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1.
Ann Neurol ; 96(1): 46-60, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38624158

RESUMEN

OBJECTIVE: Recent evidence shows that during slow-wave sleep (SWS), the brain is cleared from potentially toxic metabolites, such as the amyloid-beta protein. Poor sleep or elevated cortisol levels can worsen amyloid-beta clearance, potentially leading to the formation of amyloid plaques, a neuropathological hallmark of Alzheimer disease. Here, we explored how nocturnal neural and endocrine activity affects amyloid-beta fluctuations in the peripheral blood. METHODS: We acquired simultaneous polysomnography and all-night blood sampling in 60 healthy volunteers aged 20-68 years. Nocturnal plasma concentrations of amyloid-beta-40, amyloid-beta-42, cortisol, and growth hormone were assessed every 20 minutes. Amyloid-beta fluctuations were modeled with sleep stages, (non)oscillatory power, and hormones as predictors while controlling for age and participant-specific random effects. RESULTS: Amyloid-beta-40 and amyloid-beta-42 levels correlated positively with growth hormone concentrations, SWS proportion, and slow-wave (0.3-4Hz) oscillatory and high-band (30-48Hz) nonoscillatory power, but negatively with cortisol concentrations and rapid eye movement sleep (REM) proportion measured 40-100 minutes previously (all t values > |3|, p values < 0.003). Older participants showed higher amyloid-beta-40 levels. INTERPRETATION: Slow-wave oscillations are associated with higher plasma amyloid-beta levels, whereas REM sleep is related to decreased amyloid-beta plasma levels, possibly representing changes in central amyloid-beta production or clearance. Strong associations between cortisol, growth hormone, and amyloid-beta presumably reflect the sleep-regulating role of the corresponding releasing hormones. A positive association between age and amyloid-beta-40 may indicate that peripheral clearance becomes less efficient with age. ANN NEUROL 2024;96:46-60.


Asunto(s)
Péptidos beta-Amiloides , Polisomnografía , Sueño REM , Sueño de Onda Lenta , Humanos , Persona de Mediana Edad , Péptidos beta-Amiloides/sangre , Péptidos beta-Amiloides/metabolismo , Adulto , Masculino , Anciano , Femenino , Sueño de Onda Lenta/fisiología , Adulto Joven , Sueño REM/fisiología , Hidrocortisona/sangre , Fragmentos de Péptidos/sangre
2.
Sci Adv ; 7(50): eabj6737, 2021 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-34890240

RESUMEN

We present a three-periodic, chiral, tensegrity structure and demonstrate that it is auxetic. Our tensegrity structure is constructed using the chiral symmetry Π+ cylinder packing, transforming cylinders to elastic elements and cylinder contacts to incompressible rods. The resulting structure displays local reentrant geometry at its vertices and is shown to be auxetic when modeled as an equilibrium configuration of spatial constraints subject to a quasi-static deformation. When the structure is subsequently modeled as a lattice material with elastic elements, the auxetic behavior is again confirmed through finite element modeling. The cubic symmetry of the original structure means that the auxetic behavior is observed in both perpendicular directions and is close to isotropic in magnitude. This structure could be the simplest three-dimensional analog to the two-dimensional reentrant honeycomb. This, alongside the chirality of the structure, makes it an interesting design target for multifunctional materials.

3.
PLoS One ; 15(12): e0243692, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33347458

RESUMEN

OBJECTIVE: Rapid testing is paramount during a pandemic to prevent continued viral spread and excess morbidity and mortality. This study investigates whether testing strategies based on sample pooling can increase the speed and throughput of screening for SARS-CoV-2, especially in resource-limited settings. METHODS: In a mathematical modelling approach conducted in May 2020, six different testing strategies were simulated based on key input parameters such as infection rate, test characteristics, population size, and testing capacity. The situations in five countries were simulated, reflecting a broad variety of population sizes and testing capacities. The primary study outcome measurements were time and number of tests required, number of cases identified, and number of false positives. FINDINGS: The performance of all tested methods depends on the input parameters, i.e. the specific circumstances of a screening campaign. To screen one tenth of each country's population at an infection rate of 1%, realistic optimised testing strategies enable such a campaign to be completed in ca. 29 days in the US, 71 in the UK, 25 in Singapore, 17 in Italy, and 10 in Germany. This is ca. eight times faster compared to individual testing. When infection rates are lower, or when employing an optimal, yet more complex pooling method, the gains are more pronounced. Pool-based approaches also reduce the number of false positive diagnoses by a factor of up to 100. CONCLUSIONS: The results of this study provide a rationale for adoption of pool-based testing strategies to increase speed and throughput of testing for SARS-CoV-2, hence saving time and resources compared with individual testing.


Asunto(s)
Prueba de COVID-19/métodos , COVID-19/diagnóstico , Modelos Teóricos , Técnicas de Laboratorio Clínico , Humanos , Tamizaje Masivo/métodos
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