Value of FDG-PET/MR in Oral Focus Assessment in Head and Neck Cancer Patients-A Feasibility Study

FDG-PET/MR is a hybrid imaging modality used for the staging and restaging of advanced head & neck cancer (HNC) patients. Their treatment typically involves radiation therapy, which requires previous dental focus assessment. The aim of this study was to analyze if staging FDG-PET/MR is a valuable tool for oral focus assessment. For this purpose, FDG-PET/MR findings, such as metabolic activity of periapical radiolucencies and marginal periodontitis, were retrospectively compared with conventional standardized dental focus assessment, including dental radiographs and clinical assessment of 124 teeth in seven patients. Increased FDG uptake of periapical lesions was found in one out of 23 lesions. Increased FDG uptake of the marginal periodontium was recorded in one out of 34 lesions. In summary, standardized dental focus assessment by panoramic radiography and periapical radiographs may be enriched by information from FDG-PET/MR, showing active inflammation in dental foci. However, many dental foci have no correlate in FDG-PET/MR. The treatment decision for oral foci may benefit from the visualized presence or absence of metabolic activity on FDG-PET/MR

Serosurvey of West Nile virus (WNV) in free-ranging raptors from Brazil

Fil: Morel, Ana Paula. Instituto de Pesquisas Veterinárias Desidério Finamor (IPVDF). Centro de Pesquisa em Saúde Animal, Eldorado do Sul, Río Grande del Sur; Brasil.Fil: Webster, Anelise. Instituto de Pesquisas Veterinárias Desidério Finamor (IPVDF). Centro de Pesquisa em Saúde Animal, Eldorado do Sul, Río Grande del Sur; Brasil.Fil: Zitelli, Larissa Calo. Instituto de Pesquisas Veterinárias Desidério Finamor (IPVDF). Centro de Pesquisa em Saúde Animal, Eldorado do Sul, Río Grande del Sur; Brasil.Fil: Umeno, Karen. Instituto de Pesquisas Veterinárias Desidério Finamor (IPVDF). Centro de Pesquisa em Saúde Animal, Eldorado do Sul, Río Grande del Sur; Brasil.Fil: Souza, Ugo Araújo. Instituto de Pesquisas Veterinárias Desidério Finamor (IPVDF). Centro de Pesquisa em Saúde Animal, Eldorado do Sul, Río Grande del Sur; Brasil.Fil: Prusch, Fabiane. Clinica Veterinária Toca dos Bichos, Porto Alegre, Río Grande del Sur; Brasil.Fil: Anicet, Marina. Clinica Veterinária Toca dos Bichos, Porto Alegre, Río Grande del Sur; Brasil.Fil: Marsicano, Gleide. Clinica Veterinária Toca dos Bichos, Porto Alegre, Río Grande del Sur; Brasil.Fil: Bandarra, Paulo. Nucleo de Reabilitação da Fauna Silvestre-UFPel, Pelotas, Río Grande del Sur; Brasil.Fil: Trainini, Gustavo. Hayabusa Consultoria Ambiental, São Francisco de Paula, Río Grande del Sur; Brasil.Fil: Stocker, Julian. Hayabusa Consultoria Ambiental, São Francisco de Paula, Río Grande del Sur; Brasil.Fil: Giani, Denise. Hayabusa Consultoria Ambiental, São Francisco de Paula, Río Grande del Sur; Brasil.Fil: Fortes, Flávia Borges. Secretaria da Agricultura Pecuária e Desenvolvimento Rural (SEAPDR). Programa Estadual de Sanidade Avícola (PESA), Porto Alegre, Río Grande del Sur; Brasil.Fil: Goenaga, Silvina. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.Fil: Reck, José. Instituto de Pesquisas Veterinárias Desidério Finamor (IPVDF). Centro de Pesquisa em Saúde Animal, Eldorado do Sul, Río Grande del Sur; Brasil.West Nile virus (WNV) is a mosquito-borne Flavivirus that can affect birds, horses, and humans, and is the only zoonotic Flavivirus that has been identified in six continents. In Brazil, until 2010, there was no evidence of WNV circulation. Recently, the virus was isolated from a horse with encephalitis, and the first human cases were registered in Brazil. Despite that, there is still no information on the enzootic cycle of this virus in birds or wildlife. This study aimed to investigate whether there is evidence of WNV circulation among wild birds from Southern Brazil. For this, we used free-living wild raptors (live-trapped or rescued) as potential sentinels to investigate the presence of WNV antibodies using ELISA and plaque reduction neutralization test (PRNT) assay. In addition, the presence of nucleic acids from Flavivirus family members was investigated. None of the birds sampled presented clinical findings compatible with WNV. Of the 200 serum samples from birds of prey belonging to 21 species, ten (5%) were positive for the presence of WNV antibodies on ELISA testing. The PRNT test did not confirm the ELISA results, but indicated that three birds had possibly been exposed to Saint Louis encephalitis virus (SLEV). All samples were negative for Flavivirus RNA. The results presented here evince the need for permanent surveillance for emerging flaviviruses in Brazil, as well as for a contingency policy in the case of human/animal outbreaks, particularly in high-risk areas

Serosurvey of West Nile virus (WNV) in free-ranging raptors from Brazil

Fil: Morel, Ana Paula. Instituto de Pesquisas Veterinárias Desidério Finamor (IPVDF). Centro de Pesquisa em Saúde Animal, Eldorado do Sul, Río Grande del Sur; Brasil.Fil: Webster, Anelise. Instituto de Pesquisas Veterinárias Desidério Finamor (IPVDF). Centro de Pesquisa em Saúde Animal, Eldorado do Sul, Río Grande del Sur; Brasil.Fil: Zitelli, Larissa Calo. Instituto de Pesquisas Veterinárias Desidério Finamor (IPVDF). Centro de Pesquisa em Saúde Animal, Eldorado do Sul, Río Grande del Sur; Brasil.Fil: Umeno, Karen. Instituto de Pesquisas Veterinárias Desidério Finamor (IPVDF). Centro de Pesquisa em Saúde Animal, Eldorado do Sul, Río Grande del Sur; Brasil.Fil: Souza, Ugo Araújo. Instituto de Pesquisas Veterinárias Desidério Finamor (IPVDF). Centro de Pesquisa em Saúde Animal, Eldorado do Sul, Río Grande del Sur; Brasil.Fil: Prusch, Fabiane. Clinica Veterinária Toca dos Bichos, Porto Alegre, Río Grande del Sur; Brasil.Fil: Anicet, Marina. Clinica Veterinária Toca dos Bichos, Porto Alegre, Río Grande del Sur; Brasil.Fil: Marsicano, Gleide. Clinica Veterinária Toca dos Bichos, Porto Alegre, Río Grande del Sur; Brasil.Fil: Bandarra, Paulo. Nucleo de Reabilitação da Fauna Silvestre-UFPel, Pelotas, Río Grande del Sur; Brasil.Fil: Trainini, Gustavo. Hayabusa Consultoria Ambiental, São Francisco de Paula, Río Grande del Sur; Brasil.Fil: Stocker, Julian. Hayabusa Consultoria Ambiental, São Francisco de Paula, Río Grande del Sur; Brasil.Fil: Giani, Denise. Hayabusa Consultoria Ambiental, São Francisco de Paula, Río Grande del Sur; Brasil.Fil: Fortes, Flávia Borges. Secretaria da Agricultura Pecuária e Desenvolvimento Rural (SEAPDR). Programa Estadual de Sanidade Avícola (PESA), Porto Alegre, Río Grande del Sur; Brasil.Fil: Goenaga, Silvina. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.Fil: Reck, José. Instituto de Pesquisas Veterinárias Desidério Finamor (IPVDF). Centro de Pesquisa em Saúde Animal, Eldorado do Sul, Río Grande del Sur; Brasil.West Nile virus (WNV) is a mosquito-borne Flavivirus that can affect birds, horses, and humans, and is the only zoonotic Flavivirus that has been identified in six continents. In Brazil, until 2010, there was no evidence of WNV circulation. Recently, the virus was isolated from a horse with encephalitis, and the first human cases were registered in Brazil. Despite that, there is still no information on the enzootic cycle of this virus in birds or wildlife. This study aimed to investigate whether there is evidence of WNV circulation among wild birds from Southern Brazil. For this, we used free-living wild raptors (live-trapped or rescued) as potential sentinels to investigate the presence of WNV antibodies using ELISA and plaque reduction neutralization test (PRNT) assay. In addition, the presence of nucleic acids from Flavivirus family members was investigated. None of the birds sampled presented clinical findings compatible with WNV. Of the 200 serum samples from birds of prey belonging to 21 species, ten (5%) were positive for the presence of WNV antibodies on ELISA testing. The PRNT test did not confirm the ELISA results, but indicated that three birds had possibly been exposed to Saint Louis encephalitis virus (SLEV). All samples were negative for Flavivirus RNA. The results presented here evince the need for permanent surveillance for emerging flaviviruses in Brazil, as well as for a contingency policy in the case of human/animal outbreaks, particularly in high-risk areas

Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection

Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study

BackgroundThe PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice.MethodsFebrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed.FindingsOf 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively.InterpretationMost febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics.FundingEU Horizon 2020 grant 668303

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Improving headgear wear : why force level and direction of traction matter

Background: Empiric data on headgear wear are scarce. The aim was to examine a possible discrepancy between the duration of wearing and force application, and whether such a difference is influenced by force level or direction of traction. Materials and methods: In this retrospective analysis, 122 consecutive patients were included. All were treated with headgear (three subgroups: high-pull headgear [n = 60], cervical-pull headgear [n = 32], and high-pull headgear in combination with an activator [n = 30]) and were monitored for three successive months using an electronic module. The device recorded chronographically the measured force magnitude and temperature, allowing to differentiate between the duration of headgear wear (recorded body temperature) and actual force application (recorded force). Results: For all subgroups, the average recorded force application was lower than wear time (mean inactivity during wear: 15.9 ± 22.8 minutes/night). The direction of traction significantly influenced the extent and length of wear time without force application (P < 0.001): patients with cervical-pull headgear were more prone to inactive wear time (27.7 minutes/night) than patients with high-pull headgear (13.7 minutes/night) or with headgear-activator (7.8 minutes/night). The observed inter-individual variability of inactive wear time was considerable (0-134 minutes/night). The mean applied force was highly significantly associated with inactive wear time (correlation coefficient: -0.575; P < 0.001), and force levels below 250 g seem particularly related to episodes of inactivity. Conclusions: There is a clear incongruity between the duration of headgear wear and the duration of force application. Inactive wear time is influenced by the direction of traction and force level applied. Clinicians should be aware of the likelihood of periods of inactive wear time and researchers should search for options to reduce or even eliminate these periods

Improving headgear wear: why force level and direction of traction matter

Background: Empiric data on headgear wear are scarce. The aim was to examine a possible discrepancy between the duration of wearing and force application, and whether such a difference is influenced by force level or direction of traction. Materials and methods: In this retrospective analysis, 122 consecutive patients were included. All were treated with headgear (three subgroups: high-pull headgear [n = 60], cervical-pull headgear [n = 32], and high-pull headgear in combination with an activator [n = 30]) and were monitored for three successive months using an electronic module. The device recorded chronographically the measured force magnitude and temperature, allowing to differentiate between the duration of headgear wear (recorded body temperature) and actual force application (recorded force). Results: For all subgroups, the average recorded force application was lower than wear time (mean inactivity during wear: 15.9 ± 22.8 minutes/night). The direction of traction significantly influenced the extent and length of wear time without force application (P < 0.001): patients with cervical-pull headgear were more prone to inactive wear time (27.7 minutes/night) than patients with high-pull headgear (13.7 minutes/night) or with headgear-activator (7.8 minutes/night). The observed inter-individual variability of inactive wear time was considerable (0-134 minutes/night). The mean applied force was highly significantly associated with inactive wear time (correlation coefficient: -0.575; P < 0.001), and force levels below 250 g seem particularly related to episodes of inactivity. Conclusions: There is a clear incongruity between the duration of headgear wear and the duration of force application. Inactive wear time is influenced by the direction of traction and force level applied. Clinicians should be aware of the likelihood of periods of inactive wear time and researchers should search for options to reduce or even eliminate these periods