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The phylogenetic tree (Figure 7) in the published document has incorrect Bayesian analysis posterior probabilities. This error prevents accurate analysis by future research in parasitology. The figure is therefore replaced by the corrected figure below.
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Delta opioid receptor (DOR) displays a unique, highly conserved, structure and an original pattern of distribution in the central nervous system, pointing to a distinct and specific functional role among opioid peptide receptors. Over the last 15 years, in vivo pharmacology and genetic models have allowed significant advances in the understanding of this role. In this review, we will focus on the involvement of DOR in modulating different types of hippocampal- and striatal-dependent learning processes as well as motor function, motivation, and reward. Remarkably, DOR seems to play a key role in balancing hippocampal and striatal functions, with major implications for the control of cognitive performance and motor function under healthy and pathological conditions.
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Aprendizagem/fisiologia , Motivação/fisiologia , Receptores Opioides delta/fisiologia , Animais , Humanos , Aprendizagem/efeitos dos fármacos , Motivação/efeitos dos fármacos , Receptores Opioides delta/biossíntese , Receptores Opioides delta/efeitos dos fármacos , RecompensaRESUMO
The ornamental fish trade provides a pathway for the global translocation of aquatic parasites. We examined a total of 1020 fish imported from Singapore, Malaysia, Thailand, or Sri Lanka to Australia (including freshwater and marine fish species) for monogenean ectoparasites. Fish were received following veterinary certification that they showed no clinical signs of pests and diseases from the exporting country and visual inspection at Australian border control. Australian import conditions require mandatory treatment for goldfish with parasiticides (e.g. trichlorfon, formaldehyde, sodium chloride) for the presence of gill flukes (Dactylogyrus vastator Nybelin, 1924 and Dactylogyrus extensus Mueller and Van Cleave, 1932) prior to export. Over 950 individual parasites were detected in five imported fish species, representing 14 monogenean species. Seven Dactylogyrus spp. including D. vastator and three Gyrodactylus spp. infected goldfish, Carassius auratus Linnaeus, 1758, from Malaysia, Singapore, and Thailand. Dactylogyrus ostraviensis Rehulka, 1988, infected rosy barb, Pethia conchonius Hamilton, 1822, from Singapore, Sri Lanka, and Thailand while two Trianchoratus spp. infected three spot gourami, Trichopodus trichopterus Pallas, 1970 and pearl gourami Trichopodus leerii Bleeker, 1852, from Sri Lanka. Urocleidoides reticulatus Mizelle & Price, 1964, infected guppy, Poecilia reticulata Peters, 1859, from Sri Lanka. The discovery of D. vastator in goldfish, as well as 13 other monogenean species, shows that pre-export health requirements, which include chemical treatment of goldfish, and inspection of all ornamental fish species did not prevent infection by monogeneans. Inspection prior to exportation and at border control must account for the highly cryptic nature of monogenean parasites and consider alternatives to current pre-export conditions and visual inspection at border control.
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Antiparasitários/farmacologia , Infecções por Cestoides/prevenção & controle , Doenças dos Peixes/parasitologia , Brânquias/parasitologia , Carpa Dourada/parasitologia , Platelmintos/isolamento & purificação , Poecilia/parasitologia , Infecções por Trematódeos/prevenção & controle , Animais , Sudeste Asiático , Austrália , Infecções por Cestoides/parasitologia , Infecções por Cestoides/veterinária , Comércio , Doenças dos Peixes/diagnóstico , Água Doce , Infecções por Trematódeos/parasitologia , Infecções por Trematódeos/veterináriaRESUMO
Megalocytiviruses cause high mortality diseases that have seriously impacted aquaculture, with the most frequent outbreaks occurring in East and South-East Asia. The international trade of juvenile fish for food and ornamental aquaculture has aided the spread of these viruses, which have spread to Europe and Australia and other regions. Australian freshwater fishes were examined for susceptibility to infection with the exotic megalocytivirus, dwarf gourami iridovirus (DGIV), which belongs to a group with the type species, Infectious spleen and kidney necrosis virus (ISKNV). Fish were held at 23 ± 1 °C and challenged by intraperitoneal (IP) injection or by cohabitation with Murray cod, Maccullochella peelii (Mitchell) infected with DGIV. A species was deemed to be susceptible to DGIV based on evidence of viral replication, as determined by qPCR, and megalocytic inclusion bodies observed histologically. Horizontal transmission occurred between infected Murray cod and golden perch, Macquaria ambigua (Richardson), Macquarie perch, Macquaria australasica (Cuvier) and Murray cod. This indicated that DGIV shed from infected fish held at 23 °C can survive in fresh water and subsequently infect these naïve fish. Further, DGIV administered IP was highly pathogenic to golden perch, Macquarie perch and Murray cod. Compared to these species, the susceptibility of southern pygmy perch, Nannoperca australis (Gunther) was lower. Freshwater catfish (dewfish), Tandanus tandanus (Mitchell), were not susceptible under the experimental conditions based on the absence of clinical disease, mortality and virus replication. This study showed the potential risks associated with naïve and DGIV-infected fish sharing a common water source.
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Peixes-Gato , Infecções por Vírus de DNA/veterinária , Doenças dos Peixes/transmissão , Iridoviridae/fisiologia , Perciformes , Animais , Austrália , Infecções por Vírus de DNA/transmissão , Infecções por Vírus de DNA/virologia , Suscetibilidade a Doenças/veterinária , Suscetibilidade a Doenças/virologia , Doenças dos Peixes/virologia , Água DoceRESUMO
The neutron capture cross section of (235)U was measured for the neutron incident energy region between 4 eV and 1 MeV at the DANCE facility at the Los Alamos Neutron Science Center with an unprecedented accuracy of 2-3% at 1 keV. The new methodology combined three independent measurements. In the main experiment, a thick actinide sample was used to determine neutron capture and neutron-induced fission rates simultaneously. In the second measurement, a fission tagging detector was used with a thin actinide sample and detailed characteristics of the prompt-fission gamma rays were obtained. In the third measurement, the neutron scattering background was characterized using a sample of (208)Pb. The relative capture cross section was obtained from the experiment with the thick (235)U sample using a ratio method after the subtraction of the fission and neutron scattering backgrounds. Our result indicates errors that are as large as 30% in the 0.5-2.5 keV region, in the current knowledge of neutron capture as embodied in major nuclear data evaluations. Future modifications of these databases using the improved precision data given herein will have significant impacts in neutronics calculations for a variety of nuclear technologies.
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Viruses in three genera of the family Iridoviridae (iridoviruses) affect finfish. Ranaviruses and megalocytiviruses are recently emerged pathogens. Both cause severe systemic disease, occur globally and affect a diversity of hosts. In contrast, lymphocystiviruses cause superficial lesions and rarely cause economic loss. The ranavirus epizootic haematopoietic necrosis virus (EHNV) from Australia was the first iridovirus to cause epizootic mortality in finfish. Like other ranaviruses, it lacks host specificity. A distinct but closely related virus, European catfish virus, occurs in finfish in Europe, while very similar ranaviruses occur in amphibians in Europe, Asia, Australia, North America and South America. These viruses can be distinguished from one another by conserved differences in the sequence of the major capsid protein gene, which informs policies of the World Organisation for Animal Health to minimize transboundary spread of these agents. However, limited epidemiological information and variations in disease expression create difficulties for design of sampling strategies for surveillance. There is still uncertainty surrounding the taxonomy of some putative ranaviruses such as Singapore grouper iridovirus and Santee-Cooper ranavirus, both of which cause serious disease in fish, and confusion continues with diseases caused by megalocytiviruses. In this review, aspects of the agents and diseases caused by ranaviruses are contrasted with those due to megalocytiviruses to promote accurate diagnosis and characterization of the agents responsible. Ranavirus epizootics in amphibians are also discussed because of possible links with finfish and common anthropogenic mechanisms of spread. The source of the global epizootic of disease caused by systemic iridoviruses in finfish and amphibians is uncertain, but three possibilities are discussed: trade in food fish, trade in ornamental fish, reptiles and amphibians and emergence from unknown reservoir hosts associated with environmental change.
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Infecções por Vírus de DNA/veterinária , Doenças dos Peixes/virologia , Ranavirus/fisiologia , Anfíbios/virologia , Animais , Anticorpos Antivirais , Infecções por Vírus de DNA/epidemiologia , Infecções por Vírus de DNA/prevenção & controle , Infecções por Vírus de DNA/transmissão , Reservatórios de Doenças/veterinária , Suscetibilidade a Doenças , Doenças dos Peixes/epidemiologia , Doenças dos Peixes/prevenção & controle , Doenças dos Peixes/transmissão , Peixes/virologia , Prevalência , Ranavirus/classificação , Ranavirus/genética , Ranavirus/patogenicidade , Répteis/virologiaRESUMO
Effective border control relies on stringent biosecurity protocols to detect and prevent introductions of exotic pests and diseases. Detection of pathogens and parasites in the live ornamental fish trade using environmental DNA (eDNA) techniques has the potential to improve current biosecurity practices. We examined water samples from 11 target consignments (cyprinids susceptible to Dactylogyrus spp. infections) and seven non-target fish consignments (non-cyprinids, not susceptible to Dactylogyrus spp. infections) imported from Southeast Asia to Australia for the presence of eDNA from five Dactylogyrus species (Monogenea: Dactylogyridae). A four-step predictive framework was used to predict putative positive and putative negative detections from quantitative PCR assays. Both target and non-target consignments were positive for Dactylogyrus spp. eDNA as confirmed by Sanger sequencing. Positive detections for Dactylogyrus spp. eDNA in non-target fish consignments demonstrates the possibility of source water contamination, limiting the applicability of eDNA screening methods at border control. This study suggests that screening for parasite eDNA within ornamental fish consignments should be tested during pre-export quarantine periods to avoid false positive detections at border control. Lastly, the proposed predictive framework has a broad utility for minimizing false positive and false negative eDNA detections of aquatic organisms.
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Cyprinidae/parasitologia , DNA Ambiental/genética , Doenças dos Peixes/parasitologia , Pesqueiros/economia , Parasitos/isolamento & purificação , Animais , Temperatura de TransiçãoRESUMO
Addiction develops from the gradual adaptation of the brain to chronic drug exposure, and involves genetic reprogramming of neuronal function. The central extended amygdala (EAc) is a network formed by the central amygdala and the bed nucleus of the stria terminalis. This key site controls drug craving and seeking behaviors, and has not been investigated at the gene regulation level. We used Affymetrix microarrays to analyze transcriptional activity in the murine EAc, with a focus on mu-opioid receptor-associated events because these receptors mediate drug reward and dependence. We identified 132 genes whose expression is regulated by a chronic escalating morphine regimen in the EAc from wild-type but not mu-opioid receptor knockout mice. These modifications are mostly EAc-specific. Gene ontology analysis reveals an overrepresentation of neurogenesis, cell growth and signaling protein categories. A separate quantitative PCR analysis of genes in the last of these groups confirms the dysregulation of both orphan (Gpr88) and known (DrD1A, Adora2A, Cnr1, Grm5, Gpr6) G protein-coupled receptors, scaffolding (PSD95, Homer1) and signaling (Sgk, Cap1) proteins, and neuropeptides (CCK, galanin). These transcriptional modifications do not occur following a single morphine injection, and hence result from long-term adaptation to excessive mu receptor activation. Proteins encoded by these genes are classically associated with spine modules function in other brain areas, and therefore our data suggest a remodeling of EAc circuits at sites where glutamatergic and monoaminergic afferences interact. Together, mu receptor-dependent genes identified in this study potentially contribute to drug-induced neural plasticity, and provide a unique molecular repertoire towards understanding drug craving and relapse.
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Tonsila do Cerebelo/efeitos dos fármacos , Analgésicos Opioides/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Receptores Opioides mu/agonistas , Ativação Transcricional/efeitos dos fármacos , Tonsila do Cerebelo/metabolismo , Animais , Regulação da Expressão Gênica/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Morfina/farmacologia , Vias Neurais/efeitos dos fármacos , Vias Neurais/metabolismo , Plasticidade Neuronal/genética , Análise de Sequência com Séries de Oligonucleotídeos , Transtornos Relacionados ao Uso de Opioides/genética , Transtornos Relacionados ao Uso de Opioides/metabolismo , Transtornos Relacionados ao Uso de Opioides/fisiopatologia , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Opioides mu/metabolismo , Núcleos Septais/efeitos dos fármacos , Núcleos Septais/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Ativação Transcricional/genéticaRESUMO
The central extended amygdala (EAc) is an ensemble of highly interconnected limbic structures of the anterior brain, and forms a cellular continuum including the bed nucleus of the stria terminalis (BNST), the central nucleus of the amygdala (CeA) and the nucleus accumbens shell (AcbSh). This neural network is a key site for interactions between brain reward and stress systems, and has been implicated in several aspects of drug abuse. In order to increase our understanding of EAc function at the molecular level, we undertook a genome-wide screen (Affymetrix) to identify genes whose expression is enriched in the mouse EAc. We focused on the less-well known BNST-CeA areas of the EAc, and identified 121 genes that exhibit more than twofold higher expression level in the EAc compared with whole brain. Among these, 43 genes have never been described to be expressed in the EAc. We mapped these genes throughout the brain, using non-radioactive in situ hybridization, and identified eight genes with a unique and distinct rostro-caudal expression pattern along AcbSh, BNST and CeA. Q-PCR analysis performed in brain and peripheral organ tissues indicated that, with the exception of one (Spata13), all these genes are predominantly expressed in brain. These genes encode signaling proteins (Adora2, GPR88, Arpp21 and Rem2), a transcription factor (Limh6) or proteins of unknown function (Rik130, Spata13 and Wfs1). The identification of genes with enriched expression expands our knowledge of EAc at a molecular level, and provides useful information to toward genetic manipulations within the EAc.
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Tonsila do Cerebelo/fisiologia , Perfilação da Expressão Gênica/métodos , Expressão Gênica/fisiologia , Proteínas do Tecido Nervoso/genética , Tonsila do Cerebelo/anatomia & histologia , Animais , Mapeamento Encefálico , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/metabolismo , Análise de Sequência com Séries de OligonucleotídeosRESUMO
The induced polarization of a beam of polar clusters or molecules passing through an electric or magnetic field region differs from the textbook Langevin-Debye susceptibility. This distinction, which is important for the interpretation of deflection and focusing experiments, arises because instead of acquiring thermal equilibrium in the field region, the beam ensemble typically enters the field adiabatically, i.e., with a previously fixed distribution of rotational states. We discuss the orientation of rigid symmetric top systems with a body-fixed electric or magnetic dipole moment. The analytical expression for their "adiabatic-entry" orientation is elucidated and compared with exact numerical results for a range of parameters. The differences between the polarization of thermodynamic and "adiabatic-entry" ensembles of prolate and oblate tops, and of symmetric top and linear rotators, are illustrated and identified.
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Large-scale transcriptome analysis in the brain is a powerful approach to identify novel genes of potential interest toward understanding cerebral organization and function. We utilized the microarray technology to measure expression levels of about 24,000 genes and expressed sequence tags in mouse hippocampus, frontal cortex and striatum. Using expression profile obtained from whole brain as a reference, we categorized the genes into groups of genes either enriched in, or restricted to, one of the three areas of interest. We found enriched genes for each target area. Further, we identified 14 genes in the category of genes restricted to the striatum, among which were the orphan G protein-coupled receptor GPR88 and retinoic acid receptor-beta. These two genes were already reported to be selectively expressed in the striatum, thus validating our experimental approach. We selected 6 striatal-restricted genes, as well as 10 striatal-enriched candidates, that were previously undescribed. We analyzed their expression by in situ hybridization analysis in the brain, and quantitative RT-PCR in both brain and peripheral organs. Two of these unknown genes displayed a notable expression pattern. The striatal-restricted gene H3076B11 shows uniform expression throughout and uniquely in the striatum, representing a genuine striatal marker. The striatal-enriched gene 4833421E05Rik is preferentially expressed in the rostral striatum, and is also abundant in kidney, liver and lung. These two genes may contribute to some of the many striatal-controlled behaviors, including initiation of movement, habit formation, or reward and motivation.
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Química Encefálica/genética , Perfilação da Expressão Gênica , Neostriado/metabolismo , Proteínas do Tecido Nervoso/biossíntese , Animais , DNA Complementar/biossíntese , DNA Complementar/genética , Interpretação Estatística de Dados , Hibridização In Situ , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/genética , Análise de Sequência com Séries de Oligonucleotídeos , RNA/biossíntese , RNA/genética , Receptores do Ácido Retinoico/biossíntese , Receptores do Ácido Retinoico/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVE: To relate cerebral perfusion abnormalities to subsequent changes in clinical status among patients with mild cognitive impairment (MCI). METHODS: Perfusion single photon emission computed tomography (SPECT) images were acquired in 105 elderly patients without dementia with MCI, using 99mTc-HMPAO. Clinical outcome after a 5-year follow-up period was heterogeneous. RESULTS: Baseline SPECT data differed in those patients with MCI who were later diagnosed with Alzheimer's disease (the converter group) from those patients with MCI who experienced clinically evident decline but did not progress to a diagnosis of Alzheimer's disease within the follow-up period (the decliner group), from patients with MCI who had no clinical evidence of progression (the stable group), and from a group of 19 normal subjects (the control group). The most consistent decreases in relative perfusion in converters compared with the normal, stable and decliner groups were observed in the caudal anterior cingulate, and in the posterior cingulate. In addition, converters showed increased relative perfusion in the rostral anterior cingulate in comparison to the stable and decliner groups. A group of patients with Alzheimer's disease were also included for purposes of comparison. The group of patients with Alzheimer's disease at baseline differed from each of the other groups, with temporoparietal regions showing the most significant reductions in perfusion. CONCLUSIONS: These results suggest that clinical heterogeneity in MCI is reflected in SPECT perfusion differences, and that the pattern of perfusion abnormalities evolves with increasing clinical severity.
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Doença de Alzheimer/diagnóstico por imagem , Transtornos Cognitivos/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Idoso de 80 Anos ou mais , Encéfalo/irrigação sanguínea , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Compostos Radiofarmacêuticos , Fluxo Sanguíneo Regional , Tecnécio Tc 99m ExametazimaRESUMO
In this study, experiments were conducted to examine the effect of an acute necrotic bacterial gill infection on the metabolic rate (M(O2)) of Atlantic salmon Salmo salar. Fed and unfed Atlantic salmon smolts were exposed to a high concentration (5 x 10(12) CFU ml(-1)) of the bacteria Tenacibaculum maritimum, their routine and maximum metabolic rates (M(O2rout) and M(O2max), respectively) were measured, and relative metabolic scope determined. A significant decrease in metabolic scope was found for both fed and unfed infected groups. Fed infected fish had a mean +/- standard error of the mean (SEM) decrease of 2.21 +/- 0.97 microM O2 g(-1) h(-1), whilst unfed fish a mean +/- SEM decrease of 3.16 +/- 1.29 microM O2 g(-1) h(-1). The decrease in metabolic scope was a result of significantly increased M(O2rout) of both fed and unfed infected salmon. Fed infected fish had a mean +/- SEM increase in M(O2rout) of 1.86 +/- 0.66 microM O2 g(-1) h(-1), whilst unfed infected fish had a mean +/- SEM increase of 2.16 +/- 0.72 microM O2 g(-1) h(-1). Interestingly, all groups maintained M(O2max) regardless of infection status. Increases in M(O2rout) corresponded to a significant increase in blood plasma osmolality. A decrease in metabolic scope has implications for how individuals allocate energy; fish with smaller metabolic scope will have less energy to allocate to functions such as growth, reproduction and immune response, which may adversely affect the efficiency of fish growth.
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Infecções por Cytophagaceae/veterinária , Doenças dos Peixes/metabolismo , Doenças dos Peixes/microbiologia , Flexibacter/crescimento & desenvolvimento , Privação de Alimentos , Salmão/metabolismo , Animais , Infecções por Cytophagaceae/metabolismo , Infecções por Cytophagaceae/microbiologia , Metabolismo Energético , Brânquias/microbiologia , Necrose , Consumo de OxigênioRESUMO
The hypersensitive reaction (HR) is an inducible plant response that is associated with disease resistance. It is characterized by rapid, localized cell death at the site of infection and is believed to inhibit the spread of invading pathogens. We have isolated a cDNA clone, designated Hra32 (for hypersensitive reaction associated), corresponding to an RNA transcript that accumulates in bean during an HR. The predicted protein product of the Hra32 cDNA is an approximately 17 kDa protein of 161 amino acids, with four putative EF-hand calcium-binding domains. The temporal pattern of Hra32 transcript accumulation correlated closely with the onset of the HR in bean after inoculation with incompatible Pseudomonas syringae pv. tabaci and pv. tomato and with tobacco necrosis virus. Hra32 transcript also accumulated in bean in response to compatible P. syringae pv. phaseolicola and was correlated with necrotic cell death associated with disease lesion formation. A more transient pattern of Hra32 transcript accumulation occurred in bean in response to general stimuli that did not result in the HR or host cell death. These treatments included infiltration with a P. syringae pv. tabaci Hrp- mutant, P. syringae pv. tabaci cells treated with kanamycin, Escherichia coli, P. fluorescens, or glutathione, and in response to wounding. Thus, there was differential accumulation of the Hra32 transcript in response to specific stimuli resulting in the HR, compared with general stimuli that did not result in cell death. We hypothesize that the Hra32 product may be a component of the pathway that leads to hypersensitive cell death.
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Proteínas de Ligação ao Cálcio/genética , DNA Complementar/genética , DNA de Plantas/genética , Fabaceae/genética , Proteínas de Plantas/genética , Plantas Medicinais , Sequência de Aminoácidos , Morte Celular/genética , Fabaceae/citologia , Fabaceae/metabolismo , Expressão Gênica , Genes Bacterianos , Dados de Sequência Molecular , Doenças das Plantas/genética , Pseudomonas/genética , Pseudomonas/patogenicidade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA de Plantas/genética , RNA de Plantas/metabolismo , Homologia de Sequência de Aminoácidos , Virulência/genéticaRESUMO
We determined the factors related to left ventricular mass adjusted for body size in 60 black (mean age, 13 +/- 2 years) and 40 white (mean age, 14 +/- 2 years) normotensive youths. The factors examined included age, sex, systolic blood pressure, diastolic blood pressure, plasma renin activity, plasma aldosterone concentration, and sodium and potassium intake as determined by 24-hour excretion. Sex (beta = 13.3, P < .003), age (beta = 2.88, P < .001), and systolic blood pressure (beta = 0.41, P < .02) were independent predictors in the sample as a whole, accounting for 37% of the variance of left ventricular mass adjusted for height. Separate analyses were performed for black and white subjects. In the black subjects, age (beta = 4.4, P < .004) followed by sex (beta = 11.85, P < .02) were independent factors, accounting for 43% of the variance of left ventricular mass adjusted for height. In contrast, in white subjects systolic blood pressure (beta = 0.4, P < .003) followed by sodium excretion (beta = 0.13, P < .05) were independent factors, with gender (beta = 8.89, P < .07) tending to account for 36% of the variance. Similar results were observed for left ventricular mass adjusted for body surface area. In conclusion, the age-related increase in adjusted left ventricular mass in black but not white youths may in part account for the early development of cardiovascular disease among the black population.
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Envelhecimento/fisiologia , População Negra , Coração/anatomia & histologia , População Branca , Adolescente , Aldosterona/sangue , Pressão Sanguínea , Criança , Feminino , Ventrículos do Coração , Humanos , Masculino , Natriurese , Potássio/urina , Valores de Referência , Renina/sangueRESUMO
BACKGROUND: Regional cerebral perfusion measured by single photon emission computed tomography (SPECT) was examined as a preclinical predictor of the development of Alzheimer's disease (AD). METHODS: Singular value decomposition was used to produce 20 SPECT factors (known as vectors) (n=152). Vector scores were then computed for four groups (n=136), differing in cognitive status: Group 1--normal controls at both baseline and follow-up; Group 2--subjects with "questionable" AD at both baseline and follow-up; Group 3--subjects with questionable AD at baseline who converted to AD on follow-up (Converters); Group 4--subjects with AD at baseline. All SPECT data in the analyses were gathered at baseline. RESULTS: The four groups could be distinguished on the basis of their baseline SPECT data (p < or = 0.00005; hit rate=83%). Regional decreases in perfusion were most prominent among Converters in the hippocampal-amygdaloid complex, the posterior cingulate, the anterior thalamus, and the anterior cingulate. Inclusion of apolipoprotein E status did not significantly improve the discrimination. CONCLUSIONS: SPECT data gathered and analyzed in this manner may be useful as one aspect of the preclinical prediction of AD. Three of the four brain regions important for discriminating Converters from normal controls involve a distributed brain network pertaining to memory, suggesting that this network may be selectively affected in the earliest stages of AD.
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Doença de Alzheimer/diagnóstico , Doença de Alzheimer/fisiopatologia , Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Doença de Alzheimer/psicologia , Encéfalo/patologia , Análise Discriminante , Progressão da Doença , Feminino , Previsões , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes NeuropsicológicosRESUMO
Lyme encephalopathy (LE) presents with subtle neuropsychiatric symptoms months to years after onset of infection with Borrelia burgdorferi. Brain magnetic resonance images are usually normal. We asked whether quantitative single photon emission computed tomography (SPECT) is a useful method to diagnose LE, to measure the response to antibiotic therapy, and to determine its neuroanatomic basis. In 13 patients with objective evidence of LE, SPECT demonstrated reduced cerebral perfusion (mean perfusion defect index [PDI] = 255), particularly in frontal subcortical and cortical regions. Six months after treatment with 1 month of intravenous ceftriaxone, perfusion significantly improved in all 13 patients (mean PDI = 188). In nine patients with neuropsychiatric symptoms following Lyme disease, but without objective abnormalities (e.g., possible LE), perfusion was similar to that of the treated LE group (mean PDI = 198); six possible LE patients (67%) had already received ceftriaxone prior to our evaluation. Perfusion was significantly lower in patients with LE and possible LE than in 26 normal subjects (mean PDI = 136), but 4 normal subjects (15%) had low perfusion in the LE range. We conclude that LE patients have hypoperfusion of frontal subcortical and cortical structures that is partially reversed after ceftriaxone therapy. However, SPECT cannot be used alone to diagnose LE or determine the presence of active CNS infection.
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Encefalopatias/complicações , Isquemia Encefálica/etiologia , Isquemia Encefálica/fisiopatologia , Doença de Lyme/complicações , Adulto , Idoso , Encefalopatias/diagnóstico , Encefalopatias/microbiologia , Isquemia Encefálica/diagnóstico , Ceftriaxona/uso terapêutico , Cefalosporinas/uso terapêutico , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Doença de Lyme/diagnóstico , Doença de Lyme/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Transtornos Mentais/etiologia , Pessoa de Meia-Idade , Valores de Referência , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
To improve the diagnostic utility of brain single-photon emission computed tomography (SPECT) in Alzheimer's disease (AD), we have developed and evaluated an objective method of differentiating patients and healthy elderly controls using a quantitative image analysis protocol. HMPAO-SPECT image datasets from 29 patients with probable AD and 78 age-matched controls were registered to a common anatomic frame of reference. Activity levels within 120 standardized cortical volumes were determined by an automated procedure. Subjects were classified into normal and AD groups by quadratic discriminant analysis using two features: global average activity level and average normalized activity levels within the two clusters of standardized volumes identified as most significantly different in AD by analysis of covariance. The classification used split-half replication to ensure valid results. Classification performance quantified by the area under a binormal ROC curve fitted to the data was 0.923 +/- 0.036; at a threshold likelihood ratio of 1, the sample sensitivity was 91% and specificity was 86%. We conclude that quantitative SPECT accurately distinguishes AD patients from elderly controls.
Assuntos
Envelhecimento/patologia , Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Organotecnécio , Oximas , Tecnécio Tc 99m ExametazimaRESUMO
UNLABELLED: Artificial neural networks have been applied to a variety of pattern recognition tasks in medical imaging and have been shown to be a powerful classification tool. The potential usefulness to discriminate normal from abnormal cerebral perfusion patterns was investigated. METHODS: Cerebral perfusion imaging with 99mTc-labeled hexamethylpropyleneimine oxime was performed on 52 normal control subjects, 29 patients with clinically diagnosed Alzheimer's disease (AD) and 25 patients with chronic cocaine polydrug abuse. Each study was registered and scaled to a common anatomic coordinate system, yielding 120 standardized cortical regions. A back-propagation neural network classifier based on regional perfusion was used to classify normal and abnormal perfusion patterns. The neural network was trained to discriminate patients with AD from age-matched normal controls and cocaine polydrug abuse patients from normal controls. The performance of the neural network in these two tasks was evaluated quantitatively by receiver operating characteristic (ROC) analysis using cross-validation. RESULTS: For patients with AD, the area under the ROC curve was 0.93 +/- 0.04. When testing with the cocaine polydrug abuser data, the area under the ROC curve was 0.89 +/- 0.04. CONCLUSION: Neural networks provide a potentially useful tool in the decision-making task to discriminate patients with AD and cocaine abuse from normal controls.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Redes Neurais de Computação , Adulto , Idoso , Idoso de 80 Anos ou mais , Cocaína , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Organotecnécio , Oximas , Curva ROC , Cintilografia , Transtornos Relacionados ao Uso de Substâncias/diagnóstico por imagem , Tecnécio Tc 99m ExametazimaRESUMO
UNLABELLED: The main objective of this study was to characterize changes in brain perfusion associated with normal aging and gender. METHODS: Perfusion SPECT images using 99mTc-hexamethyl propyleneamine oxime (HMPAO) were obtained from 152 healthy subjects (67 men, 85 women) aged 50-92 yr. An automated method was developed to objectively assess image data from a large number of brain regions. Image data were reduced with singular value decomposition (SVD), which produced 20 eigenvectors capturing 97.05% of the total information content of 4320 regions from each subject. Subjects were scored individually on each vector. RESULTS: Multivariate analyses demonstrated that there were no significant differences in whole-brain HMPAO uptake with age, but age-related regional declines were seen in lateral ventricular regions. Women had higher HMPAO uptake than men in estimates of global perfusion and regional perfusion in the midcingulate/corpus callosum, inferior temporal and inferior parietal areas. CONCLUSION: These discriminations demonstrate that singular value deomposition of SPECT data may be used to assess differences in perfusion patterns between groups of subjects. They replicate several previous findings, both with respect to age-related changes in perfusion and with respect to gender differences. In addition, they identify a previously unreported gender difference in biparietal regions.