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An Amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Dietary habits and vascular risk factors promote both Alzheimer's disease and cognitive impairment caused by vascular factors1-3. Furthermore, accumulation of hyperphosphorylated tau, a microtubule-associated protein and a hallmark of Alzheimer's pathology4, is also linked to vascular cognitive impairment5,6. In mice, a salt-rich diet leads to cognitive dysfunction associated with a nitric oxide deficit in cerebral endothelial cells and cerebral hypoperfusion7. Here we report that dietary salt induces hyperphosphorylation of tau followed by cognitive dysfunction in mice, and that these effects are prevented by restoring endothelial nitric oxide production. The nitric oxide deficiency reduces neuronal calpain nitrosylation and results in enzyme activation, which, in turn, leads to tau phosphorylation by activating cyclin-dependent kinase 5. Salt-induced cognitive impairment is not observed in tau-null mice or in mice treated with anti-tau antibodies, despite persistent cerebral hypoperfusion and neurovascular dysfunction. These findings identify a causal link between dietary salt, endothelial dysfunction and tau pathology, independent of haemodynamic insufficiency. Avoidance of excessive salt intake and maintenance of vascular health may help to stave off the vascular and neurodegenerative pathologies that underlie dementia in the elderly.
Assuntos
Disfunção Cognitiva/induzido quimicamente , Neurônios/metabolismo , Cloreto de Sódio na Dieta/efeitos adversos , Proteínas tau/metabolismo , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Animais , Encéfalo/metabolismo , Disfunção Cognitiva/metabolismo , Humanos , Camundongos , Camundongos Knockout , Fosforilação , Cloreto de Sódio na Dieta/farmacologiaRESUMO
OBJECTIVE: Whereas left atrial (LA) strain has been well-validated using transthoracic echocardiography (TTE), its detection using transesophageal echocardiography (TEE) has not been studied. Conventional transesophageal views are known to be limited due to the posterior location of the LA. Here, the feasibility and accuracy of the deep transgastric long-axis LA focused view for peak atrial longitudinal strain (PALS) quantification was tested. DESIGN: This was a retrospective study of patients who underwent elective cardiac surgery between 2018 and 2020. TEE deep transgastric long-axis view was compared to TTE 4-chamber atrial focused view as the reference standard. LA area, volume, and PALS were quantified independently. SETTING: At Weill Cornell Medicine, a single, large academic medical center. PARTICIPANTS: The population comprised 42 patients undergoing cardiac surgery who had a TTE and TEE within 14.9 ± 20.8 days. INTERVENTIONS: TTE, TEE, and cardiac surgery. MEASUREMENTS AND MAIN RESULTS: TEE-derived PALS strongly correlated with TTE- derived PALS (r = 0.92, p < 0.001), though absolute PALS were lower (20.7 ± 6.0% v 25.7 ± 6.8%; p < 0.001). Mean TEE-derived atrial length was similar to TTE-derived length (5.18 ± 0.61 cm v 5.24 ± 0.61 cm; p = 0.38), but mean LA area was significantly smaller (16.7 ± 3.5 cm2v 18.9 ± 3.7 cm2; p < 0.001), with significant correlations between the 2 modalities for both (r = 0.74, 0.74, respectively; all p < 0.001). CONCLUSION: This exploratory study supported the feasibility of TEE for assessing LA longitudinal strain. There was an excellent correlation between atrial strain derived via TEE versus TTE, although values tended to be smaller on TEE, and bias between values was highly variable, suggesting that the values were not interchangeable.
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Apêndice Atrial , Ecocardiografia Transesofagiana , Ecocardiografia , Átrios do Coração/diagnóstico por imagem , Humanos , Estudos RetrospectivosRESUMO
Fabrication of microstructures for imparting omniphobicity to a surface generally requires the use of lithographic techniques and specialized equipment. We report instead a simple strategy for the synthesis of microstructured surfaces via metalorganic framework (MOF) self-assembly. Our method allows us to localize epitaxial growth of MOF at the tips of needle crystals to create mushroom-shaped structures, thus conferring re-entrant textures to the MOF-functionalized surfaces. These structures synthesized via wet chemistry were found to have omniphobic properties due to the resulting re-entrant texture.
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Compostos Organometálicos/química , Interações Hidrofóbicas e Hidrofílicas , Compostos Organometálicos/síntese química , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
In patients with acute ischemic stroke, pial collaterals play a key role in limiting neurological disability by maintaining blood flow to ischemic penumbra. We hypothesized that patient with poor pial collaterals will have greater corneal nerve and endothelial cell abnormalities. In a cross-sectional study, 35 patients with acute ischemic stroke secondary to middle cerebral artery (MCA) occlusion with poor (n = 12) and moderate-good (n = 23) pial collaterals and 35 healthy controls underwent corneal confocal microscopy and quantification of corneal nerve and endothelial cell morphology. In patients with MCA stroke, corneal nerve fibre length (CNFL) (P < 0.001), corneal nerve fibre density (CNFD) (P = 0.025) and corneal nerve branch density (CNBD) (P = 0.002) were lower compared to controls. Age, BMI, cholesterol, triglycerides, HDL, LDL, systolic blood pressure, NIHSS and endothelial cell parameters did not differ but mRS was higher (p = 0.023) and CNFL (p = 0.026) and CNBD (p = 0.044) were lower in patients with poor compared to moderate-good collaterals. CNFL and CNBD distinguished subjects with poor from moderate-good pial collaterals with an AUC of 72% (95% CI 53-92%) and 71% (95% CI 53-90%), respectively. Corneal nerve loss is greater in patients with poor compared to moderate-good pial collaterals and may act as a surrogate marker for pial collateral status in patients with ischemic stroke.
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Biomarcadores , Circulação Cerebrovascular , Circulação Colateral , Córnea/inervação , AVC Isquêmico/complicações , AVC Isquêmico/diagnóstico , Adulto , Idoso , Estudos de Casos e Controles , Córnea/patologia , Células Endoteliais/metabolismo , Feminino , Humanos , AVC Isquêmico/etiologia , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
The aim of this study was to enhance the biogas productivity of two-phase thermophilic anaerobic digestion (AD) using food waste (FW) as the primary substrate. The influence of adding four trace metals (Ca, Mg, Co, and Ni) as micronutrient supplement in the methanogenic phase of the thermophilic system was investigated. Initially, Response Surface Methodology (RSM) was applied to determine the optimal concentration of micronutrients in batch experiments. The results showed that optimal concentrations of 303, 777, 7 and 3mg/L of Ca, Mg, Co and Ni, respectively, increased the biogas productivity as much as 50% and significantly reduced the processing time. The formulated supplement was tested in continuous two-phase thermophilic AD system with regard to process stability and productivity. It was found that a destabilized thermophilic AD process encountering high VFA accumulation recovered in less than two weeks, while the biogas production was improved by 40% yielding 0.46L CH4/gVSadded/day. There was also a major increase in soluble COD utilization upon the addition of micronutrient supplement. The results of this study indicate that a micronutrient supplement containing Ca, Mg, Co and Ni could probably remedy any type of thermophilic AD process.
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Biocombustíveis , Reatores Biológicos , Micronutrientes/química , Anaerobiose , Análise da Demanda Biológica de Oxigênio , Cálcio/química , Cobalto/química , Temperatura Alta , Concentração de Íons de Hidrogênio , Magnésio/química , Metano/química , Nitrogênio/química , EsgotosRESUMO
Growth of NH(2)-MIL-53(Al) on alumina microparticles followed by post-synthetic modification with perfluorooctyl or caproic groups produces highly hydrophobic microparticles which are utilized for the formation of liquid marbles. Interfacial polymerization of ethyl-2-cyanoacrylate on the surface of the liquid marbles produces stable liquid capsules.