Association of phosphorylated tau biomarkers with amyloid positron emission tomography vs tau positron emission tomography

Importance The recent proliferation of phosphorylated tau (p-tau) biomarkers has raised questions about their preferential association with the hallmark pathologies of Alzheimer disease (AD): amyloid-β plaques and tau neurofibrillary tangles. Objective To determine whether cerebrospinal fluid (CSF) and plasma p-tau biomarkers preferentially reflect cerebral β-amyloidosis or neurofibrillary tangle aggregation measured with positron emission tomography (PET). Design, Setting, and Participants This was a cross-sectional study of 2 observational cohorts: the Translational Biomarkers in Aging and Dementia (TRIAD) study, with data collected between October 2017 and August 2021, and the Alzheimer’s Disease Neuroimaging Initiative (ADNI), with data collected between September 2015 and November 2019. TRIAD was a single-center study, and ADNI was a multicenter study. Two independent subsamples were derived from TRIAD. The first TRIAD subsample comprised individuals assessed with CSF p-tau (p-tau181, p-tau217, p-tau231, p-tau235), [18F]AZD4694 amyloid PET, and [18F]MK6240 tau PET. The second TRIAD subsample included individuals assessed with plasma p-tau (p-tau181, p-tau217, p-tau231), [18F]AZD4694 amyloid PET, and [18F]MK6240 tau PET. An independent cohort from ADNI comprised individuals assessed with CSF p-tau181, [18F]florbetapir PET, and [18F]flortaucipir PET. Participants were included based on the availability of p-tau and PET biomarker assessments collected within 9 months of each other. Exclusion criteria were a history of head trauma or magnetic resonance imaging/PET safety contraindications. No participants who met eligibility criteria were excluded. Exposures Amyloid PET, tau PET, and CSF and plasma assessments of p-tau measured with single molecule array (Simoa) assay or enzyme-linked immunosorbent assay. Main Outcomes and Measures Associations between p-tau biomarkers with amyloid PET and tau PET. Results A total of 609 participants (mean [SD] age, 66.9 [13.6] years; 347 female [57%]; 262 male [43%]) were included in the study. For all 4 phosphorylation sites assessed in CSF, p-tau was significantly more closely associated with amyloid-PET values than tau-PET values (p-tau181 difference, 13%; 95% CI, 3%-22%; P = .006; p-tau217 difference, 11%; 95% CI, 3%-20%; P = .003; p-tau231 difference, 15%; 95% CI, 5%-22%; P < .001; p-tau235 difference, 9%; 95% CI, 1%-19%; P = .02) . These results were replicated with plasma p-tau181 (difference, 11%; 95% CI, 1%-22%; P = .02), p-tau217 (difference, 9%; 95% CI, 1%-19%; P = .02), p-tau231 (difference, 13%; 95% CI, 3%-24%; P = .009), and CSF p-tau181 (difference, 9%; 95% CI, 1%-21%; P = .02) in independent cohorts. Conclusions and Relevance Results of this cross-sectional study of 2 observational cohorts suggest that the p-tau abnormality as an early event in AD pathogenesis was associated with amyloid-β accumulation and highlights the need for careful interpretation of p-tau biomarkers in the context of the amyloid/tau/neurodegeneration, or A/T/(N), framework

MicroPET imaging of 5-HT1A receptors in rat brain: a test-retest [18F]MPPF study

Purpose: Earlier studies have shown that positron emission tomography (PET) imaging with the radioligand [18F]MPPF allows for measuring the binding potential of serotonin 5-hydroxytryptamine1A (5-HT1A) receptors in different regions of animal and human brain, including that of 5-HT1A autoreceptors in the raphe nuclei. In the present study, we sought to determine if such data could be obtained in rat, with a microPET (R4, Concorde Microsystems). Methods: Scans from isoflurane-anaesthetised rats (n = 18, including six test-retest) were co-registered with magnetic resonance imaging data, and binding potential, blood to plasma ratio and radiotracer efflux were estimated according to a simplified reference tissue model. Results: Values of binding potential for hippocampus (1.2), entorhinal cortex (1.1), septum (1.1), medial prefrontal cortex (1.0), amygdala (0.8), raphe nuclei (0.6), paraventricular hypothalamic nucleus (0.5) and raphe obscurus (0.5) were comparable to those previously measured with PET in cats, non-human primates or humans. Test-retest variability was in the order of 10% in the larger brain regions (hippocampus, medial prefrontal and entorhinal cortex) and less than 20% in small nuclei such as the septum and the paraventricular hypothalamic, basolateral amygdaloid and raphe nuclei. Conclusions: MicroPET brain imaging of 5-HT1A receptors with [18F]MPPF thus represents a promising avenue for investigating 5-HT1A receptor function in ra

Echocardiography and cardiovascular risk:The relationship in the renal transplant recipient

Introduction: Cardiovascular disease (CVD) is the major cause of death among renal transplant recipientes (RTR). It is not known whether echocardiographic abnormalities are useful to identify RTR at high risk of CVD. Methods: Retrospective review of RTR with functioning and stable graft and an echocardiography performed in the last year. Risk of major adverse cardiac events (MACE) and death using a risk calculator specific for RTR. Results: Among 107 patients (57.9% males, 50.4±13.9 years), 7-year risk of MACE was >10% in 30.9% of patients and 7-year risk of death >10% in 56.1%. Left ventricular hypertrophy (LVH) was found in 55.1%, diastolic dysfunction in 39.3%, dilated left atrium (LA) in 53.3%, high pulmonary artery systolic pressure (PASP) in 9.0%, valvular calcifications in 22.4% and moderate to severe mitral regurgitation (MR) in 3.7%. Mean Ejection fraction was 68.36±6.87%. Univariate analysis showed an increased risk of MACE and death in patients with LVH, diastolic dysfunction, dilated LA, high PASP, valvular calcifications and MR. Multivariate analysis identified an independente association between the risk of MACE >10% and valvular calcifications and high PASP. Risk of death>10% in multivariate analysis had an independent association with diastolic dysfunction and elevated PASP. Conclusion: Echocardiographic abnormalities identify RTR at increased risk of MACE and death. Valvular calcifications and high PASP are predictors of MACE whereas diastolic dysfunction and high PASP predict death.info:eu-repo/semantics/publishedVersio

Atividade antiparasitária do artemether na esquistossomose mansônica experimental

OBJECTIVE: To evaluate the effect of intramuscular injection of artemether in mice experimentally infected with Schistosoma mansoni , at the time of infection, during schistosomula maturation and after the beginning of egg-laying. METHODS: Eighty adult females Balb/c mice were divided into 8 groups with 10 animals each. Seven groups were infected with S. mansoni using 60 cercariae for each animal, inoculated subcutaneously, and the remaining group was maintained without infection. Among the seven infected groups, six were treated with artemether, according to the following schedule: three groups received doses of 100 mg/kg on days 0, 20 or 60 after inoculation of the cercariae; the other three received 50 mg/kg of artemether, also on days 0, 20 or 60. At the end of the 9th, 10th and 11th weeks after infection all the mice infected with S. mansoni were submitted to fecal examination using the Kato-Katz technique. On the 80th day of the experiment, the surviving animals were sacrificed and submitted to perfusion of the portal system in order to recover the worms. Body, liver and spleen weights of each animal were determined at that time. RESULTS: A reduction in egg-laying and the number of worms recovered was observed in mice treated with artemether (50 or 100 mg/kg) on the 20th day after infection. The decrease in the number of worms was more notable among S. mansoni females. A significant decrease in liver and spleen weights was also seen on the 20th day among animals treated with 50 or 100 mg/kg of artemether and also among those that received the drug at a dose of 50 mg/kg 60 days after infection. CONCLUSIONS: Evidence of the antischistosomal activity of artemether was shown, even at a dose of 50 mg/kg, when the drug was administered during the schistosomula maturation period in the portal system of the vertebrate host.OBJETIVO: Avaliar o efeito da administração intramuscular de artemether a camundongos infectados experimentalmente por Schistosoma mansoni no momento da infecção, durante a maturação dos esquistossômulos e após iniciada a oviposição. MÉTODOS: Oitenta camundongos Balb/c, fêmeas adultas, foram divididos em oito grupos com 10 animais cada. Sete grupos foram infectados por S. mansoni empregando-se 60 cercárias para cada animal, inoculadas por via subcutânea; o grupo restante foi mantido sem infecção. Entre os sete grupos infectados, seis foram tratados com artemether, segundo o seguinte esquema: três grupos receberam dose correspondente a 100 mg/kg no dia 0, 20 ou 60 após inoculação das cercárias; os demais receberam 50 mg/kg de artemether, no mesmo período que os lotes anteriores. Da 9&ordf;, 10&ordf; e 11&ordf; semanas após infecção os camundongos infectados por S. mansoni foram submetidos a exames de fezes pela técnica de Kato-Katz. No 80&ordm; dia do experimento, os animais sobreviventes foram sacrificados e submetidos à perfusão do sistema porta para recuperação de vermes. Determinaram-se, nessa ocasião, os pesos corporal, hepático e esplênico de cada animal. RESULTADOS: Observou-se queda na oviposição e no número de vermes recuperados entre os camundongos tratados com artemether (50 ou 100 mg/kg) no 20&ordm; dia após infecção. A diminuição do número de vermes foi mais expressiva no caso de fêmeas de S. mansoni. Verificou-se, ainda, diminuição significativa nos pesos hepático e esplênico entre os animais tratados com 50 e 100 mg/kg de artemether no 20&ordm; dia e também entre os que receberam a droga na dose de 50 mg/kg 60 dias após infecção. CONCLUSÕES: Ficou evidenciada a atividade anti-Schistosoma do artemether, mesmo ao se empregar dose correspondente a 50 mg/kg, quando a droga foi administrada durante o período de maturação dos esquistossômulos no sistema porta do hospedeiro vertebrado

House Price Index for Distrito Federal using Repeat Sales Model and GWR

A necessidade de monitoramento do mercado imobiliário como instrumento de avaliação da efetividade das políticas de planejamento urbano no território é etapa crucial para a boa gestão pública. Nesse sentido, o presente texto tem por objetivo construir o índice de preços para os imóveis transacionados no Distrito Federal entre 2003 e 2012 por meio do método de vendas repetidas. O índice proposto permite a avaliação de políticas públicas e seus impactos territoriais no preço dos bens imóveis, por meio do monitoramento contínuo da evolução dos preços de imóveis no Distrito Federal. Esse acompanhamento contínuo constitui-se em instrumento da política urbana no âmbito da capital federal, o qual servirá não somente para avaliação de políticas públicas, como também de operacionalização das mesmas, a partir da integração com instrumentos urbanísticos, tais como a outorga onerosa.The need for monitoring the real estate market to evaluate the effectiveness of urban planning policies in the territory is crucial step towards good governance, in this sense, this article aims to build the price index for properties transacted in Distrito Federal between 2003 and 2012 through the repeat sales method. The proposed index allows the evaluation of public policies and their territorial impact on the price of real estate, through the assessment of the evolution of real estate prices in the Distrito Federal. This continuous monitoring constitutes a tool of urban policy in the federal capital, which will serve not only for evaluation of public policies, as well as implementation of the same, from the integration with urban instruments, such as the onerous grant

Guia orientador de boas práticas para a prevenção de sintomatologia depressiva e comportamentos da esfera suicidária

Trabalho desenvolvido por: Ordem dos Enfermeiros - Mesa do Colégio da Especialidade de Enfermagem de Saúde Mental e Psiquiátrica (MCEESMP

Cholinergic Potentiation Alters Perceptual Eye Dominance Plasticity Induced by a Few Hours of Monocular Patching in Adults

A few hours of monocular deprivation with a diffuser eye patch temporarily strengthens the contribution of the deprived eye to binocular vision. This shift in favor of the deprived eye is characterized as a form of adult visual plasticity. Studies in animal and human models suggest that neuromodulators can enhance adult brain plasticity in general. Specifically, acetylcholine has been shown to improve certain aspects of visual function and plasticity in adulthood. We investigated whether a single administration of donepezil (a cholinesterase inhibitor) could further augment the temporary shift in perceptual eye dominance that occurs after 2 h of monocular patching. Twelve healthy adults completed two experimental sessions while taking either donepezil (5 mg, oral) or a placebo (lactose) pill. We measured perceptual eye dominance using a binocular phase combination task before and after 2 h of monocular deprivation with a diffuser eye patch. Participants in both groups demonstrated a significant shift in favor of the patched eye after monocular deprivation, however our results indicate that donepezil significantly reduces the magnitude and duration of the shift. We also investigated the possibility that donepezil reduces the amount of time needed to observe a shift in perceptual eye dominance relative to placebo control. For this experiment, seven subjects completed two sessions where we reduced the duration of deprivation to 1 h. Donepezil reduces the magnitude and duration of the patching-induced shift in perceptual eye dominance in this experiment as well. To verify whether the effects we observed using the binocular phase combination task were also observable in a different measure of sensory eye dominance, six subjects completed an identical experiment using a binocular rivalry task. These results also indicate that cholinergic enhancement impedes the shift that results from short-term deprivation. In summary, our study demonstrates that enhanced cholinergic potentiation interferes with the consolidation of the perceptual eye dominance plasticity induced by several hours of monocular deprivation