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1.
Artigo em Inglês | MEDLINE | ID: mdl-38865031

RESUMO

A cross-sectoral partnership was formed in 2021 in support of the recommendations in an audit on access to state-funded mental health services. In this first paper, we aimed to describe the demographic and service utilisation of adults with a mental health diagnosis in the Western Australian state-funded health system from 2005 to 2021. Inpatient, emergency department, specialised (ambulatory) community mental health service, and death records were linked in individuals aged ≥ 18 years with a mental health diagnosis in Western Australia. Altogether, 392,238 individuals with at least one mental health service contact between 1st January 2005 and 31st December 2021 were included for analysis. Females, Aboriginal and/or Torres Strait Islander people, and those who lived outside major cities or in the most disadvantaged areas were more likely to access state-funded mental health services. While the number of individuals who accessed community mental health services increased over time (from 28,769 in 2005 to 50,690 in 2021), the percentage increase relative to 2005 was notably greater for emergency department attendances (127% for emergency department; 76% for community; and 63% for inpatient). Conditions that contributed to the increase for emergency department were mainly alcohol disorder, reaction to severe stress and adjustment disorders, and anxiety disorders. Sex differences were observed between conditions. The pattern of access increased for emergency department and the community plus emergency department combination. This study confirmed that the patterns of access of state-funded mental health services have changed markedly over time and the potential drivers underlying these changes warrant further investigation.

2.
J Gen Virol ; 104(11)2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37976092

RESUMO

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 (BPSVgD), or gD and gB (BPSVgD/gB). Immunization of BPSV serologically-positive calves with BPSVgD or BPSVgD/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.


Assuntos
Doenças dos Bovinos , Herpesvirus Bovino 1 , Parapoxvirus , Estomatite , Vacinas , Vacinas Virais , Bovinos , Animais , Parapoxvirus/genética , Anticorpos Antivirais , Herpesvirus Bovino 1/genética , Vacinas Virais/genética , Doenças dos Bovinos/prevenção & controle
3.
PLoS Pathog ; 17(10): e1009971, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34614034

RESUMO

Viruses have evolved mechanisms to subvert critical cellular signaling pathways that regulate a wide range of cellular functions, including cell differentiation, proliferation and chemotaxis, and innate immune responses. Here, we describe a novel ORFV protein, ORFV113, that interacts with the G protein-coupled receptor Lysophosphatidic acid receptor 1 (LPA1). Consistent with its interaction with LPA1, ORFV113 enhances p38 kinase phosphorylation in ORFV infected cells in vitro and in vivo, and in cells transiently expressing ORFV113 or treated with soluble ORFV113. Infection of cells with virus lacking ORFV113 (OV-IA82Δ113) significantly decreased p38 phosphorylation and viral plaque size. Infection of cells with ORFV in the presence of a p38 kinase inhibitor markedly diminished ORFV replication, highlighting importance of p38 signaling during ORFV infection. ORFV113 enhancement of p38 activation was prevented in cells in which LPA1 expression was knocked down and in cells treated with LPA1 inhibitor. Infection of sheep with OV-IA82Δ113 led to a strikingly attenuated disease phenotype, indicating that ORFV113 is a major virulence determinant in the natural host. Notably, ORFV113 represents the first viral protein that modulates p38 signaling via interaction with LPA1 receptor.


Assuntos
Sistema de Sinalização das MAP Quinases/fisiologia , Infecções por Poxviridae/metabolismo , Receptores de Ácidos Lisofosfatídicos/metabolismo , Proteínas Virais/metabolismo , Animais , Parapoxvirus , Ovinos
4.
Aust N Z J Psychiatry ; 57(11): 1417-1427, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37183347

RESUMO

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.


Assuntos
Serviços de Saúde Mental , Saúde Mental , Humanos , Reforma dos Serviços de Saúde , Austrália , Programas Governamentais
5.
Australas Psychiatry ; 31(3): 295-301, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37035873

RESUMO

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.


Assuntos
Serviços de Saúde do Indígena , Transtornos Mentais , Serviços de Saúde Mental , Humanos , Adolescente , Tecnologia Digital , Austrália , Queensland
6.
J Virol ; 95(15): e0036121, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980594

RESUMO

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 2',5'-oligoadenylate synthetase (OAS)/RNase L system. Specifically, we observed that the titers of Lpro deletion virus were significantly lower than those of wild-type 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. 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 Lpro 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, Lpro inhibits apoptosis through interacting with sRNase L. This study demonstrates a novel mechanism by which FMDV has evolved to inhibit host innate immune responses.


Assuntos
2',5'-Oligoadenilato Sintetase/metabolismo , Endopeptidases/metabolismo , Endorribonucleases/metabolismo , Vírus da Febre Aftosa/imunologia , Evasão da Resposta Imune/imunologia , Imunidade Inata/imunologia , Animais , Apoptose/imunologia , Linhagem Celular , Cricetinae , Cães , Endopeptidases/genética , Endopeptidases/imunologia , Endorribonucleases/genética , Febre Aftosa/imunologia , Febre Aftosa/virologia , Células HEK293 , Haplorrinos , Humanos , Evasão da Resposta Imune/genética , Células Madin Darby de Rim Canino , Domínios Proteicos , Suínos
7.
BMC Ophthalmol ; 22(1): 209, 2022 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-35527243

RESUMO

BACKGROUND: Macular corneal dystrophy is a rare inherited disease of the cornea leading to deposits mainly in the stroma. Affected patients suffer from progressive loss of visual acuity which should be treated with penetrating keratoplasty. This is the first case report describing the clinical and histopathological findings of corneal tissue after failed phototherapeutic keratectomy (PTK) in a patient with macular corneal dystrophy. CASE PRESENTATION: A 32-year-old man presented with visual impairment, blurred vision and increasing glare sensitivity in both eyes in 2014. All symptoms had existed for several years and had recently increased sharply. A corneal dystrophy was diagnosed and penetrating keratoplasty was recommended but the patient was hesitant to undergo surgery. In 2018, in contrast to current guidelines, a PTK was performed in both eyes in Turkey for unknown reasons. In May 2019, he presented again in our clinic. Best corrected visual acuity was markedly reduced in both eyes. Slit-lamp examination revealed multiple dense, poorly circumscribed grey-white patchy changes in the stroma accompanied by corneal opacity in both eyes. In February 2020, the patient decided to have penetrating keratoplasty performed at the University Eye Hospital in Tübingen. The explanted cornea was stained for acid mucopolysaccharides (AMP) and periodic acid-Schiff staining (PAS). The histopathological examination revealed destruction of Bowman's layer and a subepithelial fibrosis band due to the PTK previously performed. The AMP staining demonstrated blue deposits typical of macular corneal dystrophy, mainly in the stroma but also in the endothelium. Interestingly, the acidic mucopolysaccharides were found increased in the PTK-induced subepithelial fibrosis band. The postoperative course after keratoplasty was favourable with a significant increase in visual acuity and a clear graft. CONCLUSIONS: This report presents the first case of a histologically evident exacerbation of macular corneal dystrophy after PTK and emphasizes the relevance of thorough pre-interventional diagnosis and patient selection to consider other therapeutic approaches, such as penetrating keratoplasty.


Assuntos
Distrofias Hereditárias da Córnea , Ceratectomia Fotorrefrativa , Adulto , Humanos , Masculino , Córnea/patologia , Córnea/cirurgia , Distrofias Hereditárias da Córnea/diagnóstico , Distrofias Hereditárias da Córnea/patologia , Distrofias Hereditárias da Córnea/cirurgia , Fibrose , Seguimentos , Glicosaminoglicanos , Ceratectomia , Lasers de Excimer
8.
BMC Ophthalmol ; 22(1): 207, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524196

RESUMO

BACKGROUND: This study aimed to analyze if the outcome after corneal crosslinking (CXL) in progressive keratoconus patients depends on the stage at which the procedure is performed. This knowledge would help to improve success of CXL and to define surgery indications in those patients. METHODS: In this retrospective study, 124 consecutive eyes of 100 patients with progressive keratoconus undergoing corneal CXL at the University Eye Hospital Tübingen were included. The eyes were graded according to modified Krumeich stages depending on induced myopia or astigmatism, corneal radii, minimum corneal thickness, and morphological changes. The observation period covered November 2008 to September 2018. Preoperatively, 12 and 24 months after CXL, the best corrected visual acuity (BCVA) was determined and astigmatism as well as tomographic parameters (Kmax, Kmin, central corneal thickness (CCT), minimum corneal thickness (MCT)) were measured by means of a Scheimpflug camera system. RESULTS: BCVA results showed significant differences between the modified Krumeich stages at 12 months (p = 0.014) and at 24 months postoperatively (p = 0.032). Also, astigmatism differed significantly among the stages at 24 months after CXL (p = 0.023). However, no significant differences regarding astigmatism were detectable after 12 months. In terms of Kmax, Kmin, CCT, and MCT, no significant differences between the Krumeich stages were observed. CONCLUSIONS: BCVA showed a significantly higher improvement after CXL in the early stage of keratoconus compared to a higher stage. However, the postinterventional tomographic values did not differ significantly between the different modified Krumeich stages. The significantly higher improvement in BCVA after CXL in the early stage might indicate that earlier intervention provides a higher subjective benefit to the individual. Further studies with larger sample sizes are needed to confirm these findings.


Assuntos
Astigmatismo , Ceratocone , Colágeno , Córnea , Topografia da Córnea , Reagentes de Ligações Cruzadas/uso terapêutico , Humanos , Ceratocone/tratamento farmacológico , Ceratocone/cirurgia , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Retrospectivos , Riboflavina/uso terapêutico , Raios Ultravioleta , Acuidade Visual
9.
Klin Monbl Augenheilkd ; 238(11): 1229-1235, 2021 Nov.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-33607693

RESUMO

BACKGROUND: Since 2019, corneal collagen crosslinking (CXL) is included in the catalog of procedures covered by statutory health insurance in Germany. CXL is an established ophthalmological procedure for the last 20 years. The aim of this investigation was the measurement of progression before and after CXL. MATERIAL UND METHODS: 65 consecutive eyes with progressive keratoconus from 53 patients were included in the retrospective study, which were observed at the University Eye Hospital Tübingen at least two years before and at least two years after CXL. The time of observation took place from October 2009 until March 2018. Parameters of interest had been the best corrected visual acuity (BCVA) and the keratometric values from the elevation maps measured by a Scheimpflug camera. RESULTS: 65 eyes of 53 patients had been documented. The study population included 46 (86.8%) male and 7 (13.2%) female subjects. The mean age was 24 ± 8 years. The averaged observation time between the primary consultation and CXL showed 25 ± 15 months. Preoperatively the mean BCVA pointed out in a significant increase (0.13 ± 0.17 [first visit] vs. 0.23 ± 0.22 [preOP], p < 0.0001) while the mean Kmax resulted in a statistically significant increase (46.34 ± 3.33 dpt [first visit] vs. 48.78 ± 4.17 dpt [preOP], p < 0.0001). The mean thinnest point of the cornea showed a significant decrease (490.48 ± 34.23 µm [first visit] vs. 468.62 ± 29.84 µm [preop], p < 0.0001). Postoperatively the mean BCVA resulted in a significant improvement at the 12th postoperative month in comparison to the preoperative measurement (0.23 ± 0.22 [preOP] vs. 0.16 ± 0.14 [12 months], p = 0.04 respectively 0.17 ± 0.17 [24 months], p = 0.0006). The mean Kmax demonstrated in the 12th postoperative month a significant reduction (48.78 ± 4.17 dpt [preOP] vs. 47.91 ± 3.41 dpt [12 months], p = 0.0009 respectively 48 ± 4.56 dpt [24 months], p = 0.0051). The mean thinnest point of the cornea indicated a decrease at the 12th postoperative month (468.62 ± 29.84 µm [preOP] vs. 459.82 ± 35.88 µm [12 months], p = 0.0078 respectively 453.47 ± 43.39 µm [24 months], p = 0.0227). CONCLUSION: CXL is a successful procedure for the therapy of progressive keratoconus.


Assuntos
Ceratocone , Fotoquimioterapia , Adolescente , Adulto , Colágeno/uso terapêutico , Córnea , Topografia da Córnea , Reagentes de Ligações Cruzadas/uso terapêutico , Feminino , Humanos , Ceratocone/diagnóstico , Ceratocone/tratamento farmacológico , Masculino , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Retrospectivos , Riboflavina/uso terapêutico , Raios Ultravioleta , Acuidade Visual , Adulto Jovem
10.
Clin Infect Dis ; 70(8): 1768-1773, 2020 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-31620776

RESUMO

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.


Assuntos
Borrelia burgdorferi , Ixodes , Doença de Lyme , Carrapatos , Vacinas , Animais , Humanos , Doença de Lyme/prevenção & controle , Vacinação
11.
Can J Psychiatry ; 65(10): 721-730, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32720514

RESUMO

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.


Assuntos
Atenção à Saúde/organização & administração , Serviços de Saúde Mental , Saúde Mental , Serviços de Saúde Rural , Adulto , Austrália , Canadá , Finlândia , Acessibilidade aos Serviços de Saúde , Humanos , População Rural
12.
Cogn Behav Ther ; 49(4): 307-326, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31553266

RESUMO

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.


Assuntos
Ansiedade/terapia , Depressão/terapia , Intervenção Baseada em Internet/estatística & dados numéricos , Encaminhamento e Consulta , Transtornos Relacionados ao Uso de Substâncias/terapia , Adulto , Feminino , Humanos , Masculino , Satisfação do Paciente , Resultado do Tratamento
13.
J Gen Virol ; 100(2): 259-265, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30628881

RESUMO

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.


Assuntos
Vírus da Febre Suína Africana/imunologia , Epitopos de Linfócito T , Lectinas Tipo C/imunologia , Proteínas Virais/imunologia , Animais , ELISPOT , Mapeamento de Epitopos , Interferon gama/metabolismo , Suínos
14.
PLoS Pathog ; 13(12): e1006779, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29244863

RESUMO

Poxviruses have evolved multiple strategies to subvert signaling by Nuclear Factor κB (NF-κB), a crucial regulator of host innate immune responses. Here, we describe an orf virus (ORFV) virion-associated protein, ORFV119, which inhibits NF-κB signaling very early in infection (≤ 30 min post infection). ORFV119 NF-κB inhibitory activity was found unimpaired upon translation inhibition, suggesting that virion ORFV119 alone is responsible for early interference in signaling. A C-terminal LxCxE motif in ORFV119 enabled the protein to interact with the retinoblastoma protein (pRb) a multifunctional protein best known for its tumor suppressor activity. Notably, experiments using a recombinant virus containing an ORFV119 mutation which abrogates its interaction with pRb together with experiments performed in cells lacking or with reduced pRb levels indicate that ORFV119 mediated inhibition of NF-κB signaling is largely pRb dependent. ORFV119 was shown to inhibit IKK complex activation early in infection. Consistent with IKK inhibition, ORFV119 also interacted with TNF receptor associated factor 2 (TRAF2), an adaptor protein recruited to signaling complexes upstream of IKK in infected cells. ORFV119-TRAF2 interaction was enhanced in the presence of pRb, suggesting that ORFV119-pRb complex is required for efficient interaction with TRAF2. Additionally, transient expression of ORFV119 in uninfected cells was sufficient to inhibit TNFα-induced IKK activation and NF-κB signaling, indicating that no other viral proteins are required for the effect. Infection of sheep with ORFV lacking the ORFV119 gene led to attenuated disease phenotype, indicating that ORFV119 contributes to virulence in the natural host. ORFV119 represents the first poxviral protein to interfere with NF-κB signaling through interaction with pRb.


Assuntos
NF-kappa B/fisiologia , Vírus do Orf/fisiologia , Vírus do Orf/patogenicidade , Proteína do Retinoblastoma/fisiologia , Proteínas Virais/fisiologia , Sequência de Aminoácidos , Animais , Linhagem Celular , Células Cultivadas , Ectima Contagioso/etiologia , Técnicas de Silenciamento de Genes , Genes Virais , Células HEK293 , Células HeLa , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Interações Hospedeiro-Patógeno/fisiologia , Humanos , Quinase I-kappa B/metabolismo , Imunidade Inata , Mutação , NF-kappa B/antagonistas & inibidores , Vírus do Orf/genética , Proteína do Retinoblastoma/antagonistas & inibidores , Proteína do Retinoblastoma/genética , Ovinos , Transdução de Sinais , Fator 2 Associado a Receptor de TNF/metabolismo , Proteínas Virais/genética , Proteínas Virais/imunologia , Virulência/genética , Virulência/imunologia , Virulência/fisiologia
15.
PLoS Pathog ; 13(8): e1006561, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28787456

RESUMO

Poxviruses have evolved unique proteins and mechanisms to counteract the nuclear factor κB (NF-κB) signaling pathway, which is an essential regulatory pathway of host innate immune responses. Here, we describe a NF-κB inhibitory virion protein of orf virus (ORFV), ORFV073, which functions very early in infected cells. Infection with ORFV073 gene deletion virus (OV-IA82Δ073) led to increased accumulation of NF-κB essential modulator (NEMO), marked phosphorylation of IκB kinase (IKK) subunits IKKα and IKKß, IκBα and NF-κB subunit p65 (NF-κB-p65), and to early nuclear translocation of NF-κB-p65 in virus-infected cells (≤ 30 min post infection). Expression of ORFV073 alone was sufficient to inhibit TNFα induced activation of the NF-κB signaling in uninfected cells. Consistent with observed inhibition of IKK complex activation, ORFV073 interacted with the regulatory subunit of the IKK complex NEMO. Infection of sheep with OV-IA82Δ073 led to virus attenuation, indicating that ORFV073 is a virulence determinant in the natural host. Notably, ORFV073 represents the first poxviral virion-associated NF-κB inhibitor described, highlighting the significance of viral inhibition of NF-κB signaling very early in infection.


Assuntos
Ectima Contagioso/virologia , Evasão da Resposta Imune/fisiologia , NF-kappa B/imunologia , Vírus do Orf/patogenicidade , Vírion/imunologia , Animais , Ectima Contagioso/imunologia , Células HeLa , Humanos , Imunoprecipitação , Vírus do Orf/imunologia , Vírus do Orf/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Ovinos , Transdução de Sinais/imunologia , Proteínas Virais/imunologia , Virulência/fisiologia
16.
Med Sci Monit ; 25: 7976-7981, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31647055

RESUMO

BACKGROUND This study aimed to investigate the effectiveness of conjunctival autograft compared with primary closure and amniotic membrane transplantation for primary pterygium excision. MATERIAL AND METHODS Data were retrospectively studied from all primary pterygium excisions from January 2002 to December 2017 from the electronic database at the University Eye Hospital, Tübingen. RESULTS From 521 primary pterygium excisions, 284 (54.5%) were primary closures, 203 (39.0%) were conjunctival autografts, and 34 (6.5%) were amniotic membrane transplants. The mean number of primary pterygium excisions was 33 per year (range, 14-56 per year). The mean patient age was 58±15 years. Younger age was associated with a significantly increased recurrence rate (P=0.002). The mean pterygium recurrence rate in the three study groups at 12 months after surgery was 11.3% (range, 6.4-14.7%). Recurrence occurred 13 patients (6.4%) in the conjunctival autograft group, 41 patients (14.4%) in the primary closure group, and five patients (14.7%) in the amniotic membrane transplantation group. Conjunctival autograft was associated with a significantly lower recurrence rate (P=0.005). CONCLUSIONS A retrospective study at a single center to compare conjunctival autograft with primary closure and amniotic membrane transplantation for primary pterygium excision showed a significantly lower recurrence rate after surgery using a conjunctival autograft.


Assuntos
Túnica Conjuntiva/anormalidades , Pterígio/cirurgia , Adulto , Idoso , Âmnio/transplante , Autoenxertos/transplante , Túnica Conjuntiva/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Transplante Autólogo/métodos , Resultado do Tratamento
17.
Aust N Z J Psychiatry ; 53(10): 1000-1012, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31250654

RESUMO

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.


Assuntos
Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Mão de Obra em Saúde/estatística & dados numéricos , Serviços de Saúde Mental/estatística & dados numéricos , Avaliação das Necessidades/estatística & dados numéricos , População Rural/estatística & dados numéricos , Diversidade Cultural , Humanos , New South Wales , Austrália Ocidental
18.
Biochim Biophys Acta Mol Basis Dis ; 1863(11): 2973-2986, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28768149

RESUMO

A variable-length poly-T variant in intron 6 of the TOMM40 gene, rs10524523, is associated with risk and age-of-onset of sporadic (late-onset) Alzheimer's disease. In Caucasians, the three predominant alleles at this locus are Short (S), Long (L) or Very long (VL). On an APOE ε3/3 background, the S/VL and VL/VL genotypes are more protective than S/S. The '523 poly-T has regulatory properties, in that the VL poly-T results in higher expression than the S poly-T in luciferase expression systems. The aim of the current work was to identify effects on cellular bioenergetics of increased TOM40 protein expression. MitoTracker Green fluorescence and autophagic vesicle staining was the same in control and over-expressing cells, but TOM40 over-expression was associated with increased expression of TOM20, a preprotein receptor of the TOM complex, the mitochondrial chaperone HSPA9, and PDHE1a, and increased activities of the oxidative phosphorylation complexes I and IV and of the TCA member α-ketoglutaric acid dehydrogenase. Consistent with the complex I findings, respiration was more sensitive to inhibition by rotenone in control cells than in the TOM40 over-expressing cells. In the absence of inhibitors, total cellular ATP, the mitochondrial membrane potential, and respiration were elevated in the over-expressing cells. Spare respiratory capacity was greater in the TOM40 over-expressing cells than in the controls. TOM40 over-expression blocked Ab-elicited decreases in the mitochondrial membrane potential, cellular ATP levels, and cellular viability in the control cells. These data suggest elevated expression of TOM40 may be protective of mitochondrial function.


Assuntos
Doença de Alzheimer , Regulação da Expressão Gênica , Potencial da Membrana Mitocondrial/genética , Proteínas de Membrana Transportadoras , Mitocôndrias , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Feminino , Loci Gênicos , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Células HeLa , Humanos , Complexo Cetoglutarato Desidrogenase/genética , Complexo Cetoglutarato Desidrogenase/metabolismo , Proteínas de Membrana Transportadoras/biossíntese , Proteínas de Membrana Transportadoras/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Receptores de Superfície Celular/biossíntese , Receptores de Superfície Celular/genética
19.
Health Care Women Int ; 38(7): 705-714, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28362243

RESUMO

Australian women attending community mental health services were surveyed to determine the relationship between sexual trauma, sexual activity, and sexual health seeking behaviors. Self-reported history of "forced sex" was 58.4% (n = 122 out of 220). Latent class analysis revealed a three-class model: "sexually active and health seeking," "low sexual activity and health seeking" and "low sexual activity and not health seeking." An association with general practitioner engagement and sexual health seeking behaviors was found. Rates of self-reported sexual trauma reinforce the need for screening and trauma informed care. Groupings may reflect different aspects of recovery associated with sexual health behaviors.


Assuntos
Vítimas de Crime/estatística & dados numéricos , Transtornos Mentais/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde , Delitos Sexuais/psicologia , Comportamento Sexual/psicologia , Ferimentos e Lesões/epidemiologia , Adolescente , Adulto , Austrália , Serviços Comunitários de Saúde Mental , Vítimas de Crime/psicologia , Estudos Transversais , Humanos , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Saúde Sexual , Populações Vulneráveis
20.
Arch Virol ; 160(1): 253-66, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25385177

RESUMO

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.


Assuntos
Ectima Contagioso/virologia , Vírus do Orf/genética , Parapoxvirus/genética , Animais , China/epidemiologia , Ectima Contagioso/epidemiologia , Regulação Viral da Expressão Gênica , Genoma Viral , Dados de Sequência Molecular , Vírus do Orf/classificação , Parapoxvirus/classificação , Ovinos , Sequências Repetidas Terminais , Proteínas Virais/genética , Proteínas Virais/metabolismo
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