Infection with Possible Novel Parapoxvirus in Horse, Finland, 2013.
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ABSTRACT:
SUBMITTER: Airas N
PROVIDER: S-EPMC4918186 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Replicating viruses for the treatment of cancer have a number of advantages over traditional therapeutic modalities. They are highly targeted, self-amplifying, and have the added potential to act as both gene-therapy delivery vehicles and oncolytic agents. Parapoxvirus ovis or Orf virus (ORFV) is the prototypic species of the Parapoxvirus genus, causing a benign disease in its natural ungulate host. ORFV possesses a number of unique properties that make it an ideal viral backbone for the development of a cancer therapeutic: it is safe in humans, has the ability to cause repeat infections even in the presence of antibody, and it induces a potent T(h)-1-dominated immune response. Here, we show that live replicating ORFV induces an antitumor immune response in multiple syngeneic mouse models of cancer that is mediated largely by the potent activation of both cytokine-secreting, and tumoricidal natural killer (NK) cells. We have also highlighted the clinical potential of the virus by demonstration of human cancer cell oncolysis including efficacy in an A549 xenograft model of cancer.
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Project description:OBJECTIVES:The objective was to investigate trends in the incidence of recognized and suspected cases of occupational diseases in Finland from 1975 to 2013, including variations by industry - and describe and recognize factors affecting variations in incidence. DESIGN:A register study. SETTING:The data consisted of recognized and suspected cases of occupational diseases recorded in the Finnish Registry of Occupational Diseases (FROD) in 1975-2013. PARTICIPANTS:Altogether 240 000 cases of suspected and recognized ODs were analysed. PRIMARY AND SECONDARY OUTCOME MEASURES:From the annual workforce statistics and FROD data, we calculated the incidence of ODs and suspected ODs per 10 000 employees. For time trends by industrial sector, we used a 5-year moving average and a Poisson regression analysis. RESULTS:Annual average rates of ODs have varied from year to year. The total number was 25.0/10 000 employees in 1975 and 20.1/10 000 employees in 2013. Screening campaigns and legislative changes have caused temporary increases. When the financial sector was the reference (1.0), the highest incidence rates according to industrial sector were in mining and quarrying (9.87; 95% CI 8.65 to 11.30), construction (9.11; 95% CI 9.98 to 10.43), manufacturing (9.04; 95% CI 7.93 to 10.36) and agriculture (8.78; 95% CI 7.69 to 10.06). There is a distinct decreasing trend from 2005 onwards: the average annual change in incidence was, for example, -9.2% in agriculture, -10.3% in transportation and -4.7% in construction. The average annual decline was greatest in upper limb strain injuries (-11.1%). CONCLUSION:This study provides a useful overview of the status of ODs in Finland over several decades. These data are a valuable resource for determining which occupations are at an increased risk and where preventive actions should be targeted. It is important to study long-term trends in the statistics of ODs to see beyond the year-to-year fluctuations.
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Project description:During the early stage of the avian influenza A(H7N9) epidemic in China in March 2013, a strain of the virus was identified in a 4-year-old boy with mild influenza symptoms. Phylogenetic analysis indicated that this strain, which has similarity to avian subtype H9N2 viruses, may represent a precursor of more-evolved H7N9 subtypes co-circulating among humans.
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Project description:Staphylococcus sciuri is known as an opportunistic pathogen colonizing domesticated animals and has also been associated with wound infections in humans. Particularly over the last decade, oxacillin (methicillin) resistant strains had been emerged, which now increase the medical relevance of this species. This report describes the identification of an oxacillin-resistant S. sciuri isolate from a wound infection of a horse. We determined the absence of coagulase and hyaluronidase activity and analysed the antibiotic resistance profile.
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Project description:To characterize parapoxviruses causing severe disease in wild ruminants in Stelvio Park, Italy, we sequenced and compared the DNA of several isolates. Results demonstrated that the red deer isolates are closely related to the parapox of red deer in New Zealand virus.
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Project description:BackgroundHealth care-associated infective endocarditis (HAIE) and intravenous drug use-related IE (IDUIE) have emerged as major groups in infective endocarditis (IE). We studied their role and clinical picture in a population-based survey.MethodsA population-based retrospective study including all adult patients diagnosed with definite or possible IE in Southern Finland in 2013-2017. IE episodes were classified according to the mode of acquisition into 3 groups: community-acquired IE (CAIE), HAIE, and IDUIE.ResultsTotal of 313 episodes arising from 291 patients were included. Incidence of IE was 6.48/100 000 person-years. CAIE accounted for 38%, HAIE 31%, and IDUIE 31% of IE episodes. Patients in the IDUIE group were younger, and they more frequently had right-sided IE (56.7% vs 5.0%; P < .001) and S. aureus as etiology (74.2% vs 17.6%; P < .001) compared with the CAIE group. In-hospital (15.1% vs 9.3%; P = .200) and cumulative 1-year case fatality rates (18.5% vs 17.5%; P = .855) were similar in CAIE and IDUIE. Patients with HAIE had more comorbidities, prosthetic valve involvement (29.9% vs 10.9%; P = .001), enterococcal etiology (20.6% vs 5.9%; P = .002), and higher in-hospital (27.8% vs 15.1%; P = .024) and cumulative 1-year case fatality rates (43.3% vs 18.5%; P < .001) than patients with CAIE. Staphylococcus aureus caused one-fifth of IE episodes in both groups.ConclusionsOur study indicates that in areas where injection drug use is common IDUIE should be regarded as a major risk group for IE, along with HAIE, and not seen as part of CAIE. Three different risk groups, CAIE, HAIE, and IDUIE, with variable characteristics and outcome should be recognized in IE.
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Project description:BACKGROUND:The success of new sequencing technologies and informatic methods for identifying genes has made establishing gene product function a critical rate limiting step in progressing the molecular sciences. We present a method to functionally mine genomes for useful activities in vivo, using an unusual property of a member of the poxvirus family to demonstrate this screening approach. RESULTS:The genome of Parapoxvirus ovis (Orf virus) was sequenced, annotated, and then used to PCR-amplify its open-reading-frames. Employing a cloning-independent protocol, a viral expression-library was rapidly built and arrayed into sub-library pools. These were directly delivered into mice as expressible cassettes and assayed for an immune-modulating activity associated with parapoxvirus infection. The product of the B2L gene, a homolog of vaccinia F13L, was identified as the factor eliciting immune cell accumulation at sites of skin inoculation. Administration of purified B2 protein also elicited immune cell accumulation activity, and additionally was found to serve as an adjuvant for antigen-specific responses. Co-delivery of the B2L gene with an influenza gene-vaccine significantly improved protection in mice. Furthermore, delivery of the B2L expression construct, without antigen, non-specifically reduced tumor growth in murine models of cancer. CONCLUSION:A streamlined, functional approach to genome-wide screening of a biological activity in vivo is presented. Its application to screening in mice for an immune activity elicited by the pathogen genome of Parapoxvirus ovis yielded a novel immunomodulator. In this inverted discovery method, it was possible to identify the adjuvant responsible for a function of interest prior to a mechanistic study of the adjuvant. The non-specific immune activity of this modulator, B2, is similar to that associated with administration of inactivated particles to a host or to a live viral infection. Administration of B2 may provide the opportunity to significantly impact host immunity while being itself only weakly recognized. The functional genomics method used to pinpoint B2 within an ORFeome may be more broadly applicable to screening for other biological activities in an animal.
| S-EPMC3283511 | biostudies-literature
Project description:The parapoxvirus orf virus (ORFV) is a pathogen of sheep and goats that has been used as a preventive and therapeutic immunomodulatory agent in several animal species. However, the functions (genes, proteins, and mechanisms of action) evolved by ORFV to modulate and manipulate immune responses are poorly understood. Here, the novel ORFV protein ORFV024 was shown to inhibit activation of the NF-kappaB signaling pathway, an important modulator of early immune responses against viral infections. Infection of primary ovine cells with an ORFV024 deletion mutant virus resulted in a marked increase in expression of NF-kappaB-regulated chemokines and other proinflammatory host genes. Expression of ORFV024 in cell cultures significantly decreased lipopolysaccharide (LPS)- and tumor necrosis factor alpha (TNF-alpha)-induced NF-kappaB-responsive reporter gene expression. Further, ORFV024 expression decreased TNF-alpha-induced phosphorylation and nuclear translocation of NF-kappaB-p65, phosphorylation, and degradation of IkappaBalpha, and phosphorylation of IkappaB kinase (IKK) subunits IKKalpha and IKKbeta, indicating that ORFV024 functions by inhibiting activation of IKKs, the bottleneck for most NF-kappaB activating stimuli. Although ORFV024 interferes with activation of the NF-kappaB signaling pathway, its deletion from the OV-IA82 genome had no significant effect on disease severity, progression, and time to resolution in sheep, indicating that ORFV024 is not essential for virus virulence in the natural host. This represents the first description of a NF-kappaB inhibitor encoded by a parapoxvirus.
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Project description:BackgroundWe assessed population-level changes in glioblastoma survival between 2000 and 2013 in Finland, with focus on elderly patients (>70 y) in order to assess if changes in treatment of glioblastoma are reflected also in population-based survival rates.MethodsWe identified all patients (age ?18 y) from the Finnish Cancer Registry (FCR) with a histopathological diagnosis of primary glioblastoma in 2000-2013. Patients were followed up until December 2015. The accuracy of register-based search of glioblastoma patients was internally validated. We report age-standardized relative survival ratios and relative excess risks (RERs) of death in 2000-2006 (pre-period) and 2007-2013 (post-period).ResultsWe identified 2045 glioblastoma patients from the FCR. The accuracy of the FCR-based search was 97%. Median age was 63.3 years, and 42% were women. Incidence increased on average by 1.6% (P = 0.004) and median age by 0.4 years per calendar year. Between the pre- and post-periods, the proportion of patients >70 years increased from 24% to 27%. In >70-year-old patients, the median survival time increased from 3.6 months in 2000-2006 to 4.5 months in 2007-2013 (RER 0.82, 95% CI: 0.68-0.98). In ?70-year-old patients, the median survival time increased from 9.3 months in 2000-2006 to 11.7 months in 2007-2013 (RER 0.74, 95% CI: 0.67-0.82).ConclusionDespite the increased proportion of elderly glioblastoma patients, population-level survival of glioblastoma patients has improved since the year 2000. However, increasing incidence, increasing age of patients, and poor survival in elderly are alarming, and future studies should perhaps focus more on elderly.
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