RESUMO
INTRODUCTION: Behavioral variant frontotemporal dementia (bvFTD) may present sporadically or due to an autosomal dominant mutation. Characterization of both forms will improve understanding of the generalizability of assessments and treatments. METHODS: A total of 135 sporadic (s-bvFTD; mean age 63.3 years; 34% female) and 99 familial (f-bvFTD; mean age 59.9; 48% female) bvFTD participants were identified. f-bvFTD cases included 43 with known or presumed chromosome 9 open reading frame 72 (C9orf72) gene expansions, 28 with known or presumed microtubule-associated protein tau (MAPT) mutations, 14 with known progranulin (GRN) mutations, and 14 with a strong family history of FTD but no identified mutation. RESULTS: Participants with f-bvFTD were younger and had earlier age at onset. s-bvFTD had higher total Neuropsychiatric Inventory Questionnaire (NPI-Q) scores due to more frequent endorsement of depression and irritability. DISCUSSION: f-bvFTD and s-bvFTD cases are clinically similar, suggesting the generalizability of novel biomarkers, therapies, and clinical tools developed in either form to the other.
Assuntos
Demência Frontotemporal , Predisposição Genética para Doença , Mutação/genética , Testes Neuropsicológicos/estatística & dados numéricos , Fatores Etários , Idoso , Encéfalo/patologia , Proteína C9orf72/genética , Feminino , Demência Frontotemporal/classificação , Demência Frontotemporal/genética , Humanos , Masculino , Pessoa de Meia-Idade , América do Norte , Progranulinas/genética , Proteínas tau/genéticaRESUMO
INTRODUCTION: Leisure activities impact brain aging and may be prevention targets. We characterized how physical and cognitive activities relate to brain health for the first time in autosomal dominant frontotemporal lobar degeneration (FTLD). METHODS: A total of 105 mutation carriers (C9orf72/MAPT/GRN) and 69 non-carriers reported current physical and cognitive activities at baseline, and completed longitudinal neurobehavioral assessments and brain magnetic resonance imaging (MRI) scans. RESULTS: Greater physical and cognitive activities were each associated with an estimated >55% slower clinical decline per year among dominant gene carriers. There was also an interaction between leisure activities and frontotemporal atrophy on cognition in mutation carriers. High-activity carriers with frontotemporal atrophy (-1 standard deviation/year) demonstrated >two-fold better cognitive performances per year compared to their less active peers with comparable atrophy rates. DISCUSSION: Active lifestyles were associated with less functional decline and moderated brain-to-behavior relationships longitudinally. More active carriers "outperformed" brain volume, commensurate with a cognitive reserve hypothesis. Lifestyle may confer clinical resilience, even in autosomal dominant FTLD.
Assuntos
Cognição/fisiologia , Exercício Físico , Degeneração Lobar Frontotemporal , Atividades de Lazer , Testes Neuropsicológicos/estatística & dados numéricos , Idoso , Atrofia/patologia , Feminino , Degeneração Lobar Frontotemporal/genética , Degeneração Lobar Frontotemporal/patologia , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
We wanted to examine tolerability and efficacy of NSI-189, a benzylpiperizine-aminiopyridine neurogenic compound for treating major depressive disorder (MDD). This was a Phase 1B, double blind, randomized, placebo controlled, multiple-dose study with three cohorts. The first cohort received 40 mg q.d. (n=6) or placebo (n=2), the second cohort 40 mg b.i.d. (n=6) or placebo (n=2), and the third cohort 40 mg t.i.d. (n=6) or placebo (n=2). Twenty-four patients with MDD were recruited, with the diagnosis and severity confirmed through remote interviews. Eligible patients received NSI-189 or placebo for 28 days in an inpatient setting with assessments for safety, pharmacokinetics (PK) and efficacy. Outpatient follow-up visits were conducted until day 84 (±3). NSI-189 was relatively well tolerated at all doses, with no serious adverse effects. NSI-189 area under the curve increased in a dose-related and nearly proportional manner across the three cohorts, with a half-life of 17.4-20.5 h. The exploratory efficacy measurements, including Symptoms Of Depression Questionnaire (SDQ), Montgomery-Asberg Depression Scale (MADRS), Clinical Global Impressions-Improvement (CGI-I), and The Massachusetts General Hospital (MGH) Cognitive and Physical Functioning Questionnaire (CPFQ) showed a promising reduction in depressive and cognitive symptoms across all measures for NSI-189, with significant improvement in the SDQ and CPFQ, and a medium to large effect size for all measures. These improvements persisted during the follow-up phase. In summary, NSI-189 shows potential as a treatment for MDD in an early phase study. The main limitation of this preliminary study was the small sample size of each cohort.
Assuntos
Aminopiridinas/administração & dosagem , Transtorno Depressivo Maior/tratamento farmacológico , Piperazinas/administração & dosagem , Adulto , Aminopiridinas/farmacocinética , Biomarcadores Farmacológicos/sangue , Depressão/sangue , Depressão/tratamento farmacológico , Depressão/metabolismo , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/metabolismo , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piperazinas/farmacocinética , Escalas de Graduação Psiquiátrica , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/farmacocinética , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Resultado do TratamentoRESUMO
Hereditary frontotemporal dementia associated with mutations in the microtubule-associated protein tau gene (MAPT) is a protean disorder. Three neuropathologic subtypes can be recognized, based on the presence of inclusions made of tau isoforms with three and four repeats, predominantly three repeats and mostly four repeats. This is relevant for establishing a correlation between structural magnetic resonance imaging and positron emission tomography using tracers specific for aggregated tau. Longitudinal studies will be essential to determine the evolution of anatomical alterations from the asymptomatic stage to the various phases of disease following the onset of symptoms.
Assuntos
Encéfalo/patologia , Demência Frontotemporal/genética , Demência Frontotemporal/patologia , Mutação , Proteínas tau/genética , Encéfalo/diagnóstico por imagem , Feminino , Demência Frontotemporal/diagnóstico por imagem , Humanos , Corpos de Inclusão/metabolismo , Corpos de Inclusão/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fosforilação , Tomografia por Emissão de Pósitrons , Isoformas de Proteínas/genética , Tomografia Computadorizada de Emissão , Proteínas tau/metabolismoRESUMO
Population loss is often a harbinger of species extinction, but few opportunities exist to follow a species' demography and genetics through both time and space while this occurs. Previous research has shown that the northern fur seal (Callorhinus ursinus) was extirpated from most of its range over the past 200-800 years and that some of the extirpated populations had unique life history strategies. In this study, widespread availability of subfossils in the eastern Pacific allowed us to examine temporal changes in spatial genetic structure during massive population range contraction and partial recovery. We sequenced the mitochondrial control region from 40 ancient and 365 modern samples and analyzed them through extensive simulations within a serial Approximate Bayesian Computation framework. These analyses suggest that the species maintained a high abundance, probably in subarctic refugia, that dispersal rates are likely 85% per generation into new breeding colonies, and that population structure was not higher in the past. Despite substantial loss of breeding range, this species' high dispersal rates and refugia appear to have prevented a loss of genetic diversity. High dispersal rates also suggest that previous evidence for divergent life history strategies in ancient populations likely resulted from behavioral plasticity. Our results support the proposal that panmictic, or nearly panmictic, species with large ranges will be more resilient to future disturbance and environmental change. When appropriately verified, evidence of low population structure can be powerful information for conservation decision-making.
Assuntos
Otárias/genética , Variação Genética , Genética Populacional , Animais , Teorema de Bayes , DNA Mitocondrial/genética , Fósseis , Densidade Demográfica , Dinâmica Populacional , Análise de Sequência de DNARESUMO
Advances in magnetic resonance imaging (MRI) have contributed greatly to the study of neurodegenerative processes, psychiatric disorders, and normal human development, but the effect of such improvements on the reliability of downstream morphometric measures has not been extensively studied. We examined how MRI-derived neurostructural measures are affected by three technological advancements: parallel acceleration, increased spatial resolution, and the use of a high bandwidth multiecho sequence. Test-retest data were collected from 11 healthy participants during 2 imaging sessions occurring approximately 2 weeks apart. We acquired 4 T1-weighted MP-RAGE sequences during each session: a non-accelerated anisotropic sequence (MPR), a non-accelerated isotropic sequence (ISO), an accelerated isotropic sequence (ISH), and an accelerated isotropic high bandwidth multiecho sequence (MEM). Cortical thickness and volumetric measures were computed for each sequence to assess test-retest reliability and measurement bias. Reliability was extremely high for most measures and similar across imaging parameters. Significant measurement bias was observed, however, between MPR and all isotropic sequences for all cortical regions and some subcortical structures. These results suggest that these improvements in MRI acquisition technology do not compromise data reproducibility, but that consistency should be maintained in choosing imaging parameters for structural MRI studies.
Assuntos
Algoritmos , Artefatos , Córtex Cerebral/anatomia & histologia , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Adulto , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To use functional MRI (fMRI) to investigate whether hippocampal activation during a memory task can predict cognitive decline in individuals with mild cognitive impairment (MCI). METHODS: 25 older individuals with MCI performed a visual scene encoding task during fMRI scanning, and were followed clinically for at least 4 years after scanning. A hypothesis driven analysis of fMRI data was performed. First, fMRI data were analysed at the group level to identify the regions of the hippocampal formation that were engaged by this memory task. Parameter estimates of each subject's memory related hippocampal activation (% signal change) were extracted and were analysed with a linear regression model to determine whether hippocampal activation predicted the degree or rate of cognitive decline, as measured by change in Clinical Dementia Rating Sum-of-Boxes (CDR-SB). RESULTS: Over 5.9 (1.2) years of follow-up after scanning, subjects varied widely in degree and rate of cognitive decline (change in CDR-SB ranged from 0 to 6, and the rate ranged from 0 to 1 CDR-SB unit/year). Greater hippocampal activation predicted greater degree and rate of subsequent cognitive decline (p<0.05). This finding was present even after controlling for baseline degree of impairment (CDR-SB), age, education and hippocampal volume, as well as gender and apolipoprotein E status. In addition, an exploratory whole brain analysis produced convergent results, demonstrating that the hippocampal formation was the only brain region where activation predicted cognitive decline. CONCLUSIONS: In individuals with MCI, greater memory task related hippocampal activation is predictive of a greater degree and rate of cognitive decline subsequent to scanning. fMRI may provide a physiological imaging biomarker useful for identifying the subgroup of MCI individuals at highest risk of cognitive decline for potential inclusion in disease modifying clinical trials.
Assuntos
Doença de Alzheimer/fisiopatologia , Transtornos Cognitivos/fisiopatologia , Hipocampo/fisiopatologia , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Rememoração Mental/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Transtornos Cognitivos/diagnóstico , Progressão da Doença , Feminino , Humanos , Modelos Lineares , Estudos Longitudinais , Masculino , Testes NeuropsicológicosRESUMO
Introduction: Suspected non-Alzheimer's pathophysiology (SNAP) is a biomarker driven designation that represents a heterogeneous group in terms of etiology and prognosis. SNAP has only been identified by cross-sectional neurodegeneration measures, whereas longitudinal measures might better reflect "active" neurodegeneration and might be more tightly linked to prognosis. We compare neurodegeneration defined by cross-sectional 'hippocampal volume' only (SNAP/L-) versus both cross-sectional and longitudinal 'hippocampal atrophy rate' (SNAP/L+) and investigate how these definitions impact prevalence and the clinical and biomarker profile of SNAP in Mild Cognitive Impairment (MCI). Methods: 276 MCI patients from ADNI-GO/2 were designated amyloid "positive" (A+) or "negative" (A-) based on their florbetapir scan and neurodegeneration 'positive' or 'negative' based on cross-sectional hippocampal volume and longitudinal hippocampal atrophy rate. Results: 74.1% of all SNAP participants defined by the cross-sectional definition of neurodegeneration also met the longitudinal definition of neurodegeneration, whereas 25.9% did not. SNAP/L+ displayed larger white matter hyperintensity volume, a higher conversion rate to dementia over 5â¯years and a steeper decline on cognitive tasks compared to SNAP/L- and the A- CN group. SNAP/L- had more abnormal values on neuroimaging markers and worse performance on cognitive tasks than the A- CN group, but did not show a difference in dementia conversion rate or longitudinal cognition. Discussion: Using a longitudinal definition of neurodegeneration in addition to a cross-sectional one identifies SNAP participants with significant cognitive decline and a worse clinical prognosis for which cerebrovascular disease may be an important driver.
Assuntos
Disfunção Cognitiva/etiologia , Hipocampo/diagnóstico por imagem , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina , Biomarcadores , Disfunção Cognitiva/diagnóstico por imagem , Estudos Transversais , Etilenoglicóis , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
A central paradigm in conservation biology is that population bottlenecks reduce genetic diversity and population viability. In an era of biodiversity loss and climate change, understanding the determinants and consequences of bottlenecks is therefore an important challenge. However, as most studies focus on single species, the multitude of potential drivers and the consequences of bottlenecks remain elusive. Here, we combined genetic data from over 11,000 individuals of 30 pinniped species with demographic, ecological and life history data to evaluate the consequences of commercial exploitation by 18th and 19th century sealers. We show that around one third of these species exhibit strong signatures of recent population declines. Bottleneck strength is associated with breeding habitat and mating system variation, and together with global abundance explains much of the variation in genetic diversity across species. Overall, bottleneck intensity is unrelated to IUCN status, although the three most heavily bottlenecked species are endangered. Our study reveals an unforeseen interplay between human exploitation, animal biology, demographic declines and genetic diversity.
Assuntos
Caniformia/genética , Variação Genética , Modelos Estatísticos , Animais , Caniformia/classificação , Conservação dos Recursos Naturais , Ecossistema , Técnicas de Genotipagem , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Repetições de Microssatélites , Dinâmica Populacional/históriaRESUMO
Originally, the middle longitudinal fascicle (MdLF) was defined as a long association fiber tract connecting the superior temporal gyrus and temporal pole with the angular gyrus. More recently its description has been expanded to include all long postrolandic cortico-cortical association connections of the superior temporal gyrus and dorsal temporal pole with the parietal and occipital lobes. Despite its location and size, which makes MdLF one of the most prominent cerebral association fiber tracts, its discovery in humans is recent. Given the absence of a gold standard in humans for this fiber tract, its precise and complete connectivity remains to be determined with certainty. In this study using high angular resolution diffusion MRI (HARDI), we delineated for the first time, six major fiber connections of the human MdLF, four of which are temporo-parietal and two temporo-occipital, by examining morphology, topography, cortical connections, biophysical measures, volume and length in seventy brains. Considering the cortical affiliations of the different connections of MdLF we suggested that this fiber tract may be related to language, attention and integrative higher level visual and auditory processing associated functions. Furthermore, given the extensive connectivity provided to superior temporal gyrus and temporal pole with the parietal and occipital lobes, MdLF may be involved in several neurological and psychiatric conditions such as primary progressive aphasia and other aphasic syndromes, some forms of behavioral variant of frontotemporal dementia, atypical forms of Alzheimer's disease, corticobasal degeneration, schizophrenia as well as attention-deficit/hyperactivity Disorder and neglect disorders.
Assuntos
Lobo Occipital/anatomia & histologia , Lobo Parietal/anatomia & histologia , Lobo Temporal/anatomia & histologia , Substância Branca/anatomia & histologia , Adolescente , Adulto , Imagem de Difusão por Ressonância Magnética/métodos , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/anatomia & histologia , Vias Neurais/diagnóstico por imagem , Lobo Occipital/diagnóstico por imagem , Tamanho do Órgão , Lobo Parietal/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto JovemRESUMO
Functional MRI is a non-invasive imaging technology that can illuminate regional brain activity during the performance of a task, such as a memory paradigm, or at rest. fMRI data can be acquired during a session in which MRI data is also acquired to measure grey and white matter regional brain structure, and these measures can be analyzed together to investigate the relationships between altered regional brain function, structure, and cognitive task performance in neurologic illness. Data will be reviewed on the application of fMRI to the early detection of physiologic abnormalities associated with neurodegenerative diseases that cause dementia, and to differential diagnosis of dementias. Recent fMRI work will also be reviewed on the identification of abnormalities in regional brain function prior to dementia, the use of these measures to predict cognitive decline, and their application in investigations of alterations in regional brain networks that subserve cognitive function. Finally, the use of fMRI as a biomarker in clinical trials of putative neurotherapeutics for dementias will be discussed.
Assuntos
Encéfalo/patologia , Demência/diagnóstico , Imageamento por Ressonância Magnética , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Mapeamento Encefálico , Cognição , Demência/psicologia , HumanosRESUMO
Insects perform fast rotational manoeuvres during flight. While two insect orders use flapping halteres (specialized organs evolved from wings) to detect body dynamics, it is unknown how other insects detect rotational motions. Like halteres, insect wings experience gyroscopic forces when they are flapped and rotated and recent evidence suggests that wings might indeed mediate reflexes to body rotations. But, can gyroscopic forces be detected using only changes in the structural dynamics of a flapping, flexing insect wing? We built computational and robotic models to rotate a flapping wing about an axis orthogonal to flapping. We recorded high-speed video of the model wing, which had a flexural stiffness similar to the wing of the Manduca sexta hawkmoth, while flapping it at the wingbeat frequency of Manduca (25 Hz). We compared the three-dimensional structural dynamics of the wing with and without a 3 Hz, 10° rotation about the yaw axis. Our computational model revealed that body rotation induces a new dynamic mode: torsion. We verified our result by measuring wing tip displacement, shear strain and normal strain of the robotic wing. The strains we observed could stimulate an insect's mechanoreceptors and trigger reflexive responses to body rotations.
Assuntos
Asas de Animais/fisiologia , Animais , Fenômenos Biomecânicos , Simulação por Computador , Voo Animal/fisiologia , Insetos/fisiologia , Manduca , Modelos Biológicos , Movimento , Oscilometria , Amplitude de Movimento Articular , Robótica , Rotação , Resistência ao Cisalhamento , Estresse MecânicoRESUMO
A new protocol for measuring the volume of the entorhinal cortex (EC) from magnetic resonance images (MRI) was developed specifically to measure the EC from oblique coronal sections used in hippocampal volumetric studies. The relative positions of the anatomic landmarks demarcating EC boundaries were transposed from standard coronal sections to oblique ones. The lateral EC border, which is the most controversial among anatomists, was defined in a standard and conservative manner at the medial edge of the collateral sulcus. Two raters measured the EC twice for 78 subjects (healthy aged individuals, very mild AD patients, and elderly patients who did not meet criteria for dementia) to study intra- and inter-rater reproducibility and reliability of measurements. The level of accuracy achieved (coefficients of reproducibility of 1.40-3.86%) and reliability of measurements (intraclass correlation coefficients of 0.959-0.997) indicated that this method provides a feasible tool for measuring the volume of the EC in vivo.
Assuntos
Córtex Entorrinal/anatomia & histologia , Córtex Entorrinal/patologia , Imageamento por Ressonância Magnética/normas , Adulto , Idoso , Envelhecimento/patologia , Doença de Alzheimer/patologia , Hipocampo/anatomia & histologia , Hipocampo/patologia , Humanos , Giro Para-Hipocampal/anatomia & histologia , Giro Para-Hipocampal/patologia , Valores de Referência , Reprodutibilidade dos TestesRESUMO
With high resolution, quantitative magnetic resonance imaging (MRI) techniques, it is now possible to examine alterations in brain anatomy in vivo and to identify regions affected in the earliest stages of Alzheimer's disease (AD). In this study, we compared MRI-derived entorhinal and hippocampal volume in healthy elderly controls, patients who presented at the clinic with cognitive complaints, but did not meet criteria for dementia (non-demented), and patients with very mild AD. The two patient groups differed significantly from controls in entorhinal volume, but not from each other; in contrast, they differed from each other, as well as from controls, in hippocampal volume, with the mild AD cases showing the greatest atrophy. Follow-up clinical evaluations available on 23/28 non-demented patients indicated that 12/23 had converted to AD within 12-77 months from the baseline MRI examination. Converters could be best differentiated from non-converters on the basis of entorhinal, but not hippocampal volume. These data suggest that although both the EC and hippocampal formation degenerate before the onset of overt dementia, EC volume is a better predictor of conversion.
Assuntos
Doença de Alzheimer/patologia , Córtex Entorrinal/patologia , Hipocampo/patologia , Imageamento por Ressonância Magnética , Idoso , Idoso de 80 Anos ou mais , Atrofia , Transtornos Cognitivos/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Transtornos da Memória/patologia , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
Using quantitative structural MRI protocols, we examined the effects of age on alterations in entorhinal cortex (EC) volume. The left EC was found to be smaller than the right in both young and healthy aged subjects. More importantly, the right EC, but not the left, was significantly smaller in elderly participants compared to young controls. In an attempt to determine the earliest sites of involvement in mild and incipient Alzheimer's disease (AD), we compared entorhinal and hippocampal volume in (1) healthy elderly controls, (2) patients with very mild AD, and (3) elderly patients who were evaluated for cognitive complaints, but did not meet criteria for dementia. Both patient groups differed from controls in EC volume, but not from each other. In contrast, the two patient groups differed in hippocampal volume from controls, as well as from each other, with the mild AD cases showing the greatest atrophy. These results suggest that degeneration of the EC and hippocampal formation occurs before the onset of overt dementia. In fact, follow-up clinical evaluations available on 23 of 28 nondemented patients indicated that 12 of 23 had converted to AD. Converters could be best differentiated from nonconverters on the basis of entorhinal volume.
Assuntos
Envelhecimento/fisiologia , Doença de Alzheimer/patologia , Córtex Entorrinal/patologia , Doença de Alzheimer/diagnóstico , Atrofia , Córtex Entorrinal/fisiologia , Hipocampo/fisiologia , Humanos , Imageamento por Ressonância Magnética , Memória/fisiologia , Valores de Referência , Fatores de TempoRESUMO
Neonatal lung injury from hyperoxia and mechanical hyperventilation was studied in newborn piglets hyperventilated (arterial PCO2 15-20 Torr) for 24-48 h with 100% O2 and compared with unventilated controls. Pulmonary function testing was performed, and biochemical indicators of lung injury were analyzed from tracheobronchial aspirates at 0, 24, and 48 h. Lung sections were obtained for light and electron microscopy, and bronchoalveolar lavage fluid was analyzed for surfactant composition and activity. At 24 h significant changes in tracheobronchial aspirate albumin concentrations (up 78%) and percent of polymorphonuclear cells (up 16%) were demonstrated. At 48 h a 35% decrease in dynamic lung compliance (P less than 0.05) and a 36% increase in pulmonary resistance (P less than 0.05) were noted. Further biochemical abnormalities occurred with total cell counts increased by 271% (P less than 0.02), albumin 163% (P less than 0.05), total protein 217% (P less than 0.01), and elastase 108% (P less than 0.02). Pathological analyses revealed mild lung injury at 24 h and marked inflammation, abnormal inflation patterns, flattening of Clara cells, fibrinous exudate and edema, early collagen formation, and cell necrosis observed at 48 h. Bronchoalveolar lavage surfactant had normal biophysical activity. Results demonstrate that exposure of neonatal piglets to O2 and mechanical hyperventilation for 48 h cause severe progressive lung injury.
Assuntos
Lesão Pulmonar , Oxigênio , Respiração Artificial/efeitos adversos , Animais , Animais Recém-Nascidos , Pulmão/patologia , Pulmão/fisiopatologia , Surfactantes Pulmonares/metabolismo , SuínosRESUMO
In order to differentiate the effects of hyperoxia and barotrauma in the pathogenesis of acute neonatal lung injury, piglets were either hyperventilated (Paco2, 15-20 torr) for 48 hours with 100% oxygen (Group I), hyperventilated with 21% oxygen (Group II), normally ventilated (Paco2, 40-45 torr) with 100% oxygen (Group III), or normally ventilated with 21% O2 (Group IV) and compared to unventilated controls. Pulmonary function was tested, and biochemical indicators of lung injury were analyzed in tracheo-bronchial aspirates at 0, 24, and 48 hours. Bronchoalveolar lavage fluid was analyzed for surfactant composition and activity at the end of the study. At 48 hours, hyperoxic, hyperventilated piglets had significantly decreased dynamic lung compliance (30%) and increased pulmonary resistance (16%), aspirate cell count (190%), elastase activity (88%), albumin (214%), and total protein (150%) concentration. Qualitative light microscopy showed moderate to severe atelectasis, fibrinous exudate, edema, and inflammation. Normoxic, hyperventilated animals had comparable changes in pulmonary mechanics, but significantly milder cellular, biochemical, and morphologic changes. In hyperoxic, normocarbic animals pulmonary physiologic, cellular, and biochemical variables changed comparably to hyperoxic, hyperventilated animals; the pathologic changes were intermediate between hyperoxic, hyperventilated and normoxic, hyperventilated piglets. Normoxic, normocarbic animals had no significant changes in most variables over 48 hours; on morphologic examination their lungs were similar to unventilated controls and showed only mild edema. Surfactant had normal biophysical activity in all animals. Our results demonstrate that hyperoxia causes more significant physiologic, inflammatory, and histologic changes than barotrauma alone. Future attempts to prevent lung injury in neonates should be directed primarily at oxygen toxicity.
Assuntos
Barotrauma/complicações , Displasia Broncopulmonar/fisiopatologia , Oxigênio/efeitos adversos , Doença Aguda , Animais , Líquido da Lavagem Broncoalveolar/citologia , Displasia Broncopulmonar/metabolismo , Displasia Broncopulmonar/patologia , Humanos , Recém-Nascido , Complacência Pulmonar , Respiração Artificial , Mecânica Respiratória , SuínosRESUMO
In 2010, Coxiella burnetii was identified at a high prevalence in the placentas of Northern fur seals (Callorhinus ursinus) collected at a single rookery on St. Paul Island Alaska; an area of the United States where the agent was not known to be present. As contamination was hypothesized as a potential cause of false positives, but nothing was known about environmental C. burnetii in the region, an environmental survey was conducted to look for the prevalence and distribution of the organism on the island. While environmental prevalence was low, two strains of the organism were identified using PCR targeting the COM1 and IS1111 genes. The two strains are consistent with the organism that has been increasingly identified in marine mammals as well as a strain type more commonly found in terrestrial environments and associated with disease in humans and terrestrial animals. Further work is needed to elucidate information regarding the ecology of this organism in this region, particularly in association with the coastal environment.
Assuntos
Coxiella burnetii/classificação , Meio Ambiente , Otárias/microbiologia , Febre Q/epidemiologia , Alaska/epidemiologia , Animais , Coxiella burnetii/genética , Coxiella burnetii/isolamento & purificação , DNA Bacteriano/genética , Ilhas , Reação em Cadeia da Polimerase , Prevalência , Febre Q/microbiologia , Febre Q/veterináriaRESUMO
The middle longitudinal fascicle (MdLF) is a major fiber connection running principally between the superior temporal gyrus and the parietal lobe, neocortical regions of great biological and clinical interest. Although one of the most prominent cerebral association fiber tracts, it has only recently been discovered in humans. In this high angular resolution diffusion imaging (HARDI) MRI study, we delineated the two major fiber connections of the human MdLF, by examining morphology, topography, cortical connections, biophysical measures, volume and length in seventy-four brains. These two fiber connections course together through the dorsal temporal pole and the superior temporal gyrus maintaining a characteristic topographic relationship in the mediolateral and ventrodorsal dimensions. As these pathways course towards the parietal lobe, they split to form separate fiber pathways, one following a ventrolateral trajectory and connecting with the angular gyrus and the other following a dorsomedial route and connecting with the superior parietal lobule. Based on the functions of their cortical affiliations, we suggest that the superior temporal-angular connection of the MdLF, i.e., STG(MdLF)AG plays a role in language and attention, whereas the superior temporal-superior parietal connection of the MdLF, i.e., STG(MdLF)SPL is involved in visuospatial and integrative audiovisual functions. Furthermore, the MdLF may have clinical implications in neurodegenerative disorders such as primary progressive aphasia, frontotemporal dementia, posterior cortical atrophy, corticobulbar degeneration and Alzheimer's disease as well as attention-deficit/hyperactivity disorder and schizophrenia.