Polioencefalomalacia experimental induzida por amprólio em bovinos

Para estabelecer um modelo experimental para o estudo da etiologia, patologia e patogênese da polioencefalomalacia (PEM) em bovinos, a condição foi induzida em quatro novilhos pela administração oral de amprólio nas doses diárias de 500 e 350mg/kg de peso vivo, respectivamente por 22 e 26-28 dias. Todos os bovinos morreram espontaneamente ou foram eutanasiados in extremis após um curso clínico de 4-7 dias. Três bovinos que receberam 1.000mg/kg de amprólio e dois que receberam 500mg/kg morreram espontaneamente com quadro clínico agudo a subagudo sem desenvolverem sinais e lesões de PEM. Nos novilhos que PEM foi reproduzida, os sinais neurológicos incluíram marcada apatia, incoordenação, posição de cavalete, quedas ocasionais, hiperexcitabilidade, tremores musculares, cegueira, bruxismo, estrabismo, nistagmo, midríase, opistótono, decúbito lateral e movimentos de pedalagem. Os principais achados de necropsia eram restritos ao encéfalo e consistiam de tumefação, achatamento, amolecimento e amarelamento das circunvoluções cerebrais. Histologicamente, havia necrose neuronal segmentar e laminar (neurônios vermelhos) associada a edema, tumefação endotelial, separação das lâminas de neurônios do córtex telencefálico ou entre as substâncias cinzenta e branca e infiltração moderada a acentuada de macrófagos espumosos. Essas alterações eram mais acentuadas nos lobos telencefálicos frontal, parietal e occipital. Adicionalmente, lesões similares e moderadas foram detectadas no mesencéfalo e hipocampo. A necrose neuronal e o edema afetaram uniformemente as camadas de neurônios da substância cinzenta dos lobos telencefálicos frontal, parietal e occipital. Esse modelo experimental de PEM com administração oral de amprólio parece ser útil para o estudo da doença em bovinos, conforme observado anteriormente em ovinos.In order to establish an experimental model for the study of the etiology, pathology, and pathogenesis of polioencephalomalacia (PEM) in cattle, the condition was induced into four steers by oral administration of amprolium at daily doses of 500 and 350mg per kg of body weight respectively for 22 and 26-28 days. All steers died spontaneously or were euthanized in extremis after being sick for 4-7 days. Three steers that received the drug at 1,000mg/kg and two that received 500mg/kg died spontaneously with acute or subacute clinical signs and without lesions and signs of PEM. In those steers in which PEM was reproduced, the neurological signs included marked apathy, incoordination, sawhorse stance, occasional falls, hyperexcitability, muscle tremors, blindness, grinding of teeth, strabismus, nystagmus, mydriasis, opisthotonus, and lateral recumbency with paddling movements. Main gross lesions were restricted to the brain and included swelling, flattening, softening and yellow discoloration of the cerebral circumvolutions. Histologically, there was segmental laminar neuronal necrosis (red neurons) associated with edema, swelling of endothelial cells, cleavage of laminar neuronal layers or between gray and white matter and moderate to severe infiltration by foamy macrophages (gitter cells). These changes were more marked in the frontal, parietal and occipital telencephalic lobes. Additionally, similar and moderate lesions were detected in the midbrain and hippocampus. Neuronal necrosis and edema affected uniformly the neurons layers of the grey matter of the frontal, parietal and occipital lobes. This experimental model of PEM with oral administration of amprolium may be useful for the study in cattle, as previously observed in sheep

Amyloid and tau pathology associations with personality traits, neuropsychiatric symptoms, and cognitive lifestyle in the preclinical phases of sporadic and autosomal dominant Alzheimer’s disease

Background Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Feasibility study of the establishment of a terminological data bank in the UK

SIGLELD:2113.56(BLRDR--5642). / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Specifications of a linguistic data bank for the U.K

SIGLELD:2113.56F(BLRDR--5644). / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Selective survey of existing linguistics data banks in Europe

SIGLELD:2113.56F(BLRDR--5643). / BLDSC - British Library Document Supply CentreGBUnited Kingdo