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1.
Neurobiol Dis ; 181: 106128, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37075948

RESUMO

RGS14 is a complex multifunctional scaffolding protein that is highly enriched within pyramidal cells (PCs) of hippocampal area CA2. In these neurons, RGS14 suppresses glutamate-induced calcium influx and related G protein and ERK signaling in dendritic spines to restrain postsynaptic signaling and plasticity. Previous findings show that, unlike PCs of hippocampal areas CA1 and CA3, CA2 PCs are resistant to a number of neurological insults, including degeneration caused by temporal lobe epilepsy (TLE). While RGS14 is protective against peripheral injury, similar roles for RGS14 during pathological injury in hippocampus remain unexplored. Recent studies showed that area CA2 modulates hippocampal excitability, generates epileptiform activity and promotes hippocampal pathology in animal models and patients with TLE. Because RGS14 suppresses CA2 excitability and signaling, we hypothesized that RGS14 would moderate seizure behavior and early hippocampal pathology following seizure activity, possibly affording protection to CA2 PCs. Using kainic acid (KA) to induce status epilepticus (KA-SE) in mice, we show that the loss of RGS14 (RGS14 KO) accelerated onset of limbic motor seizures and mortality compared to wild type (WT) mice, and that KA-SE upregulated RGS14 protein expression in CA2 and CA1 PCs of WT. Our proteomics data show that the loss of RGS14 impacted the expression of a number of proteins at baseline and after KA-SE, many of which associated unexpectedly with mitochondrial function and oxidative stress. RGS14 was shown to localize to the mitochondria in CA2 PCs of mice and reduce mitochondrial respiration in vitro. As a readout of oxidative stress, we found that RGS14 KO dramatically increased 3- nitrotyrosine levels in CA2 PCs, which was greatly exacerbated following KA-SE and correlated with a lack of superoxide dismutase 2 (SOD2) induction. Assessing for hallmarks of seizure pathology in RGS14 KO, we unexpectedly found no differences in neuronal injury in CA2 PCs. However, we observed a striking and surprising lack of microgliosis in CA1 and CA2 of RGS14 KO compared to WT. Together, our data demonstrate a newly appreciated role for RGS14 in limiting intense seizure activity and pathology in hippocampus. Our findings are consistent with a model where RGS14 limits seizure onset and mortality and, after seizure, is upregulated to support mitochondrial function, prevent oxidative stress in CA2 PCs, and promote microglial activation in hippocampus.


Assuntos
Epilepsia do Lobo Temporal , Proteínas RGS , Estado Epiléptico , Animais , Camundongos , Hipocampo/metabolismo , Convulsões , Células Piramidais/metabolismo , Epilepsia do Lobo Temporal/metabolismo , Estresse Oxidativo , Ácido Caínico/toxicidade , Proteínas RGS/efeitos adversos , Proteínas RGS/metabolismo
2.
Postharvest Biol Technol ; 173: 111420, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33658745

RESUMO

Continuous ethylene supplementation suppresses postharvest sprouting, but it can increase reducing sugars, limiting its use as an alternative to chlorpropham for processing potatoes. To elucidate the mechanisms involved, tubers were treated after curing with or without the ethylene binding inhibitor 1-methylcyclopropene (1-MCP at 1 µL L-1 for 24 h), and then stored in air or air supplemented with continuous ethylene (10 µL L-1). Across three consecutive seasons, changes in tuber physiology were assessed alongside transcriptomic and metabolomic analysis. Exogenous ethylene alone consistently induced a respiratory rise and the accumulation of undesirable reducing sugars. The transient respiratory peak was preceded by the strong upregulation of two genes encoding 1-aminocyclopropane-1-carboxylate oxidase (ACO), typical of wound and stress induced ethylene production. Profiles of parenchymatic tissue highlighted that ethylene triggered abscisic acid (ABA) catabolism, evidenced by a steep fall in ABA levels and a transient rise in the catabolite phaseic acid, accompanied by upregulation of transcripts encoding an ABA 8'-hydroxylase. Moreover, analysis of non-structural carbohydrate-related genes revealed that ethylene strongly downregulated the expression of the Kunitz-type invertase inhibitor, already known to be involved in cold-induced sweetening. All these ethylene-induced effects were negated by 1-MCP with one notable exception: 1-MCP enhanced the sprout suppressing effect of ethylene whilst preventing ethylene-induced sweetening. This study supports the conclusions that: i) tubers adapt to ethylene by regulating conserved pathways (e.g. ABA catabolism); ii) ethylene-induced sweetening acts independently from sprout suppression, and is similar to cold-induced sugar accumulation.

3.
Curr Oncol ; 23(4): e369-76, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27536186

RESUMO

PURPOSE: A new scheduling strategy was implemented. Before implementation, treatments and planning computed tomography (ct) imaging were both scheduled at the same time. Maximal wait times for treatment are defined by the Quebec Ministry of Health's plan of action according to treatment aim and site. After implementation, patients requiring rapid treatment (priorities 0-3) continued to have their treatments scheduled at the same time as their planning ct; treatments for priority 4 (P4) patients were scheduled only after the treatment plan was approved. That approach aims to compensate for unexpected increases in planning workload by relocating less delay-sensitive cases to other time slots. We evaluated the impact on the patient experience, workload in various sectors, the care team's perception of care delivery, access to care, and the department's efficiency in terms of hours worked per treatment delivered. METHODS: Three periods were defined for analysis: the pre-transitional phase, for baseline evaluation; the transitional phase, during which there was an overlap in the way patients were being scheduled; and the post-transitional phase. Wait times were calculated from the date that patients were ready to treat to the date of their first treatment. Surveys were distributed to pre- and post-transitional phase patients. Care team members were asked to complete a survey evaluating their perception of how the change affected workload and patient care. Operational data were analyzed. RESULTS: We observed a 24% increase in the number of treatments delivered in the post-transitional phase. Before implementation, priority 0-3 patients waited a mean of 7.9 days to begin treatments (n = 241); afterward, they waited 6.3 days (n = 340, p = 0.006). Before implementation, P4 patients waited a mean 15.1 days (n = 233); after implementation, they waited 16.1 days (n = 368, p = 0.22). Surveys showed that patients felt that the time it took to inform them of treatment appointments was acceptable in both phases. No significant change in overtime hours occurred in dosimetry (p = 0.7476) or globally (p = 0.4285) despite the increased number of treatments. However, departmental efficiency improved by 16% (p = 0.0001). CONCLUSIONS: This new scheduling strategy for P4 cases resulted in improved access to care for priority 0-3 patients. Departmental efficiency was improved, and overtime hours did not increase. Patient satisfaction remained high.

4.
J Environ Health ; 77(10): 8-12, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26058216

RESUMO

Follow-up inspections are recommended by the Food and Drug Administration as a tool to verify corrections to violations cited during restaurant inspections. The effectiveness of follow-up inspections as a tool in reducing critical violations is unknown, however. The purpose of the authors' study was to assess whether a serious violation that leads to a follow-up inspection reduces the probability of specific critical violations occurring during the next routine inspection. Outcome measures included poor personal hygiene, improper holding temperatures, substandard equipment cleanliness, potential cross contamination, and improper sanitizer concentration. The risk of having a violation increased for all targeted critical violations during inspections conducted after a follow-up inspection compared to restaurant inspections without a prior follow-up, when adjusting for restaurant type, inspector experience, and season.


Assuntos
Inspeção de Alimentos/métodos , Saúde Pública , Restaurantes , Inspeção de Alimentos/estatística & dados numéricos , Estudos Retrospectivos , Estados Unidos
5.
Psychol Med ; 44(3): 607-16, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23591000

RESUMO

BACKGROUND: Structural models of emotional disorders propose that anxiety disorders can be classified into fear and distress disorders. Sources of evidence for this distinction come from genetic, self-report and neurophysiological data from adults. The present study examined whether this distinction relates to cognitive processes, indexed by attention bias towards threat, which is thought to cause and maintain anxiety disorders. METHOD: Diagnostic and attention bias data were analysed from 435 children between 5 and 13 years of age; 158 had principal fear disorder (specific phobia, social phobia or separation anxiety disorder), 75 had principal distress disorder (generalized anxiety disorder, GAD) and 202 had no psychiatric disorder. Anxious children were a clinic-based treatment-seeking sample. Attention bias was assessed on a visual-probe task with angry, neutral and happy faces. RESULTS: Compared to healthy controls, children with principal distress disorder (GAD) showed a significant bias towards threat relative to neutral faces whereas children with principal fear disorder showed an attention bias away from threat relative to neutral faces. Overall, children displayed an attention bias towards happy faces, irrespective of diagnostic group. CONCLUSIONS: Our findings support the distinction between fear and distress disorders, and extend empirically derived structural models of emotional disorders to threat processing in childhood, when many anxiety disorders begin and predict lifetime impairment.


Assuntos
Transtornos de Ansiedade/psicologia , Atenção/fisiologia , Medo/psicologia , Estresse Psicológico/psicologia , Adolescente , Adulto , Análise de Variância , Transtornos de Ansiedade/classificação , Estudos de Casos e Controles , Criança , Pré-Escolar , Manual Diagnóstico e Estatístico de Transtornos Mentais , Expressão Facial , Feminino , Humanos , Entrevista Psicológica , Masculino , Estimulação Luminosa/métodos , Tempo de Reação/fisiologia , Autorrelato , Índice de Gravidade de Doença
6.
J Gen Intern Med ; 28(4): 530-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23150070

RESUMO

BACKGROUND: Multi-faceted depression care programs based within the healthcare system have been found to be effective, but may not fully address the needs of African American Intimate Partner Violence (IPV) survivors, many of whom are not seeking depression care in healthcare settings. OBJECTIVES: To develop and evaluate a multifaceted, community-based depression care program (the Interconnections Project) for African American women with a history of IPV. METHODS: We used a community-based participatory research (CBPR) approach to develop, implement, and evaluate the intervention. Participants were African American women who had current depressive symptoms and a lifetime history of IPV. They participated in a 6-month intervention where a peer advocate provided education, skills training, and case management services, and used Motivational Interviewing to support self-management behaviors. We conducted pre-intervention and post-intervention assessments using quantitative and qualitative data. RESULTS: Fifty-nine women participated, with 92 % attending any sessions and 51 % attending at least 6 h of intervention activities. Intervention changes made to better accommodate participants' unpredictable schedules improved participation rates. Participants noted high levels of satisfaction with the program. There were significant improvements in depression severity (PHQ-9 13.9 to 7.9, p < 0.001), self-efficacy, self-management behaviors, and self-esteem (all p < 0.001), but no increase in use of antidepressants. Common themes related to why the program was helpful included that the program was by and for African American women, that it fostered trust, and that it taught self-management strategies with practical, lasting value. CONCLUSION: Culturally specific, community-based interventions led by peer advocates may be a promising way to help African American IPV survivors effectively address depression.


Assuntos
Negro ou Afro-Americano/psicologia , Serviços Comunitários de Saúde Mental/organização & administração , Depressão/terapia , Maus-Tratos Conjugais/psicologia , Sobreviventes/psicologia , Adulto , Idoso , Pesquisa Participativa Baseada na Comunidade , Depressão/etnologia , Depressão/etiologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oregon , Aceitação pelo Paciente de Cuidados de Saúde , Satisfação do Paciente , Projetos Piloto , Avaliação de Programas e Projetos de Saúde , Escalas de Graduação Psiquiátrica , Fatores Socioeconômicos , Maus-Tratos Conjugais/etnologia , Adulto Jovem
7.
Clin Exp Dermatol ; 38(3): 262-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23517356

RESUMO

BACKGROUND: Mohs micrographic surgery (MMS) is the gold-standard treatment for high-risk basal cell carcinomas and a variety of other cutaneous tumours, including dermatofibromasarcoma protuberans and microcystic adnexal carcinoma. Previous large-scale case series, audits and reviews have allowed evaluation of MMS outcomes, such as BCC recurrence rates. However, to date there has been no systematic UK MMS audit, and certain important aspects of care, such as postoperative functional outcomes, have not yet been subject to scrutiny. AIMS: To review audit data from our centre, and from this to develop a minimum dataset and audit standards for UK MMS centres, on behalf of the British Society of Dermatological Surgery (BSDS). METHODS: An MMS database was developed locally and modified in response to repeated audit cycles since the introduction of the MMS service. A minimum dataset was developed using this experience. RESULTS: In our department, primary BCC recurrence rates are reassuringly low at 0.3%, at both 2 and 5 years. Histopathological discordance is < 2%, and aesthetic and functional outcomes at 3 months are good. CONCLUSIONS: The collation of audit data has been simplified by use of the minimum dataset, which we propose for all UK MMS centres, on behalf of the BSDS.


Assuntos
Carcinoma Basocelular/cirurgia , Cirurgia de Mohs/normas , Neoplasias Cutâneas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Basocelular/patologia , Auditoria Clínica/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Neoplasias Cutâneas/patologia , Reino Unido , Adulto Jovem
8.
Water Sci Technol ; 67(8): 1764-72, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23579831

RESUMO

Acid mine drainage (AMD) has degraded water quality and ecology in streams on the Stockton Plateau, the site of New Zealand's largest open-cast coal mining operation. This has previously been attributed largely to the effects of acidity and elevated aluminium (Al) concentrations. However, the toxicity of dissolved Al is dependent on speciation, which is influenced by pH which affects Al hydrolysis, as well as the concentrations of organic carbon and sulphate which complex Al. Methods for the assessment of the toxic fraction of Al, by chemical analysis and geochemical modelling, have been investigated in selected streams on the Stockton Plateau, where dissolved Al concentrations ranged from 0.034 to 27 mg L(-1). Modelling using PHREEQC indicated that between 0.2 and 85% of the dissolved Al was present as the free ion Al(3+), the most toxic Al species, which dominated in waters of pH = 3.8-4.8. Al-sulphate complexation reduced the Al(3+) concentration at lower pH, while Al-organic and -hydroxide complexes dominated at higher pH. Macroinvertebrate richness in the streams identified an Al(3+) 'threshold' of approximately 0.42 mg/L, above which taxa declined rapidly. Colorimetric 'Aluminon' analysis on unpreserved, unfiltered waters provided a better estimation of Al(3+) concentrations than inductively couple plasma-mass spectrometry (ICP-MS) on filtered, acidified waters. The Aluminon method does not react with particulate Al or strong Al complexes, often registering as little as 53% of the dissolved Al concentration determined by ICP-MS.


Assuntos
Alumínio/toxicidade , Invertebrados/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Resíduos Industriais , Mineração , Modelos Teóricos
9.
J Environ Health ; 75(10): 8-12, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23858661

RESUMO

Posting restaurant inspection scores on the Internet as a tool for improving food safety is becoming more common. The purpose of the study described in this article was to evaluate the association between Internet posting of restaurant inspection scores and the five most frequently cited critical violations in Salt Lake County, Utah. The study examined 2,995 inspections conducted at 796 full service and fast food restaurants for a one-year period before and after launch of a restaurant inspection Web site. Critical violations decreased significantly after the Web site launch compared to before-launch levels. The greatest improvements were found in temperature holding violations (odds ratio = 0.75, p < .001), hygiene practices violations (odds ratio = 0.68, p < .001) and equipment cleanliness violations (odds ratio = 0.58, p < .001). Restaurant type (full service, fast food), inspector experience, and season were significantly associated with the decrease in violations.


Assuntos
Benchmarking , Fiscalização e Controle de Instalações/estatística & dados numéricos , Inocuidade dos Alimentos , Disseminação de Informação , Internet , Restaurantes , Humanos , Estudos Longitudinais , Avaliação de Programas e Projetos de Saúde , Utah
10.
J Environ Health ; 76(2): 8-12, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24073484

RESUMO

In 2010 the Salt Lake Valley Health Department conducted a pilot of an announced inspection program utilizing a randomized assignment of restaurants to an intervention group with announced inspections and a control group that remained on the usual schedule of unannounced inspections. After adjusting for food type, visible kitchen, outside quality assurance, season, and standardized inspector, significant reductions were found in the odds ratios of personal hygiene (adjusted odds ratios [aOR] = 0.11, p = .00) and equipment cleanliness (aOR = 0.19, p = .00) violations. In the models for the control group, none of the odds ratios were statistically different from one, indicating no change in the postintervention time period as compared to the preintervention period.


Assuntos
Saúde Ambiental/organização & administração , Manipulação de Alimentos/normas , Higiene/normas , Restaurantes/normas , Razão de Chances , Projetos Piloto , Saúde Pública , Utah
11.
Euro Surveill ; 17(49)2012 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-23231894

RESUMO

In 2011, there was a large measles outbreak in Dublin. Nationally 285 cases were notified to the end of December 2011, and 250 (88%) were located in the Dublin region. After the first case was notified in week 6, numbers gradually increased, with 25 notified in June and a peak of 53 cases in August. Following public health intervention including a measles-mumps-rubella (MMR) vaccination campaign, no cases were reported in the Dublin region in December 2011. Most cases (82%) were children aged between 6 months and 14 years, and 46 cases (18%) were under 12 months-old. This is the first outbreak in Dublin to utilise a geographic information system for plotting measles cases on a digital map in real time. This approach, in combination with the analysis of case notifications, assisted the department of public health in demonstrating the extent of the outbreak. The digital mapping documented the evolution of two distinct clusters of 87 (35%) cases. These measles cases were infected with genotype D4-Manchester recently associated with large outbreaks across Europe. The two clusters occurred in socio-economically disadvantaged areas and were attributable to inadequate measles vaccination coverage due in part to the interruption of a school-based MMR2 vaccination programme.


Assuntos
Notificação de Doenças , Surtos de Doenças , Sistemas de Informação Geográfica , Sarampo/epidemiologia , Adolescente , Criança , Pré-Escolar , Controle de Doenças Transmissíveis/organização & administração , Feminino , Humanos , Incidência , Lactente , Irlanda/epidemiologia , Masculino , Sarampo/prevenção & controle , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Distribuição por Sexo
12.
Ir Med J ; 105(4): 108-10, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22708222

RESUMO

The aim was to study road-related injuries and fatalities in under 15 year olds in two time periods (1996-2000 and 2004-2008 inclusive) to assess whether progress has been made via cross-sectoral efforts to reduce this injury toll in Ireland. For pedestrian and car-related accidents, police assistance is required and at the time a detailed CT 68 form is completed by the attending officer and sent to the Road Safety Authority for analysis. Details re the severity of injury, light and road conditions and safety measures such as seat belt or car restraint use, seat position and helmet use if a cyclist were recorded. Injuries were sub-classified as fatalities, serious (detained in hospital, fractures, severe head injury, severe internal injuries or shock requiring treatment) or minor. All data for the two time periods was entered onto an SPSS database. A concerted national campaign re road safety media campaign allied to random breath testing, penalty points for driving offences, on the spot fines for speeding and far greater police enforcement took place between the two time frames and continues to this day. When looked at as most likely estimates of death ratios the results were found to be statistically significant with an overall p value of < 0.0001 CI [0.39, 0.69]. When broken down into specific age ranges all were significant apart from the 0-3 age range with a p value of 0.69 CI [0.26, 1.1]. The most significant changes were found in the 7-9 years, 10-12 and 13-15 year age ranges with p values of < 0.0001, 0.0002 and 0.0007 respectively. When results were compared between the two cohorts, car occupant fatalities between both groups dropped by 36%. Pedestrian injuries dropped from 1719 to 1232, pedestrian fatalities decreased by almost 50% as did serious pedestrian injuries from 261 down to 129. Cyclist fatalities saw the most significant fall (76%) with a dramatic reduction in cyclist injuries from 25 down to 6 (63%). The 13-15 year old age group had the highest mortality and morbidity in both cohorts. Documented restraint use was less than 70% in both cohorts. A national road safety campaign, greater police enforcement and a cultural change has seen road-related injuries in children drop very significantly (by 50%) over the two time periods and this campaign should continue.


Assuntos
Acidentes de Trânsito/mortalidade , Ferimentos e Lesões/prevenção & controle , Acidentes de Trânsito/legislação & jurisprudência , Acidentes de Trânsito/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Dispositivos de Proteção da Cabeça , Humanos , Lactente , Irlanda , Cintos de Segurança/legislação & jurisprudência
13.
Ir Med J ; 105(2): 39-42, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22455236

RESUMO

We conducted a case-control study to estimate the 2010/2011 trivalent influenza vaccine effectiveness (TIVE) using the Irish general practitioners' influenza sentinel surveillance scheme. Cases were influenza-like illness (ILI) patients with laboratory-confirmed influenza. Controls were ILI patients who tested negative for influenza. Participating sentinel general practitioners (GP) collected swabs from patients presenting with ILI along with their vaccination history and other individual characteristics. The TIVE was computed as (1 - odds ratiofor vaccination) x100%. Of 60 sentinel GP practices, 22 expressed interest in participating in the study and 17 (28%) recruited at least one ILI patient. In the analysis, we included 106 cases and 85 controls. Seven controls (8.2%) and one influenza case (0.9%) had been vaccinated in 2010/2011. The estimated TIVE against any influenza subtype was 89.4% [95% CI: 13.8; 99.8%], suggesting a protective effect against GP-attended laboratory confirmed influenza. This study design could be used to monitor influenza vaccine effectiveness annually but sample size and vaccination coverage should be increased to obtain precise and adjusted estimates.


Assuntos
Vacinas contra Influenza , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Estudos de Casos e Controles , Humanos , Irlanda/epidemiologia , Vigilância da População
14.
J Exp Med ; 185(8): 1499-503, 1997 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-9126931

RESUMO

The recently developed transfection systems for Plasmodium berghei and Plasmodium falciparum offer important new tools enabling further insight into the biology of malaria parasites. These systems rely upon artificial parasite-host combinations which do not allow investigation into the complex interactions between parasites and their natural hosts. Here we report on stable transfection of Plasmodium knowlesi (a primate malaria parasite that clusters phylogenetically with P. vivax) for which both natural and artificial experimental hosts are available. Transfection of this parasite offers the opportunity to further analyze the biology of antigens not only in a natural host but also in hosts that are closely related to humans. To facilitate future development of integration-dependent transfection in P. knowlesi, completely heterologous plasmids that would reduce homologous recombination at unwanted sites in the genome were constructed. These plasmids contained the pyrimethamine-resistant form of dihydrofolate reductase-thymidylate synthase (dhfr-ts) from Toxoplasma gondii or P. berghei, under control of either (a) P. berghei or (b) P. falciparum promoters. Plasmids were electroporated into mature P. knowlesi schizonts and these cells were injected into rhesus monkeys (Macaca mulatta). After pyrimethamine treatment of these monkeys, resistant parasites were obtained that contained the plasmids. Promoter regions of both P. berghei and P. falciparum controlling dhfr-ts expression were effective in conferring pyrimethamine resistance in P. knowlesi, indicating that common signals control gene expression in phylogenetically distant Plasmodium species.


Assuntos
Plasmodium knowlesi/genética , Transfecção/métodos , Animais , DNA de Protozoário/genética , Expressão Gênica , Macaca mulatta , Pirimetamina/farmacologia , Especificidade da Espécie , Tetra-Hidrofolato Desidrogenase/genética
15.
J Exp Med ; 192(1): 63-75, 2000 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-10880527

RESUMO

The use of peptide-human histocompatibility leukocyte antigen (HLA) class I tetrameric complexes to identify antigen-specific CD8(+) T cells has provided a major development in our understanding of their role in controlling viral infections. However, questions remain about the exact function of these cells, particularly in HIV infection. Virus-specific cytotoxic T lymphocytes exert much of their activity by secreting soluble factors such as cytokines and chemokines. We describe here a method that combines the use of tetramers and intracellular staining to examine the functional heterogeneity of antigen-specific CD8(+) T cells ex vivo. After stimulation by specific peptide antigen, secretion of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, macrophage inflammatory protein (MIP)-1beta, and perforin is analyzed by FACS((R)) within the tetramer-positive population in peripheral blood. Using this method, we have assessed the functional phenotype of HIV-specific CD8(+) T cells compared with cytomegalovirus (CMV)-specific CD8(+) T cells in HIV chronic infection. We show that the majority of circulating CD8(+) T cells specific for CMV and HIV antigens are functionally active with regards to the secretion of antiviral cytokines in response to antigen, although a subset of tetramer-staining cells was identified that secretes IFN-gamma and MIP-1beta but not TNF-alpha. However, a striking finding is that HIV-specific CD8(+) T cells express significantly lower levels of perforin than CMV-specific CD8(+) T cells. This lack of perforin is linked with persistent CD27 expression on HIV-specific cells, suggesting impaired maturation, and specific lysis ex vivo is lower for HIV-specific compared with CMV-specific cells from the same donor. Thus, HIV-specific CD8(+) T cells are impaired in cytolytic activity.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/virologia , Citocinas/biossíntese , Infecções por HIV/imunologia , HIV/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/virologia , Quimiocina CCL4 , Células Clonais , Citomegalovirus/imunologia , Citometria de Fluxo , Soronegatividade para HIV/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Interferon gama/biossíntese , Proteínas Inflamatórias de Macrófagos/biossíntese , Valores de Referência , Fator de Necrose Tumoral alfa/biossíntese
16.
Am J Transplant ; 10(1): 168-72, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19951285

RESUMO

Factor H (CFH) autoantibodies are associated with atypical hemolytic uremic syndrome (aHUS). Peritransplantation plasma exchange therapy and intensification of immunosuppression, with adjuvant use of anti-CD20 monoclonal antibodies has recently been advocated for cases of CFH-autoantibody associated aHUS. In this report, we describe successful deceased donor renal transplantation in a case of CFH-autoantibody associated aHUS with combined CFHR1 and 3 deficiency in addition to the CFH sequence variant, (cG2850T, pGln950His). CFH-autoantibodies were detected 2 weeks prior to transplantation. Disease recurrence was not observed using basiliximab, an IL2-receptor antagonist and high-dose corticosteroids with mycophenolate mofetil. Adjuvant therapies such as Rituximab nor intensification of plasma therapy were employed. Consequently, careful consideration needs to be given to the use of additional immunosuppression in certain cases of CFH-autoantibody associated aHUS. Serial measurement of CFH-autoantibodies is required in the immediate pre- and posttransplantation period to further clarify their role as a factor in the recurrence of aHUS posttransplantation. Furthermore, delineation of the functional significance of CFH-autoantibodies is warranted in individual cases.


Assuntos
Autoanticorpos/sangue , Proteínas Sanguíneas/deficiência , Proteínas Inativadoras do Complemento C3b/deficiência , Fator H do Complemento/genética , Fator H do Complemento/imunologia , Síndrome Hemolítico-Urêmica/imunologia , Síndrome Hemolítico-Urêmica/cirurgia , Transplante de Rim , Substituição de Aminoácidos , Criança , Feminino , Variação Genética , Síndrome Hemolítico-Urêmica/sangue , Síndrome Hemolítico-Urêmica/genética , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Transplante de Rim/patologia , Transplante de Rim/fisiologia , Polimorfismo de Nucleotídeo Único
17.
Psychol Med ; 40(7): 1125-36, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19903363

RESUMO

BACKGROUND: Several theories have posited a common internalizing factor to help account for the relationship between mood and anxiety disorders. These disorders are often co-morbid and strongly covary. Other theories and data suggest that personality traits may account, at least in part, for co-morbidity between depression and anxiety. The present study examined the relationship between neuroticism and an internalizing dimension common to mood and anxiety disorders. METHOD: A sample of ethnically diverse adolescents (n=621) completed self-report and peer-report measures of neuroticism. Participants also completed the Structured Clinical Interview for DSM-IV (SCID). RESULTS: Structural equation modeling showed that a single internalizing factor was common to lifetime diagnosis of mood and anxiety disorders, and this internalizing factor was strongly correlated with neuroticism. Neuroticism had a stronger correlation with an internalizing factor (r=0.98) than with a substance use factor (r=0.29). Therefore, neuroticism showed both convergent and discriminant validity. CONCLUSIONS: These results provide further evidence that neuroticism is a necessary factor in structural theories of mood and anxiety disorders. In this study, the correlation between internalizing psychopathology and neuroticism approached 1.0, suggesting that neuroticism may be the core of internalizing psychopathology. Future studies are needed to examine this possibility in other populations, and to replicate our findings.


Assuntos
Transtornos Neuróticos/diagnóstico , Adolescente , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/psicologia , Diagnóstico Diferencial , Manual Diagnóstico e Estatístico de Transtornos Mentais , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Masculino , Transtornos do Humor/diagnóstico , Transtornos do Humor/psicologia , Transtornos Neuróticos/psicologia , Inquéritos e Questionários
18.
Am J Public Health ; 100(8): 1470-6, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20558811

RESUMO

OBJECTIVES: We sought to understand how African American women's beliefs regarding depression and depression care are influenced by racism, violence, and social context. METHODS: We conducted a focus group study using a community-based participatory research approach. Participants were low-income African American women with major depressive disorder and histories of violence victimization. RESULTS: Thirty women participated in 4 focus groups. Although women described a vicious cycle of violence, depression, and substance abuse that affected their health, discussions about health care revolved around their perception of racism, with a deep mistrust of the health care system as a "White" system. The image of the "strong Black woman" was seen as a barrier to both recognizing depression and seeking care. Women wanted a community-based depression program staffed by African Americans that addressed violence and drug use. CONCLUSIONS: Although violence and drug use were central to our participants' understanding of depression, racism was the predominant issue influencing their views on depression care. Providers should develop a greater appreciation of the effects of racism on depression care. Depression care programs should address issues of violence, substance use, and racism.


Assuntos
Negro ou Afro-Americano/etnologia , Depressão/etnologia , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Preconceito , Maus-Tratos Conjugais/etnologia , Mulheres/psicologia , Adulto , Atitude do Pessoal de Saúde/etnologia , Pesquisa Participativa Baseada na Comunidade , Competência Cultural , Depressão/prevenção & controle , Feminino , Grupos Focais , Necessidades e Demandas de Serviços de Saúde , Disparidades em Assistência à Saúde , Humanos , Pessoa de Meia-Idade , Modelos Psicológicos , Oregon/epidemiologia , Relações Profissional-Paciente , Autoimagem , Transtornos Relacionados ao Uso de Substâncias/etnologia , Confiança , População Branca/etnologia
19.
Int J STD AIDS ; 21(1): 30-3, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19884355

RESUMO

In recent years, the sexual health of the nation has risen in profile. We face increasing demands and targets, in particular the 48-hour waiting time directive, and as a result clinic access has become a priority. eTriage is a novel, secure, web-based service designed specifically to increase access to our clinics. It has proved a popular booking method, providing access to 10% of all appointments across the Directorate within six months of introduction. KC60 analyses revealed that the majority of users (58%) underwent asymptomatic screening with the remainder having some degree of pathology. There was a greater percentage prevalence of human papilloma virus, chlamydia, non-specific urethritis, gonorrhoea, herpes and trichomonas in the eTriage population when compared with the general clinic population. A notes review illustrated a high degree of concordance between data entered on eTriage registration and clinical review (97%). A patient survey revealed high levels of patient satisfaction with the service. As an adjunct to our existing booking services, eTriage has served to increase patient choice and has proved itself to be a safe, efficient and effective means of improving patient access.


Assuntos
Acessibilidade aos Serviços de Saúde , Internet , Infecções Sexualmente Transmissíveis/diagnóstico , Triagem/métodos , Adolescente , Adulto , Idoso , Agendamento de Consultas , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Satisfação do Paciente/estatística & dados numéricos , Reino Unido
20.
Addict Behav Rep ; 11: 100220, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31890851

RESUMO

Cigarette smoking remains an important public health concern, and novel smoking cessation interventions are needed. Craving for cigarettes is a well-established target for intervention. Recent research has identified cognitive processes associated with craving, such as attentional bias to smoking cues, as targets for intervention. One intervention that may be effective in reducing attentional bias is hypnotic suggestion. Using a counterbalanced within-subjects design in a sample of active smokers (N = 33), this laboratory study examined if hypnotic suggestion can modify attention, assessed by the classic and smoking Stroop tasks, and craving. Hypnotic susceptibility was assessed using the Stanford Scale of Hypnotic Susceptibility. There was no evidence that hypnotic susceptibility moderated the effect of hypnotic suggestion on the classic or smoking Stroop effects. However, hypnotic susceptibility did moderate the effect of hypnotic suggestion on craving, such that hypnotic suggestion reduced craving in individuals with high levels of susceptibility. Further research into the mechanisms by which hypnotic suggestion reduces craving is warranted.

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