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A foxhound from a hunting kennel in the United Kingdom was euthanized after being hospitalized with progressive neurologic signs, including tremors, seizures, and obtunded mentation. No abnormalities were appreciated on gross postmortem examination. Histologically, severe meningoencephalomyelitis and mild neuritis of the brachial plexus were present. Molecular analysis of brain tissue detected louping ill virus. In addition, louping ill virus-specific antigens were detected in neurons within the brainstem, the entire length of the spinal cord, as well as in rare cells in the brachial plexus using immunohistochemistry. The genetic sequence of the virus appears most closely related to a previously detected virus in a dog from a similar geographic location in 2015. This is the first characterization of the inflammatory lesions and viral distribution of louping ill virus in a naturally infected dog within the spinal cord and brachial plexus.
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Newcastle disease (ND) is a notifiable disease affecting chickens and other avian species caused by virulent strains of Avian paramyxovirus type 1 (APMV-1). While outbreaks of ND can have devastating consequences, avirulent strains of APMV-1 generally cause subclinical infections or mild disease. However, viruses can cause different levels of disease in different species and virulence can evolve following cross-species transmission events. This report describes the detection of three cases of avirulent APMV-1 infection in Great Britain (GB). Case 1 emerged from the 'testing to exclude' scheme in chickens in Shropshire while cases 2 and 3 were made directly from notifiable avian disease investigations in chicken broilers in Herefordshire and on premises in Wiltshire containing ducks and mixed species, respectively). Class II/genotype I.1.1 APMV-1 from case 1 shared 99.94% identity to the Queensland V4 strain of APMV-1. Class II/genotype II APMV-1 was detected from case 2 while the class II/genotype I.2 virus from case 3 aligned closely with strains isolated from Anseriformes. Exclusion of ND through rapid detection of avirulent APMV-1 is important where clinical signs caused by avirulent or virulent APMV-1s could be ambiguous. Understanding the diversity of APMV-1s circulating in GB is critical to understanding disease threat from these adaptable viruses.
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Doenças das Aves , Doença de Newcastle , Animais , Galinhas , Reino Unido/epidemiologia , Vírus da Doença de Newcastle/genética , Doença de Newcastle/epidemiologia , Doença de Newcastle/diagnóstico , FilogeniaRESUMO
Relatively little research has focused on children and young people (CYP) whose mental health and wellbeing improved during Covid-19 lockdown measures. We aimed to (1) determine the proportion of CYP who self-reported improvement in their mental wellbeing during the first Covid-19 lockdown and (2) describe the characteristics of this group in relation to their peers. We conducted a descriptive analysis of data from the 2020 OxWell Student Survey, a self-report, cross-sectional survey of English CYP. A total of 16,940 CYP primarily aged 8-18 years reported on change in mental wellbeing during lockdown. We characterised these CYP in terms of school, home, relational, and lifestyle factors as well as feelings about returning to school. One-third (33%) of CYP reported improved mental wellbeing during the first UK national lockdown. Compared with peers who reported no change or deterioration, a higher proportion of CYP with improved mental wellbeing reported improved relationships with friends and family, less loneliness and exclusion, reduced bullying, better management of school tasks, and more sleep and exercise during lockdown. In conclusion, a sizeable minority of CYP reported improved mental wellbeing during lockdown. Determining the reasons why these CYP felt they fared better during lockdown and considering how these beneficial experiences can be maintained beyond the pandemic might provide insights into how to promote the future mental health and wellbeing of school-aged CYP. All those working with CYP now have an opportunity to consider whether a systemic shift is needed in order to understand and realise any learnings from experiences during the pandemic.
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COVID-19 , Criança , Humanos , Adolescente , Autorrelato , Estudos Transversais , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis , Estudantes , Reino Unido/epidemiologiaRESUMO
The 2016-17 European outbreak of H5N8 HPAIV (Clade 2.3.4.4b) affected a wider range of avian species than the previous H5N8 outbreak (2014-15), including an incursion of H5N8 HPAIV into gamebirds in England. Natural infection of captive-reared pheasants (Phasianus colchicus) led to variable disease presentation; clinical signs included ruffled feathers, reluctance to move, bright green faeces, and/or sudden mortality. Several birds exhibited neurological signs (nystagmus, torticollis, ataxia). Birds exhibiting even mild clinical signs maintained substantial levels of virus replication and shedding, with preferential shedding via the oropharyngeal route. Gross pathology was consistent with HPAIV, in gallinaceous species but diphtheroid plaques in oropharyngeal mucosa associated with necrotising stomatitis were novel but consistent findings. However, minimal or modest microscopic pathological lesions were detected despite the systemic dissemination of the virus. Serology results indicated differences in the timeframe of exposure for each case (n = 3). This supported epidemiological conclusions confirming that the movement of birds between sites and other standard husbandry practices with limited hygiene involved in pheasant rearing (including several fomite pathways) contributed to virus spread between premises.
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Vírus da Influenza A Subtipo H5N8 , Vírus da Influenza A , Influenza Aviária , Animais , Aves , Surtos de Doenças/veterinária , VirulênciaRESUMO
In 2011, a neurological disease was reported in a herd of goats (Capra hircus) in Asturias, Spain. Initial sequencing identified the causative agent as louping ill virus (LIV). Subsequently, with the application of whole genome sequencing and phylogenetic analysis, empirical data demonstrates that the LIV-like virus detected is significantly divergent from LIV and Spanish sheep encephalitis virus (SSEV). This virus encoded an amino acid sequence motif at the site of a previously identified marker for differentiating tick-borne flaviviruses that was shared with a virus previously isolated in Ireland in 1968. The significance of these observations reflects the diversity of tick-borne flaviviruses in Europe. These data also contribute to our knowledge of the evolution of tick-borne flaviviruses and could reflect the movement of viruses throughout Europe. Based on these observations, the proposed name for this virus is Spanish goat encephalitis virus (SGEV), to distinguish it from SSEV.
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Vírus da Encefalite Transmitidos por Carrapatos/isolamento & purificação , Encefalite Transmitida por Carrapatos/veterinária , Genoma Viral , Doenças das Cabras/virologia , Cabras/virologia , RNA Viral/genética , Análise de Sequência de DNA , Animais , Análise por Conglomerados , Vírus da Encefalite Transmitidos por Carrapatos/genética , Encefalite Transmitida por Carrapatos/virologia , Irlanda , Dados de Sequência Molecular , Filogenia , Homologia de Sequência , EspanhaRESUMO
The past three decades have seen an increasing number of emerging arthropod-borne viruses in temperate regions This process is ongoing, driven by human activities such as inter-continental travel, combined with the parallel emergence of invasive arthropods and an underlying change in climate that can increase the risk of virus transmission and persistence. In addition, natural events such as bird migration can introduce viruses to new regions. Despite the apparent regularity of virus emergence, arthropod-borne viruses circulating in temperate regions face the challenge of the late autumn and winter months where the arthropod vector is inactive. Viruses therefore need mechanisms to overwinter or they will fail to establish in temperate zones. Prolonged survival of arthropod-borne viruses within the environment, outside of both vertebrate host and arthropod vector, is not thought to occur and therefore is unlikely to contribute to overwintering in temperate zones. One potential mechanism is continued infection of a vertebrate host. However, infection is generally acute, with the host either dying or producing an effective immune response that rapidly clears the virus. There are few exceptions to this, although prolonged infection associated with orbiviruses such as bluetongue virus occurs in certain mammals, and viraemic vertebrate hosts therefore can, in certain circumstances, provide a route for long-term viral persistence in the absence of active vectors. Alternatively, a virus can persist in the arthropod vector as a mechanism for overwintering. However, this is entirely dependent on the ecology of the vector itself and can be influenced by changes in the climate during the winter months. This review considers the mechanisms for virus overwintering in several key arthropod vectors in temperate areas. We also consider how this will be influenced in a warming climate.
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Ticks are the main arthropod vector of pathogens to humans and livestock in the British Isles. Despite their role as a vector of disease, many aspects of tick biology, ecology, and microbial association are poorly understood. To address this, we investigated the composition of the microbiome of adult and nymphal Ixodes ricinus ticks. The ticks were collected on a dairy farm in Southwest England and RNA extracted for whole genome sequencing. Sequences were detected from a range of microorganisms, particularly tick-associated viruses, bacteria, and nematodes. A majority of the viruses were attributed to phlebo-like and nairo-like virus groups, demonstrating a high degree of homology with the sequences present in I. ricinus from mainland Europe. A virus sharing a high sequence identity with Chimay rhabdovirus, previously identified in ticks from Belgium, was detected. Further investigations of I. ricinus ticks collected from additional sites in England and Wales also identified Chimay rhabdovirus viral RNA with varying prevalence in all tick populations. This suggests that Chimay rhabdovirus has a wide distribution and highlights the need for an extended exploration of the tick microbiome in the United Kingdom (UK).
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Ixodes , Filogenia , Rhabdoviridae , Animais , Ixodes/virologia , Ixodes/microbiologia , Inglaterra , País de Gales , Rhabdoviridae/genética , Rhabdoviridae/classificação , Rhabdoviridae/isolamento & purificação , Genoma Viral , RNA Viral/genética , Microbiota , Sequenciamento Completo do Genoma , Ninfa/virologia , Ninfa/microbiologiaRESUMO
Behavioral and brain potential measures were employed to compare interference in Eriksen and Simon tasks. Assuming a dual-process model of interference elicited in speeded response tasks, we hypothesized that only lateralized stimuli in the Simon task induce fast S-R priming via direct unconditional processes, while Eriksen interference effects are induced later via indirect conditional processes. Delays to responses for incongruent trials were indeed larger in the Eriksen than in the Simon task. Only lateralized stimuli in the Simon task elicited early S-R priming, maximal at parietal areas. Incongruent flankers in the Eriksen task elicited interference later, visible as a lateralized N2. Eriksen interference also elicited an additional component (N350), which accounted for the larger behavioral interference effects in the Eriksen task. The findings suggest that interference and its resolution involve different processes for Simon and Eriksen tasks.
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Córtex Cerebral/fisiologia , Comportamento de Escolha/fisiologia , Cognição/fisiologia , Potenciais Evocados Visuais , Adulto , Feminino , Lateralidade Funcional , Humanos , Masculino , Modelos Psicológicos , Testes Neuropsicológicos , Adulto JovemRESUMO
Given well-established links between socio-economic adversity and mental health, it is unsurprising that young people's mental health is deteriorating amidst economic crises. The World Health Organisation (WHO) recognises mental health as "crucial to personal, community, and socio-economic development" and outlines goals to reshape environments such as schools to protect mental health. Schools offer an ideal setting to promote wellbeing and prevent mental ill-health during a key developmental window. We describe how social inequalities present a challenge to designing school-based interventions for prevention and promotion for mental health and wellbeing, and suggest priorities to aid and evaluate their effectiveness.
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Batai virus (BATV) is a zoonotic orthobunyavirus transmitted by a wide range of mosquito vectors. The virus is distributed throughout Asia and parts of Africa and has been sporadically detected in several European countries. There is increasing evidence that BATV is emerging in Europe as a potential threat to both animal and human health, having been detected in mosquitoes, mammals, birds and humans. In recent years, serological surveillance in cattle, sheep and goats has suggested an antibody prevalence of up to 46% in European livestock, although human serological prevalence remains generally low. However, the recent and continued spread of invasive mosquito species into Europe may facilitate the establishment of competent populations of mosquitoes leading to increased BATV transmission. Migratory birds may also potentially facilitate the emergence of BATV in geographical locations where it was previously undetected. Although BATV has the potential to cause disease in humans and livestock, our understanding of the impact in wild animal populations is extremely limited. Therefore, there is a need for increased surveillance for BATV in mosquitoes, livestock, wild mammals and birds in Europe to understand the true impact of this virus.
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Vírus Bunyamwera , Culicidae , Orthobunyavirus , Animais , Bovinos , Europa (Continente)/epidemiologia , Cabras , Humanos , Filogenia , OvinosRESUMO
Background: Little is known about the perceived acceptability and usefulness of supports that adolescents have accessed following self-harm, especially since the onset of the COVID-19 pandemic. Aims: To examine the utilization and acceptability of formal, informal, and online support accessed by adolescents following self-harm before and during the pandemic. Method: Cross-sectional survey (OxWell) of 10,560 secondary school students aged 12-18 years in the south of England. Information on self-harm, support(s) accessed after self-harm, and satisfaction with support received were obtained via a structured, self-report questionnaire. No tests for significance were conducted. Results: 1,457 (12.5%) students reported having ever self-harmed and 789 (6.7%) reported self-harming during the first national lockdown. Informal sources of support were accessed by the greatest proportion of respondents (friends: 35.9%; parents: 25.0%). Formal sources of support were accessed by considerably fewer respondents (Child and Adolescent Mental Health Services: 12.1%; psychologist/ psychiatrist: 10.2%; general practitioner: 7.4%). Online support was accessed by 8.6% of respondents, and 38.3% reported accessing no support at all. Informal sources of support were rated as most helpful, followed by formal sources, and online support. Of the respondents who sought no support, 11.3% reported this as being helpful. Conclusions: More than a third of secondary school students in this sample did not seek any help following self-harm. The majority of those not seeking help did not find this to be a helpful way of coping. Further work needs to determine effective ways of overcoming barriers to help-seeking among adolescents who self-harm and improving perceived helpfulness of the supports accessed.
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STUDY OBJECTIVES: Sleep is essential to young people's wellbeing, yet may be constricted by the adolescent delayed sleep phase coupled with school start times. COVID-19 restrictions caused major disruptions to everyday routines, including partial school closures. We set out to understand changes in students' self-reported sleep quality, and associations with mental wellbeing and interpersonal functioning, during these restrictions. METHODS: The OxWell school survey-a cross-sectional online survey-collected data from 18 642 children and adolescents (aged 8-19 years, 60% female, school year 4-13) from 230 schools in southern England, in June-July 2020. Participants completed self-report measures of the impact of COVID-19 restrictions on sleep quality, happiness, and social relationships. Sleep timing was compared with data collected from 4222 young people in 2019. RESULTS: Females and older adolescents were more likely to report deteriorations in sleep during the national lockdown. Regression analysis revealed that changes in happiness (ß = .34) and how well students were getting on with others in their household (ß = .07) predicted change in sleep quality. Students' bedtimes and wake times were later, and sleep duration was longer in 2020 compared to the 2019 survey. Secondary school students reported the greatest differences, especially later wake times. CONCLUSIONS: During COVID-19 restrictions, sleep patterns consistent with adolescent delayed sleep phase were observed, with longer sleep times for secondary school students in particular. Perceived deteriorations in sleep quality were associated with reductions in happiness and interpersonal functioning, highlighting the importance of including sleep measures in adolescent wellbeing research.
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Where ticks are found, tick-borne diseases can present a threat to human and animal health. The aetiology of many of these important diseases, including Lyme disease, bovine babesiosis, tick-borne fever and louping ill, have been known for decades whilst others have only recently been documented in the United Kingdom (UK). Further threats such as the importation of exotic ticks through human activity or bird migration, combined with changes to either the habitat or climate could increase the risk of tick-borne disease persistence and transmission. Prevention of tick-borne diseases for the human population and animals (both livestock and companion) is dependent on a thorough understanding of where and when pathogen transmission occurs. This information can only be gained through surveillance that seeks to identify where tick populations are distributed, which pathogens are present within those populations, and the periods of the year when ticks are active. To achieve this, a variety of approaches can be applied to enhance knowledge utilising a diverse range of stakeholders (public health professionals and veterinarians through to citizen scientists). Without this information, the application of mitigation strategies to reduce pathogen transmission and impact is compromised and the ability to monitor the effects of climate change or landscape modification on the risk of tick-borne disease is more challenging. However, as with many public and animal health interventions, there needs to be a cost-benefit assessment on the most appropriate intervention applied. This review will assess the challenges of tick-borne diseases in the UK and argue for a cross-disciplinary approach to their surveillance and control.
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Doença de Lyme , Saúde Única , Doenças Transmitidas por Carrapatos , Carrapatos , Animais , Doença de Lyme/epidemiologia , Doença de Lyme/prevenção & controle , Doenças Transmitidas por Carrapatos/epidemiologia , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Japanese encephalitis virus (JEV) is the principal cause of mosquito-borne encephalitis in human populations within Asia. If introduced into new geographic areas, it could have further implications for public and animal health. However, potential mosquito vectors for virus transmission have not been fully investigated. The Asian tiger mosquito, Aedes albopictus, has emerged in Europe and is now expanding its geographical range into more northerly latitudes. Culex quinquefasciatus, although absent from Europe, has been detected in Turkey, a country with territory in Europe, and could act as a vector for JEV in other regions. To assess the risk of these invasive species acting as vectors for JEV and therefore potentially contributing to its geographical expansion, we have investigated the vector competence of Ae. albopictus and Cx. quinquefasciatus. METHODS: Two colonised lines of Ae. albopictus (Italy and Spain) and a line of Cx. quinquefasciatus (Tanzania) were compared for susceptibility to infection by oral feeding with JEV strain SA-14, genotype III at 106 PFU/ml and maintained at 25 °C. Specimens were processed at 7 and 14 days post-inoculation (dpi). Rates of infection, dissemination and transmission were assessed through detection of viral RNA by real-time polymerase chain reaction (RT-PCR) in mosquito body, legs and saliva, respectively, at each time point. Where possible, infection and dissemination were confirmed by immunohistochemical (IHC) detection of the JEV envelope protein. RESULTS: Aedes albopictus from Italy showed no susceptibility to infection with JEV strain SA-14. Conversely, Ae. albopictus colonised in Spain was susceptible and 100% of infected mosquitoes that were subjected to saliva screening expressed viral RNA at 14 dpi. Culex quinquefasciatus was highly susceptible to infection as early as 7 dpi and 50% of infected mosquitoes that were subjected to saliva screening expressed viral RNA at 14 dpi. Infection and dissemination were confirmed in Cx. quinquefasciatus by IHC detection of JEV envelope protein in both the mid-gut and salivary glands. CONCLUSIONS: Aedes albopictus from two different locations in Europe range from being susceptible to JEV and capable of transmission through to being resistant. Culex quinquefasciatus also appears highly susceptible; therefore, both species could potentially act as vectors for JEV and facilitate the emergence of JEV into new regions.
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Aedes , Culex , Vírus da Encefalite Japonesa (Espécie) , Animais , Suscetibilidade a Doenças , Vírus da Encefalite Japonesa (Espécie)/genética , Mosquitos Vetores , RNA Viral/genéticaRESUMO
Usutu virus (USUV) is an emerging zoonotic arbovirus in Europe, where it primarily impacts Eurasian blackbirds (Turdus merula). For mosquito-borne viruses to persist in temperate areas, transovarial transmission in vectors or overwintering in either hosts or diapausing vectors must occur to facilitate autochthonous transmission. We undertook surveillance of hosts and vectors in 2021 to elucidate whether USUV had overwintered in the United Kingdom (UK) following its initial detection there in 2020. From 175 dead bird submissions, we detected 1 case of USUV infection, in a blackbird, from which a full USUV genome was derived. Using a molecular clock analysis, we demonstrate that the 2021 detection shared a most recent common ancestor with the 2020 Greater London, UK, USUV sequence. In addition, we identified USUV-specific neutralizing antibodies in 10 out of 86 serum samples taken from captive birds at the index site, demonstrating in situ cryptic infection and potential sustained transmission. However, from 4966 mosquitoes, we detected no USUV RNA suggesting that prevalence in the vector community was absent or low during sampling. Combined, these results suggest that USUV overwintered in the UK, thus providing empirical evidence for the continued northward expansion of this vector-borne viral disease. Currently, our detection indicates geographically restricted virus persistence. Further detections over time will be required to demonstrate long-term establishment. It remains unclear whether the UK, and by extension other high-latitude regions, can support endemic USUV infection.
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Doenças das Aves , Infecções por Flavivirus , Flavivirus , Aves Canoras , Animais , Mosquitos Vetores , Flavivirus/genética , Infecções por Flavivirus/epidemiologia , Infecções por Flavivirus/veterinária , Reino Unido/epidemiologiaRESUMO
Dengue viruses (DENV) cause countless human deaths each year, whilst West Nile virus (WNV) has re-emerged as an important human pathogen. There are currently no WNV or DENV vaccines licensed for human use, yet vaccines exist against other flaviviruses. To investigate flavivirus cross-reactivity, sera from a human cohort with a history of vaccination against tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV) and yellow fever virus (YFV) were tested for antibodies by plaque reduction neutralization test. Neutralization of louping ill virus (LIV) occurred, but no significant neutralization of Murray Valley encephalitis virus was observed. Sera from some individuals vaccinated against TBEV and JEV neutralized WNV, which was enhanced by YFV vaccination in some recipients. Similarly, some individuals neutralized DENV-2, but this was not significantly influenced by YFV vaccination. Antigenic cartography techniques were used to generate a geometric illustration of the neutralization titres of selected sera against WNV, TBEV, JEV, LIV, YFV and DENV-2. This demonstrated the individual variation in antibody responses. Most sera had detectable titres against LIV and some had titres against WNV and DENV-2. Generally, LIV titres were similar to titres against TBEV, confirming the close antigenic relationship between TBEV and LIV. JEV was also antigenically closer to TBEV than WNV, using these sera. The use of sera from individuals vaccinated against multiple pathogens is unique relative to previous applications of antigenic cartography techniques. It is evident from these data that notable differences exist between amino acid sequence identity and mapped antigenic relationships within the family Flaviviridae.
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Anticorpos Antivirais/sangue , Vírus da Dengue/imunologia , Vírus da Encefalite Japonesa (Espécie)/imunologia , Vírus da Encefalite Transmitidos por Carrapatos/imunologia , Vírus do Nilo Ocidental/imunologia , Vírus da Febre Amarela/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Reações Cruzadas , Vacinas contra Dengue/imunologia , Humanos , Testes de Neutralização/métodos , Ensaio de Placa Viral/métodos , Vacina contra Febre Amarela/imunologiaRESUMO
BACKGROUND: Understanding adolescents' mental health during lockdown and identifying those most at risk is an urgent public health challenge. This study surveyed school pupils across Southern England during the first COVID-19 school lockdown to investigate situational factors associated with mental health difficulties and how they relate to pupils' access to in-school educational provision. METHODS: A total of 11,765 pupils in years 8-13 completed a survey in June-July 2020, including questions on mental health, risk indicators and access to school provision. Pupils at home were compared to those accessing in-school provision on risk and contextual factors and mental health outcomes. Multilevel logistic regression analyses compared the effect of eight risk and contextual factors, including access to in-school provision, on depression, anxiety and self-reported deterioration in mental wellbeing. RESULTS: Females, pupils who had experienced food poverty and those who had previously accessed mental health support were at greatest risk of depression, anxiety and a deterioration in wellbeing. Pupils whose parents were going out to work and those preparing for national examinations in the subsequent school year were also at increased risk. Pupils accessing in-school provision had poorer mental health, but this was accounted for by the background risk and contextual factors assessed, in line with the allocation of in-school places to more vulnerable pupils. CONCLUSIONS: Although the strongest associations with poor mental health during school closures were established risk factors, further contextual factors of particular relevance during lockdown had negative impacts on wellbeing. Identifying those pupils at greatest risk for poor outcomes is critical for ensuring that appropriate educational and social support can be given to pupils either at home or in-school during subsequent lockdowns.
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BACKGROUND: Vaccine hesitancy has affected COVID-19 adult vaccination programs in many countries. Data on hesitancy amongst child and adolescent populations is largely confined to parent opinion. We investigated the characteristics of vaccine hesitant children and adolescents using results from a large, school-based self-report survey of the willingness to have a COVID-19 vaccination in students aged 9 -18 years in England. METHODS: Data from the OxWell Student Survey on mental health, life experiences and behaviours were used, collected from four counties across England. Local authority partners recruited schools. The vaccine hesitancy question gave six response options and were clustered to inform delivery: eager and willing were categorised as vaccination 'opt-in', don't know and not bothered categorised as 'undecided', and unwilling and anti-vaccination categorised as 'opt-out'. We conducted a multinomial regression to determine associations between vaccine hesitancy and sociodemographic, health behaviour and social connection variables. FINDINGS: 27,910 students from 180 schools answered the vaccine hesitancy question between 14th May and 21st July 2021, of whom 13984 (50.1%) would opt-in to take a vaccination, 10322 (37.0%) were undecided, and 3604 (12.9%) would opt-out. A lower percentage of younger students reported that they would opt-in to vaccination, for example, 35.7% of 9-year-olds and 51.3% of 13-year-olds compared to 77.8% of 17-year-olds would opt-in to take a vaccination. Students who were 'opt-out' or 'undecided' (a combined 'vaccine hesitant' group) were more likely to come from deprived socioeconomic contexts with higher rates of home rental versus home ownership and their school locations were more likely to be in areas of greater deprivation. They were more likely to smoke or vape, spend longer on social media, feel that they did not belong in their school community but had lower levels of anxiety and depression. The vaccine hesitant students- the undecided and opt-out groups- were similar in profile, although the opt-out students had higher reported confirmed or probable previous COVID-19 infection than the opt-in group, whereas those undecided, did not. INTERPRETATION: If government vaccination strategies move towards vaccinating younger school-aged students, efforts to increase vaccination uptake may be necessary. Compared with students who would opt-in, those who were vaccine hesitant had greater indicators of social deprivation and felt a lack of community cohesion by not feeling a sense of belonging at their school. There were indications that those students who would opt-out had higher levels of marginalisation and mistrust. If programmes are rolled out, focus on hesitant younger students will be important, targeting more marginalised and deprived young people with information from trusted sources utilising social media; improving access to vaccination centres with provision both in and outside school; and addressing fears and worries about the effects of the vaccine. The main limitation of this study is that the participant group may not be wholly representative of England or the UK, which may bias population-level estimates of willingness to be vaccinated. FUNDING: The Westminster Foundation, the National Institute for Health Research (NIHR) Applied Research Collaboration Oxford and Thames Valley at Oxford Health NHS Foundation Trust and the NIHR Oxford Health Biomedical Research Centre.
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Over the last 20â¯years, natural peptides playing a key role in defense mechanisms and innate immunity have been isolated from unicellular organisms. Amphibian skin secretes dermaseptins, 24-34 amino acids in length that have a wide antimicrobial spectrum incorporating yeast, fungi, protozoa, bacteria and enveloped viruses. The anti-rabies virus (RABV) activity of dermaseptins S3 (30aa) and S4 (28aa) from Phyllomedusa sauvagei has been investigated, and further dissected its molecular basis by comparing punctual mutation or deletion of S4 analogues. The results showed that: (1) S4 is more active than S3 against RABV infection, 89% versus 38% inhibition at 7.5⯵M; (2) the 5 NH2-aa of S4 are crucial for its inhibitory potential (S46-28 lost any inhibition) but the COOH terminus stabilizes the inhibitory potential (S41-16 showed only 23% inhibition at 7.5⯵M); (3) there is a correlation between viral inhibition and dermaseptin cytotoxicity, which remains however moderated for BSR cells (≤12% at 10⯵M). A single mutation in position 4 (S4M4K) slightly reduced cytotoxicity while keeping its antiviral activity, 97% at 7.5⯵M. S4 and S4M4K showed an antiviral activity in vitro when provided 1â¯h after infection. In vivo experiments in mice by intramuscular injection of non-toxic doses of dermaseptin S4M4K 1â¯h post-infection by a lethal dose of RABV at the same site allowed more than 50% improvement in mice survival. This study highlights the potential interest of dermaseptins as non-expansive alternatives to rabies immunoglobulins for the treatment of rabies that continues to claim about 60,000 human lives per year worldwide, almost exclusively in developing countries.
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Proteínas de Anfíbios/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Antivirais/uso terapêutico , Raiva/tratamento farmacológico , Proteínas de Anfíbios/administração & dosagem , Proteínas de Anfíbios/efeitos adversos , Proteínas de Anfíbios/genética , Animais , Peptídeos Catiônicos Antimicrobianos/administração & dosagem , Peptídeos Catiônicos Antimicrobianos/efeitos adversos , Peptídeos Catiônicos Antimicrobianos/genética , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Relação Dose-Resposta a Droga , Feminino , Injeções Intramusculares , Camundongos , Mutação/genética , Relação Estrutura-AtividadeRESUMO
Newcastle disease is a devastating disease of poultry caused by Newcastle disease virus (NDV), a virulent form of avian avulavirus 1 (AAvV-1). A rapid, sensitive and specific means for the detection of NDV is fundamental for the control of this notifiable transboundary virus. Although several real-time RT-PCR assays exist for the detection of AAvV-1, diagnostic sensitivity and specificities can be sub-optimal. In this study, we describe a modification to an existing AAvV-1 l-gene RT-PCR screening assay, where the original probe set was replaced with minor groove binding (MGB) probes, to create the MGB l-gene assay. The diagnostic sensitivity and specificity of this assay was evaluated against a broad panel of both Class I and Class II AAvV-1 viruses of diverse and representative lineages/genotypes in both clinical samples and amplified viruses, and compared with a number of previously published real-time RT-PCR screening assays for AAvV-1. The MGB l-gene assay outperformed all other assays in this assessment, with enhanced sensitivity and specificity, detecting isolates from a broad range of virus lineages/genotypes (including contemporaneously-circulating strains). The assay has also proved its value for screening original clinical samples for the presence of AAvV-1, thus providing an improved screening assay for routine detection of this notifiable disease agent.