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Foot-and-mouth disease virus (FMDV) is the pathogen of foot-and-mouth disease (FMD), which is a highly contagious disease in cloven-hoofed animals. To survive in the host, FMDV has evolved multiple strategies to antagonize host innate immune responses. In this study, we showed that the leader protease (Lpro) of FMDV, a papain-like proteinase, promoted viral replication by evading the antiviral interferon response through counteracting the 29,59-oligoadenylate synthetase (OAS)/RNase L system. Specifically, we observed that the titers of Lpro deletion virus were significantly lower than those of wildtype FMDV (FMDV-WT) in cultured cells. Our mechanistic studies demonstrated that Lpro interfered with the OAS/RNase L pathway by interacting with the N-terminal domain of swine RNase L (sRNase L). Remarkably, Lpro of FMDV exhibited species-specific binding to RNase L in that the interaction was observed only in swine cells, not human, monkey, or canine cells. Lastly, we presented evidence that by interacting with sRNase L, FMDV Lpro inhibited cellular apoptosis. Taken together, these results demonstrate a novel mechanism that Lpro utilizes to escape the OAS/RNase L-mediated antiviral defense pathway. [ABSTRACT FROM AUTHOR]

Objective: Mental health (MH) care in remote areas is frequently scarce and fragmented and difficult to compare objectively with other areas even in the same country. This study aimed to analyze the adult MH service provision in 3 remote areas of Organization for Economic Cooperation and Development countries in the world.Methods: We used an internationally agreed set of systems indicators, terminology, and classification of services (Description and Evaluation of Services and DirectoriEs for Long Term Care). This instrument provided a standard description of MH care provision in the Kimberley region (Australia), Nunavik (Canada), and Lapland (Finland), areas characterized by an extremely low population density and high relative rates of Indigenous peoples.Results: All areas showed high rates of deprivation within their national contexts. MH services were mostly provided by the public sector supplemented by nonprofit organizations. This study found a higher provision per inhabitant of community residential care in Nunavik in relation to the other areas; higher provision of community outreach services in the Kimberley; and a lack of day services except in Lapland. Specific cultural-based services for the Indigenous population were identified only in the Kimberley. MH care in Lapland was self-sufficient, and its care pattern was similar to other Finnish areas, while the Kimberley and Nunavik differed from the standard pattern of care in their respective countries and relied partly on services located outside their boundaries for treating severe cases.Conclusion: We found common challenges in these remote areas but a huge diversity in the patterns of MH care. The implementation of care interventions should be locally tailored considering both the environmental characteristics and the existing pattern of service provision. [ABSTRACT FROM AUTHOR]

Lyme disease, caused by some Borrelia burgdorferi sensu lato , is the most common tick-borne illness in the Northern Hemisphere and the number of cases, and geographic spread, continue to grow. Previously identified B. burgdorferi proteins, lipid immunogens, and live mutants lead the design of canonical vaccines aimed at disrupting infection in the host. Discovery of the mechanism of action of the first vaccine catalyzed the development of new strategies to control Lyme disease that bypassed direct vaccination of the human host. Thus, novel prevention concepts center on proteins produced by B. burgdorferi during tick transit and on tick proteins that mediate feeding and pathogen transmission. A burgeoning area of research is tick immunity as it can unlock mechanistic pathways that could be targeted for disruption. Studies that shed light on the mammalian immune pathways engaged during tick-transmitted B. burgdorferi infection would further development of vaccination strategies against Lyme disease. [ABSTRACT FROM AUTHOR]

Objective: Access to services and workforce shortages are major challenges in rural areas worldwide. In order to improve access to mental health care, it is imperative to understand what services are available, what their capacity is and where existing funds might be spent to increase availability and accessibility. The aim of this study is to investigate mental health service provision in a selection of rural and remote areas across Australia by analysing service availability, placement capacity and diversity. Method: This research studies the health regions of Western New South Wales and Country Western Australia and their nine health areas. Service provision was analysed using the DESDE-LTC system for long-term care service description and classification that allows international comparison. Rates per 100,000 inhabitants were calculated to compare the care availability and placement capacity for children and adolescents, adults and older adults. Results: The lowest diversity was found in northern Western Australia. Overall, Western New South Wales had a higher availability of non-acute outpatient services for adults, but hardly any acute outpatient services. In Country Western Australia, substantially fewer non-acute outpatient services were found, while acute services were much more common. Acute inpatient care services were more common in Western New South Wales, while sub-acute inpatient services and non-acute day care services were only found in Western New South Wales. Conclusion: The number and span of services in the two regions showed discrepancies both within and between regions, raising issues on the equity of access to mental health care in Australia. The standard description of the local pattern of rural mental health care and its comparison across jurisdictions is critical for evidence-informed policy planning and resource allocation. [ABSTRACT FROM AUTHOR]

In humans and most other species, changes in the intensity and duration of light provide a critical set of signals for the synchronisation of the circadian system to the astronomical day. The timing of activity within the 24 h day defines an individual’s chronotype, i.e. morning, intermediate or evening type. The aim of this study was to investigate the associations between environmental light exposure, due to geographical location, on the chronotype of university students. Over 6 000 university students from cities in the Northern Hemisphere (Oxford, Munich and Groningen) and Southern Hemisphere (Perth, Melbourne and Auckland) completed the Munich ChronoType Questionnaire. In parallel, light measures (daily irradiance, timing of sunrise and sunset) were compiled from satellite or ground stations at each of these locations. Our data shows that later mid-sleep point on free days (corrected for oversleep on weekends MFSsc) is associated with (i) residing further from the equator, (ii) a later sunset, (iii) spending more time outside and (iv) waking from sleep significantly after sunrise. However, surprisingly, MSFsc did not correlate with daily light intensity at the different geographical locations. Although these findings appear to contradict earlier studies suggesting that in the wider population increased light exposure is associated with an earlier chronotype, our findings are derived exclusively from a student population aged between 17 and 26 years. We therefore suggest that the age and occupation of our population increase the likelihood that these individuals will experience relatively little light exposure in the morning whilst encountering more light exposure later in the day, when light has a delaying effect upon the circadian system. [ABSTRACT FROM AUTHOR]

Objective Orf virus (ORFV) is the pathogen causing contagious pustular dermatitis in goats, sheep and herdsmen. Evidence has confirmed that ORFV can be used as a preventive and therapeutic immunomodulatory agent in several animal models. Our previous data demonstrated that ORFV024 is able to inhibit activation of the NF-κB signaling pathway and act as an important modulator for early immune responses against viral infection. However, the molecular mechanism by which ORFV024 exerting biological function remains unclear. In the present study, we explored and analyzed the function of host cellular proteins that interact with ORFV024. Methods The yeast two-hybrid (Y2H) assay was performed to screen proteins interacting with ORFV024 using a cDNA library derived from primary ovine fetal turbinate cells (OFTu). Two of the screened proteins were further confirmed by confocal microscopy, His-tag pull-down assay and CO-Immunoprecipitation (CO-IP) assay. In addition, the ORFV024 interaction network was constructed using the STRING database. Results In this study, 11 ovine cellular proteins were found to interact with ORFV024. In view of the importance of LAGE3 and IGFBP6 in the ORFV024 functional analysis, we further constructed LAGE3 and IGFBP6 interaction networks. The interactions between ORFV024 and LAGE3 or IGFBP6 were confirmed by confocal microscopy, LAGE3 was further confirmed in the His-tag pull-down assay and CO-IP assay. Conclusions Our findings indicate that ORFV024 can interact with ovine cellular proteins LAGE3 and IGFBP6. [ABSTRACT FROM AUTHOR]

Bovine papular stomatitis virus (BPSV) infects cattle and, occupationally, humans. Prevalent subclinical infections, frequent reinfections, and virus persistence in healthy animals compound a poorly understood, but likely complex, scenario of BPSV perpetuation and transmission in nature. Here, we report the isolation of multiple BPSV strains coinfecting a single animal. Whole-genome analysis of isolated BPSV strains revealed genomic variability likely affecting virus virulence and infectivity. Further, incongruent phylogenetic relationships between viruses suggested genomic recombination. These results have significant implications for parapoxvirus infection biology and virus evolution in nature. [ABSTRACT FROM AUTHOR]

Orf virus (ORFV) is a typical member of the genus Parapoxvirus. The parapoxvirus genome consists of highly variable terminal regions and relatively conserved central regions with a high G + C content. In our previous study, a novel ORFV strain, NA1/11, was isolated from northeastern China. To fully characterize this strain, we sequenced the entire genome of NA1/11 and conducted a comparative analysis using multiple parapoxviruses. The genomic sequence of NA1/11 was found to consist of 137,080 nucleotides with a G + C content of 63.6 %, but it did not contain the terminal hairpin sequence. Alignment of ORFs from NA1/11 with NZ2, IA82 and SA00 revealed several highly variable ORFs, while the most evident ones are ORFs 001, 103, 109-110, 116 and 132. An odd phenomenon in the region of ORFs 118-120 is that the non-coding fragments are almost as long as the coding fragments. By comparative analysis of inverted terminal repeats, we identified one repeat motif and a long conserved fragment. By comparing the ITRs of SA00 with those of three other ORFVs, more clues were obtained about the correlation between ITR sequence and host adaption. Comparison of the NA1/11 genome with the sequences of other strains of ORFV revealed highly variable regions, thus providing new insights into the genetic diversity of ORFV. [ABSTRACT FROM AUTHOR]

Goatpox virus (GTPV), a member of the Capripoxvirus genus of the Poxviridae family, is the causative agent of variolo caprina (goatpox). GTPV can cause significant economic losses of domestic ruminants in endemic regions and can threaten breeding stocks. In this study, we report on the compilation of the complete genomic sequence of an isolated GTPV field strain FZ (GTPV_FZ). The 150,194 bp GTPV genome consists of a central coding region bounded by two identical 2301 bp inverted terminal repeats and contains 151 putative genes. Comparative genomic analysis reveals the apparent genetic relationships among Capripoxviruses are close, but sufficient genomic variants in the field isolate strain FZ have been identified to distinguish it from other GTPV strains and other Capripoxvirus species. Phylogenetic analysis based on the p32 and complete GTPV genome can be used to differentiate SPPVs, GTPVs and LSDVs. These data may contribute to the epidemiological study of the Chinese capripoxvirus and help to develop more specific detection methods to distinguish GTPVs, SPPVs and LSDVs. [ABSTRACT FROM AUTHOR]

Objectives. To explore how Western Australian mental health clinicians want to evaluate their care. Methods. Using a participatory action research framework, 10 senior psychiatrists and 11 clinical nurse specialists working in an inpatient mental health setting participated in individual interviews, focus groups and meetings. All interviews were de-identified during transcription and transcripts and field notes were analysed for common themes. Results. Participants identified what they wanted to measure, how they wanted to measure it and how these changes could be implemented. Clinicians stressed the importance of measuring context (physical, clinical and service) and process as well as outcome, and of evaluating care at an individual and service level with consumer involvement. What is known about the topic? Completion rates of mandatory national outcome measures in mental health in Australia are variable and clinicians have mixed views as to their value. Several barriers have been identified as to their use including clinical, resource and ownership issues. What does this paper add? Some studies have identified areas of good practice and elicited practical suggestions for improvement but few have asked clinicians how they actually want to evaluate the care they provide. This study explored how mental health clinicians wanted to evaluate their care, using a participatory action research framework that encouraged participants to pinpoint problems and issues, account for their social context and develop actions to address them. What are the implications for practitioners? Clinicians were enthusiastic for high quality care and evaluation, but pessimistic about their ability to introduce sustainable change. Establishing and supporting active and responsible leadership at service level may solve this, as may encouraging local standard setting and benchmarking in collaboration with consumers and carers. [ABSTRACT FROM AUTHOR]

The relationship between psychotropic drugs and sleep remains poorly understood. In this study, we examined the relationship between the number (and dosage) of concurrently-taken antipsychotic medications and sleep in a psychiatric inpatient population. Eighty-three long-stay inpatients with severe mental disorders were administered the Pittsburgh Sleep Quality Index questionnaire (PSQI). Results showed that increasing antipsychotics dosages were linked to better sleep, although antipsychotic medications only accounted for a relatively small amount of the variance in sleep quality. The results also showed that, when taken in combination with several antipsychotics, SSRI/SNRI antidepressants failed to show the expected disruptive effects on sleep patterns and daytime functions. Altogether, sleep complaints remained pervasive in 70% of this medicated clinical sample. This suggests that the use of the sedative properties of antipsychotic medication has limited efficacy as a treatment option for sleep dysfunctions, and is not an appropriate substitute for other sleep interventions. Altogether, the results support the case for more systematic screening and interventions for sleep problems in patients with severe psychiatric illness. [ABSTRACT FROM AUTHOR]

A novel phenotyping strategy in schizophrenia, targeting different neurocognitive domains, neurobehavioral features, and selected personality traits, has allowed us to identify a homogeneous familial subtype of the disease, characterized by pervasive neurocognitive deficit. Our genome scan data indicate that this subtype, which accounts for up to 50% of our sample, has a distinct genetic basis and explains linkage to chromosome 6p24 reported previously. If representative of other populations, the ratio of schizophrenia subtypes observed in our families could have a profound impact on sample heterogeneity and on the power of genetic studies to detect linkage and association. Our proposed abbreviated battery of tests should facilitate phenotype characterization for future genetic analyses and allow a focus on a crisply defined schizophrenia subtype, thus promoting a more informed search for susceptibility genes. [ABSTRACT FROM AUTHOR]

African swine fever (ASF) is a hemorrhagic disease of swine characterized by massive lymphocyte depletion in lymphoid tissues due to the apoptosis of B and T cells, a process likely triggered by factors released or secreted by infected macrophages. ASFV CD2v (EP402R) has been implicated in viral virulence and immunomodulation in vitro; however, its actual function(s) remains unknown. We found that CD2v expression in swine PK15 cells induces NF-κB-dependent IFN-β and ISGs transcription and an antiviral state. Similar results were observed for CD2v protein treated swine PBMCs and macrophages, the major ASFV target cell. Notably, treatment of swine PBMCs and macrophages with CD2v protein induced apoptosis. Immunoprecipitation and colocalization studies revealed that CD2v interacts with CD58, the natural host CD2 ligand. Additionally, CD58 knockdown in cells or treatment of cells with an NF-κB inhibitor significantly reduced CD2v-mediated NF-κB activation and IFN-β induction. Further, antibodies directed against CD2v inhibited CD2v-induced NF-κB activation and IFN-β transcription in cells. Overall, results indicate that ASFV CD2v activates NF-κB, which induces IFN signaling and apoptosis in swine lymphocytes/macrophages. We propose that CD2v released from infected macrophages may be a significant factor in lymphocyte apoptosis observed in lymphoid tissue during ASFV infection in pigs. [ABSTRACT FROM AUTHOR]

Anxiety disorders is ranked as the most common class of mental illness disorders globally, affecting hundreds of millions of people and significantly impacting daily life. Developing reliable predictive models for anxiety treatment outcomes holds immense potential to help guide the development of personalised care, optimise resource allocation and improve patient outcomes. This research investigates whether community mental health treatment for anxiety disorder is associated with reliable changes in Kessler psychological distress scale (K10) scores and whether pre-treatment K10 scores and past health service interactions can accurately predict reliable change (improvement). The K10 assessment was administered to 46,938 public patients in a community setting within the Western Australia dataset in 2005-2022; of whom 3794 in 4067 episodes of care were reassessed at least twice for anxiety disorders, obsessive-compulsive disorder, or reaction to severe stress and adjustment disorders (ICD-10 codes F40-F43). Reliable change on the K10 was calculated and used with the post-treatment score as the outcome variables. Machine learning models were developed using features from a large health service administrative linked dataset that includes the pre-treatment K10 assessment as well as community mental health episodes of care, emergency department presentations, and inpatient admissions for prediction. The classification model achieved an area under the receiver operating characteristic curve of 0.76 as well as an F1 score, precision and recall of 0.69, and the regression model achieved an R 2 of 0.37 with mean absolute error of 5.58 on the test dataset. While the prediction models achieved moderate performance, they also underscore the necessity for regular patient monitoring and the collection of more clinically relevant and contextual patient data to further improve prediction of treatment outcomes., (© 2024. The Author(s).)

Standard description of local care provision is essential for evidence-informed planning. This study aimed to map and compare the availability and diversity of current mental health service provision for children and adolescents in Australia. We used a standardised service classification instrument, the Description and Evaluation of Services and DirectoriEs (DESDE) tool, to describe service availability in eight urban and two rural health districts in Australia. The pattern of care was compared with that available for other age groups in Australia. Outpatient care was found to be the most common type of service provision, comprising 212 (81.2%) of all services identified. Hospital care (acute and non-acute) was more available in urban than in rural areas (20 services [9.7%] vs 1 [1.8%]). The level of diversity in the types of care available for children and adolescents was lower than that for the general adult population, but slightly higher than that for older people in the same areas. Standardised comparison of the pattern of care across regions reduces ambiguity in service description and classification, enables gap analysis and can inform policy and planning., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Several authors of this paper participated in the development of DESDE-LTC (LSC, JAS, MRGC). These authors do not have any commercial interest in this instrument.

Research is needed to estimate how jobs may be affected.

Competing Interests: We declare no competing interests.

Background: Mental illness is a public health challenge disproportionately affecting rural Australians. GPs provide most of the mental health care, and they report increasing levels of burnout and unsustainable workload in the context of increased patient complexity. This may be more salient in rural settings characterised by resource constraints. In this paper, we use evaluation data from a GP psychiatry phone line established in Western Australia's Great Southern region in 2021 to describe GPs' perspectives on the service and reflect on how it may help alleviate rural GP workload., Methods: The sample was recruited among GPs practicing in the region. Data were collected through an online survey and semistructured interviews. Descriptive statistics were used to analyse the survey data. Interview data were subjected to thematic analysis; qualitative survey data were used for triangulation., Results: A total of 45GPs completed the survey and 14 were interviewed. Interview data yielded three themes: the criticality of timeliness; the building blocks of confidence; and trust. GPs were highly satisfied with the service, and timeliness and trust were the characteristics underpinning its effectiveness. The service built GPs' confidence in managing mental health and alcohol and other drug use issues through strengthening knowledge and providing reassurance., Conclusions: Our results suggest that a telephone line operated by trusted, local psychiatrists with knowledge of the local mental health ecosystem of support can reduce rural GP workload through building confidence and strengthening personal agency, helping GPs navigate the ethical and clinical labyrinth of managing patient complexity in rural settings.

Virus vectored vaccines are not available commercially for cattle even though compelling potential applications exist. Bovine papular stomatitis virus (BPSV), a highly prevalent parapoxvirus, causes self-limited oral lesions in cattle. Ability of virus to accommodate large amounts of foreign DNA, induce low level of antiviral immunity, and circulate and likely persist in cattle populations, make BPSV an attractive candidate viral vector. Here, recombinant BPSV were constructed expressing either Bovine herpesvirus 1 (BoHV-1) glycoprotein gD (BPSV gD ), or gD and gB (BPSV gD/gB ). Immunization of BPSV serologically-positive calves with BPSV gD or BPSV gD/gB induced BoHV-1 neutralization antibodies and provided protection for three of four animals following a high dose BoHV-1 challenge at day 70 pi. Results indicate BPSV suitability as a candidate virus vector for cattle vaccines.

Australia's Fifth National Mental Health Plan required governments to report, not only on the progress of changes to mental health service delivery, but to also plan for services that should be provided. Future population demand for treatment and care is challenging to predict and one solution involves modelling the uncertain demands on the system. Modelling can help decision-makers understand likely future changes in mental health service demand and more intelligently choose appropriate responses. It can also support greater scrutiny, accountability and transparency of these processes. Australia has an emerging national capacity for systems modelling in mental health which can enhance the next phase of mental health reform. This paper introduces concepts useful for understanding mental health modelling and identifies where modelling approaches can support health service planners to make evidence-informed decisions regarding planning and investment for the Australian population., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: This study utilised digital technology to assess the clinical needs of young people presenting for care at headspace centres across Australia., Method: 1490 young people (12-25 years) who presented to one of 11 headspace services from four geographical locations (urban New South Wales, urban South Australia, regional New South Wales, and regional Queensland) completed a digital multidimensional assessment at initial presentation. Characteristics were compared between services and geographical locations., Results: We identified major variation in the demographics, and the type and severity of needs across different services. Individuals from regional services were more likely to be younger, of Aboriginal and Torres Strait Islander origin, and present with psychotic-like symptoms and suicidality, while those in urban areas were more likely to have previously sought help and have problematic alcohol use. Further differences in age, distress, depressive symptoms, psychotic-like experiences, trauma, family history, alcohol use, education/employment engagement, and days out of role were identified between different urban sites., Conclusions: The variability between services provides insight into the heterogeneity of youth mental health populations which has implications for appropriate early intervention and prevention service provisions. We propose that integrating digital technologies has the potential to provide insights for smarter service planning and evaluation.

Introduction: Mental healthcare systems are primarily designed to urban populations. However, the specific characteristics of rural areas require specific strategies, resource allocation, and indicators which fit their local conditions. This planning process requires comparison with other rural areas. This demonstration study aimed to describe and compare specialized rural adult mental health services in Australia, Norway, and Spain; and to demonstrate the readiness of the healthcare ecosystem approach and the DESDE-LTC mapping tool (Description and Evaluation of Services and Directories of Long Term Care) for comparing rural care between countries and across areas., Methods: The study described and classified the services using the DESDE-LTC. The analyses included context analysis, care availability, placement capacity, balance of care, and diversity of care. Additionally, readiness (Technology Readiness Levels - TRL) and impact analyses (Adoption Impact Ladder - AIL) were also assessed by two independent raters., Results: The findings demonstrated the usability of the healthcare ecosystem approach and the DESDE-LTC to map and identify differences and similarities in the pattern of care of highly divergent rural areas. Day care had a greater weight in the European pattern of care, while it was replaced by social outpatient care in Australian areas. In contrast, care coordination was more common in Australia, pointing to a more fragmented system that requires navigation services. The share between hospital and community residential care showed no differences between the two regions, but there were differences between catchment areas. The healthcare ecosystem approach showed a TRL 8 (the tool has been demonstrated in a real-world environment and it is ready for release and general use) and an AIL of 5 (the target public agencies provided resources for its completion). Two experts evaluated the readiness of the use of DESDE-LTC in their respective regional studies. All of them were classified using the TRL., Discussion: In conclusion, this study strongly supports gathering data on the provision of care in rural areas using standardized methods to inform rural service planning. It provides information on context and service availability, capacity and balance of care that may improve, directly or through subsequent analyses, the management and planning of services in rural areas., Competing Interests: DR participated in the design and authorship of this manuscript, is a Principal Advisor and Research Director at WAPHA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Salinas-Perez, Gutierrez-Colosia, Garcia-Alonso, Furst, Tabatabaei-Jafari, Kalseth, Perkins, Rosen, Rock and Salvador-Carulla.)

The COVID-19 pandemic demonstrated the significant value of systems modelling in supporting proactive and effective public health decision making despite the complexities and uncertainties that characterise an evolving crisis. The same approach is possible in the field of mental health. However, a commonly levelled (but misguided) criticism prevents systems modelling from being more routinely adopted, namely, that the presence of uncertainty around key model input parameters renders a model useless. This study explored whether radically different simulated trajectories of suicide would result in different advice to decision makers regarding the optimal strategy to mitigate the impacts of the pandemic on mental health. Using an existing system dynamics model developed in August 2020 for a regional catchment of Western Australia, four scenarios were simulated to model the possible effect of the COVID-19 pandemic on levels of psychological distress. The scenarios produced a range of projected impacts on suicide deaths, ranging from a relatively small to a dramatic increase. Discordance in the sets of best-performing intervention scenarios across the divergent COVID-mental health trajectories was assessed by comparing differences in projected numbers of suicides between the baseline scenario and each of 286 possible intervention scenarios calculated for two time horizons; 2026 and 2041. The best performing intervention combinations over the period 2021-2041 (i.e., post-suicide attempt assertive aftercare, community support programs to increase community connectedness, and technology enabled care coordination) were highly consistent across all four COVID-19 mental health trajectories, reducing suicide deaths by between 23.9-24.6% against the baseline. However, the ranking of best performing intervention combinations does alter depending on the time horizon under consideration due to non-linear intervention impacts. These findings suggest that systems models can retain value in informing robust decision making despite uncertainty in the trajectories of population mental health outcomes. It is recommended that the time horizon under consideration be sufficiently long to capture the full effects of interventions, and efforts should be made to achieve more timely tracking and access to key population mental health indicators to inform model refinements over time and reduce uncertainty in mental health policy and planning decisions.

Digital mental health services (DMHSs) deliver mental health information, assessment, and treatment, via the internet, telephone, or other digital channels. The current study compares two DMHSs operating in Western Australia (WA)-The Practitioner Online Referral System (PORTS) and MindSpot. Both provide telephone and online psychological services at no cost to patients or referrers. However, PORTS is accessed by patients via referral from health practitioners, and is designed to reach those who are financially, geographically, or otherwise disadvantaged. In contrast, MindSpot services are available to all Australian residents and patients can self-refer. This observational study compares characteristics and treatment outcomes for patients of PORTS and MindSpot in WA. Eligible patients were people who resided in WA and registered with either clinic from January 2019 to December 2020. Results showed that PORTS patients were more likely to be older, male, and unemployed. They were less likely to report a tertiary education and were more likely to live in areas with higher levels of socioeconomic disadvantage. Despite these differences, treatment outcomes were excellent for patients from both clinics. Results provide further evidence for the accessibility, acceptability, and effectiveness of DMHSs regardless of referral pathway or patient characteristics.

Foot-and-mouth disease virus (FMDV) is the pathogen of foot-and-mouth disease (FMD), which is a highly contagious disease in cloven-hoofed animals. To survive in the host, FMDV has evolved multiple strategies to antagonize host innate immune responses. In this study, we showed that the leader protease (L pro ) of FMDV, a papain-like proteinase, promoted viral replication by evading the antiviral interferon response through counteracting the 2',5'-oligoadenylate synthetase (OAS)/RNase L system. Specifically, we observed that the titers of L pro deletion virus were significantly lower than those of wild-type FMDV (FMDV-WT) in cultured cells. Our mechanistic studies demonstrated that L pro interfered with the OAS/RNase L pathway by interacting with the N-terminal domain of swine RNase L (sRNase L). Remarkably, L pro of FMDV exhibited species-specific binding to RNase L in that the interaction was observed only in swine cells, not human, monkey, or canine cells. Lastly, we presented evidence that by interacting with sRNase L, FMDV L pro inhibited cellular apoptosis. Taken together, these results demonstrate a novel mechanism that L pro utilizes to escape the OAS/RNase L-mediated antiviral defense pathway. IMPORTANCE FMDV is a picornavirus that causes a significant disease in agricultural animals. FMDV has developed diverse strategies to escape the host interferon response. Here, we show that L pro of FMDV antagonizes the OAS/RNase L pathway, an important interferon effector pathway, by interacting with the N-terminal domain of sRNase L. Interestingly, such a virus-host interaction is species-specific because the interaction is detected only in swine cells, not in human, monkey, or canine cells. Furthermore, L pro inhibits apoptosis through interacting with sRNase L. This study demonstrates a novel mechanism by which FMDV has evolved to inhibit host innate immune responses.

African swine fever (ASF) is an acute viral hemorrhagic disease of domestic swine with mortality rates approaching 100%. Devastating ASF outbreaks and continuing epidemics starting in the Caucasus region and now in the Russian Federation, Europe, China, and other parts of Southeast Asia (2007 to date) highlight its significance. ASF strain Georgia-07 and its derivatives are now endemic in extensive regions of Europe and Asia and are "out of Africa" forever, a situation that poses a grave if not an existential threat to the swine industry worldwide. While our current concern is Georgia-07, other emerging ASFV strains will threaten for the indefinite future. Economic analysis indicates that an ASF outbreak in the U.S. would result in approximately $15 billion USD in losses, assuming the disease is rapidly controlled and the U.S. is able to reenter export markets within two years. ASF's potential to spread and become endemic in new regions, its rapid and efficient transmission among pigs, and the relative stability of the causative agent ASF virus (ASFV) in the environment all provide significant challenges for disease control. Effective and robust methods, including vaccines for ASF response and recovery, are needed immediately.

The Practitioner Online Referral and Treatment Service (PORTS) is a new digital mental health service (DMHS) providing assessment, treatment, and consultation across Western Australia, for adults with anxiety, depression, or substance use problems, and experiencing financial hardship or geographical disadvantage. From July 2017 to December 2018, a total of 2,527 individuals were referred to PORTS. Of these, 150 (6%) did not give consent for their results to be analysed. Of the remaining 2,377 patients, 615 (26%) could not be contacted to confirm the referral, 596 (25%) received assessment or information from PORTS, 427 (18%) were referred to another service, and 739 (31%) commenced treatment at PORTS. Almost half (47%) of patients were from areas with significant socio-economic disadvantage. Those referred by another mental health service were more likely to engage in treatment than those referred by a General Practitioner (GP). Overall outcomes were excellent, with large effect sizes (Cohen's d : 1.1-1.4), from assessment to post-treatment and 3-month follow-up, reliable deterioration was low, and GP and patient satisfaction was high. These results indicate that the PORTS DMHS model is a promising method for engaging primary care patients with anxiety and depression, including those experiencing financial and geographical disadvantage.

African swine fever (ASF) is an emerging disease threat for the swine industry worldwide. No ASF vaccine is available, and progress is hindered by lack of knowledge concerning the extent of ASF virus (ASFV) strain diversity and the viral antigens conferring type-specific protective immunity in pigs. Previously, we demonstrated that ASFV serotype-specific proteins CD2v (EP402R) and/or C-type lectin (EP153R) are important for protection against homologous ASF infection. Here, we identified six discrete T-cell epitope regions present on CD2v and C-type lectin using IFN-γ ELISpot assay and PBMCs from ASF immune animals, indicating cellular reactivity to these proteins in the context of ASFV infection and protective immunity. Notably, three of the epitope regions map to previously described serotype-specific signature regions of these proteins. Improved understanding of ASFV protective antigens, relevant epitopes and their diversity in nature will facilitate ASFV subunit vaccine design and development.

Here, we report the complete genome sequencing of strains A/equine/Kostanay/9/2012(H3N8) and A/equine/LKZ/9/2012(H3N8) of the equine influenza virus belonging to Florida sublineage, clade 2. The strains were isolated in 2012 in the northern and southern regions of Kazakhstan, respectively., (Copyright © 2018 Burashev et al.)

Apoptosis, a significant form of cell death, has a leading role in the host cell defense against virus infection. Viruses have evolved a series of strategies that block apoptosis during the early stage of viral infection to enhance viral replication, and induce apoptosis in the late stages to facilitate viral particle release from the cells. Here we show that orf virus (ORFV), the causative agent of orf, encodes an apoptosis-inducing protein ORFV119. ORFV119 targets the mitochondria in host cells, inhibits cell proliferation, and induces cell apoptosis. Protein array data indicated that ORFV119 could induce apoptosis via up-regulation of Smac, Bak, and Bax and down-regulation of anti-apoptotic proteins Bcl-2 and cIAP-2. Activation of caspase-9 and caspase-3, and consequent PARP cleavage, ultimately lead to apoptosis. ORFV119 could also directly activate caspase-8 and induce Bid, involved in the extrinsic pathway, to achieve cell death. Furthermore, sequence analysis and experiments with mutants of ORFV119 introduced revealed that ORFV119 contains a key N-terminal domain that is necessary and sufficient to direct the protein to the mitochondria. Together, we report, for the first time, the identification of the novel apoptosis-inducing protein ORFV119 encoded by a parapoxvirus. This provides an important reference for the study of pathogenesis, identification of immunomodulation mechanisms of ORFV, and may lead to new strategies for orf disease control.

The primary aim was to assess usability of the My Medicines and Me Questionnaire (M3Q) as a self-reported questionnaire for mental health patients to subjectively express side effects experienced with their psychotropic medications. The secondary aim was to evaluate patients' attitudes towards treatment and psychotropic medications following dialogue with their clinicians about side effects. Questionnaires were administered at six adult mental health facilities. A total of 205 participants were divided into intervention (facilitated dialogue) and non-intervention groups (no facilitated dialogue). The mean completion time for the M3Q was 15min (SD=6.5) with only 11 (5%) patients requiring assistance. The most commonly reported side effect was sedation (77%) and weight gain was ranked as the most bothersome (23%). The previously validated M3Q provided patients with the opportunity to express the impact these effects had on their lives. Side effects were the most common reason given for non-adherence. There were no significant changes in patient attitudes towards treatment and medications in the intervention group, mainly due to the logistical challenges in the clinicians' ability to view the questionnaire for the subsequent meeting with the patient. The M3Q demonstrated its usability in allowing patients to easily express their subjective experiences with side effects., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Orf is a zoonotic and epitheliotrophic contagious disease that mainly affects sheep, goats, wild ruminants, and humans with a worldwide distribution. To date, there is little information on the characterization of ORFV strains that are endemic in Mainland China. In addition, the relationship between the severity of disease and the molecular profile of ORFV strains has not been fully elucidated., Results: From the recent outbreak of a sheep herd in Nongan, northeast of China, the novel orf virus (ORFV) strain NA1/11 was successfully isolated. Western blot analysis indicated that the NA1/11 strain cross reacts with monoclonal antibody A3 and infected sheep ORFV antiserum. The purified virions revealed the typical ovoid shape when observed by atomic force microscopy. To determine the genetic characteristics of the NA1/11 strain, the sequences of ORFV011 (B2L), ORFV059 (F1L), ORFV109, ORFV110 and ORFv132 (VEGF) genes were amplified and compared with reference parapoxvirus strains. Non-metric multidimensional scaling (nMDS) was performed to analyze the nucleotide similarities between different ORFV strains., Conclusions: Phylogenetic analysis based on ORFV 011 nucleotide sequences showed that the NA1/11strain was closely related to Xinjiang and Gansu strains. ORFV110 and ORFV132 genes are highly variable. The results revealed that precise phylogenetic analysis might provide evidence for genetic variation and movement of circulating ORFV strains in Northeast China. In addition, nMDS analysis showed that geographic isolation and animal host are likely major factors resulting in genetic differences between ORFV strains.

Background: Reporter genes are often used as a selectable marker for generation of recombinant viruses in order to investigate the mechanism of pathogenesis and to obtain candidate vaccine viruses. Routine selection of the recombinant parapoxvirus is time-consuming and labor intensive. Therefore, developing a novel method for selection is critical., Results: In this study, we developed a rapid method to generate recombinant Orf viruses (ORFV) based on the enhanced green fluorescent protein (EGFP) reporter gene as a selectable marker. The coding sequence of EGFP gene was amplified from pEGFP-N1 vector and subcloned into the pZIPPY-neo/gus plasmid under the control of the early-late vaccinia virus (VACV) VV7.5 promoter and flanked by two multiple cloning sites (MCS) to generate a novel transfer vector pSPV-EGFP. Using the pSPV-EGFP, two recombination cassettes pSPV-113LF-EGFP-113RF and pSPV-116LF-EGFP-116RF were constructed by cloning the flanking regions of the ORFV113 and ORFV116 and inserted into two MCS flanking the EGFP gene. Using this novel system, two single gene deletion mutants OV-IA82Δ113 and OV-IA82Δ116 were successfully generated., Conclusions: This approach shortens the time needed to generate recombinant ORFVs (rORFVs). Thus, the pSPV-EGFP vector provides a direct, fast, and convenient way to manipulate the recombinant viruses, indicating that it is highly suited for its designed purpose.

Women with a serious mental illness (SMI), notably schizophrenia, bipolar disorder, and personality disorders are considered high risk for adverse pregnancy and birth outcomes, which in turn, are associated with poor neurodevelopment in the child. Failure to access antenatal care, poor adherence with folate supplementation, an unhealthy lifestyle, and inappropriate health decisions can contribute to poor outcomes. Many women with SMI continue contact with mental health services while pregnant. This primary prevention project aimed to develop a framework for community mental health clinicians to improve the reproductive health outcomes for women with SMI. The consultation process involved discussions with key stakeholders, an environmental scan to determine current service delivery issues, a literature review, and individual and group interviews with community mental health clinicians, consumers, general practitioners, and midwives. Three key elements underpin the framework: early detection and monitoring of pregnancy, providing reproductive choices, and implementing a 'small known team approach' in the management of the pregnant client. Specific modules within the framework focus upon establishing a professional support network, assessing the risk of pregnancy, the early detection of pregnancy, monitoring during pregnancy, preparing for birth, and planning for the postnatal period. Implementation of the framework has the potential to significantly improve obstetric and neonatal outcomes for this high-risk group.

Investigating the seasonal asymmetry of violent behaviour has a long history. Despite this, there still remains considerable debate about the nature and aetiology of this phenomenon. Reports on homicide, for example, are mixed: some have found homicide seasonality but most have not. In contrast, all published studies on assault report that this behaviour is seasonal. Moreover, only two studies, both using US data, have examined the seasonal variation of assault and homicide in the same population over the same period of time. One group found assault was seasonal but homicide was not, whilst the other found, overall, that both homicide and assault were seasonal. This first of these findings seems paradoxical, in that there is no seasonal variation in injury related deaths (i.e. homicides), despite the antecedent behaviour (i.e. assaults) having a seasonal pattern of occurrence. We examined the seasonal variation in homicide and assault in UK and found a similar result. Furthermore, our findings are not easily understandable using conventional social models of seasonal behaviour and we suggest biologically mediated seasonal variation in the capacity of equally injured individuals to survive trauma may also play a role, which should be investigated further.

Background: Although behavioural dominance of the right hand in humans is likely to be under genetic control, departures from this population norm, i.e. left- or non-right-handedness, are believed to be influenced by environmental factors. Among many such environmental factors including, for example, low birth weight, testosterone level, and maternal age at birth, season of birth has occasionally been investigated. The overall empirical evidence for the season of birth effect is mixed., Methods: We have investigated the effect of season of birth in an epidemiologically robust sample of randomly selected young people (n = 977), all born in the same year. A Kolmogorov-Smirnov type statistical test was used to determine season of birth., Results: Neither the right-handed nor the non-right-handed groups demonstrated birth asymmetry relative to the normal population birth distribution. There was no between-group difference in the seasonal distribution of birth when comparing the right-handed to the non-right-handed groups., Conclusion: The present study failed to provide support for a season of birth effect on atypical lateralisation of handedness in humans.

Groups at seasonal risk for deliberate self-harm (DSH) vary according to their geographic location. It is unknown, however, if seasonal risk factors for DSH are associated with place of birth or place of residence as these are confounded in all studies to date. In order to disaggregate place of birth from place of residence we examined general and seasonal risk factors for DSH in three different population birth groups living in Western Australia: Australian Aborigines, Australian born non-Aborigines, and UK migrants. We found Aborigines are at much higher general risk for DSH than non-Aborigines, but are not at seasonal risk, whereas non-Aboriginal Australians and UK migrants are. For UK migrants, this is only found for females. For all groups at seasonal risk this peaks during the austral (southern hemisphere) spring/summer. Furthermore, non-Aboriginal Australians and UK migrants show a consistent pattern of increased case fatality with increasing age. In contrast, case fatality does not increase with age among Australian Aborigines. Overall, despite living in the same environment, the three birth groups show different patterns of seasonal risk for DSH. In particular, the sex difference found between UK migrants and non-Aboriginal Australian birth groups suggests that predisposition toward seasonal risk for DSH is established early in life, but when present this is expressed according to local conditions.

A number of differences exist between the seasonality of suicide and suicidal behaviour. Case fatality is one index of the relationship between these phenomena. The purpose of this study was to use contemporaneous data to examine the impact of case fatality on the seasonality of suicidal behaviour. All deliberate self-harm (ICD9 E950-58) hospitalisations (DSH) and deaths (suicide) for 1984-93 were extracted from the Western Australia case register (N=22 883). Case fatality was calculated by method of suicide. Data were arranged in time series by standardised month according to case fatality; sex and age and analysed using spectral analysis. We found that DSH involving low case fatal methods is seasonal with a spring peak (95% confidence interval). The explained variance of the seasonal rhythm increases with age. Suicide involving high case fatal methods is not seasonal. The increase in DSH seasonality with age may be related to a parallel increase in case fatality.

Background: With the increased accessibility of the CT scanner, psychiatrists managing schizophrenia and first-episode psychosis have incorporated this imaging technique into their diagnostic work-up. This practice has been reinforced by published criteria for CT scanning in psychiatric patients suggesting that cranial CT should be used as a screening tool to exclude intracranial pathology in all patients with a first presentation of schizophrenia or first psychotic episode., Objectives: This study reviews the performance of these criteria., Method: This consisted of a 3-year retrospective case-note audit, using published criteria, of all male in-patients with an established diagnosis of schizophrenia who had a cranial CT during the review period., Results: The efficacy of the published criteria is not supported. In addition, non-specific abnormalities on cranial CT are related to duration of illness and not age in this sample., Conclusions: There is a need to establish new and clinically meaningful approaches for the use of cranial CT and similar technologies in clinical psychiatry. Cranial CT performs poorly as a universal screening tool in this population. The decision to use such imaging techniques should be made on a case-by-case basis using all available clinical evidence.

Previous studies have found that rates of suicide have a distinct annual rhythm with a peak in spring. Two recent European studies, however, have found that the amplitude of this rhythm has decreased over time. The purpose of this study was to examine whether such effects are found in Australia. Australian Bureau of Statistics data on all suicides in Australia 1970-1999 were analysed by spectral analysis. We found that suicide, violent suicide and suicide by males are seasonal and that the seasonal amplitude has increased over time. Males who use violent methods determine the seasonal effect. These results support previous findings that suicide and particularly violent suicide have a characteristic seasonal rhythm. However, the progressive increase in the amplitude of this rhythm over time in Australia is in direct contrast to other European findings. We suggest that this may be related to differences in patterns of anti-depressant use and also the effect of migration on the number of seasonally vulnerable individuals in Australia.

Objective: To evaluate a portable real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay designed to detect all 7 viral serotypes of foot-and-mouth disease virus (FMDV)., Design: Laboratory and animal studies., Study Population: Viruses grown in tissue culture and animals experimentally infected with FMDV., Procedure: 1 steer, pig, and sheep were infected with serotype O FMDV. Twenty-four hours later, animals were placed in separate rooms that contained 4 FMDV-free, healthy animals of the same species. Oral and nasal swab specimens, oropharyngeal specimens obtained with a probang, and blood samples were obtained at frequent intervals, and animals were observed for fever and clinical signs of foot-and-mouth disease (FMD). Samples from animals and tissue cultures were assayed for infectious virus and viral RNA., Results: The assay detected viral RNA representing all 7 FMDV serotypes grown in tissue culture but did not amplify a panel of selected viruses that included those that cause vesicular diseases similar to FMD; thus, the assay had a specificity of 100%, depending on the panel selected. The assay also met or exceeded sensitivity of viral culture on samples from experimentally infected animals. In many instances, the assay detected viral RNA in the mouth and nose 24 to 96 hours before the onset of clinical disease., Conclusions and Clinical Relevance: The assay reagents are produced in a vitrified form, which permits storage and transportation at ambient temperatures. The test can be performed in 2 hours or less on a portable instrument, thus providing a rapid, portable, sensitive, and specific method for detection of FMDV.