis of the 40S ribosomal subunit. The Emg1 protein is distributed throughout the cell; however, its nuclear localization depends on physical interaction with a newly characterized nucleolar protein, Nop14. Yeast depleted of Nop14 or harboring a temperature-sensitive allele of emg1 have selectively reduced levels of the 20S pre-rRNA and mature18S rRNA and diminished cellular levels of the 40S ribosomal subunit. Neither Emg1 nor Nop14 contain any characterized functional motifs; however, isolation and functional analyses of mammalian orthologues of Emg1 and Nop14 suggest that these proteins are functionally conserved among eukaryotes. We conclude that Emg1 and Nop14 are novel proteins whose interaction is required for the maturation of the 18S rRNA and for 40S ribosome production.

Withering syndrome of the small abalone, Haliotis diversicolor supertexta, is caused by Vibrio parahaemolyticus and associated with thermal induction.

The susceptibility of the small abalone Haliotis diversicolor supertexta to Vibrio parahaemolyticus 880915 strain and its extracellular products (ECP) at different temperatures was investigated. The strain was previously isolated from the haemolymph of the moribund small abalone with withering syndrome during an outbreak of mass mortality among the cultured animals in September 1999 in I-Lan, Taiwan. The bacterium and its ECP were lethal to the small abalone. Onset of the withering syndrome in the moribund or dead animals could be observed at 4-7 d post-bacterial challenge. The same bacterial strain could be isolated from the haemolymph of the moribund animals with or without the syndrome post-bacterial challenge. This syndrome could not be observed in the moribund or dead animals post-ECP challenge. The animals were more susceptible to the bacterium and ECP challenge at higher temperature (28 degrees C) indicating that the outbreak of the disease in warmer season is associated with thermal induction.

The loop domain of heat shock transcription factor 1 dictates DNA-binding specificity and responses to heat stress.

Eukaryotic heat shock transcription factors (HSF) regulate an evolutionarily conserved stress-response pathway essential for survival against a variety of environmental and developmental stresses. Although the highly similar HSF family members have distinct roles in responding to stress and activating target gene expression, the mechanisms that govern these roles are unknown. Here we identify a loop within the HSF1 DNA-binding domain that dictates HSF isoform specific DNA binding in vitro and preferential target gene activation by HSF family members in both a yeast transcription assay and in mammalian cells. These characteristics of the HSF1 loop region are transposable to HSF2 and sufficient to confer DNA-binding specificity, heat shock inducible HSP gene expression and protection from heat-induced apoptosis in vivo. In addition, the loop suppresses formation of the HSF1 trimer under basal conditions and is required for heat-inducible trimerization in a purified system in vitro, suggesting that this domain is a critical part of the HSF1 heat-stress-sensing mechanism. We propose that this domain defines a signature for HSF1 that constitutes an important determinant for how cells utilize a family of transcription factors to respond to distinct stresses.

Pathogenicity of Vibrio alginolyticus isolated from diseased small abalone Haliotis diversicolor supertexta.

Outbreaks of mass mortality among cultured small abalone Haliotis diversicolor supertexta with abscess/ulcers in the mantle occurred in 1998 at Kao-Hsiung, Taiwan. A swarming bacterium, strain H-11 was isolated from the haemolymph of the moribund small abalone using tryptic soy agar supplemented with 3% NaCl and/or thiosulphate citrate bile salt sucrose agar. This strain was characterized and identified as Vibrio alginolyticus on the basis of various biochemical tests. The H-11 strain and its extracellular products were virulent to small abalones with LD50 values of 3.6 x 10(5) colony forming units and 2.96 microg protein/g body weight, respectively.

Virulence of Vibrio parahaemolyticus isolated from cultured small abalone, Haliotis diversicolor supertexta, with withering syndrome.

Outbreaks of mass mortality among cultured small abalone Haliotis diversicolor supertexta with withering syndrome occurred in May and September 1998 in Kao-Hsiung, Taiwan. Bacterial strains CH-1 and B4 were isolated from the haemolymph of the moribund small abalone using tryptic soy agar supplemented with 3% NaCl and/or thiosulphate citrate bile salt sucrose agar. These two strains were characterized and identified as Vibrio parahaemolyticus on the basis of various biochemical tests. The B4 strain and its extracellular products were virulent to small abalone with LD(50) values of 1.6 x 10(5) colony-forming units and 7.58 microg protein g-1 body weight, respectively.

Lethal attribute of serine protease secreted by Vibrio alginolyticus strains in kuruma prawn Penaeus japonicus.

Toxicity of the extracellular products (ECP) and the lethal attribute of serine protease secreted by five pathogenic Vibrio alginolyticus strains from various sources in kuruma prawn Penaeus japonicus were studied. The ECPs of organisms originally isolated from diseased kuruma prawn or small abalone Haliotis diversicolor supertexta were more lethal (LD50 value of 0.48 or 0.41 microg protein/g prawn) than those from diseased tiger prawn P. monodon, yellowfin porgy Acanthopagrus latus or horse mackerel (LD50 value of 0.98-1.17 microg protein/g prawn). All the ECPs manifested strong, weak and no activities against gelatin, sheep erythrocytes and chitin, respectively. In immunodiffusion tests using rabbit antiserum to a purified 33 kDa serine protease of strain Swy against ECP of each tested strain produced one single precipitation band in each treatment. Furthermore, the serine protease was suggested to be the dominant protease secreted by V. alginolyticus strains tested since the majority of enzymatic activity of the respective ECP was inhibited by phenylmethanesulfonyl fluoride (PMSF). A higher inhibition of serine protease activity by PMSF resulted in lower mortality rate of the ECPs injected into the prawns suggesting that the protease is one of the major lethal factor(s) secreted by V. alginolyticus.

Electrophoretic characterization of a novel cysteine protease produced by Vibrio harveyi.

Electrophoretic characterization of a novel cysteine protease produced by pathogenic luminous Vibrio harveyi, originally isolated from diseased tiger prawn Penaeus monodon in Taiwan, is demonstrated in the present study using native polyacrylamide gel electrophoresis (native PAGE), sodium dodecyl sulfate-PAGE (SDS-PAGE), crossed immunoelectrophoresis (CIE) and isoelectric focusing (IEF) gels. The protease has a pI of 6.4 and exhibits a fast-migrating feature in native-PAGE and CIE gels indicating that it is a negatively charged protease. The protease electrophoresed as a 22 kDa protein band in native- and SDS-PAGE (in SDS - buffer with or without the presence of 2-mercaptoethanol) while it electrophoresed as a 38 kDa protein band in SDS-PAGE when the samples were boiled for 10 min prior to electrophoresis. The results reveal that the enzyme is an SDS-resistant monomeric protease and its high negative charge is not influenced by SDS (detergent) without boiling the sample. The present results are useful in determining proteins of similar nature to this unique cysteine protease.

Characterization and chromosomal mapping of a mouse ortholog of the late-infantile ceroid-lipofuscinosis gene CLN2.

Late-infantile ceroid-lipofuscinosis (CLN2) is an autosomal recessively inherited, neurodegenerative disease in humans. The CLN2 locus has been mapped to Chromosome (Chr) 11p15, and its sequence and genomic organization have recently been reported. In the present study, the cDNA sequence, exon/intron organization, and chromosomal localization of a mouse ortholog of the CLN2 gene are described. The mouse cDNA contains an open reading frame that predicts a protein product of 562 amino acids. The mouse and human coding regions are 86% and 88% identical at the nucleic acid and amino acid levels, respectively. One less codon appears in the mouse cDNA when compared with the human ortholog. The mouse gene (Cln2) spans more than 6 kb and consists of 13 exons separated by introns ranging in size from 111 to 1259 bp. Length polymorphism in an (AC)(n) microsatellite in intron 3 of the mouse Cln2 gene was used to perform segregation analysis with The Jackson Laboratory DNA Panel Mapping Resource. On the basis of this analysis, the Cln2 gene was localized to a region of mouse Chr 7 that corresponds to human Chr 11p15. Characterization of the mouse Cln2 gene will facilitate generation of a mouse model for late-infantile ceroid-lipofuscinosis by gene targeting and identification of functionally important regions of the Cln2 protein.