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Monkeypox virus (MPXV) is a re-emerging zoonotic poxvirus responsible for producing skin lesions in humans. Endemic in sub-Saharan Africa, the 2022 outbreak with a clade IIb strain has resulted in ongoing sustained transmission of the virus worldwide. MPXV has a relatively wide host range, with infections reported in rodent and non-human primate species. However, the susceptibility of many domestic livestock species remains unknown. Here, we report on a susceptibility/transmission study in domestic pigs that were experimentally inoculated with a 2022 MPXV clade IIb isolate or served as sentinel contact control animals. Several principal-infected and sentinel contact control pigs developed minor lesions near the lips and nose starting at 12 through 18 days post-challenge (DPC). No virus was isolated and no viral DNA was detected from the lesions; however, MPXV antigen was detected by IHC in tissue from a pustule of a principal infected pig. Viral DNA and infectious virus were detected in nasal and oral swabs up to 14 DPC, with peak titers observed at 7 DPC. Viral DNA was also detected in nasal tissues or skin collected from two principal-infected animals at 7 DPC post-mortem. Furthermore, all principal-infected and sentinel control animals enrolled in the study seroconverted. In conclusion, we provide the first evidence that domestic pigs are susceptible to experimental MPXV infection and can transmit the virus to contact animals.
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Monkeypox virus , Mpox , Doenças dos Suínos , Animais , Monkeypox virus/fisiologia , Monkeypox virus/patogenicidade , Monkeypox virus/genética , Suínos , Mpox/transmissão , Mpox/virologia , Mpox/veterinária , Doenças dos Suínos/virologia , Doenças dos Suínos/transmissão , DNA Viral/genética , Anticorpos Antivirais/sangue , Humanos , Pele/virologia , Nariz/virologiaRESUMO
Since emerging in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has repeatedly crossed the species barrier with natural infections reported in various domestic and wild animal species. The emergence and global spread of SARS-CoV-2 variants of concern (VOCs) has expanded the range of susceptible host species. Previous experimental infection studies in cattle using Wuhan-like SARS-CoV-2 isolates suggested that cattle were not likely amplifying hosts for SARS-CoV-2. However, SARS-CoV-2 sero- and RNA-positive cattle have since been identified in Europe, India, and Africa. Here, we investigated the susceptibility and transmission of the Delta and Omicron SARS-CoV-2 VOCs in cattle. Eight Holstein calves were co-infected orally and intranasally with a mixed inoculum of SARS-CoV-2 VOCs Delta and Omicron BA.2. Twenty-four hours post-challenge, two sentinel calves were introduced to evaluate virus transmission. The co-infection resulted in a high proportion of calves shedding SARS-CoV-2 RNA at 1- and 2-days post-challenge (DPC). Extensive tissue distribution of SARS-CoV-2 RNA was observed at 3 and 7 DPC and infectious virus was recovered from two calves at 3 DPC. Next-generation sequencing revealed that only the SARS-CoV-2 Delta variant was detected in clinical samples and tissues. Similar to previous experimental infection studies in cattle, we observed only limited seroconversion and no clear evidence of transmission to sentinel calves. Together, our findings suggest that cattle are more permissive to infection with SARS-CoV-2 Delta than Omicron BA.2 and Wuhan-like isolates but, in the absence of horizontal transmission, are not likely to be reservoir hosts for currently circulating SARS-CoV-2 variants.
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COVID-19 , Coinfecção , Animais , Bovinos , COVID-19/veterinária , Coinfecção/veterinária , RNA Viral/genética , SARS-CoV-2/genéticaRESUMO
The objective of this work was to evaluate the safety and efficacy of a recombinant, subunit SARS-CoV-2 animal vaccine in cats against virulent SARS-CoV-2 challenge. Two groups of cats were immunized with two doses of either a recombinant SARS-CoV-2 spike protein vaccine or a placebo, administered three weeks apart. Seven weeks after the second vaccination, both groups of cats were challenged with SARS-CoV-2 via the intranasal and oral routes simultaneously. Animals were monitored for 14 days post-infection for clinical signs and viral shedding before being humanely euthanized and evaluated for macroscopic and microscopic lesions. The recombinant SARS-CoV-2 spike protein subunit vaccine induced strong serologic responses post-vaccination and significantly increased neutralizing antibody responses post-challenge. A significant difference in nasal and oral viral shedding, with significantly reduced virus load (detected using RT-qPCR) was observed in vaccinates compared to mock-vaccinated controls. Duration of nasal, oral, and rectal viral shedding was also significantly reduced in vaccinates compared to controls. No differences in histopathological lesion scores were noted between the two groups. Our findings support the safety and efficacy of the recombinant spike protein-based SARS-CoV-2 vaccine which induced high levels of neutralizing antibodies and reduced nasal, oral, and rectal viral shedding, indicating that this vaccine will be efficacious as a COVID-19 vaccine for domestic cats.
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African swine fever (ASF) is an infectious viral disease caused by African swine fever virus (ASFV), that causes high mortality in domestic swine and wild boar (Sus scrofa). Currently, outbreaks are mitigated through strict quarantine measures and the culling of affected herds, resulting in massive economic losses to the global pork industry. In 2019, an ASFV outbreak was reported in Mongolia, describing a rapidly progressing clinical disease and gross lesions consistent with the acute form of ASF; the virus was identified as a genotype II virus. Due to the limited information on clinical disease and viral dynamics within hosts available from field observations of the Mongolian isolates, we conducted the present study to further evaluate the progression of clinical disease, virulence, and pathology of an ASFV Mongolia/2019 field isolate (ASFV-MNG19), by experimental infection of domestic pigs. Intramuscular inoculation of domestic pigs with ASFV-MNG19 resulted in clinical signs and viremia at 3 days post challenge (DPC). Clinical disease rapidly progressed, resulting in the humane euthanasia of all pigs by 7 DPC. ASFV-MNG19 infected pigs had viremic titers of 108 TCID50/mL by 5 DPC and shed virus in oral secretions late in disease, as determined from oropharyngeal swabs. Whole-genome sequencing confirmed that the ASFV-MNG19 strain used in this study was a genotype II strain highly similar to other regional strains. In conclusion, we demonstrate that ASFV-MNG19 is a virulent genotype II ASFV strain that causes acute ASF in domestic swine.
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Vírus da Febre Suína Africana , Febre Suína Africana , Suínos , Animais , Febre Suína Africana/epidemiologia , Mongólia/epidemiologia , Virulência , Viremia/veterinária , Sus scrofaRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic that has had significant impacts on human health and economies worldwide. SARS-CoV-2 is highly transmissible and the cause of coronavirus disease 2019 in humans. A wide range of animal species have also been shown to be susceptible to SARS-CoV-2 by experimental and/or natural infections. Sheep are a commonly farmed domestic ruminant that have not been thoroughly investigated for their susceptibility to SARS-CoV-2. Therefore, we performed in vitro and in vivo studies which consisted of infection of ruminant-derived cells and experimental challenge of sheep to investigate their susceptibility to SARS-CoV-2. Our results showed that sheep-derived kidney cells support SARS-CoV-2 replication. Furthermore, the experimental challenge of sheep demonstrated limited infection with viral RNA shed in nasal and oral swabs at 1 and 3-days post challenge (DPC); viral RNA was also detected in the respiratory tract and lymphoid tissues at 4 and 8 DPC. Sero-reactivity was observed in some of the principal infected sheep but not the contact sentinels, indicating that transmission to co-mingled naïve sheep was not highly efficient; however, viral RNA was detected in respiratory tract tissues of sentinel animals at 21 DPC. Furthermore, we used a challenge inoculum consisting of a mixture of two SARS-CoV-2 isolates, representatives of the ancestral lineage A and the B.1.1.7-like alpha variant of concern, to study competition of the two virus strains. Our results indicate that sheep show low susceptibility to SARS-CoV-2 infection and that the alpha variant outcompeted the lineage A strain.
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COVID-19 , Coinfecção , Ovinos/virologia , Animais , COVID-19/veterinária , Coinfecção/veterinária , SARS-CoV-2RESUMO
ABSTRACTSARS-CoV-2 was first reported circulating in human populations in December 2019 and has since become a global pandemic. Recent history involving SARS-like coronavirus outbreaks have demonstrated the significant role of intermediate hosts in viral maintenance and transmission. Evidence of SARS-CoV-2 natural infection and experimental infections of a wide variety of animal species has been demonstrated, and in silico and in vitro studies have indicated that deer are susceptible to SARS-CoV-2 infection. White-tailed deer (WTD) are amongst the most abundant and geographically widespread wild ruminant species in the US. Recently, WTD fawns were shown to be susceptible to SARS-CoV-2. In the present study, we investigated the susceptibility and transmission of SARS-CoV-2 in adult WTD. In addition, we examined the competition of two SARS-CoV-2 isolates, representatives of the ancestral lineage A and the alpha variant of concern (VOC) B.1.1.7 through co-infection of WTD. Next-generation sequencing was used to determine the presence and transmission of each strain in the co-infected and contact sentinel animals. Our results demonstrate that adult WTD are highly susceptible to SARS-CoV-2 infection and can transmit the virus through direct contact as well as vertically from doe to fetus. Additionally, we determined that the alpha VOC B.1.1.7 isolate of SARS-CoV-2 outcompetes the ancestral lineage A isolate in WTD, as demonstrated by the genome of the virus shed from nasal and oral cavities from principal infected and contact animals, and from the genome of virus present in tissues of principal infected deer, fetuses and contact animals.
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Doenças dos Animais/epidemiologia , Doenças dos Animais/transmissão , Doenças dos Animais/virologia , COVID-19/veterinária , Cervos , Complicações Infecciosas na Gravidez , SARS-CoV-2 , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Linhagem Celular , Suscetibilidade a Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Especificidade de Órgãos , Gravidez , RNA Viral , SARS-CoV-2/classificação , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Eliminação de Partículas ViraisRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic that has had significant impacts on human health and economies worldwide. SARS-CoV-2 is highly transmissible and the cause of coronavirus disease 2019 (COVID-19) in humans. A wide range of animal species have also been shown to be susceptible to SARS-CoV-2 infection by experimental and/or natural infections. Domestic and large cats, mink, ferrets, hamsters, deer mice, white-tailed deer, and non-human primates have been shown to be highly susceptible, whereas other species such as mice, dogs, pigs, and cattle appear to be refractory to infection or have very limited susceptibility. Sheep (Ovis aries) are a commonly farmed domestic ruminant that have not previously been thoroughly investigated for their susceptibility to SARS-CoV-2. Therefore, we performed in vitro and in vivo studies which consisted of infection of ruminant-derived cell cultures and experimental challenge of sheep to investigate their susceptibility to SARS-CoV-2. Our results showed that sheep-derived cell cultures support SARS-CoV-2 replication. Furthermore, experimental challenge of sheep demonstrated limited infection with viral RNA shed in nasal and oral swabs primarily at 1-day post challenge (DPC), and also detected in the respiratory tract and lymphoid tissues at 4 and 8 DPC. Sero-reactivity was also observed in some of the principal infected sheep but not the contact sentinels, indicating that transmission to co-mingled naive sheep was not highly efficient; hovewer, viral RNA was detected in some of the respiratory tract tissues of sentinel animals at 21 DPC. Furthermore, we used challenge inoculum consisting of a mixture of two SARS-CoV-2 isolates, representatives of the ancestral lineage A and the B.1.1.7-like alpha variant of concern (VOC), to study competition of the two virus strains. Our results indicate that sheep show low susceptibility to SARS-CoV-2 infection, and that the alpha VOC outcompeted the ancestral lineage A strain.
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SARS-CoV-2, a novel Betacoronavirus, was first reported circulating in human populations in December 2019 and has since become a global pandemic. Recent history involving SARS-like coronavirus outbreaks (SARS-CoV and MERS-CoV) have demonstrated the significant role of intermediate and reservoir hosts in viral maintenance and transmission cycles. Evidence of SARS-CoV-2 natural infection and experimental infections of a wide variety of animal species has been demonstrated, and in silico and in vitro studies have indicated that deer are susceptible to SARS-CoV-2 infection. White-tailed deer (Odocoileus virginianus) are amongst the most abundant, densely populated, and geographically widespread wild ruminant species in the United States. Human interaction with white-tailed deer has resulted in the occurrence of disease in human populations in the past. Recently, white-tailed deer fawns were shown to be susceptible to SARS-CoV-2. In the present study, we investigated the susceptibility and transmission of SARS-CoV-2 in adult white-tailed deer. In addition, we examined the competition of two SARS-CoV-2 isolates, representatives of the ancestral lineage A (SARS-CoV-2/human/USA/WA1/2020) and the alpha variant of concern (VOC) B.1.1.7 (SARS-CoV-2/human/USA/CA_CDC_5574/2020), through co-infection of white-tailed deer. Next-generation sequencing was used to determine the presence and transmission of each strain in the co-infected and contact sentinel animals. Our results demonstrate that adult white-tailed deer are highly susceptible to SARS-CoV-2 infection and can transmit the virus through direct contact as well as vertically from doe to fetus. Additionally, we determined that the alpha VOC B.1.1.7 isolate of SARS-CoV-2 outcompetes the ancestral lineage A isolate in white-tailed deer, as demonstrated by the genome of the virus shed from nasal and oral cavities from principal infected and contact animals, and from virus present in tissues of principal infected deer, fetuses and contact animals.
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SARS-CoV-2 is the causative agent of COVID-19 and responsible for the current global pandemic. We and others have previously demonstrated that cats are susceptible to SARS-CoV-2 infection and can efficiently transmit the virus to naïve cats. Here, we address whether cats previously exposed to SARS-CoV-2 can be re-infected with SARS-CoV-2. In two independent studies, SARS-CoV-2-infected cats were re-challenged with SARS-CoV-2 at 21 days post primary challenge (DPC) and necropsies performed at 4, 7 and 14 days post-secondary challenge (DP2C). Sentinels were co-mingled with the re-challenged cats at 1 DP2C. Clinical signs were recorded, and nasal, oropharyngeal, and rectal swabs, blood, and serum were collected and tissues examined for histologic lesions. Viral RNA was transiently shed via the nasal, oropharyngeal and rectal cavities of the re-challenged cats. Viral RNA was detected in various tissues of re-challenged cats euthanized at 4 DP2C, mainly in the upper respiratory tract and lymphoid tissues, but less frequently and at lower levels in the lower respiratory tract when compared to primary SARS-CoV-2 challenged cats at 4 DPC. Viral RNA and antigen detected in the respiratory tract of the primary SARS-CoV-2 infected cats at early DPCs were absent in the re-challenged cats. Naïve sentinels co-housed with the re-challenged cats did not shed virus or seroconvert. Together, our results indicate that cats previously infected with SARS-CoV-2 can be experimentally re-infected with SARS-CoV-2; however, the levels of virus shed was insufficient for transmission to co-housed naïve sentinels. We conclude that SARS-CoV-2 infection in cats induces immune responses that provide partial, non-sterilizing immune protection against re-infection.
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Anticorpos Antivirais/sangue , COVID-19/transmissão , Suscetibilidade a Doenças/imunologia , Reinfecção/veterinária , Eliminação de Partículas Virais , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/veterinária , Gatos , Linhagem Celular , Chlorocebus aethiops , RNA Viral/isolamento & purificação , Reinfecção/imunologia , Reinfecção/virologia , SARS-CoV-2/imunologia , Células Vero , Carga ViralRESUMO
This case report highlights the initial presentation of Addison's disease in a 19-year-old individual with coronavirus disease. Coronavirus disease is an infectious disease, which often presents with fever and respiratory and gastrointestinal symptoms. Here, we describe a challenging case of a patient with coronavirus disease, who initially presented with altered mental status, hyponatremia, and cerebral edema, with subsequent workup leading to the diagnosis of Addison's disease.
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The emergence of SARS-CoV-2 has resulted in an ongoing global pandemic with significant morbidity, mortality, and economic consequences. The susceptibility of different animal species to SARS-CoV-2 is of concern due to the potential for interspecies transmission, and the requirement for pre-clinical animal models to develop effective countermeasures. In the current study, we determined the ability of SARS-CoV-2 to (i) replicate in porcine cell lines, (ii) establish infection in domestic pigs via experimental oral/intranasal/intratracheal inoculation, and (iii) transmit to co-housed naïve sentinel pigs. SARS-CoV-2 was able to replicate in two different porcine cell lines with cytopathic effects. Interestingly, none of the SARS-CoV-2-inoculated pigs showed evidence of clinical signs, viral replication or SARS-CoV-2-specific antibody responses. Moreover, none of the sentinel pigs displayed markers of SARS-CoV-2 infection. These data indicate that although different porcine cell lines are permissive to SARS-CoV-2, five-week old pigs are not susceptible to infection via oral/intranasal/intratracheal challenge. Pigs are therefore unlikely to be significant carriers of SARS-CoV-2 and are not a suitable pre-clinical animal model to study SARS-CoV-2 pathogenesis or efficacy of respective vaccines or therapeutics.
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Betacoronavirus/patogenicidade , Infecções por Coronavirus/veterinária , Pandemias/veterinária , Pneumonia Viral/veterinária , Doenças dos Suínos/virologia , Animais , Betacoronavirus/genética , Betacoronavirus/imunologia , COVID-19 , Linhagem Celular , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/transmissão , Modelos Animais de Doenças , Reservatórios de Doenças , Suscetibilidade a Doenças , Feminino , Masculino , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/transmissão , RNA Viral/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , SARS-CoV-2 , Suínos , Doenças dos Suínos/imunologia , Doenças dos Suínos/patologia , Doenças dos Suínos/transmissão , Cultura de Vírus , Replicação Viral , Sequenciamento do ExomaRESUMO
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the cause of Coronavirus Disease 2019 (COVID-19) and responsible for the current pandemic. Recent SARS-CoV-2 susceptibility studies in cats show that the virus can replicate in these companion animals and transmit to other cats. Here, we present an in-depth study of SARS-CoV-2 infection, disease and transmission in domestic cats. Cats were challenged with SARS-CoV-2 via intranasal and oral routes. One day post challenge (DPC), two sentinel cats were introduced. Animals were monitored for clinical signs, clinicopathological abnormalities and viral shedding. Postmortem examinations were performed at 4, 7 and 21 DPC. Viral RNA was not detected in blood but transiently in nasal, oropharyngeal and rectal swabs and bronchoalveolar lavage fluid as well as various tissues. Tracheobronchoadenitis of submucosal glands with the presence of viral RNA and antigen was observed in airways of the infected cats. Serology showed that both, principals and sentinels, developed antibodies to SARS-CoV-2. All animals were clinically asymptomatic during the course of the study and capable of transmitting SARS-CoV-2 to sentinels. The results of this study are critical for understanding the clinical course of SARS-CoV-2 in a naturally susceptible host species, and for risk assessment.
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Betacoronavirus/isolamento & purificação , Doenças do Gato/transmissão , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/veterinária , Suscetibilidade a Doenças , Pandemias/veterinária , Pneumonia Viral/transmissão , Pneumonia Viral/veterinária , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Líquido da Lavagem Broncoalveolar/química , COVID-19 , Doenças do Gato/patologia , Doenças do Gato/virologia , Gatos , Linhagem Celular , Chlorocebus aethiops , Infecções por Coronavirus/patologia , Masculino , Pneumonia Viral/patologia , RNA Viral/análise , RNA Viral/isolamento & purificação , SARS-CoV-2 , Células Vero , Replicação ViralRESUMO
The emergence of SARS-CoV-2 has resulted in an ongoing global pandemic with significant morbidity, mortality, and economic consequences. The susceptibility of different animal species to SARS-CoV-2 is of concern due to the potential for interspecies transmission, and the requirement for pre-clinical animal models to develop effective countermeasures. In the current study, we determined the ability of SARS-CoV-2 to (i) replicate in porcine cell lines, (ii) establish infection in domestic pigs via experimental oral/intranasal/intratracheal inoculation, and (iii) transmit to co-housed naive sentinel pigs. SARS-CoV-2 was able to replicate in two different porcine cell lines with cytopathic effects. Interestingly, none of the SARS-CoV-2-inoculated pigs showed evidence of clinical signs, viral replication or SARS-CoV-2-specific antibody responses. Moreover, none of the sentinel pigs displayed markers of SARS-CoV-2 infection. These data indicate that although different porcine cell lines are permissive to SARS-CoV-2, five-week old pigs are not susceptible to infection via oral/intranasal/intratracheal challenge. Pigs are therefore unlikely to be significant carriers of SARS-CoV-2 and are not a suitable pre-clinical animal model to study SARS-CoV-2 pathogenesis or efficacy of respective vaccines or therapeutics.
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African swine fever virus (ASFV) is the sole member of the family Asfarviridae, and the only known DNA arbovirus. Since its identification in Kenya in 1921, ASFV has remained endemic in Africa, maintained in a sylvatic cycle between Ornithodoros soft ticks and warthogs (Phacochoerus africanus) which do not develop clinical disease with ASFV infection. However, ASFV causes a devastating and economically significant disease of domestic (Sus scrofa domesticus) and feral (Sus scrofa ferus) swine. There is no ASFV vaccine available, and current control measures consist of strict animal quarantine and culling procedures. The virus is highly stable and easily spreads by infected swine, contaminated pork products and fomites, or via transmission by the Ornithodoros vector. Competent Ornithodoros argasid soft tick vectors are known to exist not only in Africa, but also in parts of Europe and the Americas. Once ASFV is established in the argasid soft tick vector, eradication can be difficult due to the long lifespan of Ornithodoros ticks and their proclivity to inhabit the burrows of warthogs or pens and shelters of domestic pigs. Establishment of endemic ASFV infections in wild boar populations further complicates the control of ASF. Between the late 1950s and early 1980s, ASFV emerged in Europe, Russia and South America, but was mostly eradicated by the mid-1990s. In 2007, a highly virulent genotype II ASFV strain emerged in the Caucasus region and subsequently spread into the Russian Federation and Europe, where it has continued to circulate and spread. Most recently, ASFV emerged in China and has now spread to several neighboring countries in Southeast Asia. The high morbidity and mortality associated with ASFV, the lack of an efficacious vaccine, and the complex makeup of the ASFV virion and genome as well as its lifecycle, make this pathogen a serious threat to the global swine industry and national economies. Topics covered by this review include factors important for ASFV infection, replication, maintenance, and transmission, with attention to the role of the argasid tick vector and the sylvatic transmission cycle, current and future control strategies for ASF, and knowledge gaps regarding the virus itself, its vector and host species.
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Purpose Pictures consistently referred to by the same name (high agreement) are named faster than pictures that elicit inconsistent responses across individuals (low agreement). Although this effect is more pronounced in older adults apparently due to slower lexical selection, it is unclear whether this is consistent for different types of low agreement pictures. We investigated whether pictures with different sources of disagreement have differing selection requirements, as indexed by naming latencies. Method Picture naming latencies were compared for 20 young (ages 18-35 years) and 20 older adults (ages 60-80 years) across 3 object naming conditions: high name agreement, low name agreement due to multiple correct names, and low agreement due to abbreviations and elaborations. Results Compared to high agreement items, responses were slower specifically for low agreement items with multiple names, and to a lesser extent, items with abbreviations and elaborations ( p < .001). Older adults were slower than younger adults, especially for low agreement items with abbreviations and elaborations ( p = .031). Conclusions Our findings indicate differential lexical selection requirements for low agreement pictures, depending on the reason for agreement being low. This demonstrates the importance of differentiating the source of disagreement in any experimental or clinical assessment of picture naming.
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Semântica , Terminologia como Assunto , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Progressive supranuclear palsy (PSP) is an atypical parkinsonian disorder that can present with language production deficits in addition to the characteristic progressive parkinsonian motor symptoms. Although typical parkinsonism treatments such as pharmacotherapy are not effective in PSP, non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) have shown promise for treating cognitive deficits relating to this disorder. We report the case of KN, who presented with reduced verbal fluency and connected speech production in the context of PSP. KN completed a set of language tasks, followed by an alternate version of the tasks in conjunction with either sham or active tDCS over the left dorsolateral prefrontal cortex (DLPFC) across four sessions. Results showed improved performance with active stimulation compared to sham stimulation for phonemic fluency and action naming, as well as mixed results suggesting possible benefits for connected speech production. There were no benefits of active stimulation for control tasks, indicating that tDCS can produce specific benefits for phonemic fluency, action naming, and connected speech production in PSP. These promising, preliminary findings warrant further investigation into whether these benefits of tDCS can be a useful therapeutic tool for PSP patients to maintain language.
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Idioma , Paralisia Supranuclear Progressiva/psicologia , Paralisia Supranuclear Progressiva/terapia , Estimulação Transcraniana por Corrente Contínua/métodos , Idoso , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/psicologia , Humanos , Testes de Linguagem , Masculino , Testes Neuropsicológicos , Córtex Pré-Frontal , Desempenho Psicomotor , Leitura , Medida da Produção da Fala , Resultado do Tratamento , Comportamento VerbalRESUMO
African swine fever virus (ASFV) causes serious disease in domestic pigs for which there is no vaccine currently available. ASFV is a large DNA virus that encodes for more than 150 proteins, thus making the identification of viral antigens that induce a protective immune response difficult. Based on the functional roles of several ASFV proteins found in previous studies, we selected combinations of ASFV recombinant proteins and pcDNAs-expressing ASFV genes, to analyze their ability to induce humoral and cellular immune responses in pigs. Pigs were immunized using a modified prime-boost approach with combinations of previously selected viral DNA and proteins, resulting in induction of antibodies and specific cell-mediated immune response, measured by IFN-γ ELISpots. The ability of antibodies from pigs immunized with various combinations of ASFV-specific antigens to neutralize infection in vitro, and antigen-specific activation of the cellular immune response were analyzed.
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Febre Suína Africana/prevenção & controle , DNA Viral/imunologia , Proteínas Virais/imunologia , Vacinas Virais/imunologia , Febre Suína Africana/imunologia , Vírus da Febre Suína Africana , Animais , Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , DNA Viral/administração & dosagem , ELISPOT , Imunidade Celular , Interferon gama/imunologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/imunologia , Sus scrofa , Suínos , Proteínas Virais/administração & dosagem , Vacinas Virais/administração & dosagemRESUMO
African swine fever virus (ASFV) causes high morbidity and mortality in swine (Sus scrofa), for which there is no commercially available vaccine. Recent outbreaks of the virus in Trans-Caucasus countries, Eastern Europe, Belgium and China highlight the urgent need to develop effective vaccines against ASFV. Previously, we evaluated the immunogenicity of a vaccination strategy designed to test various combinations of ASFV antigens encoded by DNA plasmids and recombinant proteins with the aim to activate both humoral and cellular immunity. Based on our previous results, the objective of this study was to test the combined DNA-protein vaccine strategy using a cocktail of the most immunogenic antigens against virulent ASFV challenge. Pigs were vaccinated three times with a cocktail that included ASFV plasmid DNA (CD2v, p72, p32, +/-p17) and recombinant proteins (p15, p35, p54, +/-p17). Three weeks after the third immunization, all pigs were challenged with the virulent ASFV Armenia 2007 strain. The results showed that vaccinated pigs were not protected from ASFV infection or disease. Compared to the non-vaccinated controls, earlier onset of clinical signs, viremia, and death were observed for the vaccinated animals following virulent ASFV challenge. ASFV induced pathology was also enhanced in the vaccinated pigs. Furthermore, while the vaccinated pigs developed antigen-specific antibodies, immunized pig sera at the time of challenge lacked the capacity to neutralize virus, and instead was observed to enhance ASFV infection in vitro. The results of this work points to a putative immune enhancement mechanism involved in ASFV pathogenesis that warrants further investigation. This pilot study provides insight for the selection of appropriate combinations of ASFV antigens for the development of a rationally-designed, safe, and efficacious vaccine for ASF.
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Conceptual preparation mechanisms such as novel idea generation and selection from amongst competing alternatives are critical for language production and may contribute to age-related language deficits. This study investigated whether older adults show diminished idea generation and selection abilities, compared to younger adults. Twenty younger (18-35 years) and 20 older (60-80 years) adults completed two novel experimental tasks, an idea generation task and a selection task. Older participants were slower than younger participants overall on both tasks. Importantly, this difference was more pronounced for task conditions with greater demands on generation and selection. Older adults were also significantly reduced on a semantic, but not phonemic, word fluency task. Overall, the older group showed evidence of age-related decline specific to idea generation and selection ability. This has implications for the message formulation stage of propositional language decline in normal aging.
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Envelhecimento/psicologia , Formação de Conceito/fisiologia , Idioma , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Adulto JovemRESUMO
INTRODUCTION: Normal aging is associated with deficits in various aspects of spoken language production, including idea generation and selection, and involves activity in frontal brain areas including left inferior frontal cortex (LIFG). These conceptual preparation processes, largely involving executive control, precede formulation and articulation stages and are critical for language production. Noninvasive brain stimulation (e.g., transcranial direct current stimulation, tDCS) has proven beneficial for age-related fluency and naming deficits, but this has not been extended to conceptual preparation mechanisms. METHOD: We investigated whether tDCS could facilitate idea generation and selection in 24 older adults aged 60-80 years. In the first phase, participants completed an idea generation test and a selection test with no stimulation. In the second phase they completed an alternate version of the tests in conjunction with either active or sham stimulation. Active stimulation applied 1-mA anodal tDCS over LIFG for the test duration (10 min). RESULTS: Responses were faster following active stimulation than following sham. Furthermore, improvements were specific to test conditions involving novel generation (p = .030) and selection (p = .001) and were not observed in control conditions for which these mechanisms were minimally involved. CONCLUSIONS: We concluded that tDCS benefits conceptual preparation mechanisms. This preliminary evidence is an important step for addressing age-related decline in propositional language generation, which is integral to conversational speech. This approach could also be extended toward rehabilitation in neurological patients with deficits in these processes.