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OBJECTIVE: Depression and anxiety are common in dementia. There is a need to develop effective psychosocial interventions. This study sought to develop a group-based adapted mindfulness programme for people with mild to moderate dementia in care homes and to determine its feasibility and potential benefits. METHODS: A manual for a 10-session intervention was developed. Participants were randomly allocated to the intervention plus treatment as usual (n = 20) or treatment as usual (n = 11). Measures of mood, anxiety, quality of life, cognitive function, stress and mindfulness were administered at baseline and 1 week post-intervention. RESULTS: There was a significant improvement in quality of life in the intervention group compared to controls (p = 0.05). There were no significant changes in other outcomes. CONCLUSIONS: The intervention was feasible in terms of recruitment, retention, attrition and acceptability and was associated with significant positive changes in quality of life. A fully powered randomised controlled trial is required. Copyright © 2017 John Wiley & Sons, Ltd.
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Transtornos de Ansiedade/terapia , Demência/terapia , Transtorno Depressivo/terapia , Atenção Plena , Idoso , Idoso de 80 Anos ou mais , Cognição , Demência/psicologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Qualidade de Vida , Estresse PsicológicoRESUMO
Mutations in transmembrane domains of the KCNQ1 subunit of the I(Ks) potassium channel have been associated with familial atrial fibrillation. We have investigated mechanisms by which the S1 domain S140G KCNQ1 mutation influences atrial arrhythmia risk and, additionally, whether it can affect ventricular electrophysiology. In perforated-patch recordings, S140G-KCNQ1+KCNE1 exhibited leftward-shifted activation, slowed deactivation and marked residual current. In human atrial action potential (AP) simulations, AP duration and refractoriness were shortened and rate-dependence flattened. Simulated I(Ks) but not I(Kr) block offset AP shortening produced by the mutation. In atrial tissue simulations, temporal vulnerability to re-entry was little affected by the S140G mutation. Spatial vulnerability was markedly increased, leading to more stable and stationary spiral wave re-entry in 2D stimulations, which was offset by I(Ks) block, and to scroll waves in 3D simulations. These changes account for vulnerability to AF with this mutation. Ventricular AP clamp experiments indicate a propensity for increased ventricular I(Ks) with the S140G KCNQ1 mutation and ventricular AP simulations showed model-dependent ventricular AP abbreviation.
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Fibrilação Atrial/genética , Fibrilação Atrial/fisiopatologia , Canal de Potássio KCNQ1/genética , Mutação , Potenciais de Ação/fisiologia , Animais , Células CHO , Simulação por Computador , Cricetulus , Humanos , Técnicas de Patch-Clamp , Disfunção Ventricular/genética , Disfunção Ventricular/fisiopatologiaRESUMO
BACKGROUND: The nine-item Patient Health Questionnaire (PHQ-9) and seven-item Generalised Anxiety Disorder (GAD-7) scale are widely used clinically and within research, and so it is important to determine how the measures, and individual items within the measures, are answered by adults of differing ages. This study sought to evaluate measurement invariance and differential item functioning (DIF) of the PHQ-9 and GAD-7 between working age and older adults seeking routine psychological treatment. METHODS: Data of working age (18-64 years old) and older (≥65) adults in eight Improving Access to Psychological Therapies (IAPT) services were used. Confirmatory factor analysis (CFA) was used to establish unidimensionality of the PHQ-9 and GAD-7, with multiple-group CFA to test measurement invariance and The Multiple Indicators, Multiple Causes Models approach to assess DIF. The employed methods were applied to a propensity score matched (PSM) sample in sensitivity analyses to control for potential confounding. RESULTS: Data from 166,816 patients (159,325 working age, 7491 older) were used to show measurement invariance for the PHQ-9 and GAD-7, with limited evidence of DIF and similar results found with a PSM sample (n = 5868). LIMITATIONS: The localised sample creates an inability to detect geographical variance, and the potential effect of unmeasured confounders cannot be ruled out. CONCLUSIONS: The findings support the use of the PHQ-9 and GAD-7 measures for working age and older adults, both clinically and in research settings. This study validates using the measures for these age groups to assess clinically significant symptom thresholds, and monitor treatment outcomes between them.
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Transtornos de Ansiedade , Questionário de Saúde do Paciente , Humanos , Idoso , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/terapia , Transtornos de Ansiedade/psicologia , Resultado do Tratamento , Inquéritos e Questionários , PsicometriaRESUMO
Approximately half of generalised anxiety disorder (GAD) patients do not recover from first-line treatments, and no validated prediction models exist to inform individuals or clinicians of potential treatment benefits. This study aimed to develop and validate an accurate and explainable prediction model of post-treatment GAD symptom severity. Data from adults receiving treatment for GAD in eight Improving Access to Psychological Therapies (IAPT) services (n=15,859) were separated into training, validation and holdout datasets. Thirteen machine learning algorithms were compared using 10-fold cross-validation, against two simple clinically relevant comparison models. The best-performing model was tested on the holdout dataset and model-specific explainability measures identified the most important predictors. A Bayesian Additive Regression Trees model out-performed all comparison models (MSE=16.54 [95 % CI=15.58; 17.51]; MAE=3.19; R²=0.33, including a single predictor linear regression model: MSE=20.70 [95 % CI=19.58; 21.82]; MAE=3.94; R²=0.14). The five most important predictors were: PHQ-9 anhedonia, GAD-7 annoyance/irritability, restlessness and fear items, then the referral-assessment waiting time. The best-performing model accurately predicted post-treatment GAD symptom severity using only pre-treatment data, outperforming comparison models that approximated clinical judgement and remaining within the GAD-7 error of measurement and minimal clinically important differences. This model could inform treatment decision-making and provide desired information to clinicians and patients receiving treatment for GAD.
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Transtornos de Ansiedade , Aprendizado de Máquina , Índice de Gravidade de Doença , Humanos , Transtornos de Ansiedade/terapia , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Psicoterapia/métodos , Teorema de Bayes , Adulto JovemRESUMO
BACKGROUND: Sleep disturbance may impact response to psychological treatment for depression. Understanding how sleep disturbance changes during the course of psychological treatment, and identifying the risk factors for sleep disturbance response may inform clinical decision-making. METHOD: This analysis included 18,915 patients receiving high-intensity psychological therapy for depression from one of eight London-based Improving Access to Psychological Therapies (IAPT) services between 2011 and 2020. Distinct trajectories of change in sleep disturbance were identified using growth mixture modelling. The study also investigated associations between identified trajectory classes, pre-treatment patient characteristics, and eventual treatment outcomes from combined PHQ-9 and GAD-7 metrics used by the services. RESULTS: Six distinct trajectories of sleep disturbance were identified: two demonstrated improvement, while one showed initial deterioration and the other three groups displayed only limited change in sleep disturbance, each with varying baseline sleep disturbance. Associations with trajectory class membership were found based on: gender, ethnicity, unemployment status, antidepressant medication use, long-term health condition status, severity of depressive symptom, and functional impairment. Groups that showed improvement in sleep had the best eventual outcomes from depression treatment, followed by groups that consistently slept well. LIMITATION: Single item on sleep disturbance used, no data on treatment adherence. CONCLUSIONS: These findings reveal heterogeneity in the course of sleep disturbance during psychological treatment for depression. Closer monitoring of changes in sleep disturbance during treatment might inform treatment planning. This includes decisions about when to incorporate sleep management interventions, and whether to change or augment therapy with interventions to reduce sleep disturbance.
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BACKGROUND: Sleep disturbance is a common symptom of depression. There is conflicting evidence whether improvements in sleep might impact depressive symptoms, or whether treating the core depressive symptoms might improve sleep disturbance. This study explored the bi-directional impact of sleep and depressive symptom change among individuals receiving psychological treatment. METHODS: Session-by-session change in sleep disturbance and depressive symptom severity scores were explored in patients receiving psychological therapy for depression from Improving Access to Psychological Therapies services in England. Bi-directional change in sleep disturbance and depressive symptoms was modelled using random-intercept cross-lagged panel models with items from the PHQ-9. RESULTS: The sample included 17,732 adults that had received three or more treatment sessions. Both depressive symptoms and sleep disturbance scores decreased. Between initial timepoints, higher sleep disturbance was associated with lower depression scores, but after this point positive cross-lagged effects were observed for both the impact of sleep disturbance on later depressive symptoms, and depressive symptoms on later sleep disturbance scores. The magnitude of effects suggested depressive symptoms may have more impact on sleep than the reverse, and this effect was larger in sensitivity analyses. CONCLUSIONS: Findings provide evidence that psychological therapy for depression results in improvements in core depressive symptoms and sleep disturbance. There was some evidence that depressive symptoms may have more impact on sleep disturbance scores at the next therapy session, than sleep disturbance does on later depressive symptoms. Targeting the core symptoms of depression initially may optimise outcomes, but further research is needed to elucidate these relationships.
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Depressão , Transtornos do Sono-Vigília , Adulto , Humanos , Depressão/terapia , Depressão/complicações , Transtornos do Sono-Vigília/psicologia , Inglaterra , SonoRESUMO
Psychotherapy is an effective treatment for many common mental health problems, but the mechanisms of action and processes of change are unclear, perhaps driven by the focus on a single diagnosis which does not reflect the heterogeneous symptom experiences of many patients. The objective of this study was to better understand therapeutic change, by illustrating how symptoms evolve and interact during psychotherapy. Data from 113,608 patients from psychological therapy services who completed depression and anxiety symptom measures across three to six therapy sessions were analysed. A panel graphical vector-autoregression model was estimated in a model development sample (N = 68,165) and generalizability was tested in a confirmatory model, fitted to a separate (hold-out) sample of patients (N = 45,443). The model displayed an excellent fit and replicated in the confirmatory holdout sample. First, we found that nearly all symptoms were statistically related to each other (i.e. dense connectivity), indicating that no one symptom or association drives change. Second, the structure of symptom interrelations which emerged did not change across sessions. These findings provide a dynamic view of the process of symptom change during psychotherapy and give rise to several causal hypotheses relating to structure, mechanism, and process.
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Ansiedade , Psicoterapia , Ansiedade/psicologia , Ansiedade/terapia , Transtornos de Ansiedade/psicologia , Humanos , Resultado do TratamentoRESUMO
In order to develop a successful subunit vaccine against infection with the human immunodeficiency virus (HIV), protective immune effector functions must be identified. Until now, there has been only indirect evidence that HIV-specific cytotoxic T lymphocytes (CTLs) fulfill this role. Using the macaque simian immunodeficiency virus (SIV) model, the protective potential of nef-specific CTLs, stimulated by vaccination, was examined in animals challenged with a high intravenous dose of the pathogenic simian immunodeficiency virus, SIVmac251(32H)(pJ5). An inverse correlation was found between the vaccine-induced nef-specific CTL precursor frequency and virus load measured after challenge. In addition, the early decline in viraemia, observed in both vaccinated and unvaccinated control animals was associated with the development of virus-specific CTL activity and not with the presence of virus-specific neutralizing antibodies. The results imply that vaccines that stimulate strong CTL responses could protect against HIV infection.
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Produtos do Gene nef/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/fisiologia , Linfócitos T Citotóxicos/imunologia , Vacinação , Vacinas Virais/imunologia , Animais , Células Cultivadas , DNA Viral/sangue , Produtos do Gene gag/sangue , Leucócitos Mononucleares/virologia , Macaca fascicularis , Reação em Cadeia da Polimerase , Provírus/genética , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vacinas Sintéticas , Viremia/prevenção & controle , Replicação ViralRESUMO
AIMS: To determine whether age, gender and marital status are associated with prognosis for adults with depression who sought treatment in primary care. METHODS: Medline, Embase, PsycINFO and Cochrane Central were searched from inception to 1st December 2020 for randomised controlled trials (RCTs) of adults seeking treatment for depression from their general practitioners, that used the Revised Clinical Interview Schedule so that there was uniformity in the measurement of clinical prognostic factors, and that reported on age, gender and marital status. Individual participant data were gathered from all nine eligible RCTs (N = 4864). Two-stage random-effects meta-analyses were conducted to ascertain the independent association between: (i) age, (ii) gender and (iii) marital status, and depressive symptoms at 3-4, 6-8,
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Antidepressivos , Depressão , Adulto , Antidepressivos/uso terapêutico , Ansiedade , Depressão/diagnóstico , Depressão/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estado Civil , PrognósticoRESUMO
Inoculation of macaques with live attenuated SIV strains has been shown to protect against subsequent challenge with wild-type SIV. The protective mechanism(s) remain obscure. To study the effect in more detail, we have investigated the role of virus-specific CTL responses in macaques infected with an attenuated SIV strain (pC8), which has a four-amino acid deletion in the nef gene, as compared with the wild-type SIVmac32H clone (pJ5). Cynomolgus macaques infected with pC8 were protected against subsequent challenge with pJ5 and did not develop any AIDS-like symptoms in the 12 months after infection. The pC8-induced protection was associated with high levels of virus-specific CTL responses to a variety of viral antigens. In contrast, pJ5-infected macaques had little, if any, detectable CTL response to the viral proteins after three months. The latter group of macaques also showed increased Fas expression and apoptotic cell death in both the CD4(+) and CD8(+) populations. In vitro, pJ5 but not pC8 leads to an increase in FasL expression on infected cells. Thus the expression of FasL may protect infected cells from CTL attack, killing viral-specific CTLs in the process, and providing a route for escaping the immune response, leading to the increased pathogenicity of pJ5. pC8, on the other hand does not induce FasL expression, allowing the development of a protective CTL response. Furthermore, interruption of the Fas-FasL interaction allows the regeneration of viral-specific CTL responses in pJ5-infected animals. This observation suggests an additional therapeutic approach to the treatment of AIDS.
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Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Imunidade Celular , Glicoproteínas de Membrana/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia , Síndrome da Imunodeficiência Adquirida/imunologia , Animais , Proteína Ligante Fas , Citometria de Fluxo , Humanos , Células JurkatRESUMO
The Coronavirus (Covid-19) pandemic is exerting unprecedented pressure on NHS Health and Social Care provisions, with frontline staff, such as those of critical care units, encountering vast practical and emotional challenges on a daily basis. Although staff are being supported through organisational provisions, facilitated by those in leadership roles, the emergence of mental health difficulties or the exacerbation of existing ones amongst these members of staff is a cause for concern. Acknowledging this, academics and healthcare professionals alike are calling for psychological support for frontline staff, which not only addresses distress during the initial phases of the outbreak but also over the months, if not years, that follow. Fortunately, mental health services and psychology professional bodies across the United Kingdom have issued guidance to meet these needs. An attempt has been made to translate these sets of guidance into clinical provisions via the recently established Homerton Covid Psychological Support (HCPS) pathway delivered by Talk Changes (Hackney & City IAPT). This article describes the phased, stepped-care and evidence-based approach that has been adopted by the service to support local frontline NHS staff. We wish to share our service design and pathway of care with other Improving Access to Psychological Therapies (IAPT) services who may also seek to support hospital frontline staff within their associated NHS Trusts and in doing so, lay the foundations of a coordinated response. KEY LEARNING AIMS: (1)To understand the ways staff can be psychologically and emotionally impacted by working on the frontline of disease outbreaks.(2)To understand the ways in which IAPT services have previously supported populations exposed to crises.(3)To learn ways of delivering psychological support and interventions during a pandemic context based on existing guidance and research.
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Thirty-eight mature horses were assigned to one of two equal groups to evaluate two treatments consisting of either 24 hours of continuous road transport (24T) or two 12-hour periods of transport separated by off-loading, resting and feeding the horses for 12 hours (12/12T). A subset of six horses from each group served as controls for the other group. The horses were loaded into a commercial straight-deck trailer and travelled loose in one of two standard-sized compartments. After the journeys the horses were put back into their paddocks for a 24-hour recovery period. Venous blood samples were collected before loading, after unloading and after the 24-hour recovery period. Transport significantly increased the horses' cortisol concentrations, neutrophil counts and neutrophil:lymphocyte (nl) ratios, and decreased the numbers of all the lymphocyte subpopulation cell types. Collectively, no significant differences were observed between the two treatments in the horses' cortisol concentrations, total leucocyte counts, neutrophil and lymphocyte counts, nl ratios, and the cd8a+ and cd21+ lymphocyte subpopulations, but there were differences in the numbers of cd3+, cd4+, and cd8b+ subpopulations. The inclusion of a 12-hour rest-stop interrupted the transport-related decline in the lymphocyte subpopulations and allowed them to recover towards their resting levels.
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Comportamento Alimentar/fisiologia , Cavalos/imunologia , Descanso/fisiologia , Meios de Transporte/métodos , Viagem , Análise de Variância , Animais , Feminino , Cavalos/sangue , Hidrocortisona/sangue , Contagem de Leucócitos/veterinária , Leucócitos/citologia , Leucócitos/imunologia , Masculino , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/veterinária , Streptococcus equi/isolamento & purificação , Fatores de TempoAssuntos
Vacinas contra a AIDS , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Modelos Animais de Doenças , HIV-1 , HIV-2 , Animais , Gatos , HIV-1/imunologia , HIV-2/imunologia , Humanos , Macaca mulatta , Camundongos , Camundongos SCID , Pan troglodytes , Vírus da Imunodeficiência Símia/imunologia , Vacinas Atenuadas , Vacinas SintéticasRESUMO
Epizootic bovine abortion (EBA), a tick-transmitted disease of pregnant cattle grazing foothill pastures, is a major cause of reproductive failure in California and adjacent states. Affected fetuses develop a chronic disease, resulting in late-term abortion or premature calving. Despite investigations spanning 50 years, to the authors' knowledge, the etiologic agent of EBA has not yet been isolated from affected fetuses or the tick vector. The diagnosis of EBA is based on gross and microscopic lesions. Recently, documentation that the etiologic agent is susceptible to antibiotics and identification of a unique 16S deltaproteobacterial rDNA gene sequence in 90% of thymus tissues from aborted fetuses have supported the role of a bacterial infection as the cause of EBA. To determine whether bacteria could be detected in the tissues, histochemical staining and immunohistochemical procedures were used on formalin-fixed, paraffin-embedded tissues. Use of a modified Steiner silver stain revealed small numbers of intracytoplasmic bacterial rods in 37 of 42 thymic samples from EBA-affected fetuses. Improved detection was achieved by use of immunohistochemical staining with serum from EBA-affected fetuses that resulted in detection of numerous bacterial rods in the cytoplasm of histiocytic cells in the thymus from all 42 EBA-affected fetuses. Immunohistochemical examination of additional tissues from 21 field and experimental EBA cases revealed positively stained intracytoplasmic bacterial rods in many organs with inflammatory lesions. Use of the modified Steiner stain and immunohistochemical staining of tissues from negative-control fetuses failed to reveal organisms. To the authors' knowledge, this is the first report to document morphologic evidence of a bacterium associated with the lesions of EBA.
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Aborto Animal/patologia , Doenças dos Bovinos/patologia , Infecções por Bactérias Gram-Positivas/veterinária , Bacilos Gram-Positivos/isolamento & purificação , Histocitoquímica/veterinária , Imuno-Histoquímica/veterinária , Aborto Animal/microbiologia , Animais , Bovinos , Doenças dos Bovinos/microbiologia , Doenças dos Bovinos/transmissão , Deltaproteobacteria/isolamento & purificação , Feminino , Feto/microbiologia , Infecções por Bactérias Gram-Positivas/complicações , Infecções por Bactérias Gram-Positivas/transmissão , Histocitoquímica/métodos , Imuno-Histoquímica/métodos , Gravidez , Estudos Retrospectivos , Timo/embriologia , Timo/microbiologia , Infestações por Carrapato/complicações , Infestações por Carrapato/veterináriaRESUMO
The purpose of this study was to determine if Otarine Herpesvirus-1 (OtHV-1) is associated with the presence of urogenital carcinomas in California sea lions. Polymerase chain reaction (PCR) analysis with primers specific for OtHV-1 was used to compare the prevalence of OtHV-1 infection in 15 sea lions affected by urogenital carcinoma with that of age-matched and juvenile tumour-free animals, and animals with tumours of non-urogenital origin. The herpesvirus was more prevalent (100%) and more widespread in the 15 animals with urogenital carcinoma than in 25 control animals, and was most often found in the urogenital tissue (vagina and prostate) and in the draining lymph nodes. Moreover, OtHV-1 DNA was not found in any juvenile animal, or in the neoplastic tissues of animals with non-urogenital tumours. Papillomavirus-specific PCR analysis of urogenital carcinoma tissues detected papillomavirus sequences in only one carcinomatous tissue. Further studies are needed to determine if OtHV-1 contributes to oncogenesis in the California sea lion; these data show, however, that OtHV-1 is associated with urogenital carcinomas, is preferentially present in urogenital tissues, and may be sexually transmitted. Papillomaviruses, which are known to contribute to urogenital tumours in other species, did not appear to be associated with the sea lion carcinomas.
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Carcinoma/veterinária , Doenças Endêmicas , Gammaherpesvirinae/patogenicidade , Infecções por Herpesviridae/veterinária , Papillomaviridae/patogenicidade , Leões-Marinhos/virologia , Neoplasias Urogenitais/veterinária , Fatores Etários , Animais , Carcinoma/complicações , Carcinoma/epidemiologia , Carcinoma/virologia , Feminino , Gammaherpesvirinae/metabolismo , Infecções por Herpesviridae/etiologia , Masculino , Reação em Cadeia da Polimerase , Distribuição Tecidual , Neoplasias Urogenitais/complicações , Neoplasias Urogenitais/epidemiologia , Neoplasias Urogenitais/virologiaRESUMO
Micronized titanium oxide (TiO(2)) and manganese-doped titanium oxide (TiO(2):Mn) particles have been incorporated into a variety of oil-in-water (O/W) and water-in-oil-in-water (W/O/W) emulsions in conjunction with the UV-absorbing organic compounds butyl methoxydibenzoylmethane (BMDM) and octyl methoxycinnamate (OMC) and with the anti-oxidants vitamin E and vitamin C. The retention of the organics under solar exposure has been shown to be significantly enhanced by the addition of TiO(2):Mn to the formulation. In the case of BMDM and OMC, the retention is increased from 20% and 24% to 63% and 83%, respectively, after two hours of solar exposure. In this system, TiO(2) particles are shown to provide only limited protection relative to BMDM and OMC. Vitamin E and vitamin C are actively degraded by the presence of TiO(2) in the emulsion during solar exposure. This effect is reversed with TiO(2):Mn, the use of which can protect >90% of anti-oxidants in both the oil and water phases of the formulation. The absence of reactive oxygen species (ROS) generation and surface scavenging of ROS by TiO(2):Mn is responsible for a significantly reduced ROS load on the organic components and consequent photostabilization of the emulsion.
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Antioxidantes/química , Cosméticos/química , Manganês/química , Compostos Orgânicos/química , Titânio/química , Raios Ultravioleta , Emulsões , FotoquímicaRESUMO
Four monoclonal antibodies (mAbs), UC-A4, UC-D3, UC-H9, and IL-A21, specific for bovine major histocompatibility complex class II proteins are described. Sequential immunoprecipitation experiments using biotin-labeled peripheral blood mononuclear cells suggested, but did not conclusively establish, that each of these antibodies recognized a different epitope. The epitope identified by IL-A21 appeared to be common to all of the class II proteins precipitated by the four mAbs, and UC-D3 and UC-H9 each appeared to react with distinct epitopes on separate subsets of these class II proteins. Monoclonal antibody UC-A4 appeared to identify an epitope on a subset of the class II molecules identified by UC-H9. Differences found in the expression by lymphoid cells of class II proteins identified by the four mAbs were indicative of each mAb recognizing a different epitope. UC-H9 and IL-A21 class II proteins were detected on all surface immunoglobulin (S'Ig) positive cells in peripheral blood, but UC-A4 and UC-D3 class II proteins were not. Expression of UC-A4 class II proteins, detected at low density on a strikingly reduced number of S'Ig+ cells from the blood of some bovine leukosis virus-infected cattle, could be increased by culturing these B cells with lipopolysaccharide. All peripheral blood monocytes expressed UC-H9 and IL-A21 class II proteins, but only a proportion of monocytes expressed detectable UC-A4 and UC-D3 class II proteins. Almost all mitogen-stimulated BoCD4+ and BoCD8+ T cells expressed UC-H9 and IL-A21 class II proteins, whereas fewer stimulated T cells of both subsets expressed UC-A4 and UC-D3 class II proteins. All gamma/delta receptor (gamma/delta R) T cells expressed UC-D3, UC-H9, and IL-A21 class II proteins, but no cells (of gamma/delta R+ or CD4+/CD2+ phenotype) from gamma/delta R+ T cell-enriched cultures expressed UC-A4 class II proteins.
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Anticorpos Monoclonais/análise , Antígenos de Histocompatibilidade Classe II/análise , Leucócitos/citologia , Leucócitos/imunologia , Animais , Anticorpos Monoclonais/imunologia , Linfócitos B/citologia , Linfócitos B/imunologia , Linfócitos B/ultraestrutura , Antígenos CD4/análise , Antígenos CD8/análise , Bovinos , Células Cultivadas , Epitopos/imunologia , Citometria de Fluxo , Imunofluorescência , Antígenos de Histocompatibilidade Classe II/imunologia , Imuno-Histoquímica , Leucócitos/ultraestrutura , Ativação Linfocitária , Monócitos/citologia , Monócitos/imunologia , Monócitos/ultraestrutura , Fenótipo , Testes de Precipitina , Receptores de Antígenos de Linfócitos T gama-delta/análise , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/ultraestruturaRESUMO
The polymerase chain reaction (PCR) was used to determine the tissue distribution of phocine herpesvirus-1 (PhHV-1) DNA in 20 stranded Pacific harbour seals (17 pups and three seals older than one year) that died during rehabilitation. The aim was to begin to define stages of infection and to investigate the relation between the presence of PhHV-1 in tissues, histological lesions and serology. PhHV-1 DNA was detected in a wide range of tissues from 10/17 pups and 3/3 subadults or adults. Different clinical patterns emerged from the examination of ante- and post-mortem samples. These patterns probably represented pups with active PhHV-1 infection, pups recovering from infection, and older harbour seals with chronic, reactivated infection. As PhHV-1 DNA was detected in tissues in the absence of typical histological lesions in seven seals and in the absence of PhHV-1 specific antibodies in four seals, it is clear that both histological examination and serology underestimate the presence of infection. These results showed that infection can occur in the absence of obvious disease and that seroconversion may be associated with clinical recovery.
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Infecções por Herpesviridae/veterinária , Phoca/virologia , Reação em Cadeia da Polimerase/veterinária , Testes Sorológicos/veterinária , Varicellovirus/isolamento & purificação , Doenças dos Animais/epidemiologia , Doenças dos Animais/patologia , Doenças dos Animais/virologia , Animais , Anticorpos Antivirais/sangue , California/epidemiologia , Doença Crônica , DNA Viral/análise , Infecções por Herpesviridae/epidemiologia , Reação em Cadeia da Polimerase/métodos , Valor Preditivo dos Testes , Estudos Soroepidemiológicos , Testes Sorológicos/métodos , Varicellovirus/genética , Varicellovirus/imunologiaRESUMO
BACKGROUND: Vaginal agents which are antiviral and/or inhibit the entry of HIV into the cell could prevent heterosexual transmission of HIV, and protect women who cannot negotiate condom use. METHODS: Four agents have been investigated for activity in vitro and in vivo against SHIV(89.6PD): two anionic polymers, dextrin-2-sulphate (D2S) and PRO 2000 (P2K), and two virucidal agents; a non-ionic detergent, nonoxynol-9 (N9) and a cyclic peptide ionophore, gramicidin-D (GD). All four agents were investigated in rhesus macaques, using an intra-vaginal challenge of two inoculations of 1 x 104 50% tissue culture infectious doses (TCID)50 of SHIV(89.6PD). RESULTS: D2S, P2K, GD and N9 all inhibited SHIV(89.6PD) in vitro. In vivo, three out of four control macaques were infected as judged by viral culture, seroconversion, DNA and RNA PCR; infection was confirmed in four out of eight macaques pre-treated with P2K, two out of four pre-treated with D2S, one out of four pre-treated with N9, two out of four pre-treated with GD and four out of four pre-treated with D2S + GD, a combination additive in vitro. INTERPRETATION: D2S and PRO-2000, novel inhibitors of HIV entry, showed evidence of protection in vivo, comparable to that seen with the virucide, N9. These data, together with the results of phase I and phase II studies in healthy women which have shown minimal toxicity, support plans for a phase III efficacy trial of chemically simple inhibitors of HIV entry with low toxicity, for the prevention of HIV infection in women.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/prevenção & controle , HIV-1/efeitos dos fármacos , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Administração Intravaginal , Animais , Fármacos Anti-HIV/farmacologia , Linhagem Celular , Dextrinas/administração & dosagem , Dextrinas/farmacologia , Feminino , Gramicidina/administração & dosagem , Gramicidina/farmacologia , Infecções por HIV/virologia , HIV-1/patogenicidade , Humanos , Macaca , Testes de Sensibilidade Microbiana , Naftalenossulfonatos/administração & dosagem , Naftalenossulfonatos/farmacologia , Nonoxinol/administração & dosagem , Nonoxinol/farmacologia , Polímeros/administração & dosagem , Polímeros/farmacologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/patogenicidadeRESUMO
OBJECTIVE: To evaluate the efficacy of immunopurified class I human histocompatibility leukocyte antigen (HLA) to protect against SIV infection. METHODS: HLA class I antigens were immunopurified from a human B-lymphoblastoid cell line. Groups of four macaques were vaccinated subcutaneously with four doses of the immunogen in adjuvant, or with adjuvant alone and subsequently challenged intravenously with 10 median monkey infectious doses of cell-free SIVmac-32H. Infection was determined by polymerase chain reaction for SIVmac proviral DNA and by virus isolation. Antigen-specific humoral and cellular immune responses were monitored. RESULTS: Macaques immunized with the HLA molecules produced anti-HLA class I antibodies that inhibited SIV replication in vitro and downregulated autologous T-cell proliferation against irradiated C8166 cells. They were partially protected (two out of four) from virus infection for at least 33 weeks when challenged with SIV grown in human cells. All four control animals were infected. CONCLUSIONS: This demonstration of partial protection, together with our previous work reporting that vaccination with allogenic cynomolgus lymphocytes can protect against challenge infection with SIV grown in simian cells, suggests that allogenic immune response induced before or during establishment of HIV infection may have important implications for AIDS disease progression.