niryuu/sni-each-converted huggingface dataset:
Newcastle disease virus (NDV) hemagglutininneuraminidase (HN) is a multifunctional protein, which possesses both the receptor recognition and neuraminidase activities. The fusion (F) protein is a type I membrane glycoprotein that mediates the merger of the viral envelope to the host cell membrane. Although the functions of the HN and F proteins have been well studied, however, the factors shaping synonymous codon usage bias and nucleotide composition in HN and F genes have been few reported. In our study, we analyzed synonymous codon usage using the 69 NDV HN and F genes, respectively. The general correlation between base composition and codon usage bias suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in HN and F genes. In addition, other factors, such as the aromaticity and hydrophobicity, also influence the codon usage variation among HN and F genes. This study represents the most comprehensive analysis to date of NDV HN and F genes codon usage patterns and provides a basic understanding of the mechanisms for codon usage bias.
Output: Analysis of synonymous codon usage in Newcastle disease virus hemagglutinin-neuraminidase (HN) gene and fusion protein (F) gene
Background: The frequent occurrence of ferret badger-associated human rabies cases in southeast China highlights the lack of laboratory-based surveillance and urges revisiting the potential importance of this animal in rabies transmission. To determine if the ferret badgers actually contribute to human and dog rabies cases, and the possible origin of the ferret badger-associated rabies in the region, an active rabies survey was conducted to determine the frequency of rabies infection and seroprevalence in dogs and ferret badgers. Methods: A retrospective survey on rabies epidemics was performed in Zhejiang, Jiangxi and Anhui provinces in southeast China. The brain tissues from ferret badgers and dogs were assayed by fluorescent antibody test. Rabies virus was isolated and sequenced for phylogenetic analysis. The sera from ferret badgers and dogs were titrated using rabies virus neutralizing antibodies (VNA) test. The ferret badgers presented a higher percentage of rabies seroconversion than dogs did in the endemic region, reaching a maximum of 95% in the collected samples. Nine ferret badger-associated rabies viruses were isolated, sequenced, and were phylogenetically clustered as a separate group. Nucleotide sequence revealed 99.4-99.8% homology within the ferret badger isolates, and 83-89% homology to the dog isolates in the nucleoprotein and glycoprotein genes in the same rabies endemic regions. Conclusions: Our data suggest ferret badger-associated rabies has likely formed as an independent enzootic originating from dogs during the long-term rabies infestation in southeast China. The eventual role of FB rabies in public health remains unclear. However, management of ferret badger bites, rabies awareness and control in the related regions should be an immediate need.
Output: Ferret badger rabies origin and its revisited importance as potential source of rabies transmission in Southeast China
Background: Infection by multidrug-resistant (MDR) pathogens leads to poor patient outcomes in intensive care units (ICUs). Contact precautions are necessary to reduce the transmission of MDR pathogens. However, the importance of the surrounding environment is not well known. We studied the effects of ICU relocation on MDR respiratory pathogen detection rates and patient outcomes. Methods: Patients admitted to the ICU before and after the relocation were retrospectively analyzed. Baseline patient characteristics, types of respiratory pathogens detected, antibiotics used, and patient outcomes were measured. Results: A total of 463 adult patients admitted to the ICU, 4 months before and after the relocation, were included. Of them, 234 were admitted to the ICU before the relocation and 229 afterward. Baseline characteristics, including age, sex, and underlying comorbidities, did not differ between the two groups. After the relocation, the incidence rate of MDR respiratory pathogen detection decreased from 90.0 to 68.8 cases per 1,000 patient-days, but that difference was statistically insignificant. The use of colistin was significantly reduced from 53.5 days (95% confidence interval [CI], 20.3 to 86.7 days) to 18.7 days (95% CI, 5.6 to 31.7 days). Furthermore, the duration of hospital stay was significantly reduced from a median of 29 days (interquartile range [IQR], 14 to 50 days) to 21 days (IQR, 11 to 39 days). Conclusions: Incidence rates of MDR respiratory pathogen detection were not significantly different before and after ICU relocation. However, ICU relocation could be helpful in reducing the use of antibiotics against MDR pathogens and improving patient outcomes.
Output: Intensive Care Unit Relocation and Its Effect on Multidrug-Resistant Respiratory Microorganisms
Background: Lower respiratory tract infections in the first years of life are associated with later asthma, and this observation has led to a focus on the potential causal role of specific respiratory viruses, such as rhinoviruses and respiratory syncytial virus, in asthma development. However, many respiratory viruses and bacteria trigger similar respiratory symptoms and it is possible that the important risk factors for asthma are the underlying susceptibility to infection and the exaggerated reaction to such triggers rather than the particular triggering agent. Objective: We sought to study the association between specific infections in early life and development of asthma later in childhood. Methods: Three hundred thirteen children were followed prospectively in the Copenhagen Prospective Studies of Asthma in Childhood 2000 high-risk birth cohort. Nine respiratory virus types (respiratory syncytial virus, rhinoviruses, other picornaviruses, coronaviruses 229E and OC43, parainfluenza viruses 1-3, influenza viruses AH1, AH3, and B, human metapneumovirus, adenoviruses, and bocavirus) and 3 pathogenic airway bacteria (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) were identified in airway secretions sampled during episodes of troublesome lung symptoms in the first 3 years of life. Asthma was determined by age 7 years. Results: In unadjusted analyses, all viruses and pathogenic bacteria identified during episodes of troublesome lung symptoms were associated with increased risk of asthma by age 7 years with similar odds ratios for all viruses and pathogenic bacteria. After adjustment for the frequency of respiratory episodes, the particular triggers were no longer associated with asthma. Conclusion: The number of respiratory episodes in the first years of life, but not the particular viral trigger, was associated with later asthma development. This suggests that future research should focus on the susceptibility and exaggerated response to lower respiratory tract infections in general rather than on the specific triggering agent. (J Allergy Clin Immunol 2015;136:81-6.)
Output: Association between respiratory infections in early life and later asthma is independent of virus type
The following six methods for detecting rotavirus in human faecal samples were compared: electron microscopy, immune electron microscopy, immunofluoreseence in cell culture, two enzyme immunoassays (Rotazyme, Enzygnost) and a latex agglutination test (Rotalex). Specimens were collected from 112 children with diarrhoea. The relative sensitivities of the different assays for human rotavirus were as follows: electron microscopy, 84%; immunofluorescence, 86 %; Rotalex, 88 %; Rotazyme, 89 %; immune electron microscopy, 93 %; Enzygnost, 98 %. According to our findings Enzygnost is the most sensitive method, but Rotalex is more valuable for screening a small number of faecal samples. No false-positive results were observed in the two enzyme immunoassays or in Rotalex.
Output: Comparison of Six Methods for Detecting Human Rotavirus in Stools
Background. Mannose-binding lectin (MBL) is a pattern-recognition molecule, which functions as a first line of host defense. Pandemic H1N1 (pdmH1N1) influenza A virus caused massive infection in 2009 and currently circulates worldwide. Avian influenza A H9N2 (H9N2/G1) virus has infected humans and has the potential to be the next pandemic virus. Antiviral function and immunomodulatory role of MBL in pdmH1N1 and H9N2/G1 virus infection have not been investigated. Methods. In this study, MBL wild-type (WT) and MBL knockout (KO) murine models were used to examine the role of MBL in pdmH1N1 and H9N2/G1 virus infection. Results. Our study demonstrated that in vitro, MBL binds to pdmH1N1 and H9N2/G1 viruses, likely via the carbohydrate recognition domain of MBL. Wild-type mice developed more severe disease, as evidenced by a greater weight loss than MBL KO mice during influenza virus infection. Furthermore, MBL WT mice had enhanced production of proinflammatory cytokines and chemokines compared with MBL KO mice, suggesting that MBL could upregulate inflammatory responses that may potentially worsen pdmH1N1 and H9N2/G1 virus infections. Conclusions. Our study provided the first in vivo evidence that MBL may be a risk factor during pdmH1N1 and H9N2/G1 infection by upregulating proinflammatory response.
Output: Mannose-Binding Lectin Contributes to Deleterious Inflammatory Response in Pandemic H1N1 and Avian H9N2 Infection
Apoptosis has been postulated to play an important role during feline infectious peritonitis virus (FIPV) infection; however, its mechanism is not well characterized. This study is focused on apoptosis and transcriptional profiling of FIPV-infected cells following in vitro infection of CRFK cells with FIPV 79-1146 WSU. Flow cytometry was used to determine mode of cell death in first 42 h post infection (hpi). FIPV infected cells underwent early apoptosis at 9 hpi (p \ 0.05) followed by late apoptosis at 12 hpi (p \ 0.05) and necrosis from 24 hpi (p \ 0.05). Then, next generation sequencing was performed on 9 hpi and control uninfected cells by Illumina analyzer. An aggregate of 4546 genes (2229 down-regulated and 2317 up-regulated) from 17 cellular process, 11 molecular functions and 130 possible biological pathways were affected by FIPV. 131 genes from apoptosis cluster (80 down-regulated and 51 up-regulated) along with increase of apoptosis, p53, p38 MAPK, VEGF and chemokines/cytokines signaling pathways were probably involved in apoptosis process. Six of the de-regulated genes expression (RASSF1, BATF2, MAGEB16, PDCD5, TNFa and TRAF2) and TNFa protein concentration were analyzed by RT-qPCR and ELISA, respectively, at different time-points. Up-regulations of both pro-apoptotic (i.e. PDCD5) and anti-apoptotic (i.e. TRAF2) were detected from first hpi and continuing to deregulate during apoptosis process in the infected cells.
Output: Apoptosis transcriptional mechanism of feline infectious peritonitis virus infected cells
Biological attacks can cause both an epidemic of infectious disease and of fear and panic. Epidemiological triangle chain models can be used to present both these types of epidemic. By merging these two triangles we suggest a new four-sided pyramidal model of bioterrorism attack and appropriate levels of prevention. Primordial prevention of biological attacks should comprise the impeding of access of both terrorists and biological agents to the territory. The primary prevention level should comprise internal surveillance of potential sources of agents and terrorists. Secondary prevention activities should be directed toward breaking both the epidemic of infectious disease and that of fear and panic. Tertiary prevention should include measures for repair following the attack. This is a task mainly for mental health professionals, curing and rehabilitating those affected by the epidemic of fear and panic. The suggested epidemiological model can be implemented into training programmes for detecting and responding to bioterrorist attacks around the world.
Output: Bioterrorism-Types of epidemics, new epidemiological paradigm and levels of prevention
To understand mechanisms of viral diarrhea further, we studied ileal ion transport in vitro in relation to mucosal changes and epithelial differentiation in transmissible gastroenteritis in piglets, an invasive viral enteritis thought to involve mainly proximal intestine. In infected pigs, at the height of diarrhea, short-circuited ileal epithelium failed actively to transport Na+ and Cl-, and there was a defect of glucose-mediated Na+ transport. The Clsecretory response to theophylline remained intact. Conductance measurements indicate that paracellular permeability may be reduced and transcellular transport may be altered. A mucosal lesion was observed at the time of the transport changes, characterized by villus blunting, crypt hyperplasia, and immature crypt-type enterocytes on the villus epithelium, deficient in disaccharidase and (Na+, K+)A TPase activity but rich in thymidine kinase. Consideration of the major determinants of diarrhea in this invasive enteritis must take into account not only altered mucosal function and differentiation but also the extent of intestinal involvement, including the ileum, a major site of fluid absorption in the intestine.
Output: Determinants of Diarrhea in Viral Enteritis The Role of Ion Transport and Epithelial Changes in the Ileum in Transmissible Gastroenteritis in Piglets
Rotavirus NSP2 is an abundant nonstructural RNA-binding protein essential for forming the viral factories that support replication of the double-stranded RNA genome. NSP2 exists as stable doughnut-shaped octamers within the infected cell, representing the tail-to-tail interaction of two tetramers. Extending diagonally across the surface of each octamer are four highly basic grooves that function as binding sites for single-stranded RNA. Between the N and C-terminal domains of each monomer is a deep electropositive cleft containing a catalytic site that hydrolyzes the γ-β phosphoanhydride bond of any NTP. The catalytic site has similarity to those of the histidine triad (HIT) family of nucleotide-binding proteins. Due to the close proximity of the grooves and clefts, we investigated the possibility that the RNA-binding activity of the groove promoted the insertion of the 5′-triphosphate moiety of the RNA into the cleft, and the subsequent hydrolysis of its γ-β phosphoanhydride bond. Our results show that NSP2 hydrolyzes the γP from RNAs and NTPs through Mg 2+ -dependent activities that proceed with similar reaction velocities, that require the catalytic His 225 residue, and that produce a phosphorylated intermediate. Competition assays indicate that although both substrates enter the active site, RNA is the preferred substrate due to its higher affinity for the octamer. The RTPase activity of NSP2 may account for the absence of 5′-terminal γP on the (−) strands of the dsRNA genome segments. This is the first report of a HIT-like protein with a multifunctional catalytic site, capable of accommodating both NTPs and RNAs during γP hydrolysis.
Output: Histidine Triad-Like Motif of the Rotavirus NSP2 Octamer Mediates Both RTPase and NTPase Activities
Objective: Garlic is a plant has been used as a flavor, and antimicrobial and anti-diarrheal agent. Infectious bronchitis virus (IBV) is a coronavirus. The available vaccines against IBV cannot cover new variants. This study evaluated the inhibitory effects of garlic extract on IBV. Materials and Methods: The constituents of garlic extract were detected by gas chromatography. This study was done in four groups of embryonic SPF eggs; first group was used for virus titration; second group received the mixture of different virus titration and constant amount of garlic extract; third group received 10 -3 titration of virus and after 8 hr received garlic extract and the last group received different dilutions of garlic extract. Results: Based on our results, in the second group, IBV vaccine strain (4/91) at all titration and M41 in 10 -2 and 10 -3 titration and in the third group both variants of virus the embryonic Index (EI) was significantly increased. Conclusion: The garlic extract had inhibitory effects on IBV in the chickens embryo. Please cite this paper as Mohajer Shojai T, Ghalyanchi Langeroudi A, Karimi V, Barin A, Sadri N. The Effect of Allium sativum (Garlic) extract on infectious bronchitis virus in specific pathogen free embryonic egg. Avicenna J Phytomed, 2016; 6 (4): 458-467.
Output: The effect of Allium sativum (Garlic) extract on infectious bronchitis virus in specific pathogen free embryonic egg
Background: Emergency Departments (ED) are challenged during influenza season by patients who present acutely during sporadic ED visits. ED management is largely empiric, often occurring without reliable diagnostics needed for targeted therapies, safe outpatient discharge, or hospital admissions. Objective: To evaluate the impact of the influenza diagnosis on physician decision making during ED visits using the Cobas Liat ® influenza A + B assay. Study design: Prospective study assessing the impact of rapid (< 30 min), reverse-transcriptase polymerase chain reaction (RT-PCR) influenza testing on physician decision making in the ED. Physician responses established preand post-diagnosis management courses which required confirmation via secondary documentation in the medical record. Changes in physician decision making were analyzed across four clinical touchpoints: (i) admission/discharge status, (ii) medical procedures, (iii) antiviral and antibiotic prescribing, and (iv) laboratory studies. Results: An influenza diagnosis changed patient management courses, relative to empiric, pre-diagnosis plans, in in 61% of the cases resulting in cost savings of $49,420-to-$42,270 over 143 patients and 104 days during influenza season resulting in a cost savings of $200.40/ED visit. Evaluation over 2000 ED patient visits projects cost savings > $578,000 due to deferred admissions, and reduction in antiviral prescribing. Sensitivity of EDbased influenza testing using the Cobas Liat ® assay was equivalent to centralized lab testing at 98.8% sensitivity and 98.5% specificity respectively. Conclusion: Providing rapid, RT-PCR influenza testing to ED settings is actionable and used to guide patient care decisions. Understanding the cascade of events linked to the influenza diagnosis in the ED provides overall cost savings which offset the cost of providing ED-based testing.
Output: Clinical decision making in the emergency department setting using rapid PCR: Results of the CLADE study group
Purpose: Central to the use of murine models of disease is the ability to derive reproducible data. The purpose of this study was to determine factors contributing to variability in our murine model of small bowel resection (SBR). Methods: Male C57Bl/6 mice were randomized to sham or 50% SBR. The effect of housing type (pathogen-free vs standard housing), nutrition (reconstituted powder vs tube feeding formulation), and correlates of intestinal morphology with gene expression changes were investigated. Multiple linear regression modeling or 1-way analysis of variance was used for data analysis. Results: Pathogen-free mice had significantly shorter ileal villi at baseline and demonstrated greater villus growth after SBR compared to mice housed in standard rooms. Food type did not affect adaptation. Gene expression changes were more consistent and significant in isolated crypt cells that demonstrated adaptive growth when compared with crypts that did not deepen after SBR. Conclusion: Maintenance of mice in pathogen-free conditions and restricting gene expression analysis to individual animals exhibiting morphologic adaptation enhances sensitivity and specificity of data derived from this model. These refinements will minimize experimental variability and lead to improved understanding of the complex process of intestinal adaptation.
Output: Lessons learned: optimization of a murine small bowel resection model B,BB
Vectors based on different serotypes of adeno-associated virus hold great promise for human gene therapy, based on their unique tissue tropisms and distinct immunological profiles. A particularly interesting candidate is AAV8, which can efficiently and rapidly transduce a wide range of tissues in vivo. To further unravel the mechanisms behind AAV8 transduction, we used yeast twohybrid analyses to screen a mouse liver complementary DNA library for cellular proteins capable of interacting with the viral capsid proteins. In total, we recovered approximately 700 clones, comprising over 300 independent genes. Sequence analyses revealed multiple hits for over 100 genes, including two encoding the endosomal cysteine proteases cathepsins B and L. Notably, these two proteases also physically interacted with the corresponding portion of the AAV2 capsid in yeast, but not with AAV5. We demonstrate that cathepsins B and L are essential for efficient AAV2-and AAV8-mediated transduction of mammalian cells, and document the ability of purified cathepsin B and L proteins to bind and cleave intact AAV2 and AAV8 particles in vitro. These data suggest that cathepsinmediated cleavage could prime AAV capsids for subsequent nuclear uncoating, and indicate that analysis of additional genes recovered in our screen may help to further elucidate the mechanisms behind transduction by AAV8 and related serotypes.
Output: A Two-hybrid Screen Identifies Cathepsins B and L as Uncoating Factors for Adeno-associated Virus 2 and 8
Granite fines, sand, rice hulls, long wheat straw, and wood shavings were compared as bedding for 60 female dairy calves. Growth, health, stress indices, and behavior of newly born calves, along with physical characteristics and bacterial counts of bedding, were evaluated for 42 d during August to October, 2002. Overall average daily gain and dry matter intake of calves did not differ due to bedding type, although during wk 2 calves housed on rice hulls had the greatest dry matter intake and those housed on wood shavings had the lowest. During wk 2, calves housed on granite fines and sand were treated more often for scours, and calves housed on long wheat straw received the fewest antibiotic treatments (week by bedding material interaction). Granite fines formed a harder surface than other bedding, and calves housed on granite fines scored the dirtiest. When bedding materials were evaluated, sand was scored to be the dirtiest, while pens bedded with rice hulls, long wheat straw, and wood shavings scored cleaner. Long wheat straw had the warmest surface temperature, and rice hulls and wood shavings were warmer than granite fines and sand. Serum cortisol, α 1 -acid glycoprotein, immunoglobulin G concentrations, and the neutrophil:lymphocyte ratio were not affected by bedding type. On d 0, coliform counts were greatest in rice hulls. After use, coliform counts were greatest in long wheat straw (week by bedding material interaction). On d 42, the concentration of ammonia at 10 cm above the bedding was lowest for long wheat straw. Growth performance of calves bedded for 42 d with 5 bedding types did not differ; however, the number of antibiotic treatments given for scours was greatest on granite fines and sand; coliform counts in the bedding were highest in rice 3736 hulls before use and in long wheat straw after 42 d of use. (Key words: calf bedding material, growth performance, health, bacterial count) Abbreviation key: AGP = α 1 -acid glycoprotein; N:L = neutrophil:lymphocyte ratio.
Output: Growth Performance and Health of Dairy Calves Bedded with Different Types of Materials
This article takes a historical perspective on the changing position of WHO in the global health architecture over the past two decades. From the early 1990s a number of weaknesses within the structure and governance of the World Health Organization were becoming apparent, as a rapidly changing post Cold War world placed more complex demands on the international organizations generally, but significantly so in the field of global health. Towards the end of that decade and during the first half of the next, WHO revitalized and played a crucial role in setting global health priorities. However, over the past decade, the organization has to some extent been bypassed for funding, and it lost some of its authority and its ability to set a global health agenda. The reasons for this decline are complex and multifaceted. Some of the main factors include WHO's inability to reform its core structure, the growing influence of non-governmental actors, a lack of coherence in the positions, priorities and funding decisions between the health ministries and the ministries overseeing development assistance in several donor member states, and the lack of strong leadership of the organization.
Output: The World Health Organization and Global Health Governance: post-1990
The analysis of 26 longevity curves of different populations of inbred (Fischer 344) and outbred (Sprague-Dawley) rats highlighted a remarkable betweenpopulations variability in survival parameters. This variability is independent of the breeding characteristics of the strain. The two strains differed in the slope of the survival curves, with Fischer 344 rats showing a higher survival over the second year of life as well as a lower interindividual variability. A model-free approach based on principal component analysis allowed us to quantify these differences and to highlight some limitations of the classical Gompertzian approach.
Output: WITHIN-AND BETWEEN-STRAIN VARIABILITY IN LONGEVITY OF INBRED AND OUTBRED RATS UNDER THE SAME ENVIRONMENTAL CONDITIONS
Background: Given that YKL-40 is a known marker of inflammation, we sought to determine its association with urinary tract infection (UTI) in febrile children. Methods: In total, 44 children aged 0 to 24 months with febrile UTI and 35 age-and sexmatched controls with fever from other causes were enrolled in the study. ELISA was performed to determine the level of YKL-40 in urine collected from each child. The ratio of urinary YKL-40 to creatinine (Cr) was higher in the children with a UTI than in the controls (P < 0.001). The area under the ROC curve for detecting UTI was 0.88 for the urinary YKL-40/Cr ratio, 0.86 for pyuria, and 0.71 for positive nitrite on urinalysis. We applied a cut-off value of 125.23 pg/mg to urinary YKL-40/Cr for detecting UTI. Eight of nine children in the control group with pyuria had urinary YKL-40/Cr levels lower than 125.23 pg/mg, and the one child in the UTI group without pyuria or positive nitrite had a urinary YKL-40/Cr level greater than 125.23 pg/mg. Determining the levels of urinary YKL-40/Cr may help identify true cases of UTI in febrile young children, especially when they have pyuria but not nitrite, or have neither pyuria nor nitrite in the urine. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Output: Urinary YKL-40 as a Candidate Biomarker for Febrile Urinary Tract Infection in Young Children
Background: During severe acute respiratory syndrome (SARS) outbreak in Toronto, outpatient clinics at SickKids Hospital were closed to prevent further disease transmission. In response, a decision was made by the neonatal neurodevelopmental follow up (NNFU) clinic staff to select patients with scheduled appointments to have a mail/telephone assessment using Ages and Stages Questionnaire (ASQ) or to postpone/skip their visit. The objective of this study was to compare the developmental assessment and its outcome in two groups of NNFU clinic patients, SARS versus non-SARS, over three standard clinic appointments. We compared the diagnostic accuracy (identification of developmental delay), and patient management (referral for therapy or communication of a new diagnosis) of the strategies used during SARS, April/May 2003, to the standard assessment methods used for patients seen in April/May 2005 (non-SARS). In all cases data were obtained for 3 patient visits: before, during and after these 2 months and were compared using descriptive statistics. Results: There were 95 patients in the SARS group and 99 non-SARS patients. The gestational age, sex, entry diagnosis and age at the clinic visit was not different between the groups. The NNFU clinic staff mailed ASQ to 27 families during SARS, 17 (63%) were returned, and 8 of the 17 were then contacted by telephone. Criteria used to identify infants at risk selected for either mailed ASQ or phone interviews were not clearly defined in the patients' charts. There was a significant under identification of developmental delay during SARS (18% versus 45%). Of those who responded to the mailed questionnaire, referrals for therapy rates were similar to non-SARS group. The lost to follow up rate was 24% for the SARS group compared with 7% for non-SARS. There was no difference in the overall rate of developmental delay in the two groups as identified at the 'after' visit. Conclusions: Poor advanced planning led to a haphazard assessment of patients during this infectious disease outbreak. Future pandemic plans should consider planning for outpatient care as well as in hospital management of patients.
Output: Lessons from SARS: A retrospective study of outpatient care during an infectious disease outbreak
Numerous viruses are able to cause respiratory tract infections. With the availability of new molecular techniques, the number of pathogens detected in specimens from the human respiratory tract has increased. Some of these viral infections have the potential to lead to severe systemic disease. Other viruses are limited to playing a role in the pathogenesis of the common cold syndrome. This chapter focuses on the viral pathogens that are linked to common cold. It is not the intention to comprehensively review all the viruses that are able to cause respiratory tract infections -this would go beyond the scope of this book. The list of viruses that are briefly reviewed here includes rhinoviruses, respiratory syncytial virus, parainfluenza virus, adenovirus, metapneumovirus and coronavirus. Bocavirus is discussed as one example of a newly identified pathogen with a less established role in the etiology and pathogenesis of common cold.
Output: The role of viruses in the etiology and pathogenesis of common cold
The Chelonid fibropapilloma-associated herpesvirus (CFPHV) is hypothesized to be the causative agent of fibropapillomatosis, a neoplastic disease in sea turtles, given its consistent detection by PCR in fibropapilloma tumours. CFPHV has also been detected recently by PCR in tissue samples from clinically healthy (non exhibiting fibropapilloma tumours) turtles, thus representing presumably latent infections of the pathogen. Given that template copy numbers of viruses in latent infections can be very low, extremely sensitive PCR assays are needed to optimize detection efficiency. In this study, efficiency of several PCR assays designed for CFPHV detection is explored and compared to a method published previously. The results show that adoption of a triplet set of singleplex PCR assays outperforms other methods, with an approximately 3-fold increase in detection success in comparison to the standard assay. Thus, a new assay for the detection of CFPHV DNA markers is presented, and adoption of its methodology is recommended in future CFPHV screens among sea turtles.
Output: Validation of a sensitive PCR assay for the detection of Chelonid fibropapilloma-associated herpesvirus in latent turtle infections
KEYWORDS Bovine Mucosal Immunology Gastrointestinal Respiratory Reproductive Microbiome The largest organ of the immune system is the mucosa making the management of it essential for productivity and health. The mucosal barrier consists of mucous, antimicrobial peptides, and IgA and is a "kill zone" to prevent microbial invasion of the epithelium. The mucosal epithelial cells are key cells that maintain the "kill zone" and "mucosal firewall" and respond to metabolites and microbial components from the lumen and signals from immune cells to maintain tight junctions and prevent leaky gut. The mucosal immune system has a unique circulatory system where immune cells that have activated in mucosal region recirculate to mucosal regions, a system termed the common mucosal system.
Output: Mucosal Immune System of Cattle All Immune Responses Begin Here
Dust storms move an estimated 500-5000 Tg of soil through Earth's atmosphere every year. Dust-storm transport of topsoils may have positive effects such as fertilization of aquatic and terrestrial ecosystems and the evolution of soils in proximal and distal environments. Negative effects may include the stripping of nutrient-rich topsoils from source regions, sandblasting of plant life in downwind environments, the fertilization of harmful algal blooms, and the transport of toxins (e.g., metals, pesticides, herbicides, etc.) and pathogenic microorganisms. With respect to the long-range dispersion of microorganisms and more specifically pathogens, research is just beginning to demonstrate the quantity and diversity of organisms that can survive this type of transport. Most studies to date have utilized different assays to identify microorganisms and microbial communities using predominately culture-based, and more recently nonculture-based, methodologies. There is a clear need for international-scale research efforts that apply standardized methods to advance this field of science. Here we present a review of dust-borne microorganisms with a focus on their relevance to agronomy.
Output: The Global Dispersion of Pathogenic Microorganisms by Dust Storms and Its Relevance to Agriculture
Amplifying the variable (Fv or V) regions of immunoglobulins (Ig) has become a challenge in cloning antibody genes for phage display, a technique used to study protein-protein, protein-peptide, and protein-DNA interactions using bacteriophages to connect proteins with the genetic information that encodes them. Key parameters affecting the amplification of full antibody repertoires includes the availability of primers that can amplify as many V genes as possible; however the strategy used to design these primers and programs used to make the necessary alignments have not been well studied and clearly detailed in the literature. Here, we present a set of primers computationally designed by iCODEHOP based on a database of human germline Ig sequences. We used reverse transcription polymerase chain reaction (RT-PCR) protocols that would recognize the V H genes from human peripheral blood mononuclear cells. We identified the most highly conserved region in framework 1 and framework 4 of the Ig cDNA, and designed a set of degenerated 5 0 primers. The V H genes were successfully amplified by RT-PCR. This new primer has facilitated the creation of more diverse V H libraries than has been previously possible. Moreover, iCODEHOP improved the primer design efficiency and was found useful both for cloning unknown genes in gene families and for building V H gene libraries.
Output: Degenerate primer design to clone the human repertoire of immunoglobulin heavy chain variable regions
Mice on a calorie-restricted (CR) diet (total calories restricted to 70% of ad libitum; AL) for periods of time ranging from 3 to 18 months were examined for response to topical treatment with all-trans retinoic acid (RA). Daily application of a 0.1% solution of RA to the shaved skin of UM-HET3 mice on an AL diet produced a severe irritation that was evident by day 4, maximal at day 7-8 and still detectable at day 14. Skin irritation was characterized by redness, dryness, Xaking and failure of the hair to grow at the treated site. In CR mice, the same treatment produced little detectable irritation. Animals were sacri-Wced at the end of the retinoid-treatment period (day 7 or day 14) and skin from these animals was examined histologically. In both AL and CR mice, a similar degree of epidermal hyperplasia was observed. Numerous inXammatory cells (mononuclear cells and granulocytes) were present in the skin of both groups. Occasional S100-positive cells (presumably Langerhans cells) were also observed in the epidermis of skin from both groups. S100-positive cells were also observed in the dermis. When skin from CR and AL mice was incubated in organ culture for 3 days (on day 7 after initiation of RA treatment), similar levels of four diVerent pro-inXammatory cytokines were found in the conditioned medium. Soluble type I collagen levels were also similar. In contrast, the level of matrix metalloproteinase-9 was lower in the conditioned medium of skin from CR mice than in conditioned medium from skin cultures of AL mice. Taken together, these studies suggest that CR may provide a way to mitigate the irritation that normally accompanies RA treatment without compromising the ben-eWcial eVects of retinoid use. CR appears to exert a protective eVect at the target tissue level rather than by a reduction in pro-inXammatory events, per se.
Output: Inhibition of retinoic acid-induced skin irritation in calorie-restricted mice
The oligoadenylate synthetase 1 (OAS1) enzyme acts as an innate sensor of viral infection and plays a major role in the defense against a wide diversity of viruses. Polymorphisms at OAS1 have been shown to correlate with differential susceptibility to several infections of great public health significance, including hepatitis C virus, SARS coronavirus, and West Nile virus. Population genetics analyses in hominoids have revealed interesting evolutionary patterns. In Central African chimpanzee, OAS1 has evolved under longterm balancing selection, resulting in the persistence of polymorphisms since the origin of hominoids, whereas human populations have acquired and retained OAS1 alleles from Neanderthal and Denisovan origin. We decided to further investigate the evolution of OAS1 in primates by characterizing intra-specific variation in four species commonly used as models in infectious disease research: the rhesus macaque, the cynomolgus macaque, the olive baboon, and the Guinea baboon. In baboons, OAS1 harbors a very low level of variation. In contrast, OAS1 in macaques exhibits a level of polymorphism far greater than the genomic average, which is consistent with the action of balancing selection. The region of the enzyme that directly interacts with viral RNA, the RNAbinding domain, contains a number of polymorphisms likely to affect the RNA-binding affinity of OAS1. This strongly suggests that pathogen-driven balancing selection acting on the RNA-binding domain of OAS1 is maintaining variation at this locus. Interestingly, we found that a number of polymorphisms involved in RNA-binding were shared between macaques and chimpanzees. This represents an unusual case of convergent polymorphism.
Output: Contrasted patterns of variation and evolutionary convergence at the antiviral OAS1 gene in old world primates
Background: Ethiopia has the second largest human population in Africa and the largest livestock population on the continent. About 80% of Ethiopians are dependent on agriculture and have direct contact with livestock or other domestic animals. As a result, the country is vulnerable to the spread of zoonotic diseases. As the first step of the country's engagement in the Global Health Security Agenda, a zoonotic disease prioritization workshop was held to identify significant zoonotic diseases of mutual concern for animal and human health agencies. Methods: A semi-quantitative tool developed by the US CDC was used for prioritization of zoonotic diseases. Workshop participants representing human, animal, and environmental health ministries were selected as core decision-making participants. Over 300 articles describing the zoonotic diseases considered at the workshop were reviewed for disease specific information on prevalence, morbidity, mortality, and DALYs for Ethiopia or the East Africa region. Committee members individually ranked the importance of each criterion to generate a final group weight for each criterion. Results: Forty-three zoonotic diseases were evaluated. Criteria selected in order of importance were: 1)severity of disease in humans, 2)proportion of human disease attributed to animal exposure, 3)burden of animal disease, 4)availability of interventions, and 5)existing inter-sectoral collaboration. Based on the results from the decision tree analysis and subsequent discussion, participants identified the following five priority zoonotic diseases: rabies, anthrax, brucellosis, leptospirosis, and echinococcosis. Discussion: Multi-sectoral collaborations strengthen disease surveillance system development in humans and animals, enhance laboratory capacity, and support implementation of prevention and control strategies. To facilitate this, the creation of a One Health-focused Zoonotic Disease Unit is recommended. Enhancement of public health and veterinary laboratories, joint outbreak and surveillance activities, and intersectoral linkages created to tackle the prioritized zoonotic diseases will undoubtedly prepare the country to effectively address newly emerging zoonotic diseases. Published by Elsevier B.V. This is an open access article under the CC BY license
Output: Prioritizing zoonotic diseases in Ethiopia using a one health approach
Epidemiologists aim to inform the design of public health interventions with evidence on the evolution, emergence and spread of infectious diseases. Sequencing of pathogen genomes, together with date, location, clinical manifestation and other relevant data about sample origins, can contribute to describing nearly every aspect of transmission dynamics, including local transmission and global spread. The analyses of these data have implications for all levels of clinical and public health practice, from institutional infection control to policies for surveillance, prevention and treatment. This review highlights the range of epidemiological questions that can be addressed from the combination of genome sequence and traditional 'line lists' (tables of epidemiological data where each line includes demographic and clinical features of infected individuals). We identify opportunities for these data to inform interventions that reduce disease incidence and prevalence. By considering current limitations of, and challenges to, interpreting these data, we aim to outline a research agenda to accelerate the genomics-driven transformation in public health microbiology.
Output: Epidemiologic data and pathogen genome sequences: a powerful synergy for public health
The synthesis of inactive enzyme precursors, also known as ''zymogens,'' serves as a mechanism for regulating the execution of selected catalytic activities in a desirable time and/or site. Zymogens are usually activated by proteolytic cleavage. Many viruses encode proteases that execute key proteolytic steps of the viral life cycle. Here, we describe a proof of concept for a therapeutic approach to fighting viral infections through eradication of virally infected cells exclusively, thus limiting virus production and spread. Using the hepatitis C virus (HCV) as a model, we designed two HCV NS3 protease-activated ''zymogenized'' chimeric toxins (which we denote ''zymoxins''). In these recombinant constructs, the bacterial and plant toxins diphtheria toxin A (DTA) and Ricin A chain (RTA), respectively, were fused to rationally designed inhibitor peptides/ domains via an HCV NS3 protease-cleavable linker. The above toxins were then fused to the binding and translocation domains of Pseudomonas exotoxin A in order to enable translocation into the mammalian cells cytoplasm. We show that these toxins exhibit NS3 cleavage dependent increase in enzymatic activity upon NS3 protease cleavage in vitro. Moreover, a higher level of cytotoxicity was observed when zymoxins were applied to NS3 expressing cells or to HCV infected cells, demonstrating a potential therapeutic window. The increase in toxin activity correlated with NS3 protease activity in the treated cells, thus the therapeutic window was larger in cells expressing recombinant NS3 than in HCV infected cells. This suggests that the ''zymoxin'' approach may be most appropriate for application to life-threatening acute infections where much higher levels of the activating protease would be expected. Citation: Shapira A, Gal-Tanamy M, Nahary L, Litvak-Greenfeld D, Zemel R, et al. (2011) Engineered Toxins ''Zymoxins'' Are Activated by the HCV NS3 Protease by Removal of an Inhibitory Protein Domain. PLoS ONE 6(1): e15916.
Output: Engineered Toxins ''Zymoxins'' Are Activated by the HCV NS3 Protease by Removal of an Inhibitory Protein Domain
Purpose: Respiratory infection is the most common cause for acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). The aim of this work was to study the etiology of the respiratory infection in order to assess the usefulness of the clinical and analytical parameters used for COPD identification. Patients and methods: We included 132 patients over a period of 2 years. The etiology of the respiratory infection was studied by conventional sputum, paired serology tests for atypical bacteria, and viral diagnostic techniques (immunochromatography, immunofluorescence, cell culture, and molecular biology techniques). We grouped the patients into four groups based on the pathogens isolated (bacterial versus. viral, known etiology versus unknown etiology) and compared the groups. Results: A pathogen was identified in 48 patients. The pathogen was identified through sputum culture in 34 patients, seroconversion in three patients, and a positive result from viral techniques in 14 patients. No significant differences in identifying etiology were observed in the clinical and analytical parameters within the different groups. The most cost-effective tests were the sputum test and the polymerase chain reaction. Conclusion: Based on our experience, clinical and analytical parameters are not useful for the etiological identification of COPD exacerbations. Diagnosing COPD exacerbation is difficult, with the conventional sputum test for bacterial etiology and molecular biology techniques for viral etiology providing the most profitability. Further studies are necessary to identify respiratory syndromes or analytical parameters that can be used to identify the etiology of new AE-COPD cases without the laborious diagnostic techniques.
Output: Microbiological study of patients hospitalized for acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) and the usefulness of analytical and clinical parameters in its identification (VIRAE study)
Introduction: Respiratory viruses (influenza, parainfluenza, respiratory syncytial virus, coronavirus, human metapneumovirus, and rhinovirus) represent the most common causes of respiratory viral infections in immunocompromised patients. Also, these infections may be more severe in immunocompromised patients than in the general population. Early diagnosis and treatment of viral infections continue to be of paramount importance in immunocompromised patients; because once viral replication and invasive infections are evident, prognosis can be grave. Areas covered: The purpose of this review is to provide an overview of the main antiviral agents used for the treatment of respiratory viral infections in immunocompromised patients and review of the new agents in the pipeline. Expert commentary: Over the past decade, important diagnostic advances, specifically, the use of rapid molecular testing has helped close the gap between clinical scenarios and pathogen identification and enhanced early diagnosis of viral infections and understanding of the role of prolonged shedding and viral loads. Advancements in novel antiviral therapeutics with high resistance thresholds and effective immunization for preventable infections in immunocompromised patients are needed. ARTICLE HISTORY
Output: Antiviral therapy for respiratory viral infections in immunocompromised patients