niryuu/sni-each-converted huggingface dataset:
Hepatitis E virus (HEV) is an underestimated disease, leading to estimated 20 million infections and up to 70,000 deaths annually. Infections are mostly asymptomatic but can reach mortality rates up to 25% in pregnant women or become chronic in immunocompromised patients. The current therapy options are limited to the unspecific antivirals Ribavirin (RBV) and pegylated Interferon-α (pegIFN-α). RBV leads to viral clearance in only 80% of patients treated, and is, similar to pegIFN-α, contraindicated in the major risk group of pregnant women, emphasizing the importance of new therapy options. In this review, we focus on the urgent need and current efforts in HEV drug development. We provide an overview of the current status of HEV antiviral research. Furthermore, we discuss strategies for drug development and the limitations of the approaches with respect to HEV. Viruses 2019, 11, 485 2 of 16 chronic infections by the European Association for the Study of the Liver (EASL) from 2018 stipulates lowering the dose of immunosuppressive drugs and, subsequently, if no viral clearance is achieved, up to two courses of RBV. If both RBV regimens fail, pegIFN-α can be administrated, but is only suited for the subset of liver-transplant recipients [12] [13] [14] [15] . Thus, RBV is the treatment of choice but leads to viral clearance in only 80% of patients treated [16] . Similar to pegIFN-α, it is contraindicated in the major risk group of pregnant women, emphasizing the importance of new therapy options. In this review, we focus on the urgent need and current efforts in HEV drug development.
Output: viruses Hepatitis E Virus Drug Development
Newcastle disease virus (NDV) causes a highly contagious and economically important disease in poultry. Viral determinants of NDV virulence are not completely understood. The amino acid sequence at the protease cleavage site of the fusion (F) protein has been postulated as a major determinant of NDV virulence. In this study, we have examined the role of F protein cleavage site sequence in NDV virulence using reverse genetics technology. The sequence G-R-Q-G-R present at the cleavage site of the F protein of avirulent strain LaSota was mutated to R-R-Q-K-R, which is present in the F cleavage site of neurovirulent strain Beaudette C (BC). The resultant mutated LaSota V.F. virus did not require exogenous protease for infectivity in cell culture, indicating that the F protein was cleaved by intracellular proteases. The virulence of the mutant and parental viruses was evaluated in vivo by intracerebral pathogenicity index (ICPI) and intravenous pathogenicity index (IVPI) tests in chickens. Our results showed that the modification of the F protein cleavage site resulted in a dramatic increase in virulence from an ICPI value of 0.00 for LaSota to a value of 1.12 for LaSota V.F. However, the ICPI value of LaSota V.F. was lower than that of BC, which had a value of 1.58. Interestingly, the IVPI tests showed values of 0.00 for both LaSota and LaSota V.F. viruses, compared to the IVPI value of 1.45 of BC. In vitro characteristics of the viruses were also studied. Our results demonstrate that the efficiency of cleavage of the F protein plays an important role if the NDV is delivered directly into the brains of chicks, but there could be other viral factors that probably affect peripheral replication, viremia, or entry into the central nervous system. q
Output: Role of fusion protein cleavage site in the virulence of Newcastle disease virus
The study of this chapter will enable you to: 1. Discuss the importance of the Department of Health and Human Services (HHS) Category C agents. List the most important pathogens currently found on the HHS Category C list. 3. Discuss the recent history of Nipah virus, hantavirus, West Nile fever virus, and the coronaviruses that are the causes of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). West Nile fever, SARS, and MERS. Understand the challenges that public health officials and emergency management practitioners might face when an intentional release of a Category C agent occurs in their community.
Output: Category C Diseases and Agents Where the telescope ends, the microscope begins. Which of the two has the grander view?
Viral infection initiates an array of changes in host gene expression. Many viruses dampen host protein expression and attempt to evade the host anti-viral defense machinery. Host gene expression is suppressed at several stages of host messenger RNA (mRNA) formation including selective degradation of translationally competent messenger RNAs. Besides mRNAs, host cells also express a variety of noncoding RNAs, including small RNAs, that may also be subject to inhibition upon viral infection. In this review we focused on different ways viruses antagonize coding and noncoding RNAs in the host cell to its advantage.
Output: A Tale of Two RNAs during Viral Infection: How Viruses Antagonize mRNAs and Small Non-Coding RNAs in The Host Cell
Herbs and the essential oils derived from them have been used from the beginning of human history for different purposes. Their beneficial properties have been applied to mask unpleasant odors, attract the attention of other people, add flavor and aroma properties to prepared dishes, perfumes, and cosmetics, etc. Herbs and essential oils (EOs) have also been used in medicine because of their biological properties, such as larvicidal action, analgesic and anti-inflammatory properties, antioxidant, fungicide, and antitumor activities, and many more. Many EOs exhibit antimicrobial properties, which is extremely important in fields of science and industry, such as medicine, agriculture, or cosmetology. Among the 250 EOs which are commercially available, about a dozen possess high antimicrobial potential. According to available papers and patents, EOs seem to be a potential alternative to synthetic compounds, especially because of the resistance that has been increasingly developed by pathogenic microorganisms. In this review we summarize the latest research studies about the most-active EOs that are known and used because of their antimicrobial properties. Finally, it is noteworthy that the antimicrobial activities of EOs are not preeminent for all strains. Further investigations should, thus, focus on targeting EOs and microorganisms.
Output: molecules Essential Oils as Antimicrobial Agents-Myth or Real Alternative?
Statistical inference for mechanistic models of partially observed dynamic systems is an active area of research. Most existing inference methods place substantial restrictions upon the form of models that can be fitted and hence upon the nature of the scientific hypotheses that can be entertained and the data that can be used to evaluate them. In contrast, the so-called plugand-play methods require only simulations from a model and are thus free of such restrictions. We show the utility of the plug-and-play approach in the context of an investigation of measles transmission dynamics. Our novel methodology enables us to ask and answer questions that previous analyses have been unable to address. Specifically, we demonstrate that plug-and-play methods permit the development of a modelling and inference framework applicable to data from both large and small populations. We thereby obtain novel insights into the nature of heterogeneity in mixing and comment on the importance of including extra-demographic stochasticity as a means of dealing with environmental stochasticity and model misspecification. Our approach is readily applicable to many other epidemiological and ecological systems.
Output: Plug-and-play inference for disease dynamics: measles in large and small populations as a case study
Background: Bacterial pneumonia (BP) is an inflammation of the lower airways and lung parenchyma secondary to bacterial infection. The pathogenesis of BP in dogs is complex and the role of canine respiratory viruses has not been fully evaluated. Objectives: The aim of this study was to investigate the occurrence of viral co-infections in dogs with BP and to assess demographic or clinical variables as well as disease severity associated with viral co-infections. Animals: Twenty household dogs with BP caused by opportunistic bacteria and 13 dogs with chronic (>30 days) tracheobronchitis caused by Bordetella bronchiseptica (BBTB). Methods: Prospective cross-sectional observational study. Diagnosis was confirmed by clinical and laboratory findings, diagnostic imaging, and cytologic and microbiologic analysis of bronchoalveolar lavage or transtracheal wash fluid. Canine parainfluenza virus (CPIV), canine adenovirus, canine herpes virus, canine influenzavirus, canine distemper virus, canine respiratory coronavirus (CRCoV) and canine pneumovirus, as well as B. bronchiseptica and Mycoplasma spp. were analyzed in respiratory samples using PCR assays. Results: CPIV was detected in 7/20 and CRCoV in 1/20 dogs with BP. Respiratory viruses were not detected in dogs with BBTB. There were no significant differences in clinical variables between BP dogs with and without a viral co-infection. Conclusion and Clinical Importance: Respiratory viruses were found frequently in dogs with BP and may therefore play an important role in the etiology and pathogenesis of BP. Clinical variables and disease severity did not differ between BP dogs with and without viral co-infection.
Output: Co-infections with Respiratory Viruses in Dogs with Bacterial Pneumonia
The 2005 International Health Regulations (IHR) came into force for all Member States of the World Health Organization (WHO) in June 2007 and the deadline for achieving compliance was June 2012. The purpose of the IHR is to prevent, protect against, control -and provide a public health response to -international spread of disease. The territory of the United Kingdom of Great Britain and Northern Ireland and that of several other Member States, such as China, Denmark, France, the Netherlands and the United States of America, include overseas territories, which cover a total population of approximately 15 million people. Member States have a responsibility to ensure that all parts of their territory comply with the IHR. Since WHO has not provided specific guidance on compliance in the special circumstances of the overseas territories of Member States, compliance by these territories is an issue for self-assessment by Member States themselves. To date, no reports have been published on the assessment of IHR compliance in countries with overseas territories. We describe a gap analysis done in the United Kingdom to assess IHR compliance of its overseas territories. The findings and conclusions are broadly applicable to other countries with overseas territories which may have yet to assess their compliance with the IHR. Such assessments are needed to ensure compliance across all parts of a Member States' territory and to increase global health security.
Output: Achieving compliance with the International Health Regulations by overseas territories of the United Kingdom of Great Britain and Northern Ireland
The current COVID-19 pandemic is stretching the global supply situation for face masks and PPE beyond production capacity. This is a call for the R&D community, particularly in the polymer degradation and stability arena, to engage and collaborate with virology and bio-medical experts. We require comparative R&D for extended, reuse and recyclability options, as well as large scale approaches and methods that could quickly be applied on the local level by the public who are not experts and may only have limited resources.
Output: Opinion to Address a Potential Personal Protective Equipment Shortage in the Global Community During the COVID-19 Outbreak
Non-polio enteroviruses are emerging viruses known to cause outbreaks of polio-like infections in different parts of the world with several cases already reported in Asia Pacific, Europe and in United States of America. These outbreaks normally result in overstretching of health facilities as well as death in children under the age of five. Most of these infections are usually self-limiting except for the neurological complications associated with human enterovirus A 71 (EV-A71). The infection dynamics of these viruses have not been fully understood, with most inferences made from previous studies conducted with poliovirus. Non-poliovirus enteroviral infections are responsible for major outbreaks of hand, foot and mouth disease (HFMD) often associated with neurological complications and severe respiratory diseases. The myriad of disease presentations observed so far in children calls for an urgent need to fully elucidate the replication processes of these viruses. There are concerted efforts from different research groups to fully map out the role of human host factors in the replication cycle of these viral infections. Understanding the interaction between viral proteins and human host factors will unravel important insights on the lifecycle of this groups of viruses. This review provides the latest update on the interplay between human host factors/processes and non-polio enteroviruses (NPEV). We focus on the interactions involved in viral attachment, entry, internalization, uncoating, replication, virion assembly and eventual egress of the NPEV from the infected cells. We emphasize on the virus-human host interplay and highlight existing knowledge gaps that needs further studies. Understanding the NPEV-human host factors interactions will be key in the design and development of vaccines as well as antivirals against enteroviral infections. Dissecting the role of human host factors during NPEV infection cycle will provide a clear picture of how NPEVs usurp the human cellular processes to establish an efficient infection. This will be a boost to the drug and vaccine development against enteroviruses which will be key in control and eventual elimination of the viral infections.
Output: Recent advances on the role of host factors during non-poliovirus enteroviral infections
We conducted an epidemiologic investigation among survivors of an outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in Jordan. A second-trimester stillbirth occurred during the course of an acute respiratory illness that was attributed to MERS-CoV on the basis of exposure history and positive results of MERS-CoV serologic testing. This is the first occurrence of stillbirth during an infection with MERS-CoV and may have bearing upon the surveillance and management of pregnant women in settings of unexplained respiratory illness potentially due to MERS-CoV. Future prospective investigations of MERS-CoV should ascertain pregnancy status and obtain further pregnancy-related data, including biological specimens for confirmatory testing.
Output: Stillbirth During Infection With Middle East Respiratory Syndrome Coronavirus
Zika virus (ZIKV) infection in pregnant women can lead to fetal deaths and malformations. We have previously reported that ZIKV envelope protein domain III (EDIII) is a subunit vaccine candidate with cross-neutralization activity; however, like many other subunit vaccines, its efficacy is limited. To improve the efficacy of this subunit vaccine, we identified a nonneutralizing epitope on ZIKV EDIII surrounding residue 375, which is buried in the full-length envelope protein but becomes exposed in recombinant EDIII. We then shielded this epitope with an engineered glycan probe. Compared to the wild-type EDIII, the mutant EDIII induced significantly stronger neutralizing antibodies in three mouse strains and also demonstrated significantly improved efficacy by fully protecting mice, particularly pregnant mice and their fetuses, against high-dose lethal ZIKV challenge. Moreover, the mutant EDIII immune sera significantly enhanced the passive protective efficacy by fully protecting mice against lethal ZIKV challenge; this passive protection was positively associated with neutralizing antibody titers. We further showed that the enhanced efficacy of the mutant EDIII was due to the shielding of the immunodominant nonneutralizing epitope surrounding residue 375, which led to immune refocusing on the neutralizing epitopes. Taken together, the results of this study reveal that an intrinsic limitation of subunit vaccines is their artificially exposed immunodominant nonneutralizing epitopes, which can be overcome through glycan shielding. Additionally, the mutant ZIKV protein generated in this study is a promising subunit vaccine candidate with high efficacy in preventing ZIKV infections in mice. IMPORTANCE Viral subunit vaccines generally show low efficacy. In this study, we revealed an intrinsic limitation of subunit vaccine designs: artificially exposed surfaces of subunit vaccines contain epitopes unfavorable for vaccine efficacy. More specifically, we identified an epitope on Zika virus (ZIKV) envelope protein domain III (EDIII) that is buried in the full-length envelope protein but becomes exposed in recombinant EDIII. We further shielded this epitope with a glycan, and the resulting mutant EDIII vaccine demonstrated significantly enhanced efficacy over the wild-type EDIII vaccine in protecting animal models from ZIKV infections. Therefore, the intrinsic limitation of subunit vaccines can be overcome through shielding these artificially exposed unfavorable epitopes. The engineered EDIII vaccine generated in this study is a promising vaccine candidate that can be further developed to battle ZIKV infections.
Output: Rational Design of Zika Virus Subunit Vaccine with Enhanced Efficacy
With evidence of sustained transmission in more than 190 countries, coronavirus disease 2019 has been declared a global pandemic. As such, data are urgently needed about risk factors associated with clinical outcomes. A retrospective chart review of 323 hospitalized patients with COVID-19 in Wuhan was conducted. Patients were classified into three disease severity groups (non-severe, severe, and critical), based on their initial clinical presentation. Clinical outcomes were designated as favorable and unfavorable, based on disease progression and response to treatments. Logistic regression models were performed to identify factors associated with clinical outcomes, and logrank test was conducted for the association with clinical progression. Current standard treatments did not show significant improvement on patient outcomes in the study. By univariate logistic regression model, 27 risk factors were significantly associated with clinical outcomes. Further, multivariate regression indicated that age over 65 years, smoking, critical disease status, diabetes, high hypersensitive troponin I (>0.04 pg/mL), leukocytosis (>10 x 10 9 /L) and neutrophilia (>75 x 10 9 /L) predicted unfavorable clinical outcomes. By contrast, the use of hypnotics was significantly associated with favorable outcomes. Survival analysis also confirmed that patients receiving hypnotics had significantly better survival. To our knowledge, this is the first indication that hypnotics could be an effective ancillary treatment for COVID-19. We also found that novel risk factors, such as higher hypersensitive . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint .
Output: Risk Factors Associated with Clinical Outcomes in 323 COVID-19 Patients in Wuhan, China
Waste ashes from three types of hospital waste (HW) incinerators, built in SARS (Severe Acute Respiratory Syndrome) period and currently running in China, were collected and polycyclic aromatic hydrocarbons (PAH) properties in the ashes were investigated. The mean ∑PAH levels in the waste ashes varied widely from 4.16 mg kg − 1 to 198.92 mg kg − 1 , and the mean amounts of carcinogenic PAHs ranged from 0.74 to 96.77 mg kg − 1 , exceeding the limits regulated by several countries. Among the three types of incinerators, two medium-scale incinerators generated relatively high levels of PAHs (mean ∑PAH 22.50 and 198.92 mg kg − 1 ) compared to small-scale and large-scale incinerators (mean ∑PAH 4.16 and 16.43 mg kg − 1 ). Bottom ashes were dominated by low molecular weight PAHs (LM-PAH; containing two-to three-ringed PAHs) and medium molecular weight PAHs (MM-PAH; containing four-ringed PAHs), while fly ashes were abundant in MM-PAH and high molecular weight PAHs (HM-PAH, containing five-to six-ringed PAHs). Statistical analysis indicated that there was a positive relationship (R 2 = 0.88) between organic matter and total PAHs thus it has the potential to be used as an indicator for PAHs in HW ashes. Moreover, it was found that PAHs in the ashes correlated highly with some metallic elements either positively (e.g. Fe, Ti, Mg) or negatively (Ca), indicating that these elements might promote or prevent PAH formation during HW combustion. Although bottom ash resulted from HW incinerators has not been classified as hazardous material, the results of this study indicated that this type of waste ash contained high levels of PAHs thus need special treatment before landfill. Hospital waste ash Carcinogenic substance Molecular weight distribution Heavy metal ⁎ Corresponding author. Tel.: +86 10 6284 9515; fax: +86 10 6289515. a v a i l a b l e a t w w w. s c i e n c e d i r e c t . c o m w w w. e l s e v i e r. c o m / l o c a t e / s c i t o t e n v
Output: Levels of polycyclic aromatic hydrocarbons in different types of hospital waste incinerator ashes
Nurses are the largest group of healthcare providers and are often the first line responders to a disaster event. Nurses' disaster competence, motivation for disaster engagement, and factors that impact their motivation to respond to disaster events need to be understood. The purposes of the study were to determine the predictive relationships between Taiwanese nurses' disaster competence, anticipatory disaster stress, and motivation for disaster engagement. A cross-sectional design was used to analyze data collected between August 2017 and December 2017 from eight hospitals in southern Taiwan. Ninety participants who met the recruitment criteria completed and returned questionnaires with an 88.24% response rate. Data collection involved administering the Disaster Nursing Competence Questionnaire, Anticipatory Disaster Stress Questionnaire, and the Motivation of Disaster Engagement Questionnaire. The results indicated that anticipatory disaster stress was positively correlated with disaster competence and motivation for disaster engagement. Disaster competence and willingness to join a hospital disaster rescue predicts an individuals' motivation for disaster engagement. The results of the study add to the understanding of factors that correlate with nurses' motivation to participate in disaster events. By understanding these factors, the government and healthcare administrators can design disaster education plans and other strategies to improve Taiwanese nurses' motivation to engage in disaster events.
Output: 101545 and Technology
Background: In recent years, new neonatal porcine diarrhoea (NNPD) of unknown aetiology has emerged in Denmark. NNPD affects piglets during the first week of life and results in impaired welfare, decreased weight gain, and in the worst-case scenario death. Commonly used preventative interventions such as vaccination or treatment with antibiotics, have a limited effect on NNPD. Previous studies have investigated the clinical manifestations, histopathology, and to some extent, microbiological findings; however, these studies were either inconclusive or suggested that Enterococci, possibly in interaction with Escherichia coli, contribute to the aetiology of NNPD. This study examined ileal and colonic luminal contents of 50 control piglets and 52 NNPD piglets by means of the qPCR-based Gut Microbiotassay and 16 samples by 454 sequencing to study the composition of the bacterial gut microbiota in relation to NNPD. Results: NNPD was associated with a diminished quantity of bacteria from the phyla Actinobacteria and Firmicutes while genus Enterococcus was more than 24 times more abundant in diarrhoeic piglets. The number of bacteria from the phylum Fusobacteria was also doubled in piglets suffering from diarrhoea. With increasing age, the gut microbiota of NNPD affected piglet and control piglets became more diverse. Independent of diarrhoeic status, piglets from first parity sows (gilts) possessed significantly more bacteria from family Enterobacteriaceae and species E. coli, and fewer bacteria from phylum Firmicutes. Piglets born to gilts had 25 times higher odds of having NNPD compared with piglets born to multiparous sows. Finally, the co-occurrence of genus Enterococcus and species E. coli contributed to the risk of having NNPD. The results of this study support previous findings that points towards genus Enterococcus and species E. coli to be involved in the pathogenesis of NNPD. Moreover, the results indicate that NNPD is associated with a disturbed bacterial composition and larger variation between the diarrhoeic piglets.
Output: Characterization of the bacterial gut microbiota of piglets suffering from new neonatal porcine diarrhoea
Severe acute respiratory syndrome (SARS) and human infection H7N9 influenza are emerging infectious diseases having a relatively high mortality. Epidemics of each began in China. By searching through Science Citation Index, this study analyzed the article literature on SARS and H7N9 influenza, particularly papers in the leading journals The Lancet, New England Journal of Medicine (NEJM), Nature and Science. The results show that the quantity and quality of SARS and H7N9 influenza literature from mainland China changed distinctly over the course of 10 years. Researchers from mainland China published 12 article literature in the The Lancet, NEJM, Nature and Science about H7N9 influenza, whereas mainland China had only 2 article literature about SARS in the same journals. The literature reflects China's growing strength in the science and technology of emerging infectious disease.
Output: Emerging infectious disease: trends in the literature on SARS and H7N9 influenza
Bats are recognized reservoirs for many emerging zoonotic viruses of public health importance. Identifying and cataloguing the viruses of bats is a logical approach to evaluate the range of potential zoonoses of bat origin. We characterized the fecal pathogen microbiome of both insectivorous and frugivorous bats, incorporating 281 individual bats comprising 20 common species, which were sampled in three locations of Yunnan province, by combining reverse transcription polymerase chain reaction (RT-PCR) assays and next-generation sequencing. Seven individual bats were paramyxovirus-positive by RT-PCR using degenerate primers, and these paramyxoviruses were mainly classified into three genera (Rubulavirus, Henipavirus and Jeilongvirus). Various additional novel pathogens were detected in the paramyxovirus-positive bats using Illumina sequencing. A total of 7066 assembled contigs (≥200 bp) were constructed, and 105 contigs matched eukaryotic viruses (of them 103 belong to 2 vertebrate virus families, 1 insect virus, and 1 mycovirus), 17 were parasites, and 4913 were homologous to prokaryotic microorganisms. Among the Viruses 2014, 6 2139 103 vertebrate viral contigs, 79 displayed low identity (<70%) to known viruses including human viruses at the amino acid level, suggesting that these belong to novel and genetically divergent viruses. Overall, the most frequently identified viruses, particularly in bats from the family Hipposideridae, were retroviruses. The present study expands our understanding of the bat virome in species commonly found in Yunnan, China, and provides insight into the overall diversity of viruses that may be capable of directly or indirectly crossing over into humans.
Output: Evidence for Retrovirus and Paramyxovirus Infection of Multiple Bat Species in China
BRODERICK, P. A. Distinguishing effects of cocaine IV and SC on mesoaccumbens dopamine and serotonin release with chloral hydrate anesthesia. PHARMACOL BIOCHEM BEHAV 43(3) 929-937, 1992.-The effect of IV cocaine (0.5 and 1.0 mg/kg) was studied on synaptic concentrations of dopamine (DA) and serotonin [5-hydroxytryptamine (5-HT)] in the mesoaccumbens nerve terminal, the nucleus accumbens (NAcc), in chloral hydrate-anesthetized, male Sprague-Dawley rats IRequests for reprints should be addressed to Dr.
Output: Distinguishing Effects of Cocaine IV and SC on Mesoaccumbens Dopamine and Serotonin Release With Chloral Hydrate Anesthesia
Successful in vivo infection following pathogen entry requires the evasion and subversion of multiple immunological barriers. Antimicrobial peptides (AMPs) are one of the first immune pathways upregulated during infection by multiple pathogens, in multiple organs in vivo. In humans, there are many classes of AMPs exhibiting broad antimicrobial activities, with defensins and the human cathelicidin LL-37 being the best studied examples. Whereas historically the efficacy and therapeutic potential of AMPs against bacterial infection has been the primary focus of research, recent studies have begun to elucidate the antiviral properties of AMPs as well as their role in regulation of inflammation and chemoattraction. AMPs as therapeutic tools seem especially promising against emerging infectious viral pathogens for which no approved vaccines or treatments are currently available, such as dengue virus (DENV) and Zika virus (ZIKV). In this review, we summarize recent studies elucidating the efficacy and diverse mechanisms of action of various classes of AMPs against multiple viral pathogens, as well as the potential use of human AMPs in novel antiviral therapeutic strategies.
Output: viruses Human Antimicrobial Peptides as Therapeutics for Viral Infections
Paul, P.S., 1990. Applications of nucleic acid probes in veterinary infectious diseases. Vet. Microbiol., 24:409-417. Nucleic acid probe technology is increasingly being used in basic research in veterinary microbiology and in diagnosis of infectious diseases of veterinary importance. This review presents an overview of nucleic acid probe methodology and its applications in veterinary infectious diseases. The major applications of nucleic acid probes include detection of pathogens in clinical samples, especially those organisms which are fastidious and difficult to cultivate, differentiation of virulent from avirulent organisms and vaccine strains from wild type isolates, typing of microorganisms, mapping genes, screening libraries of cloned DNA for specific genes, detection of latently infected or carrier animals, study of mechanisms of pathogenesis, epidemiological studies and food safety. 0378-1135/90/$03.50
Output: Applications of nucleic acid probes in veterinary infectious diseases
A reversed passive hemagglutination (I~PHA) method was developed for the detection of bovine eoronavirus in fecal specimens. Sheep erythrocytes fixed with glutaraldehyde, and then treated with tannic acid were coated with anti-bovine coronavirus rabbit antibodies purified by affinity chromatography using bovine eoronavirus linked to Sepharose 4B. The RPHA test was carried out by a microtiter method. Erythrocytes coated with purified specific antibodies were agglutinated by bovine coronavirus, but not by bovine rotavirus or enterovirus. The reaction was inhibited by antiserum to bovine coronavirus, confirming the specificity of the reaction. The I~PIIA test detected bovine coronavirus in 13 of 22 fecal specimens (59 per cent), from natural cases of diarrhea, while the positive rates were only 14 per cent (3/22) and 22 per cent (5/22) for immunofluorescent staining of primary cultures of calf kidney cells infected with the specimens, and immune electron microscopy respectively. The advantages of the I~PHA method are its simplicity, high sensitivity and rapidity.
Output: Archives of Virology Detection of Bovine Coronavirus in Feces by Reversed Passive Hemagglutination
Co-inhibitory pathways have a fundamental function in regulating T cell responses and control the balance between promoting efficient effector functions and restricting immune pathology. The TIGIT pathway has been implicated in promoting T cell dysfunction in chronic viral infection. Importantly, TIGIT signaling is functionally linked to IL-10 expression, which has an effect on both virus control and maintenance of tissue homeostasis. However, whether TIGIT has a function in viral persistence or limiting tissue pathology is unclear. Here we report that TIGIT modulation effectively alters the phenotype and cytokine profile of T cells during influenza and chronic LCMV infection, but does not affect virus control in vivo. Instead, TIGIT has an important effect in limiting immune pathology in peripheral organs by inducing IL-10. Our data therefore identify a function of TIGIT in limiting immune pathology that is independent of viral clearance.
Output: TIGIT limits immune pathology during viral infections
Next-generation sequencing (NGS). High-throughput, massively parallel sequencing technology that is used in various applications, including whole-genome sequencing, exome sequencing and RNA sequencing. Abstract | With the emergence of RNA sequencing (RNA-seq) technologies, RNA-based biomolecules hold expanded promise for their diagnostic, prognostic and therapeutic applicability in various diseases, including cancers and infectious diseases. Detection of gene fusions and differential expression of known disease-causing transcripts by RNA-seq represent some of the most immediate opportunities. However, it is the diversity of RNA species detected through RNA-seq that holds new promise for the multi-faceted clinical applicability of RNA-based measures, including the potential of extracellular RNAs as non-invasive diagnostic indicators of disease. Ongoing efforts towards the establishment of benchmark standards, assay optimization for clinical conditions and demonstration of assay reproducibility are required to expand the clinical utility of RNA-seq. © 2 0 1 6 M a c m i l l a n P u b l i s h e r s L i m i t e d . A l l r i g h t s r e s e r v e d . A technology platform that does not depend on genome annotation, or on predesigned species-specific or transcript-specific probes, for transcript measurement. RNA-seq technology functions as an open platform allowing for unbiased detection of both known and novel transcripts.
Output: Translating RNA sequencing into clinical diagnostics: opportunities and challenges
Background: Since the discovery of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, diagnostic protocols were quickly published and deployed globally. Objectives: We set out to assess the quality of MERS-CoV molecular diagnostics worldwide. Study design: Both sensitivity and specificity were assessed using 12 samples containing different viral loads of MERS-CoV or common coronaviruses (OC43, 229E, NL63, HKU1). Results: The panel was sent to more than 106 participants, of which 99 laboratories from 6 continents returned 189 panel results.Scores ranged from 100% (84 laboratories) to 33% (1 laboratory). 15% of respondents reported quantitative results, 61% semi-quantitative (Ct-values or time to positivity) and 24% reported qualitative results. The major specific technique used was real-time RT-PCR using the WHO recommended targets upE, ORF1a and ORF1b. The evaluation confirmed that RT-PCRs targeting the ORF1b are less sensitive, and therefore not advised for primary diagnostics. Conclusions: The first external quality assessment MERS-CoV panel gives a good insight in molecular diagnostic techniques and their performances for sensitive and specific detection of MERS-CoV RNA globally. Overall, all laboratories were capable of detecting MERS-CoV with some differences in sensitivity. The observation that 8% of laboratories reported false MERS-CoV positive single assay results shows room for improvement, and the importance of using confirmatory targets.
Output: First international external quality assessment of molecular diagnostics for Mers-CoV
Background: China has become the world's second largest healthcare market based on a recent report by the World Health Organization. Eventhough China achieved universal health insurance coverage in 2011, representing the largest expansion of insurance coverage in human history achieved; health inequality remains endemic in China. Lessons from the effect of market crisis on health equity in Europe and other places has reignited interest in exploring the potential healthcare market aberrations that can trigger distributive injustice in healthcare resource allocation among China's provinces. Recently, many healthcare investors in China have become more concerned about capital preservation, and are responding by abandoning long term investments strategies in healthcare. This investment withdrawal en mass is perceived to be influenced by herding tendencies and can trigger or consolidate endemic health inequality. Methods: Our study simultaneously employs four testing models (two state spaced models and two return dispersion models) to establish the existence of procyclical (herding) behavior among the stocks and its health equity implications. These are applied to a large set of data to compare and contrast results of herd formation among investors in fourteen healthcare sectors in China. Results: The study reveals that apart from the cross sectional standard deviation (CSSD) model, the remaining two models and our augmented state space model yields significant evidence of herding in all subsectors of the healthcare market. We also find that the herding effect is more prominent during down movements of the market. Conclusion: Herding behavior may lead to contemporaneous loss of investor confidence and capital withdrawal and thereby deprive the healthcare sector of the much needed capital for expansion. Thus there may be obvious delay in efforts to bridge the gap in access to healthcare facilities, medical support services, medical supplies, pharmaceuticals, biotechnology, diagnostic substances, medical laboratory and advanced medical equipment across China. Moreover, a potential crash in the healthcare market is possible in the healthcare sector as a result of persistent herding tendencies among investors and that may have more damaging consequences for health inequality in China.
Output: The effect of herd formation among healthcare investors on health sector growth in China
Middle East respiratory syndrome coronavirus (MERS-CoV) has caused human respiratory infections with a high case fatality rate since 2012. However, the mode of virus transmission is not well understood. The findings of epidemiological and virological studies prompted us to hypothesize that the human gastrointestinal tract could serve as an alternative route to acquire MERS-CoV infection. We demonstrated that human primary intestinal epithelial cells, small intestine explants, and intestinal organoids were highly susceptible to MERS-CoV and can sustain robust viral replication. We also identified the evidence of enteric MERS-CoV infection in the stool specimen of a clinical patient. MERS-CoV was considerably resistant to fed-state gastrointestinal fluids but less tolerant to highly acidic fasted-state gastric fluid. In polarized Caco-2 cells cultured in Transwell inserts, apical MERS-CoV inoculation was more effective in establishing infection than basolateral inoculation. Notably, direct intragastric inoculation of MERS-CoV caused a lethal infection in human DPP4 transgenic mice. Histological examination revealed MERS-CoV enteric infection in all inoculated mice, as shown by the presence of virus-positive cells, progressive inflammation, and epithelial degeneration in small intestines, which were exaggerated in the mice pretreated with the proton pump inhibitor pantoprazole. With the progression of the enteric infection, inflammation, virus-positive cells, and live viruses emerged in the lung tissues, indicating the development of sequential respiratory infection. Taken together, these data suggest that the human intestinal tract may serve as an alternative infection route for MERS-CoV.
Output: Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus
We analyzed the virulence of pandemic H1N1 2009 influenza A viruses in vivo and in vitro. Selected viruses isolated in 2009Selected viruses isolated in , 2010Selected viruses isolated in , 2014Selected viruses isolated in , and 2015 were assessed using an aerosol-mediated high-dose infection model for pigs as well as air-liquid interface cultures of differentiated airway epithelial cells. Using a dyspnea score, rectal temperature, lung lesions, and viral load in the lung as parameters, the strains from 2014-2015 were significantly less virulent than the strains isolated in 2009-2010. In vitro, the viruses from 2009-2010 also differed from the 2014-2015 viruses by increased release of infectious virus, a more pronounced loss of ciliated cells, and a reduced thickness of the epithelial cell layer. Our in vivo and in vitro results reveal an evolution of A(H1N1)pdm09 viruses toward lower virulence. Our in vitro culture system can be used to predict the virulence of influenza viruses.
Output: The Journal of Infectious Diseases Infection Studies in Pigs and Porcine Airway Epithelial Cells Reveal an Evolution of A(H1N1)pdm09 Influenza A Viruses Toward Lower Virulence
Viroporins are members of a rapidly growing family of channel-forming small polypeptides found in viruses. The present review will be focused on recent structural and protein-protein interaction information involving two viroporins found in enveloped viruses that target the respiratory tract; (i) the envelope protein in coronaviruses and (ii) the small hydrophobic protein in paramyxoviruses. Deletion of these two viroporins leads to viral attenuation in vivo, whereas data from cell culture shows involvement in the regulation of stress and inflammation. The channel activity and structure of some representative members of these viroporins have been recently characterized in some detail. In addition, searches for protein-protein interactions using yeast-two hybrid techniques have shed light on possible functional roles for their exposed cytoplasmic domains. A deeper analysis of these interactions should not only provide a more complete overview of the multiple functions of these viroporins, but also suggest novel strategies that target protein-protein interactions as much needed antivirals. These should complement current efforts to block viroporin channel activity.
Output: Protein-Protein Interactions of Viroporins in Coronaviruses and Paramyxoviruses: New Targets for Antivirals?
Mannose-binding lectin (MBL) is a key soluble pathogen recognition protein of the innate immune system that binds specific mannose-containing glycans on the surfaces of microbial agents and initiates complement activation via the lectin pathway. Prior studies showed that MBL-dependent activation of the complement cascade neutralized insect cell-derived West Nile virus (WNV) in cell culture and restricted pathogenesis in mice. Here, we investigated the antiviral activity of MBL in infection by dengue virus (DENV), a related flavivirus. Using a panel of naïve sera from mouse strains deficient in different complement components, we showed that inhibition of infection by insect cell-and mammalian cell-derived DENV was primarily dependent on the lectin pathway. Human MBL also bound to DENV and neutralized infection of all four DENV serotypes through complement activation-dependent and -independent pathways. Experiments with human serum from naïve individuals with inherent variation in the levels of MBL in blood showed a direct correlation between the concentration of MBL and neutralization of DENV; samples with high levels of MBL in blood neutralized DENV more efficiently than those with lower levels. Our studies suggest that allelic variation of MBL in humans may impact complement-dependent control of DENV pathogenesis. Citation Avirutnan P, et al. 2011. Complement-mediated neutralization of dengue virus requires mannose-binding lectin. mBio 2(6):e00276-11.
Output: Complement-Mediated Neutralization of Dengue Virus Requires Mannose-Binding Lectin
A new viral sequence likely belonging to a virus of the family Astroviridae was determined using the gut content of chickens affected with the runting-stunting syndrome (RSS) in chickens. Since the appropriate virus could not be isolated in cell culture the open reading frame of the viral capsid protein was cloned to generate a recombinant baculovirus. The protein was purified and used as an experimental vaccine in broiler breeders to provide maternal derived antibodies for the protection of the offspring. The presence of specific antibodies was monitored by an ELISA. The offspring of vaccinated breeder hens were partially protected in a RSS challenge model.
Output: A purified recombinant baculovirus expressed capsid protein of a new astrovirus provides partial protection to runting-stunting syndrome in chickens
Background: Host genetic factors are important determinants in tuberculosis (TB). The SLC11A1 (or NRAMP1) gene has been studied extensively for genetic association with TB, but with inconsistent findings. In addition, no study has yet looked into the effect of sex and age on the relationship between SLC11A1 polymorphisms and TB. Methods: A case-control study was conducted. In total, 278 pulmonary TB patients and 282 sex-and agematched controls without TB were recruited. All subjects were ethnic Chinese. On the basis of linkage disequilibrium pattern, three genetic markers from SLC11A1 and one from the nearby IL8RB locus were selected and examined for association with TB susceptibility. These markers were genotyped using single strand conformation polymorphism analysis or fragment analysis of amplified products. Results: Statistically significant differences in allele (P = 0.0165, OR = 1.51) and genotype (P = 0.0163, OR = 1.59) frequencies of the linked markers SLC6a/b (classically called D543N and 3'UTR) of the SLC11A1 locus were found between patients and controls. With stratification by sex, positive associations were identified in the female group for both allele (P = 0.0049, OR = 2.54) and genotype (P = 0.0075, OR = 2.74) frequencies. With stratification by age, positive associations were demonstrated in the young age group (age ≤65 years) for both allele (P = 0.0047, OR = 2.52) and genotype (P = 0.0031, OR = 2.92) frequencies. All positive findings remained significant even after correction for multiple comparisons. No significant differences were noted in either the male group or the older age group. No significant differences were found for the other markers (one SLC11A1 marker and one IL8RB marker) either. This study confirmed the association between SLC11A1 and TB susceptibility and demonstrated for the first time that the association was restricted to females and the young age group.
Output: BMC Infectious Diseases Sex-and age-dependent association of SLC11A1 polymorphisms with tuberculosis in Chinese: a case control study