SummaryWe conducted a seroprevalence survey in Belgium, Finland, England & Wales, Italy and Poland on 13449 serum samples broadly representative in terms of geography and age.Samples were tested for the presence of immunoglobulin G antibody using a enzyme immuno-assay. The age-specific risk of infection was estimated using parametric and nonparametric statistical modeling. The age-specific risk in all 5 countries was highest in children aged 7-9 years and lower in adults. The average proportion of women in childbearing age susceptible to parvovirus B19 infection and the risk of a pregnant women acquiring B19 infection during pregnancy was estimated to be 26% and 0.61%,in Belgium, 38% and 0.69% in England & Wales, 43.5% and 1.24% in Finland, 39.9% and 0.92% in Italy and 36.8% and 1.58% in Poland, respectively. Our study indicates substantial epidemiological differences in Europe regarding parvovirus B19 infection.3
Importation of viruses from other continents caused prolonged circulation and large outbreaks in the WHO European Region.
This laboratory previously described a single-laser flow cytometric method, which effectively resolves micronucleated erythrocyte populations in rodent peripheral blood samples. Even so, the rarity and variable size of micronuclei make it difficult to configure instrument settings consistently and define analysis regions rationally to enumerate the cell populations of interest. Murine erythrocytes from animals infected with the malaria parasite Plasmodium berghei contain a high prevalence of erythrocytes with a uniform DNA content. This biological model for micronucleated erythrocytes offers a means by which the micronucleus analysis regions can be rationally defined, and a means for controlling interexperimental variation. The experiments described herein were performed to extend these studies by testing whether malaria-infected erythrocytes could also be used to enhance the transferability of the method, as well as control intra- and interlaboratory variation. For these studies, blood samples from mice infected with malaria, or treated with vehicle or the clastogen methyl methanesulfonate, were fixed and shipped to collaborating laboratories for analysis. After configuring instrumentation parameters and guiding the position of analysis regions with the malaria-infected blood samples, micronucleated reticulocyte frequencies were measured (20,000 reticulocytes per sample). To evaluate both intra- and interlaboratory variation, five replicates were analyzed per day, and these analyses were repeated on up to five separate days. The data of 14 laboratories presented herein indicate that transferability of this flow cytometric technique is high when instrumentation is guided by the biological standard Plasmodium berghei.
Ovarian cancer remains the most lethal gynecologic malignancy owing to late detection, intrinsic and acquired chemoresistance, and remarkable heterogeneity. Here, we explored approaches to inhibit metastatic growth of murine and human ovarian tumor variants resistant to paclitaxel and carboplatin by oncolytic vaccinia virus expressing a CXCR4 antagonist to target the CXCL12 chemokine/CXCR4 receptor signaling axis alone or in combination with doxorubicin. The resistant variants exhibited augmented expression of the hyaluronan receptor CD44 and CXCR4 along with elevated Akt and ERK1/2 activation and displayed an increased susceptibility to viral infection compared with the parental counterparts. The infected cultures were more sensitive to doxorubicin-mediated killing both in vitro and in tumor-challenged mice. Mechanistically, the combination treatment increased apoptosis and phagocytosis of tumor material by dendritic cells associated with induction of antitumor immunity. Targeting syngeneic tumors with this regimen increased intratumoral infiltration of antitumor CD8+ T cells. This was further enhanced by reducing the immunosuppressive network by the virally-delivered CXCR4 antagonist, which augmented antitumor immune responses and led to tumor-free survival. Our results define novel strategies for treatment of drug-resistant ovarian cancer that increase immunogenic cell death and reverse the immunosuppressive tumor microenvironment, culminating in antitumor immune responses that control metastatic tumor growth.
Objective: To examine the type specific seroprevalence of herpes simplex virus (HSV) types 1 and 2 infections, stratified by age and gender, and associated risk factors for HSV-2 seropositivity in Poland. Methods: 2257 serum samples of individuals from 15-65 years were randomly selected from serum banks in four different geographical regions of Poland, including the Zachodnio-pomorskie, Warmińsko-mazurskie, Lubelskie, and Mazowieckie districts. Type specific serum antibodies to HSV-1 and HSV-2 were detected using HerpeSelect IgG ELISA tests. Results: Overall prevalences of type specific HSV-1 and HSV-2 serum antibodies were 90.4% and 9.3%, respectively. Age standardised HSV-2 seroprevalence was higher in women (9.7%) than men (8.8%) (p = 0.06), and increased notably with age from 4% in 15-24 year olds to 12% in those aged 50-65 years. HSV-1 seroprevalence was consistently higher than HSV-2 seroprevalence in each specific age group, ranging from 74.5% in 15-24 year olds to 98.8% in 50-65 year olds. HSV-2 seroprevalence varied significantly by geographical region, with the highest prevalence in the Zachodnio-pomorskie district (12%). Significant multivariate risk factors for HSV-2 seropositivity included older age, female gender, and geographical place of residence. Conclusion: This large survey found a notably high seroprevalence of HSV-1, even among young female adolescents 15-19 years of age (80%). HSV-2 seropositivity was under 12% in all age groups surveyed in Poland, tending to be among the lowest overall HSV-2 seropositivity rates reported thus far in Europe.
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