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1.
Hum Brain Mapp ; 44(17): 5729-5748, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37787573

RESUMO

Despite the known benefits of data-driven approaches, the lack of approaches for identifying functional neuroimaging patterns that capture both individual variations and inter-subject correspondence limits the clinical utility of rsfMRI and its application to single-subject analyses. Here, using rsfMRI data from over 100k individuals across private and public datasets, we identify replicable multi-spatial-scale canonical intrinsic connectivity network (ICN) templates via the use of multi-model-order independent component analysis (ICA). We also study the feasibility of estimating subject-specific ICNs via spatially constrained ICA. The results show that the subject-level ICN estimations vary as a function of the ICN itself, the data length, and the spatial resolution. In general, large-scale ICNs require less data to achieve specific levels of (within- and between-subject) spatial similarity with their templates. Importantly, increasing data length can reduce an ICN's subject-level specificity, suggesting longer scans may not always be desirable. We also find a positive linear relationship between data length and spatial smoothness (possibly due to averaging over intrinsic dynamics), suggesting studies examining optimized data length should consider spatial smoothness. Finally, consistency in spatial similarity between ICNs estimated using the full data and subsets across different data lengths suggests lower within-subject spatial similarity in shorter data is not wholly defined by lower reliability in ICN estimates, but may be an indication of meaningful brain dynamics which average out as data length increases.


Assuntos
Mapeamento Encefálico , Imageamento por Ressonância Magnética , Humanos , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Reprodutibilidade dos Testes , Rede Nervosa/diagnóstico por imagem , Encéfalo/diagnóstico por imagem
2.
J Affect Disord ; 326: 243-248, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36632848

RESUMO

OBJECTIVE: Electroconvulsive therapy (ECT) is the most effective treatment for patients with severe major depressive disorder (MDD). Given the known sex differences in MDD, improved knowledge may provide more sex-specific recommendations in clinical guidelines and improve outcome. In the present study we examine sex differences in ECT outcome and its predictors. METHODS: Clinical data from 20 independent sites participating in the Global ECT-MRI Research Collaboration (GEMRIC) were obtained for analysis, totaling 500 patients with MDD (58.6 % women) with a mean age of 54.8 years. Severity of depression before and after ECT was assessed with validated depression scales. Remission was defined as a HAM-D score of 7 points or below after ECT. Variables associated with remission were selected based on literature (i.e. depression severity at baseline, age, duration of index episode, and presence of psychotic symptoms). RESULTS: Remission rates of ECT were independent of sex, 48.0 % in women and 45.7 % in men (X2(1) = 0.2, p = 0.70). In the logistic regression analyses, a shorter index duration was identified as a sex-specific predictor for ECT outcome in women (X2(1) = 7.05, p = 0.01). The corresponding predictive margins did show overlapping confidence intervals for men and women. CONCLUSION: The evidence provided by our study suggests that ECT as a biological treatment for MDD is equally effective in women and men. A shorter duration of index episode was an additional sex- specific predictor for remission in women. Future research should establish whether the confidence intervals for the corresponding predictive margins are overlapping, as we find, or not.


Assuntos
Transtorno Depressivo Maior , Eletroconvulsoterapia , Transtornos Psicóticos , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Transtorno Depressivo Maior/tratamento farmacológico , Escalas de Graduação Psiquiátrica , Resultado do Tratamento
3.
Brain Stimul ; 15(5): 1065-1072, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35944604

RESUMO

BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for severe depression and induces gray matter (GM) increases in the brain. Small-scale studies suggest that ECT also leads to changes in brain functioning, but findings are inconsistent. In this study, we investigated the influence of ECT on changes in both brain structure and function and their relation to clinical improvement using multicenter neuroimaging data from the Global ECT-MRI Research Collaboration (GEMRIC). METHODS: We analyzed T1-weighted structural magnetic resonance imaging (MRI) and functional resting-state MRI data of 88 individuals (49 male) with depressive episodes before and within one week after ECT. We performed voxel-based morphometry on the structural data and calculated fractional amplitudes of low-frequency fluctuations, regional homogeneity, degree centrality, functional connectomics, and hippocampus connectivity for the functional data in both unimodal and multimodal analyses. Longitudinal effects in the ECT group were compared to repeated measures of healthy controls (n = 27). RESULTS: Wide-spread increases in GM volume were found in patients following ECT. In contrast, no changes in any of the functional measures were observed, and there were no significant differences in structural or functional changes between ECT responders and non-responders. Multimodal analysis revealed that volume increases in the striatum, supplementary motor area and fusiform gyrus were associated with local changes in brain function. CONCLUSION: These results confirm wide-spread increases in GM volume, but suggest that this is not accompanied by functional changes or associated with clinical response. Instead, focal changes in brain function appear related to individual differences in brain volume increases.


Assuntos
Eletroconvulsoterapia , Encéfalo , Depressão/diagnóstico por imagem , Depressão/terapia , Eletroconvulsoterapia/métodos , Substância Cinzenta , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino
4.
Biol Bull ; 242(3): 222-237, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35767415

RESUMO

AbstractThe calyptraeids Crepidula adunca and Crepidula norrisiarum, both direct developers, are abundant in the shallow waters of the northeastern Pacific. They have long been considered as two allopatric species that live on different hosts and differ in body size. In this study, we rigorously test this historical hypothesis by assessing molecular taxonomy, museum records, new morphological and host observations, and population genetic structure along the northeast Pacific coast. Results show that, contrary to previous understanding, the distributions of the two species largely overlap and that size does not effectively distinguish them, especially in the northern part of the range where the nominal "C. adunca" has been studied. Newly recognized northern occurrences of C. norrisiarum demonstrate that both species have similar, disrupted distributions that range from British Colombia through southern California. Neither species is reported to occur on the outer shores of southern Washington or Oregon, the exception being records of C. adunca at Cape Arago, Oregon. Despite this apparent geographic gap, neither species shows appreciable genetic differentiation between the northern and southern parts of its ranges. Despite body size having been used to distinguish these species, our observations do not support body size as a species-specific trait; rather, they support a new hypothesis that body size variation reflects regional differences in host use and host availability.


Assuntos
Gastrópodes , Animais , Filogenia , Especificidade da Espécie
5.
Soc Psychiatry Psychiatr Epidemiol ; 57(3): 461-472, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34480219

RESUMO

PURPOSE: Neurocognitive difficulties and early childhood speech/motor delays are well documented amongst older adolescents and young adults considered at risk for psychosis-spectrum diagnoses. We aimed to test associations between unusual or psychotic-like experiences (PLEs), co-occurring distress/emotional symptoms, current cognitive functioning and developmental delays/difficulties in young people (aged 8-18 years) referred to Child and Adolescent Mental Health Services in South London, UK. METHODS: Study 1 examined receptive language, verbal learning and caregiver-reported speech and motor delays/difficulties in a sample of 101 clinically-referred children aged 8-14 years, comparing those reporting no PLEs (n = 19), PLEs without distress (n = 16), and PLEs with distress (n = 66). Study 2 tested associations of severity of distressing PLEs with vocabulary, perceptual reasoning, word reading and developmental delays/difficulties in a second sample of 122 adolescents aged 12-18 years with distressing PLEs. RESULTS: In Study 1, children with distressing PLEs had lower receptive language and delayed recall and higher rates of developmental delays/difficulties than the no-PLE and non-distressing PLE groups (F values: 2.3-2.8; p values: < 0.005). Receptive language (ß = 0.24, p = 0.03) and delayed recall (ß = - 0.17, p = 0.02) predicted PLE distress severity. In Study 2, the cognitive-developmental variables did not significantly predict PLE distress severity (ß values = 0.01-0.22, p values: > 0.05). CONCLUSION: Findings may be consistent with a cognitive-developmental model relating distressing PLEs in youth with difficulties in cognitive functioning. This highlights the potential utility of adjunctive cognitive strategies which target mechanisms associated with PLE distress. These could be included in cognitive-behavioural interventions offered prior to the development of an at-risk mental state in mental health, educational or public health settings.


Assuntos
Serviços de Saúde do Adolescente , Terapia Cognitivo-Comportamental , Serviços de Saúde Mental , Transtornos Psicóticos , Adolescente , Criança , Pré-Escolar , Cognição , Humanos , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Adulto Jovem
6.
Biochem Pharmacol ; 188: 114517, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33722535

RESUMO

Dipeptidyl peptidase (DPP)-4 inhibitors are a class of orally available, small molecule inhibitors that prolong the insulinotropic activity of the incretin hormone glucagon-like peptide-1 (GLP-1) and are highly effective for the treatment of Type-2 diabetes. DPP4 can also cleave several immunoregulatory peptides including chemokines. Emerging evidence continues to implicate DPP4 inhibitors as immunomodulators, with recent findings suggesting DPP4 inhibitors modify specific aspects of innate immunity. This review summarises recent insights into how DPP4 inhibitors could be implicated in endothelial, neutrophil and monocyte/macrophage mediated immunity. Additionally, this review highlights additional avenues of research with DPP4 inhibitors in the context of the COVID-19 pandemic.


Assuntos
Tratamento Farmacológico da COVID-19 , Inibidores da Dipeptidil Peptidase IV/farmacologia , Imunidade Inata/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , COVID-19/imunologia , Inibidores da Dipeptidil Peptidase IV/química , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/imunologia , Humanos , Imunidade Inata/imunologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , SARS-CoV-2/imunologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-27343357

RESUMO

The Pacific oyster Crassostrea gigas was introduced from Japan to many countries in the world for oyster farming, resulting in the establishment of wild populations in intertidal zones and resource competition with local faunas. This study examined physiological responses of wild oysters and farmed oysters to thermal (15°C, 25°C, 37°C and 44°C) and salinity stress (39, 50 and 60ppt). The wild oysters produced more 72kDa heat shock proteins when the temperature increased from 15°C to 25°C and 37°C and the salinity increased from 39 to 50 and 60ppt. However, the amount of 69kDa heat shock protein was similar between farmed and wild oysters when the temperature increased from 15°C to the sublethal temperature 37°C, but it was lower in wild oysters than in farmed oysters when the temperature increased from 15°C to the lethal temperature 44°C. In the tissues, wild oysters used more glycogen to promote metabolic activities by increasing the level of AEC (adenylate energy charge). The results suggest that farmed oysters might have limited ability to cope with heat stress due to low energy reserve and glycolysis activity for HSP synthesis. This study provides experimental evidence on differential responses between wild and farmed oysters to temperature and salinity changes, leading to a better understanding on the pattern of distribution for invading oyster species in the marine environment and the adaptation of marine invertebrates to the threat of climate change.


Assuntos
Crassostrea/fisiologia , Aclimatação , Adaptação Fisiológica , Nucleotídeos de Adenina/metabolismo , Animais , Animais Selvagens , Aquicultura , Mudança Climática , Metabolismo Energético , Glicogênio/metabolismo , Proteínas de Choque Térmico/biossíntese , Temperatura Alta , Japão , Salinidade , Estresse Fisiológico , Temperatura
8.
Mol Ecol Resour ; 16(6): 1322-1339, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27106775

RESUMO

Improving our understanding of species responses to environmental changes is an important contribution ecologists can make to facilitate effective management decisions. Novel synthetic approaches to assessing biodiversity and ecosystem integrity are needed, ideally including all species living in a community and the dynamics defining their ecological relationships. Here, we present and apply an integrative approach that links high-throughput, multicharacter taxonomy with community ecology. The overall purpose is to enable the coupling of biodiversity assessments with investigations into the nature of ecological interactions in a community-level data set. We collected 1195 gastropods and crabs in British Columbia. First, the General mixed Yule-coalescent (GMYC) and the Poisson Tree Processes (PTP) methods for proposing primary species-hypotheses based on cox1 sequences were evaluated against an integrative taxonomic framework. We then used data on the geographic distribution of delineated species to test species co-occurrence patterns for nonrandomness using community-wide and pairwise approaches. Results showed that PTP generally outperformed GMYC and thus constitutes a more effective option for producing species-hypotheses in community-level data sets. Nonrandom species co-occurrence patterns indicative of ecological relationships or habitat preferences were observed for grazer gastropods, whereas assemblages of carnivorous gastropods and crabs appeared influenced by random processes. Species-pair associations were consistent with current ecological knowledge, thus suggesting that applying community assembly within a large taxonomical framework constitutes a valuable tool for assessing ecological interactions. Combining phylogenetic, morphological and co-occurrence data enabled an integrated view of communities, providing both a conceptual and pragmatic framework for biodiversity assessments and investigations into community dynamics.


Assuntos
Biodiversidade , Braquiúros/classificação , Exposição Ambiental , Gastrópodes/classificação , Animais , Braquiúros/anatomia & histologia , Braquiúros/genética , Colúmbia Britânica , Gastrópodes/anatomia & histologia , Gastrópodes/genética , Genética Populacional , Análise de Sequência de DNA
9.
Exp Eye Res ; 146: 289-292, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26965224

RESUMO

It has been established that beyond middle age, mice are slower to recover inner retinal function following an acute intraocular pressure (IOP) injury. While 3 month old animals exhibit near-complete recovery 1 week following injury, 12 and 18 month old animals demonstrate prolonged inner retinal dysfunction. In this study we aim to determine whether age-related differences in functional recovery of the inner retina are due to differences in retinal ganglion cell (RGC) axonal transport. C57BL/6J mice at 3 (n = 8) and 18 months (n = 8) of age were used. At day 0, right eyes were cannulated and the IOP was maintained at 50 mmHg for 30 min. At day 5, mice received bilateral intravitreal injections of choleratoxin subunit B (CTB) conjugated to Alexafluor 488. At day 7, mice were euthanized and tissue was collected. Axonal transport of CTB was quantified in retinas and superior colliculi (SC) using fluorescent microscopy. In response to IOP elevation, the overall degree of axonal transport was comparable between young and old mice. Furthermore, no differences in axonal transport were detected between control eyes and injured in mice at any age. In conclusion, impaired recovery of inner retinal function 1 week following acute IOP injury in old mice is not associated with changes in active axonal transport in RGCs at this time.


Assuntos
Envelhecimento/fisiologia , Transporte Axonal/fisiologia , Traumatismos do Nervo Óptico/fisiopatologia , Recuperação de Função Fisiológica/fisiologia , Doenças Retinianas/fisiopatologia , Células Ganglionares da Retina/fisiologia , Animais , Modelos Animais de Doenças , Eletrorretinografia , Pressão Intraocular/fisiologia , Camundongos , Camundongos Endogâmicos C57BL
10.
Transl Psychiatry ; 4: e483, 2014 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-25405780

RESUMO

Previous animal models and structural imaging investigations have linked hippocampal neuroplasticity to electroconvulsive therapy (ECT) response, but the relationship between changes in hippocampal volume and temporal coherence in the context of ECT response is unknown. We hypothesized that ECT response would increase both hippocampal resting-state functional magnetic resonance imaging connectivity and hippocampal volumes. Patients with major depressive disorder (n=19) were scanned before and after the ECT series. Healthy, demographically matched comparisons (n=20) were scanned at one-time interval. Longitudinal changes in functional connectivity of hippocampal regions and volumes of hippocampal subfields were compared with reductions in ratings of depressive symptoms. Right hippocampal connectivity increased (normalized) after the ECT series and correlated with depressive symptom reduction. Similarly, the volumes of the right hippocampal cornu ammonis (CA2/3), dentate gyrus and subiculum regions increased, but the hippocampal subfields were unchanged relative to the comparison group. Connectivity changes were not evident in the left hippocampus, and volume changes were limited to the left CA2/3 subfields. The laterality of the right hippocampal functional connectivity and volume increases may be related to stimulus delivery method, which was predominately right unilateral in this investigation. The findings suggested that increased hippocampal functional connectivity and volumes may be biomarkers for ECT response.


Assuntos
Transtorno Depressivo Maior/terapia , Eletroconvulsoterapia , Hipocampo/patologia , Hipocampo/fisiopatologia , Plasticidade Neuronal/fisiologia , Idoso , Mapeamento Encefálico , Transtorno Depressivo Maior/patologia , Transtorno Depressivo Maior/fisiopatologia , Eletroconvulsoterapia/métodos , Feminino , Hipocampo/anatomia & histologia , Hipocampo/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
11.
Artigo em Inglês | MEDLINE | ID: mdl-24614024

RESUMO

Heat shock proteins (HSPs) are sensitive and readily produced under thermal stress in many fish species and thus serve as a useful stress bio-indicator. Two experiments were conducted to test the hypothesis that King George whiting (KGW) Sillaginodes punctata approaching sexual maturity exhibits a decrease in HSP production and that exposure to high temperatures provokes HSP production in juvenile whiting. Both adult and juvenile whiting expressed significant increases in HSP69 in response to temperature shocks of 24, 26, 28 and 30 °C. Juvenile whiting had significantly higher HSP69 than adults and expressed more HSP69 at 24 and 26 °C. No mortalities were observed in juvenile fish at 30 °C while 50% of adults suffered mortality at 30 °C. Following exposure of juveniles to 24, 26 and 28 °C, HSP69 was measured at 24, 96 and 168 h. HSP69 peaked at 96 h and returned to the 24h level after 168 h exposure. This study indicates that juveniles can cope with high temperatures better than adults, which offers a partial explanation to fish movement patterns in nature where younger fish inhabit near shore waters and then migrate to deep water towards maturation. Further, this work implies that KGW growth and recruitment can be affected by increasing temperatures due to global warming.


Assuntos
Envelhecimento/genética , Proteínas de Choque Térmico/biossíntese , Perciformes/fisiologia , Envelhecimento/fisiologia , Animais , Aquecimento Global , Proteínas de Choque Térmico/genética , Temperatura Alta , Perciformes/genética , Água
12.
Curr Med Chem ; 20(3): 428-37, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23157635

RESUMO

The evidence that antipsychotics improve brain function and reduce symptoms in schizophrenia is unmistakable, but how antipsychotics change brain function is poorly understood, especially within neuronal systems. In this review, we investigated the hypothesized normalization of the functional magnetic resonance imaging (fMRI) blood oxygen level dependent signal in the context of antipsychotic treatment. First, we conducted a systematic PubMed search to identify eight fMRI investigations that met the following inclusion criteria: case-control, longitudinal design; pre- and post-treatment contrasts with a healthy comparison group; and antipsychotic-free or antipsychotic-naive patients with schizophrenia at the start of the investigation. We hypothesized that aberrant activation patterns or connectivity between patients with schizophrenia and healthy comparisons at the first imaging assessment would no longer be apparent or "normalize" at the second imaging assessment. The included studies differed by analysis method and fMRI task but demonstrated normalization of fMRI activation or connectivity during the treatment interval. Second, we reviewed putative mechanisms from animal studies that support normalization of the BOLD signal in schizophrenia. We provided several neuronal-based interpretations of these changes of the BOLD signal that may be attributable to long-term antipsychotic administration.


Assuntos
Antipsicóticos/uso terapêutico , Imageamento por Ressonância Magnética , Interpretação Psicanalítica , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Animais , Humanos , Oxigênio/sangue
13.
Diabet Med ; 29(12): 1550-2, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22672290

RESUMO

AIMS: To compare the Ipswich Touch Test and the VibraTip with the Neuropathy Disability Score and the vibration perception threshold for detecting the 'at-risk' foot. METHODS: We directly compared the Ipswich Touch Test and the VibraTip with both the Neuropathy Disability Score ≥ 6 and the vibration perception threshold ≥ 25 V indicating 'at-risk' feet in 83 individuals. RESULTS: The vibration perception threshold and Neuropathy Disability Score tests exhibited almost perfect agreement with each other (P < 0.001). The VibraTip and Ipswich Touch Test results were identical (P < 0.001). The VibraTip and Ipswich Touch Test results also exhibited almost perfect agreement with the vibration perception threshold (P < 0.001) and the Neuropathy Disability Score (P < 0.001). CONCLUSIONS: These two simple and efficient tests are easy to teach, reliable and can be used in any setting, and neither requires an external power source. We conclude that both the VibraTip and the Ipswich Touch Test are reliable and sensitive tests for identifying the 'high-risk' foot.


Assuntos
Pé Diabético/fisiopatologia , Pacientes Ambulatoriais/estatística & dados numéricos , Vibração , Idoso , Índice de Massa Corporal , Pé Diabético/diagnóstico , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Medição de Risco , Sensibilidade e Especificidade , Limiar Sensorial
14.
Eur J Vasc Endovasc Surg ; 43(6): 721-5, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22507925

RESUMO

OBJECTIVES: To compare the half-life of STD and polidocanol air-based foams and the damage they inflict upon human great saphenous vein in an in-vitro model. METHODS: The time for the volume of 3% STD and polidocanol foams to reduce by 10% (T(90)) and 50% (T(50)) was recorded in an incubator at 37 °C. Segments of proximal GSV harvested during varicose vein surgery were filled with foam for 5 or 15 min. Histological analysis determined percentage endothelial cell loss and depth of media injury. RESULTS: Median (±IQR) T(90) and T(50) for polidocanol were 123.3 s (111.7-165.6) and 266.3 s (245.6-383.1) versus 102.03 s (91.1-112) and 213.13 s (201-231.6) for STD (T(90)p = 0.008, T(50)p = 0.004). Median endothelial loss with polidocanol was; 63.5% (62.2-82.8) and 85.9% (83.8-92.5) versus 86.3% (84.8-93.7) and 97.64% (97.3-97.8) for STD after 5 and 15 min (p = 0.076 and p = 0.009). The median depth and % media thickness injured were 0 µm (0-0 µm) and 0% for both assessments with polidocanol versus 37.4 µm (35.3-45.8 and 43.4 µm (42.1-46.7) and 3.5% (3.1-3.6) and 5.3% (3.7-6.0) after 5 and 15 min for STD (p < 0.01 for all comparisons). CONCLUSION: Although polidocanol foam shows greater stability than STD foam perhaps remaining in the vein for longer, endothelial cell loss and damage to the media were significantly greater with STD.


Assuntos
Polietilenoglicóis/farmacologia , Veia Safena/efeitos dos fármacos , Soluções Esclerosantes/farmacologia , Escleroterapia/métodos , Tetradecilsulfato de Sódio/farmacologia , Estabilidade de Medicamentos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Meia-Vida , Humanos , Técnicas In Vitro , Polidocanol , Polietilenoglicóis/química , Veia Safena/patologia , Soluções Esclerosantes/química , Tetradecilsulfato de Sódio/química , Fatores de Tempo , Túnica Média/efeitos dos fármacos , Túnica Média/patologia
15.
Nat Nanotechnol ; 6(12): 824-33, 2011 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-22056725

RESUMO

The use of nanoparticles in medicine is ever increasing, and it is important to understand their targeted and non-targeted effects. We have previously shown that nanoparticles can cause DNA damage to cells cultured below a cellular barrier without crossing this barrier. Here, we show that this indirect DNA damage depends on the thickness of the cellular barrier, and it is mediated by signalling through gap junction proteins following the generation of mitochondrial free radicals. Indirect damage was seen across both trophoblast and corneal barriers. Signalling, including cytokine release, occurred only across bilayer and multilayer barriers, but not across monolayer barriers. Indirect toxicity was also observed in mice and using ex vivo explants of the human placenta. If the importance of barrier thickness in signalling is a general feature for all types of barriers, our results may offer a principle with which to limit the adverse effects of nanoparticle exposure and offer new therapeutic approaches.


Assuntos
Ligas de Cromo/efeitos adversos , Citocinas/metabolismo , Dano ao DNA , Nanopartículas Metálicas/efeitos adversos , Animais , Ligas de Cromo/metabolismo , Conexinas/metabolismo , Córnea/metabolismo , Radicais Livres/metabolismo , Humanos , Bicamadas Lipídicas/química , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Oligopeptídeos , Transdução de Sinais , Trofoblastos/metabolismo
16.
Transplant Proc ; 43(5): 1418-20, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21693209

RESUMO

BACKGROUND: Increased awareness of organ donation/transplantation has been found to have a positive influence on organ donation rates. One Life … Many Gifts is a curriculum resource in Ontario, Canada, to educate and raise awareness for senior secondary school students about the importance of organ and tissue donation and transplantation. Teachers administered pre- and post- attitudinal surveys to senior secondary school students to evaluate changes in their attitudes toward organ and tissue donation and transplantation. In this study, the effect of the One Life … Many Gifts educational intervention on changing the attitudes and awareness of organ donation and transplantation of senior secondary students was assessed. METHODS: Mann-Whitney U tests were used to compare the pre- and post-surveys as a whole and then again for the data from individual schools. Kruskal-Wallis H-tests were used to compare data between schools. RESULTS: A total of 1832 pre- and 1440 post-educational surveys returned to Trillium Gift of Life Network were assessed in the 2008-2009 academic year. Overall, comparison of all pre- and post-educational program survey data showed significant improvement in the students' attitudes toward organs and tissue donation and transplantation (P = .00625). CONCLUSION: The One Life … Many Gifts program made an impact on changing the attitudes toward and awareness of organ donation among high school students in Ontario. Evaluation of its impact on donor registration and organ donation among the students and their parents is complex and remains to be seen.


Assuntos
Atitude Frente a Saúde , Transplante de Órgãos/psicologia , Estudantes/psicologia , Transplante de Tecidos/psicologia , Adolescente , Humanos , Ontário , Inquéritos e Questionários
17.
Scand J Immunol ; 73(2): 102-11, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21198750

RESUMO

Human CD26 has dipeptidyl peptidase-4 (DPP IV) enzyme activity and binds to adenosine deaminase (ADA). CD26 is costimulatory for lymphocytes and has a circulating soluble form (sCD26). DPP IV enzyme inhibition is a new successful type 2 diabetes therapy. We examined whether the ADA binding and catalytic functions of sCD26 contribute to its effects on T-cell proliferation. Wildtype soluble recombinant human CD26 (srhCD26), an enzyme inactive mutant (srhCD26E-) and an ADA non-binding mutant (srhCD26A-) were co-incubated in in vitro T-cell proliferation assays with peripheral blood mononuclear cells (PBMC) stimulated with phytohaemagglutinin (PHA), muromonab-CD3 or Herpes simplex virus antigen (HSV Ag). Both srhCD26 and srhCD26E- enhanced PHA-induced T-cell proliferation dose-dependently in all six subjects tested. srhCD26 and srhCD26A- had no overall effect on anti-CD3-stimulated PBMC proliferation in four of five subjects. srhCD26, srhCD26E- and srhCD26A- enhanced HSV Ag induced PBMC proliferation in low responders to HSV Ag, but had no effect or inhibited proliferation in HSV-high responders. Thus, effects of soluble human CD26 on human T-cell proliferation are mechanistically independent of both the enzyme activity and the ADA-binding capability of sCD26.


Assuntos
Adenosina Desaminase/metabolismo , Proliferação de Células , Dipeptidil Peptidase 4/imunologia , Linfócitos/citologia , Linfócitos/imunologia , Adulto , Células Cultivadas , Dipeptidil Peptidase 4/metabolismo , Feminino , Humanos , Ativação Linfocitária , Linfócitos/enzimologia , Masculino , Pessoa de Meia-Idade , Ligação Proteica , Solubilidade , Adulto Jovem
18.
Prog Neuropsychopharmacol Biol Psychiatry ; 35(2): 473-82, 2011 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-21185903

RESUMO

BACKGROUND: The effect of antipsychotics on the blood oxygen level dependent signal in schizophrenia is poorly understood. The purpose of the present investigation is to examine the effect of antipsychotic medication on independent neural networks during a motor task in a large, multi-site functional magnetic resonance imaging investigation. METHODS: Seventy-nine medicated patients with schizophrenia and 114 comparison subjects from the Mind Clinical Imaging Consortium database completed a paced, auditory motor task during functional magnetic resonance imaging (fMRI). Independent component analysis identified temporally cohesive but spatially distributed neural networks. The independent component analysis time course was regressed with a model time course of the experimental design. The resulting beta weights were evaluated for group comparisons and correlations with chlorpromazine equivalents. RESULTS: Group differences between patients and comparison subjects were evident in the cortical and subcortical motor networks, default mode networks, and attentional networks. The chlorpromazine equivalents correlated with the unimotor/bitemporal (rho=-0.32, P=0.0039), motor/caudate (rho=-0.22, P=0.046), posterior default mode (rho=0.26, P=0.020), and anterior default mode networks (rho=0.24, P=0.03). Patients on typical antipsychotics also had less positive modulation of the motor/caudate network relative to patients on atypical antipsychotics (t(77)=2.01, P=0.048). CONCLUSION: The results suggest that antipsychotic dose diminishes neural activation in motor (cortical and subcortical) and default mode networks in patients with schizophrenia. The higher potency, typical antipsychotics also diminish positive modulation in subcortical motor networks. Antipsychotics may be a potential confound limiting interpretation of fMRI studies on the disease process in medicated patients with schizophrenia.


Assuntos
Estimulação Acústica , Antipsicóticos/uso terapêutico , Encéfalo/efeitos dos fármacos , Córtex Cerebral/fisiopatologia , Imageamento por Ressonância Magnética , Córtex Motor/efeitos dos fármacos , Esquizofrenia/fisiopatologia , Adulto , Antipsicóticos/classificação , Encéfalo/fisiopatologia , Córtex Cerebral/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Esquizofrenia/tratamento farmacológico , Adulto Jovem
19.
Philos Trans A Math Phys Eng Sci ; 368(1924): 3551-65, 2010 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-20603367

RESUMO

Emerging technologies offer new solutions to the construction industry, improving processes, enabling automation and effective decision-making mechanisms and changing current ways of work. Previous research has tended to consider a direct causal relationship between the emerging and prospective technologies and the future of construction. However, the future of construction will be influenced not only by the developments in the information technology (IT) industry, but also by other technological changes. Societal, economic, environmental and political factors will shape the future, together with emerging technologies. This paper presents a scenario-planning exercise that aimed to identify possible futures that the construction industry might face. In order to achieve the aims of the research, a literature review was carried out on scenario planning and future studies related to construction and construction IT, which was followed by a mini survey and two prospective workshops as part of the La Prospective scenario-planning approach. In a future study, it is important to understand the forces, issues and trends in order to inform and enable further thinking and action towards achieving a preferred future state whilst being prepared for what might be round the corner. Therefore, the paper first investigates the driving forces of change, main trends, issues and factors that might shape the future, focusing on factors related to society, technology, environment, economy and politics. Secondly, four future scenarios that were developed keeping these factors in mind are presented. The scenarios start from a global view and present the images of the future world in year 2030. They later focus on the construction industry, imagining how it will be shaped by the future world and trying to visualize the information and communication technology implications for construction. Finally, a preferred future scenario for 2030 is introduced based on the principle that the future can be influenced if we know what we want it to be. Focusing mainly on the IT vision, the paper concludes with recommendations in the areas related to innovation, communication and collaboration, education and training, process improvement, interoperability, user-centred IT and sustainability, in order to reach the desired state determined by the vision.

20.
J Fish Dis ; 33(6): 461-7, 2010 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-20367738

RESUMO

The molecular phylogeny of Gyrodactylus salmonis from brook charr, Salvelinus fontinalis, rainbow trout, Oncorhynchus mykiss, cutthroat trout, O. clarkii, and Atlantic salmon, Salmo salar, in Canada is presented using sequences from ITS-rDNA and the mitochondrial COX 1 gene. Sequence variation among G. salmonis specimens from the different North American hosts was consistent with within-species variation reported for other Gyrodactylus. Sequence data are compared to those from other members of the wageneri group parasitizing salmoniform fishes in northern Europe (G. derjavini, G. derjavinoides, G. lavareti, G. salaris, G. salvelini, G. teuchis and G. truttae) and Asia (G. brachymystacis). Sequence divergence between G. salmonis and the recently described G. salvelini on Arctic charr, Salvelinus alpinus, in Finland was consistent with within-species levels of variation in Gyrodactylus; however, phylogenetic analyses and morphological comparisons provided evidence of their distinctiveness such that they appear to be sister species. They grouped with G. lavareti (a parasite of a coregonid) to form a clade separate from European and Asian species of the wageneri lineage known from salmonid fish. Further study of gyrodactylids from across salmonid, coregonid and thymallid fish in the northern hemisphere would shed more light on the phylogeography of these parasites and serves as an important backdrop to understanding the evolution of their emergent virulence.


Assuntos
Doenças dos Peixes/parasitologia , Salmonidae , Trematódeos/classificação , Trematódeos/genética , Infecções por Trematódeos/veterinária , Animais , Evolução Molecular , Filogenia , Trematódeos/anatomia & histologia , Infecções por Trematódeos/parasitologia
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