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OBJECTIVE: Biomarkers of Alzheimer disease vary between groups of self-identified Black and White individuals in some studies. This study examined whether the relationships between biomarkers or between biomarkers and cognitive measures varied by racialized groups. METHODS: Cerebrospinal fluid (CSF), amyloid positron emission tomography (PET), and magnetic resonance imaging measures were harmonized across four studies of memory and aging. Spearman correlations between biomarkers and between biomarkers and cognitive measures were calculated within each racialized group, then compared between groups by standard normal tests after Fisher's Z-transformations. RESULTS: The harmonized dataset included at least one biomarker measurement from 495 Black and 2,600 White participants. The mean age was similar between racialized groups. However, Black participants were less likely to have cognitive impairment (28% vs 36%) and had less abnormality of some CSF biomarkers including CSF Aß42/40, total tau, p-tau181, and neurofilament light. CSF Aß42/40 was negatively correlated with total tau and p-tau181 in both groups, but at a smaller magnitude in Black individuals. CSF Aß42/40, total tau, and p-tau181 had weaker correlations with cognitive measures, especially episodic memory, in Black than White participants. Correlations of amyloid measures between CSF (Aß42/40, Aß42) and PET imaging were also weaker in Black than White participants. Importantly, no differences based on race were found in correlations between different imaging biomarkers, or in correlations between imaging biomarkers and cognitive measures. INTERPRETATION: Relationships between CSF biomarkers but not imaging biomarkers varied by racialized groups. Imaging biomarkers performed more consistently across racialized groups in associations with cognitive measures. ANN NEUROL 2024;95:495-506.
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Doença de Alzheimer , Cognição , Disfunção Cognitiva , Humanos , Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano , Tomografia por Emissão de Pósitrons , Proteínas tau/líquido cefalorraquidiano , Negro ou Afro-Americano , BrancosRESUMO
INTRODUCTION: People with HIV (PWH) have increased risk of atherosclerotic cardiovascular disease (ASCVD) compared to non-PWH, but the reasons for this increased risk remain elusive. We investigated the change in ASCVD risk scores over 4-years to identify clinical factors associated with change in risk scores or high risk scores. METHODS: We conducted a preliminary study using retrospective analysis of PWH, between 40-75 years old, seen at the Evelyn Jordan Center with at least two routine HIV visits. We collected clinical and demographic data and calculated the ASCVD risk scores using the Pooled Cohort Equation. Exploratory analyses examined change in risk score categories over time. Final adjusted analysis examined factors associated with change in continuous risk scores over time. RESULTS: Our sample included 187 PWH, 166 were Black/African American and 79 were female. We found no significant change in ASCVD risk score over time. The risk score was significantly higher in PWH with hepatitis C (7.34%; 95% CI 2.59, 12.09; p=0.003) and trended higher in those with dual hepatitis B/C and hepatitis B compared to those without hepatitis (p=0.07). CONCLUSION: We found that ASCVD risk did not change over a 4-year period among predominantly Black young PWH, but infection with hepatitis C and dual hepatitis B/C were associated with higher ASCVD risk scores. Our findings illustrate the need for further longitudinal studies evaluating change in CVD risk and investigating viral hepatitis as an added potential contributor to increased CVD risk in high-risk, vulnerable populations.
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BACKGROUND: Cerebral edema has primarily been studied using midline shift or clinical deterioration as end points, which only captures the severe and delayed manifestations of a process affecting many patients with stroke. Quantitative imaging biomarkers that measure edema severity across the entire spectrum could improve its early detection, as well as identify relevant mediators of this important stroke complication. METHODS: We applied an automated image analysis pipeline to measure the displacement of cerebrospinal fluid (ΔCSF) and the ratio of lesional versus contralateral hemispheric cerebrospinal fluid (CSF) volume (CSF ratio) in a cohort of 935 patients with hemispheric stroke with follow-up computed tomography scans taken a median of 26 h (interquartile range 24-31) after stroke onset. We determined diagnostic thresholds based on comparison to those without any visible edema. We modeled baseline clinical and radiographic variables against each edema biomarker and assessed how each biomarker was associated with stroke outcome (modified Rankin Scale at 90 days). RESULTS: The displacement of CSF and CSF ratio were correlated with midline shift (r = 0.52 and - 0.74, p < 0.0001) but exhibited broader ranges. A ΔCSF of greater than 14% or a CSF ratio below 0.90 identified those with visible edema: more than half of the patients with stroke met these criteria, compared with only 14% who had midline shift at 24 h. Predictors of edema across all biomarkers included a higher National Institutes of Health Stroke Scale score, a lower Alberta Stroke Program Early CT score, and lower baseline CSF volume. A history of hypertension and diabetes (but not acute hyperglycemia) predicted greater ΔCSF but not midline shift. Both ΔCSF and a lower CSF ratio were associated with worse outcome, adjusting for age, National Institutes of Health Stroke Scale score, and Alberta Stroke Program Early CT score (odds ratio 1.7, 95% confidence interval 1.3-2.2 per 21% ΔCSF). CONCLUSIONS: Cerebral edema can be measured in a majority of patients with stroke on follow-up computed tomography using volumetric biomarkers evaluating CSF shifts, including in many without visible midline shift. Edema formation is influenced by clinical and radiographic stroke severity but also by chronic vascular risk factors and contributes to worse stroke outcomes.
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Edema Encefálico , Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/complicações , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/epidemiologia , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/epidemiologia , Edema Encefálico/etiologia , Incidência , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Biomarcadores , Edema/complicações , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Hemorrhagic transformation (HT) and cerebral edema (CED) are both major complications following ischemic stroke, but few studies have evaluated their overlap. We evaluated the frequency and predictors of CED/HT overlap and whether their co-occurrence impacts functional outcome more than each in isolation. METHODS: 892 stroke patients enrolled in a prospective study had follow-up CT imaging evaluated for HT and CED; the latter was quantified using the ratio of hemispheric CSF volumes (with hemispheric CSF ratio < 0.90 used as the CED threshold). The interaction between HT and CED on functional outcome (using modified Rankin Scale at 3 months) was compared to that for each condition separately. RESULTS: Among the 275 (31%) who developed HT, 233 (85%) manifested hemispheric CSF ratio < 0.9 (CED/HT), with this overlap group representing half of the 475 with measurable CED. Higher baseline NIHSS scores and larger infarct volumes were observed in the CED/HT group compared with those with CED or HT alone. Functional outcome was worse in those with CED/HT [median mRS 3 (IQR 2-5)] than those with CED [median 2 (IQR 1-4)] or HT alone [median 1 (IQR 0-2), p < 0.0001]. Overlap of CED/HT independently predicted worse outcome [OR 1.89 (95% CI: 1.12-3.18), p = 0.02] while HT did not; however, CED/HT was no longer associated with worse outcome after adjusting for severity of CED [adjusted OR 0.35 (95% CI: 0.23, 0.51) per 0.21 lower hemispheric CSF ratio, p < 0.001]. CONCLUSIONS: Most stroke patients with HT also have measurable CED. The co-occurrence of CED and HT occurs in larger and more severe strokes and is associated with worse functional outcome, although this is driven by greater severity of stroke-related edema in those with HT.
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The extracellular matrix (ECM) initiates mechanical cues that activate intracellular signaling through matrix-cell interactions. In blood vessels, additional mechanical cues derived from the pulsatile blood flow and pressure play a pivotal role in homeostasis and disease development. Currently, the nature of the cues from the ECM and their interaction with the mechanical microenvironment in large blood vessels to maintain the integrity of the vessel wall are not fully understood. Here, we identified the matricellular protein thrombospondin-1 (Thbs1) as an extracellular mediator of matrix mechanotransduction that acts via integrin αvß1 to establish focal adhesions and promotes nuclear shuttling of Yes-associated protein (YAP) in response to high strain of cyclic stretch. Thbs1-mediated YAP activation depends on the small GTPase Rap2 and Hippo pathway and is not influenced by alteration of actin fibers. Deletion of Thbs1 in mice inhibited Thbs1/integrin ß1/YAP signaling, leading to maladaptive remodeling of the aorta in response to pressure overload and inhibition of neointima formation upon carotid artery ligation, exerting context-dependent effects on the vessel wall. We thus propose a mechanism of matrix mechanotransduction centered on Thbs1, connecting mechanical stimuli to YAP signaling during vascular remodeling in vivo.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Integrina beta1/genética , Trombospondina 1/genética , Fatores de Transcrição/genética , Remodelação Vascular/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Aorta/crescimento & desenvolvimento , Aorta/metabolismo , Artérias Carótidas/crescimento & desenvolvimento , Artérias Carótidas/metabolismo , Microambiente Celular/genética , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Adesões Focais/genética , Via de Sinalização Hippo , Humanos , Integrina beta1/metabolismo , Mecanotransdução Celular , Camundongos , Neointima/genética , Neointima/metabolismo , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais/genética , Trombospondina 1/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Sinalização YAP , Proteínas rap de Ligação ao GTP/genéticaRESUMO
OBJECTIVE: To validate and characterize real-world functional behaviors in individuals after stroke. DESIGN: Longitudinal observational study using ecological momentary assessment (EMA) as a real-time assessment of functional behaviors in natural contexts. Wilcoxon rank-sum tests, Fisher exact tests, and Spearman correlations were used to analyze data. SETTING: Community. PARTICIPANTS: Individuals with mild to moderate stroke (N=212). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Individuals were assessed 5 times daily for 14 days with EMA surveys to determine what, with whom, and where individuals were doing activities and appraise mental, somatic, and cognitive symptoms. Individuals also completed standardized assessments during laboratory visits, including Lawton Instrumental Activities of Daily Living Scale, Activity Card Sort, Patient-Reported Outcome Measurement Information System, and Quality of Life in Neurological Disorders. RESULTS: Most individuals (median age, 60 years; 55% male) were ischemic stroke (90%) and had mild stroke severity (median National Institutes of Health Stroke Scale, 2). A total of 14,140 EMA surveys were analyzed. Individuals were home 78% of the time; primarily participated in passive, unproductive activities (27%), especially watching television and resting; and participated least in physical activities (4%). EMA was sensitive to indicators of poststroke disability; unemployed individuals reported fewer vocational activities but more activities of daily living (ADL) and passive activities than employed counterparts. Users of mobility devices and individuals with cognitive problems spent significantly less time on vocational activities and more on ADL than nonusers and those without cognitive problems. Our data supported the validity of EMA methods in stroke, with small to moderate correlations of EMA with in-laboratory measures of daily functioning (r=-0.30 to 0.35, P<.05) and very large correlations between EMA and in-laboratory measures of symptoms, especially those measuring same constructs (r=-0.64 to 0.79, P<.0001). CONCLUSIONS: Our findings reveal that EMA tracked poststroke functioning precisely. EMA may be beneficial in examining poststroke functional recovery, in monitoring patients for home-based interventions, and for longitudinal research.
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Avaliação Momentânea Ecológica , Acidente Vascular Cerebral , Atividades Cotidianas , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Qualidade de VidaRESUMO
Frequency combs (FCs)-spectra containing equidistant coherent peaks-have enabled researchers and engineers to measure the frequencies of complex signals with high precision, thereby revolutionising the areas of sensing, metrology and communications and also benefiting the fundamental science. Although mostly optical FCs have found widespread applications thus far, in general FCs can be generated using waves other than light. Here, we review and summarise recent achievements in the emergent field of acoustic frequency combs (AFCs), including phononic FCs and relevant acousto-optical, Brillouin light scattering and Faraday wave-based techniques that have enabled the development of phonon lasers, quantum computers and advanced vibration sensors. In particular, our discussion is centred around potential applications of AFCs in precision measurements in various physical, chemical and biological systems in conditions where using light, and hence optical FCs, faces technical and fundamental limitations, which is, for example, the case in underwater distance measurements and biomedical imaging applications. This review article will also be of interest to readers seeking a discussion of specific theoretical aspects of different classes of AFCs. To that end, we support the mainstream discussion by the results of our original analysis and numerical simulations that can be used to design the spectra of AFCs generated using oscillations of gas bubbles in liquids, vibrations of liquid drops and plasmonic enhancement of Brillouin light scattering in metal nanostructures. We also discuss the application of non-toxic room-temperature liquid-metal alloys in the field of AFC generation.
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PURPOSE: This study determined at two year follow-up the lifetime risk of re-operation for elderly patients with hip fractures undergoing internal fixation, dual mobility total hip arthroplasty, or bipolar hemiarthroplasty, using death of the patient as a competing risk. MATERIALS AND METHODS: With the hypothesis that arthroplasties may have less complications without increasing mortality even for Garden I and Garden II fractures, we retrospectively reviewed 317 hips with femoral neck fractures operated between January 2015 and August 2019. The mean age at time of surgical intervention was 82.4 years (range 65 to 105). Sixty patients presented a nondisplaced hip fracture (Garden I or II) treated by internal fixtion (I-F), and 257 were treated by hip arthroplasty: 118 dual mobility total hip arthroplasty (DM-THA) and 139 with a bipolar hemiarthroplaty (B-H). Demographics, surgical and complications data, and mortality were collected and compared for each group. RESULTS: The overall mortality rate was 22.4% at two years, and similar (p = 0.98) in all groups, respectively 22%, 22%, and 23% for DM-THA, B-H, and I-F groups. With dual mobility THA, the cumulative incidence of re-operations for any reason was (lower (9%) than with internal fixation (22%) or bipolar hemiarthroplasties (19%). CONCLUSION: Using a double mobility total prosthesis does not increase the post-operative mortality of the patients, nor does it increase their survival. But, reducing the risk of complications certainly improves their quality of life during the little time they have left .
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Artroplastia de Quadril , Fraturas do Colo Femoral , Hemiartroplastia , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/efeitos adversos , Fraturas do Colo Femoral/cirurgia , Hemiartroplastia/efeitos adversos , Humanos , Qualidade de Vida , Reoperação , Estudos RetrospectivosRESUMO
OBJECTIVE: Remodeling of the extracellular matrix plays a vital role in cardiovascular diseases. Using a mouse model of postnatal ascending aortic aneurysms (termed Fbln4SMKO), we have reported that abnormal mechanosensing led to aneurysm formation in Fbln4SMKO with an upregulation of the mechanosensitive transcription factor, Egr1 (Early growth response 1). However, the role of Egr1 and its upstream regulator(s) in the initiation of aneurysm development and their relationship to an aneurysmal microenvironment are unknown. Approach and Results: To investigate the contribution of Egr1 in the aneurysm development, we deleted Egr1 in Fbln4SMKO mice and generated double knockout mice (DKO, Fbln4SMKO; Egr1-/-). Aneurysms were prevented in DKO mice (42.8%) and Fbln4SMKO; Egr1+/- mice (26%). Ingenuity Pathway Analysis identified PAR1 (protease-activated receptor 1) as a potential Egr1 upstream gene. Protein and transcript levels of PAR1 were highly increased in Fbln4SMKO aortas at postnatal day 1 before aneurysm formed, together with active thrombin and MMP (matrix metalloproteinase)-9, both of which serve as a PAR1 activator. Concordantly, protein levels of PAR1, Egr1, and thrombin were significantly increased in human thoracic aortic aneurysms. In vitro cyclic stretch assays (1.0 Hz, 20% strain, 8 hours) using mouse primary vascular smooth muscle cells induced marked expression of PAR1 and secretion of prothrombin in response to mechanical stretch. Thrombin was sufficient to induce Egr1 expression in a PAR1-dependent manner. CONCLUSIONS: We propose that thrombin, MMP-9, and mechanical stimuli in the Fbln4SMKO aorta activate PAR1, leading to the upregulation of Egr1 and initiation of ascending aortic aneurysms.
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Aneurisma da Aorta Torácica/etiologia , Proteína 1 de Resposta de Crescimento Precoce/fisiologia , Proteínas da Matriz Extracelular/fisiologia , Receptor PAR-1/fisiologia , Idoso , Idoso de 80 Anos ou mais , Animais , Proteínas da Matriz Extracelular/deficiência , Feminino , Humanos , Masculino , Metaloproteinase 9 da Matriz/fisiologia , Camundongos , Pessoa de Meia-Idade , Receptor PAR-1/antagonistas & inibidores , Estresse Mecânico , Trombina/farmacologiaRESUMO
We examined the association between sexual orientation and human papillomavirus (HPV)-related risky sexual behaviors among high school students in the U.S. We used the 2015 Youth Risk Behavior Survey, a three-stage cluster sample, nationally representative, cross-sectional study. Participants were sexually active students (Grades 9-12) in public, private, and Catholic schools in 50 states and the District of Columbia (n = 5,958). Sexual orientation dimensions were: sexual self-identity (heterosexual, gay, lesbian, bisexual, and not sure) and sex of sexual contacts. HPV-associated risky sexual risk behaviors selected a priori were early sexual debut (≤ 12 or ≥ 13 years old) and number of lifetime partners (≥ 2 or ≥ 4). Separate multiple logistic regression analyses estimated association between sexual orientation and sex of sexual contacts, and HPV-associated risky sexual behaviors. Among the 5,958 high school students, a quarter had ≥ 4, and two-thirds had ≥ 2 sexual partners. Students who self-identified as bisexual (aOR = 2.43, 99% CI 1.19-4.98) or "not sure" (aOR = 4.56, 99% CI 2.54-8.17) were more likely to have sexual debut before 13 years. Similarly, students whose sexual contacts were adolescent females who had sex with females and males were more likely to have sexual debut before they turned 13 years of age (aOR = 3.46, 99% CI 1.83-6.48), or had ≥ 4 sexual partners (aOR = 2.66, 99% CI 1.74-4.08), or had ≥ 2 sexual partners (aOR = 3.09, 99% CI 1.91-5.00). In conclusion, HPV-associated risky sexual behavior is prevalent among high school students, especially sexual minorities. Interventions tailored to this population could increase HPV vaccine uptake and prevent future HPV-associated cancers and other negative outcomes.
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Alphapapillomavirus , Papillomaviridae , Adolescente , Estudos Transversais , Feminino , Humanos , Masculino , Instituições Acadêmicas , Comportamento Sexual , EstudantesRESUMO
PURPOSE: Complex regional pain syndrome (CRPS) after foot and ankle surgery has a significant impact on the ability to walk. As the symptomatic treatment of this disaster complication is poor and has low efficacy, a preventive treatment would be beneficial. Vitamin C has been reported to be efficient in preventing CRPS in elective scheduled surgery. Few authors explored this efficiency in foot and ankle surgery. We, therefore, evaluated the efficacy of vitamin C in preventing this complication after foot and ankle surgeries for both trauma and elective surgery. MATERIAL AND METHODS: Between January 2018 and December 2019, 329 patients were included in the study. We conducted a prospective randomized study on the efficiency of vitamin C (one group with and one without vitamin C) to prevent CRPS risk in patients operated in our institution on foot or ankle surgery. The incidence of CRPS after foot and ankle surgery was evaluated in both groups; the diagnostic of CRPS was made using the Budapest criteria associated with three-phase bone scintigraphy. RESULTS: Among the 329 patients included in the study (232 women and 97 men), 121 patients were included in the vitamin C group and 208 in the control group (without vitamin C). Vitamin C was statistically linked with a decreased risk of CRPS (OR 0.19; CI 95% from 0.05 to 0.8; p = 0.021). Alcoholism and cast immobilization were increased risks factors of CRPS (respectively p = 0.001 and p = 0.034). CONCLUSION: Taking 1 g per day of vitamin C during 40 days after a foot or ankle surgery reduces the risk of CRPS.
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Tornozelo , Síndromes da Dor Regional Complexa , Tornozelo/cirurgia , Ácido Ascórbico/uso terapêutico , Síndromes da Dor Regional Complexa/epidemiologia , Síndromes da Dor Regional Complexa/prevenção & controle , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Masculino , Estudos ProspectivosRESUMO
A novel tunable erbium-doped fiber ring laser (EDFRL) using a cascaded-chirped long period fiber grating (C-CLPG) as a wavelength selection element is proposed. The oscillation wavelength is determined by the one of the spectral peaks of the C-CLPG used, and the oscillation output provides a high signal to noise (S/N) ratio detection and a highly sensitive measurement of the temperature due to its high power and narrow spectral output. In the experiment, it is confirmed that the wavelength of the output shifts in accordance with the temperature-induced spectral shift of the C-CLPG transmittance spectrum and the temperature sensitivity is obtained to be â¼-0.2â nm/°C within the wavelength range of 1567.30 â¼ 1575.78â nm. The oscillation wavelength range is to be limited depending on the fringe spacing of the channeled spectrum of C-CLPG, which limits the temperature measurement range, but a data processing approach to solve this problem is additionally proposed and its availability is also presented.
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A fiber Bragg grating (FBG)-based multi-point sensing system for the simultaneous measurement of strain and temperature is proposed, with a Fabry-Perot interferometer (FPI) consisting of low reflective FBGs inscribed inside a polarization-maintaining (PM) fiber is introduced as a sensor head. A multi-point sensing method with high dynamic range and short measurement time can be realized by analyzing the reflection spectrum of low reflective FBG-FPIs, and a simultaneous measurement of strain and temperature using two orthogonal polarization modes is enabled by the high birefringence of a PM fiber. An experimental demonstration of multi-point measurement utilizing the proposed system is reported.
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RATIONALE: Abnormal mechanosensing of smooth muscle cells (SMCs) resulting from the defective elastin-contractile units has been suggested to drive the formation of thoracic aortic aneurysms; however, the precise molecular mechanism has not been elucidated. OBJECTIVE: The aim of this study was to identify the crucial mediator(s) involved in abnormal mechanosensing and propagation of biochemical signals during the aneurysm formation and to establish a basis for a novel therapeutic strategy. METHODS AND RESULTS: We used a mouse model of postnatal ascending aortic aneurysms ( Fbln4SMKO; termed SMKO [SMC-specific knockout]), in which deletion of Fbln4 (fibulin-4) leads to disruption of the elastin-contractile units caused by a loss of elastic lamina-SMC connections. In this mouse, upregulation of Egr1 (early growth response 1) and angiotensin-converting enzyme leads to activation of Ang II (angiotensin II) signaling. Here, we showed that the matricellular protein, Thbs1 (thrombospondin-1), was highly upregulated in SMKO ascending aortas and in human thoracic aortic aneurysms. Thbs1 was induced by mechanical stretch and Ang II in SMCs, for which Egr1 was required, and reduction of Fbln4 sensitized the cells to these stimuli and led to higher expression of Egr1 and Thbs1. Deletion of Thbs1 in SMKO mice prevented the aneurysm formation in ≈80% of DKO (SMKO;Thbs1 knockout) animals and suppressed Ssh1 (slingshot-1) and cofilin dephosphorylation, leading to the formation of normal actin filaments. Furthermore, elastic lamina-SMC connections were restored in DKO aortas, and mechanical testing showed that structural and material properties of DKO aortas were markedly improved. CONCLUSIONS: Thbs1 is a critical component of mechanotransduction, as well as a modulator of elastic fiber organization. Maladaptive upregulation of Thbs1 results in disruption of elastin-contractile units and dysregulation of actin cytoskeletal remodeling, contributing to the development of ascending aortic aneurysms in vivo. Thbs1 may serve as a potential therapeutic target for treating thoracic aortic aneurysms.
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Aneurisma da Aorta Torácica/metabolismo , Mecanotransdução Celular , Músculo Liso Vascular/metabolismo , Trombospondina 1/metabolismo , Remodelação Vascular , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/patologia , Idoso , Idoso de 80 Anos ou mais , Animais , Aorta Torácica/metabolismo , Aorta Torácica/patologia , Aneurisma da Aorta Torácica/genética , Aneurisma da Aorta Torácica/patologia , Aneurisma da Aorta Torácica/prevenção & controle , Células Cultivadas , Cofilina 2/metabolismo , Dilatação Patológica , Modelos Animais de Doenças , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Tecido Elástico/metabolismo , Tecido Elástico/patologia , Elastina/metabolismo , Proteínas da Matriz Extracelular/deficiência , Proteínas da Matriz Extracelular/genética , Feminino , Humanos , Masculino , Camundongos Knockout , Pessoa de Meia-Idade , Músculo Liso Vascular/patologia , Fosfoproteínas Fosfatases/metabolismo , Fosforilação , Pressorreceptores/metabolismo , Ratos , Estresse Mecânico , Trombospondina 1/deficiência , Trombospondina 1/genéticaRESUMO
Highly conductive molecular wires are an important component for realizing molecular electronic devices and have to be explored in terms of interactions between molecules and electrodes in their molecular junctions. Here, new molecular wire junctions are reported to enhance charge transport through gold nanoparticle (AuNP)-linked double self-assembled monolayers (SAMs) of cobalt (II) bis-terpyridine molecules (e.g., Co(II)(tpyphS)2 ). Electrical characteristics of the double-SAM devices are explored in terms of the existence of AuNP. The AuNP linker in the Co(II)(tpyphS)2 -AuNP-Co(II)(tpyphS)2 junction acts as an electronic contact that is transparent to electrons. The weak temperature dependency of the AuNP-linked molecular junctions strongly indicates sequential tunneling conduction through the highest occupied molecular orbitals (HOMOs) of Co(II)(tpyphS)2 molecules. The electrochemical characteristics of the AuNP-Co(II)(tpyphS)2 SAMs reveal fast electron transfer through molecules linked by AuNP. Density functional theory calculations reveal that the molecular HOMO levels are dominantly affected by the formation of junctions. The intermolecular charge transport, controlled by the AuNP linker, can provide a rational design for molecular connection that achieves a reliable electrical connectivity of molecular electronic components for construction of molecular electronic circuits.
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OBJECTIVE: Several studies have reported abnormal oculomotor capacities leading to reading/writing difficulties among dyslexic children. However, no randomized clinical trial has been conducted to determine whether oculomotor training improves reading/writing skills of these children. The present study aims to evaluate the efficacy of computer-based oculomotor training among dyslexic children. METHOD: Crossover randomized trial with enrollment from January 12, 2015 to July 24, 2015, and follow-up to February 4, 2016. Eleven children (aged 7 to 12 years old) with dyslexia were included in a French psychiatric unit. The computer-based oculomotor training consisted of exercises focused on control of saccadic movements (reflexes and voluntary saccades), vergences and visual attention and memory. At baseline, 3 and 6 months, participants were assessed on reading and writing skills as well as phonological skills, visuo-attentional skills and verbal memory using the French batterie analytique du langage écrit (BALE). Saccadic and antisaccadic ocular movements (latencies and gains) were recorded using a specific device. Several Anova models were performed to test whether oculomotor training improves reading, writing and phonological, verbal memory and visuo-attentional skills. Our analyses were considered exploratory (alpha at 5%). RESULTS: No effect of oculomotor training was found on reading skills. However, oculomotor training was associated with a short-term effect (after 3 months of training) on several tests measuring phonological skills (syllabic suppression; P-value=0.022), visuo-attentional skills (search of anarchic verbal cues; P-value=0.035) and verbal memory (digit span backward; P-value=0.022) and with a long-term effect (3 months after the end of the 3 months of training) on a measure of writing skills (regular words; P-value=0.019). Finally, training was associated with an increase of saccadic latencies indicating an increase of visuo-attentional skills (P-value=0.026). CONCLUSIONS: Our results suggested that computer-based oculomotor training might be effective on writing skills and several cognitive skills among dyslexic children, but future clinical trials are needed to confirm our results.
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Dislexia/terapia , Músculos Oculomotores , Atenção , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Criança , Estudos Cross-Over , Dislexia/complicações , Dislexia/psicologia , Feminino , Humanos , Masculino , Memória , Destreza Motora , Educação Física e Treinamento , Leitura , Movimentos Sacádicos , Resultado do Tratamento , RedaçãoRESUMO
To test the hypothesis that the relationship between fat mass (FM) and bone mineral density (BMD) is mediated by leptin. The study involved 611 individuals aged 20-89 years who were randomly sampled from Ho Chi Minh City (Vietnam). BMD at the femoral neck (FN), lumbar spine (LS), and whole body (WB) was measured by DXA. Lean mass and FM were derived from the WB DXA scan. Leptin was measured by ELISA (DRG Diagnostics, Germany). The regression method was used to partition the variance of leptin and FM on BMD. The mediated effect of leptin was analyzed by the mediation analysis model. In the multiple linear regression, leptin, FM, and age collectively accounted for ~34 % variation in FNBMD in men and women. However, only 0.5 % of this explained variance was due to leptin. Of the total effect of FM on FNBMD, the mediated effect of leptin accounted for 6.1 % (P = 0.38) in men and 7.1 % (P = 0.99) in women. The same trend was observed for LS and WBBMD. These data suggest that greater FM is associated with greater BMD, but the association is not mediated by leptin, and that leptin has a non-significant influence on bone mass.
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Tecido Adiposo/metabolismo , Composição Corporal/fisiologia , Densidade Óssea/fisiologia , Leptina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/metabolismo , Adulto JovemAssuntos
COVID-19 , Transtornos do Olfato , Humanos , Transtornos do Olfato/epidemiologia , Prevalência , SARS-CoV-2 , OlfatoRESUMO
This research outlines the application of an enzyme-linked immunosorbent assay (ELISA) for the analysis of clenbuterol in animal products. Our assay showed good sensitivity for clenbuterol (0.4 ng/g or 0.4 ppb) and low detection limit (0.09 ng/g or 0.09 ppb). A low cross-reactivity for other ß2-agonist drugs such as salbutamol, terbutaline, and epinephrine led to formatting an ELISA kit considered to have a high specificity for clenbuterol. A survey of Ho Chi Minh City pork market was conducted as part of the validation of our ELISA. ELISA results showed a surprisingly high value of contamination. However, it will be necessary to conduct a more statistically valid replicated survey with evaluation by other instrumental methods to obtain a definite conclusion. This ELISA kit will be used to monitor growth promoter residues in Vietnam's animal products.
Assuntos
Agonistas Adrenérgicos beta/análise , Clembuterol/análise , Ensaio de Imunoadsorção Enzimática/métodos , Contaminação de Alimentos/análise , Haptenos/química , Carne Vermelha/análise , Agonistas Adrenérgicos beta/imunologia , Animais , Formação de Anticorpos , Clembuterol/imunologia , Feminino , Haptenos/imunologia , Limite de Detecção , Coelhos , SuínosRESUMO
MOTIVATION: Knowledge of drug-drug interactions (DDIs) is crucial for health-care professionals to avoid adverse effects when co-administering drugs to patients. As most newly discovered DDIs are made available through scientific publications, automatic DDI extraction is highly relevant. RESULTS: We propose a novel feature-based approach to extract DDIs from text. Our approach consists of three steps. First, we apply text preprocessing to convert input sentences from a given dataset into structured representations. Second, we map each candidate DDI pair from that dataset into a suitable syntactic structure. Based on that, a novel set of features is used to generate feature vectors for these candidate DDI pairs. Third, the obtained feature vectors are used to train a support vector machine (SVM) classifier. When evaluated on two DDI extraction challenge test datasets from 2011 and 2013, our system achieves F-scores of 71.1% and 83.5%, respectively, outperforming any state-of-the-art DDI extraction system. AVAILABILITY AND IMPLEMENTATION: The source code is available for academic use at http://www.biosemantics.org/uploads/DDI.zip.