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BACKGROUND: Large vessel occlusion acute ischemic stroke prognosis improved following the 2015 endovascular therapy (EVT) trials. Blood-based biomarkers may improve outcome prediction. We aimed to assess plasma brain-derived tau (BD-Tau) performance in predicting post-EVT large vessel occlusion acute ischemic stroke outcomes. METHODS: We included 2 temporally independent prospective cohorts of anterior circulation in patients with large vessel occlusion acute ischemic stroke who successfully recanalized post-EVT. We measured plasma BD-Tau, GFAP (glial-fibrillary-acidic-protein), NfL (neurofilament-light-chain), and total-Tau upon admission, immediately, 24 hours, and 72 hours post-EVT. Twenty-four-hour neuroimaging and 90-day functional outcomes were independently assessed using the Alberta Stroke Program Early Computed Tomography Score (good outcome: >7 or unchanged) and the modified Rankin Scale (favorable outcome <3 or unchanged), respectively. Based on the first cohort (derivation), we built a multivariable logistic regression model to predict a 90-day functional outcome. Model results were evaluated using the second cohort (evaluation). RESULTS: In the derivation cohort (n=78, mean age=72.9 years, 50% women), 62% of patients had a good 24-hour neuroimaging outcome, and 45% had a favorable 90-day functional outcome. GFAP admission-to-EVT rate-of-change was the best predictor for early neuroimaging outcome but not for 90-day functional outcome. At admission, BD-Tau levels presented the highest discriminative performance for 90-day functional outcomes (area under the curve, 0.76 [95% CI, 0.65-0.87]; P<0.001). The model incorporating age, admission BD-Tau, and 24-hour Alberta Stroke Program Early Computed Tomography Score achieved excellent discrimination of 90-day functional outcome (area under the curve, 0.89 [95% CI, 0.82-0.97]; P<0.001). The score's predictive performance was maintained in the evaluation cohort (n=66; area under the curve, 0.82 [95% CI, 0.71-0.92]; P<0.001). CONCLUSIONS: Admission plasma BD-Tau accurately predicted 90-day functional outcomes in patients with large vessel occlusion acute ischemic stroke after successful EVT. The proposed model may predict functional outcomes using objective measures, minimizing human-related biases and serving as a simplified prognostic tool for AIS.
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The contribution of astrocytes to Alzheimer's disease (AD) is still ill defined. AD involves an abnormal accumulation of amyloid-ß peptides (Aß) and increased production of danger signals such as ATP. ATP can direct or indirectly, through its metabolism into adenosine, trigger adaptive astrocytic responses resulting from intracellular Ca2+ oscillations. AD also triggers an upregulation of astrocytic adenosine A2A receptors (A2AR), which blockade prevents memory dysfunction in AD. We now investigated how Aß peptides affect ATP-mediated Ca2+ responses in astrocytes measured by fluorescence live-cell imaging and whether A2AR control astrocytic Ca2+ responses mediated by ATP receptors, mainly P2X7R and P2Y1R. In primary cultures of rat astrocytes exposed to Aß1-42, ATP-evoked Ca2+ responses had a lower amplitude but a longer duration than in control astrocytes and involved P2X7R and P2Y1R, the former potentiating the later. Moreover, Aß1-42 exposure increased protein levels of P2Y1R in astrocytes. A2AR antagonism with SCH58261 controlled in a protein kinase A-dependent manner both P2X7R- and P2Y1R-mediated Ca2+ responses in astrocytes. The interplay between these purinoceptors in astrocytes was blunted upon exposure to Aß1-42. These findings uncover the ability of A2AR to regulate the inter-twinned P2X7R- and P2Y1R-mediated Ca2+ dynamics in astrocytes, which is disrupted in conditions of early AD.
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Enfermedad de Alzheimer , Astrocitos , Adenosina/metabolismo , Adenosina Trifosfato/metabolismo , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Astrocitos/metabolismo , Calcio/metabolismo , Células Cultivadas , Fragmentos de Péptidos , Ratas , Receptor de Adenosina A2A/metabolismo , Receptores Purinérgicos P2X7 , Receptores Purinérgicos P2Y1RESUMEN
BACKGROUND: Major depressive disorder (MDD) affects millions of people worldwide, but timely treatment is not often received owing in part to inaccurate subjective recall and variability in the symptom course. Objective and frequent MDD monitoring can improve subjective recall and help to guide treatment selection. Attempts have been made, with varying degrees of success, to explore the relationship between the measures of depression and passive digital phenotypes (features) extracted from smartphones and wearables devices to remotely and continuously monitor changes in symptomatology. However, a number of challenges exist for the analysis of these data. These include maintaining participant engagement over extended time periods and therefore understanding what constitutes an acceptable threshold of missing data; distinguishing between the cross-sectional and longitudinal relationships for different features to determine their utility in tracking within-individual longitudinal variation or screening individuals at high risk; and understanding the heterogeneity with which depression manifests itself in behavioral patterns quantified by the passive features. OBJECTIVE: We aimed to address these 3 challenges to inform future work in stratified analyses. METHODS: Using smartphone and wearable data collected from 479 participants with MDD, we extracted 21 features capturing mobility, sleep, and smartphone use. We investigated the impact of the number of days of available data on feature quality using the intraclass correlation coefficient and Bland-Altman analysis. We then examined the nature of the correlation between the 8-item Patient Health Questionnaire (PHQ-8) depression scale (measured every 14 days) and the features using the individual-mean correlation, repeated measures correlation, and linear mixed effects model. Furthermore, we stratified the participants based on their behavioral difference, quantified by the features, between periods of high (depression) and low (no depression) PHQ-8 scores using the Gaussian mixture model. RESULTS: We demonstrated that at least 8 (range 2-12) days were needed for reliable calculation of most of the features in the 14-day time window. We observed that features such as sleep onset time correlated better with PHQ-8 scores cross-sectionally than longitudinally, whereas features such as wakefulness after sleep onset correlated well with PHQ-8 longitudinally but worse cross-sectionally. Finally, we found that participants could be separated into 3 distinct clusters according to their behavioral difference between periods of depression and periods of no depression. CONCLUSIONS: This work contributes to our understanding of how these mobile health-derived features are associated with depression symptom severity to inform future work in stratified analyses.
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Trastorno Depresivo Mayor , Telemedicina , Dispositivos Electrónicos Vestibles , Humanos , Teléfono Inteligente , Estudios Transversales , Trastorno Depresivo Mayor/diagnóstico , Estudios RetrospectivosRESUMEN
The HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is the most common neurological manifestation associated with human T-cell lymphotropic virus type-1 (HTLV-1) infection. Although cognitive impairment has been highlighted in the spectrum of HTLV-1 neurological manifestations, it may go unnoticed in those who do not spontaneously report it. We aimed at evaluating the applicability of a self-perceived memory score (SMS) and the cognitive event-related potential (P300) for early detection of cognitive impairment in HTLV-1-infected people. The SMS was measured by a 0-10 point numeric scale combined with a sad-happy face rating scale. The higher the number, the better was the SMS. The P300 was obtained through an oddball paradigm with a mental counting task. The participants were 15 (21.4%) individuals with HAM/TSP, 20 (28.6%) HTLV-1 asymptomatic carriers, and 35 (50%) seronegative controls. We found that SMS (p < 0.001) and P300 latency (p < 0.001) got progressively worse from the seronegative controls to the asymptomatic carriers and then to the HAM/TSP. The results that indicated cognitive impairment were SMS < 7.2 points and P300 latency > 369.0 ms. The HAM/TSP group showed the highest prevalence of altered P300 (80%) and SMS (87%). Interestingly, the asymptomatic group also presented significantly higher prevalence of altered SMS (60%) and P300 (35%) when compared to controls (< 10%). The frequency of cognitive impairment was 16 times higher in the HTLV-1 asymptomatic group and 69 times higher in the HAM/TSP group when compared to controls. The use of SMS in the medical consultation was a useful and easy-to-apply method to screen HTLV-1-infected subjects for everyday memory complaints.
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Disfunción Cognitiva , Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Portador Sano/diagnóstico , Cognición , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/diagnóstico , Infecciones por HTLV-I/complicaciones , Infecciones por HTLV-I/diagnóstico , HumanosRESUMEN
While network analyses have stimulated a renewed interest in understanding patterns and drivers of specialization within communities, few studies have explored specialization within populations. Thus, in plant populations, causes and consequences of individual variation in their interactions with mutualistic animals remain poorly understood. Studying a Brazilian pepper (Schinus terebinthifolia) population, we measured the extent of individual variation in interactions with seed dispersers and tested whether connectivity (number of seed dispersers) and specialization (exclusiveness of partners) are associated with phenotypic and phenological traits of individuals and their spatial context. We found that: (i) individuals varied broadly in their connectivity and specialization on seed dispersers; (ii) phenotypic traits and spatial context matter more than fruiting duration in determining how many and how exclusive are seed dispersers of an individual; (iii) the individual-based network was nested and indicated that the less connected individuals were shorter, occurred in neighborhoods with fewer fruits, and tended to interact with a subset of the partners of more generalist individuals which, in turn, were taller and inserted in higher fruit density neighborhoods; (iv) modularity indicated the existence of subsets of individuals that interacted disproportionately with distinct groups of partners, which may occur due to differences in bird habitat use across the landscape. Our study underlines a remarkable interindividual variation that is overlooked when interactions are compiled to describe species-level interactions. Traits and spatial contexts that define variation among individuals may have important implications not only for fitness but also for sampling and description of interactions at species level.
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Plantas , Árboles , Animales , Aves , Ecosistema , SemillasRESUMEN
BACKGROUND AND OBJECTIVES: Intravenous thrombolysis (IV-rtPA) has been suggested as a potential cause of myocardial infarction (MI) after acute ischemic stroke (AIS), with randomized clinical trials showing a higher number of cardiac events within the thrombolysis group. We assessed the prevalence and MI mechanisms after IV-rtPA for AIS. METHODS: Retrospective review of consecutive AIS patients admitted to six stroke units and systematic literature review searching for AIS patients who suffered a MI less than 24 h after IV-rtPA. In those with available coronary angiography, MI etiology was defined as atherosclerotic or embolic. Patients' characteristics were compared between groups. RESULTS: Fifty-two patients were included. Thirty-two patients (61.5%) derived from hospital cases, after reviewing 6958 patients treated with IV-rtPA [0.5% (95% CI 0.38-0.54) of total hospital cases]. After coronary angiography (n = 25, 48.1%), 14 (54%) patients were considered to have an atherosclerotic MI, and 11 (46%) due to coronary embolism. Patients with an embolic MI more frequently had a cardioembolic AIS (72.7% vs 28.6%; p-value = 0.047) and an intracardiac thrombus (27.3% vs 0.0%; p-value = 0.044). Although not statistically significant, patients with an embolic MI had apparent lower time intervals between starting IV-rtPA infusion and MI occurrence [2 h (0.2-3.0) vs 3 h (1.0-15.0); p-value = 0.134]. CONCLUSIONS: MI within the first 24 h after IV-rtPA for AIS is an infrequent event, and more frequently non-embolic. However, the prevalence of embolic MI was superior to what is found in the general population with MI. There was an association between the pathophysiology of AIS and MI. The low number of events and publication bias may have limited our conclusions.
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Accidente Cerebrovascular Isquémico , Infarto del Miocardio , Terapia Trombolítica , Activador de Tejido Plasminógeno , Administración Intravenosa , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/epidemiología , Estudios Retrospectivos , Terapia Trombolítica/efectos adversos , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/efectos adversosRESUMEN
BACKGROUND: The Score Committee of the European Foot and Ankle Society (EFAS) developed, validated, and published the EFAS Score in ten languages (English, German, French, Italian, Polish, Dutch, Swedish, Finnish, Turkish, Portuguese). From other languages under validation, the Portuguese version completed data acquisition and underwent further validation. METHODS: The Portuguese version of the EFAS Score was developed and validated in three stages: 1) item (question) identification (completed during initial validation study), 2) item reduction and scale exploration (completed during initial validation study), 3) confirmatory analyses and responsiveness of Portuguese version (completed during initial validation study in nine other languages). The data were collected pre-operatively and post-operatively at a minimum follow-up of 3 months and mean follow-up of 6 months. Item reduction, scale exploration, confirmatory analyses and responsiveness were executed using classical test theory and item response theory. RESULTS: The internal consistency was confirmed in the Portuguese version (Cronbach's Alpha 0.84). The Standard Error of Measurement (SEM) was 0.27 and is similar to other language versions. Between baseline and follow-up, 69.4% of patients showed an improvement on their EFAS score, with adequate responsiveness (effect size 0.64). CONCLUSIONS: The Portuguese EFAS Score version was successfully validated in patients with a wide variety of foot and ankle pathologies. All score versions are freely available at www.efas.net.
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Tobillo , Lenguaje , Tobillo/cirugía , Articulación del Tobillo , Humanos , Portugal , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
BACKGROUND AND PURPOSE: The mechanisms linking systemic inflammation to poor outcome in ischemic stroke are not fully understood. The authors investigated if peripheral inflammation following reperfusion therapy leads to an increase in cerebral edema (CED), thus hindering the clinical recovery. METHODS: We designed a single-center study conducted at Centro Hospitalar Universitário São João between 2017 and 2019. Inclusion criteria were being adult, having an anterior circulation acute ischemic stroke, and receiving reperfusion therapy. Neutrophil-to-lymphocyte, platelet-to-lymphocyte ratios, and the systemic inflammatory response syndrome criteria were determined. The presence and grade of CED were evaluated on the computed tomography performed 24 hours following event. The clinical outcomes included early neurological deterioration and functional dependence at 90 days. Adjusted odds ratio and 95% CI were obtained by ordinal and logistic regression models. Optimal cutoff values were defined using receiver operating characteristic analysis in the training cohort and validated in an independent data set. RESULTS: Five hundred fifty-three patients were included. Neutrophil-to-lymphocyte increased with higher degrees of CED at 24 hours (adjusted odds ratio, 1.34 [1.09-1.68], P<0.01) and was associated with early neurological deterioration (adjusted odds ratio, 1.30 [1.04-1.63], P<0.05) and poor functional status at 90 days (adjusted odds ratio, 1.79 [1.28-2.48], P<0.01). Platelet-to-lymphocyte was not associated with the outcomes. Systemic inflammatory response syndrome was related to CED due to altered white blood cell counts. Neutrophil-to-lymphocyte was the best predictor with an area under the curve around 0.7. Neutrophil-to-lymphocyte ≥7 had and accuracy, sensitivity, and specificity around 60%. CONCLUSIONS: Increased systemic inflammation is linked to the severity of CED early after reperfusion therapy in stroke. Easily obtained inflammatory markers convey early warning alerts for patients at risk of severe neurological complications with an impact on long-term functional outcome. CED quantification should be included as an end point in proof-of-concept trials in immunomodulation in stroke.
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Linfocitos/citología , Neutrófilos/citología , Reperfusión/métodos , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/terapia , Adolescente , Adulto , Anciano , Plaquetas , Edema Encefálico/patología , Recuento de Células , Edema , Humanos , Inflamación , Recuento de Linfocitos , Persona de Mediana Edad , Oportunidad Relativa , Estudios Prospectivos , Curva ROC , Análisis de Regresión , Estudios Retrospectivos , Trombectomía/métodos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto JovenRESUMEN
Brain morphology varies across the ageing trajectory and the prediction of a person's age using brain features can aid the detection of abnormalities in the ageing process. Existing studies on such "brain age prediction" vary widely in terms of their methods and type of data, so at present the most accurate and generalisable methodological approach is unclear. Therefore, we used the UK Biobank data set (N = 10,824, age range 47-73) to compare the performance of the machine learning models support vector regression, relevance vector regression and Gaussian process regression on whole-brain region-based or voxel-based structural magnetic resonance imaging data with or without dimensionality reduction through principal component analysis. Performance was assessed in the validation set through cross-validation as well as an independent test set. The models achieved mean absolute errors between 3.7 and 4.7 years, with those trained on voxel-level data with principal component analysis performing best. Overall, we observed little difference in performance between models trained on the same data type, indicating that the type of input data had greater impact on performance than model choice. All code is provided online in the hope that this will aid future research.
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Encéfalo/anatomía & histología , Encéfalo/diagnóstico por imagen , Aprendizaje Automático , Imagen por Resonancia Magnética/normas , Neuroimagen/normas , Factores de Edad , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Neuroimagen/métodos , Análisis de Regresión , Máquina de Vectores de SoporteRESUMEN
INTRODUCTION: Surgically assisted rapid maxillary expansion is a widely used surgical procedure for resolving transverse maxillary occlusal changes in patients with bone maturity. However, few studies about the postoperative morphologic alterations in the nasal cavity in its inferior portion and the nasal septum positioning exist. METHODS: The linear nasal septum measurements of 26 adult patients treated with surgically assisted rapid maxillary expansion from 2009 to 2013 were assessed through a retrospective analysis of cone-beam computed tomographies, in Digital Imaging and Communications in Medicine files, through the Dolphin Imaging program (Dolphin Imaging and Management Solutions, Chatsworth, Calif), aimed to identify significant changes during 3 time periods of the treatment: preoperative, immediately after the palatal expansion device locking (immediate postoperative), and 6-months postoperative (late postoperative). The analyses were performed in the inferior third of the nasal septum, from 4 equidistant points in anteroposterior position and height, using fixed cranial references for lateral measures of displacement. RESULTS: No significant difference was found between preoperative, immediate postoperative, and late postoperative measurements in the 4 fixed nasal septum measurements, applying the analysis of variance test with a significance level of 5%. Comparing the surgical times alone, we found no statistically significant difference between the right and left sides applying the Student t test, which also showed symmetry in the nasal septum. CONCLUSIONS: The measurements of the nasal septum did not change in the different surgical times throughout their inferior extension, and they remained symmetrical throughout patients' follow-up period.
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Tabique Nasal , Técnica de Expansión Palatina , Adulto , Tomografía Computarizada de Haz Cónico , Humanos , Maxilar , Cavidad Nasal , Tabique Nasal/diagnóstico por imagen , Tabique Nasal/cirugía , Estudios RetrospectivosRESUMEN
Because lignin is a macromolecule that is a sustainable source of aromatic compounds, model substrates are commonly used to increase our understanding of its complex structure. However, few methods have been described for the synthesis of these models. Herein, we describe a new route towards the synthesis of ß-O-4 lignin models by intermolecular O-H insertion reactions with simple and stable diazocarbonyls. The benefits of this developed method were shorter reaction times and high yields, as well as mild and environmentally friendly conditions.
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Grazioli, R, Loturco, I, Baroni, BM, Oliveira, GS, Saciura, V, Vanoni, E, Dias, R, Veeck, F, Pinto, RS, and Cadore, EL. Coronavirus disease-19 quarantine is more detrimental than traditional off-season on physical conditioning of professional soccer players. J Strength Cond Res 34(12): 3316-3320, 2020-Beyond the severe health crisis, the coronavirus disease 2019 has also affected the high-performance sports scenario. In soccer, practitioners are concerned about the effects of long-term detraining on players' conditioning, and caution is required when activities return. This study assessed body composition, jump and sprint performance, hamstring eccentric strength, and intermittent cardiorespiratory fitness of 23 male professional soccer players who returned to training activities after 63 days of quarantine. The results were compared with their physical condition assessed before a pre-season phase as soon as they returned to training after a regular 24-day off-season period. In comparison with after off-season assessments, the quarantine induced significant increases in body mass, body fat mass, 10- and 20-m sprint times as well as decreases in countermovement jump height (p < 0.05). There were no significant changes in hamstring eccentric strength, squat jump height, and cardiorespiratory fitness (p > 0.05). In summary, we showed that 63 days of quarantine impaired several physical performance measures compared with regular off-season in soccer players. Given the present results, special attention should be given to body composition-related and speed power-related capabilities after long-term detraining in professional soccer.
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COVID-19/epidemiología , Cuarentena/estadística & datos numéricos , Fútbol/fisiología , Adulto , Rendimiento Atlético , Composición Corporal , Capacidad Cardiovascular/fisiología , Ejercicio Físico , Prueba de Esfuerzo , Músculos Isquiosurales/fisiología , Humanos , Masculino , Fuerza Muscular/fisiología , Pandemias , Postura , Carrera/fisiología , SARS-CoV-2 , Adulto JovenRESUMEN
South America holds 30% of the world's avifauna, with the Atlantic Forest representing one of the richest regions of the Neotropics. Here we have compiled a data set on Brazilian Atlantic Forest bird occurrence (150,423) and abundance samples (N = 832 bird species; 33,119 bird individuals) using multiple methods, including qualitative surveys, mist nets, point counts, and line transects). We used four main sources of data: museum collections, on-line databases, literature sources, and unpublished reports. The data set comprises 4,122 localities and data from 1815 to 2017. Most studies were conducted in the Florestas de Interior (1,510 localities) and Serra do Mar (1,280 localities) biogeographic sub-regions. Considering the three main quantitative methods (mist net, point count, and line transect), we compiled abundance data for 745 species in 576 communities. In the data set, the most frequent species were Basileuterus culicivorus, Cyclaris gujanensis, and Conophaga lineata. There were 71 singletons, such as Lipaugus conditus and Calyptura cristata. We suggest that this small number of records reinforces the critical situation of these taxa in the Atlantic Forest. The information provided in this data set can be used for macroecological studies and to foster conservation strategies in this biodiversity hotspot. No copyright restrictions are associated with the data set. Please cite this Data Paper if data are used in publications and teaching events.
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An enantiodivergent method for the synthesis of multiply substituted allenes is described. Highly enantioenriched, point-chiral boronic esters were synthesized by homologation of α-seleno alkenyl boronic esters with lithiated carbamates and eliminated to form axially chiral allene products. By employing either oxidative or alkylative conditions, both syn and anti elimination could be achieved with complete stereospecificity. The process enables the synthesis of either M or Pâ allenes from a single isomer of a point-chiral precursor and can be employed for the enantioselective assembly of di-, tri-, and tetrasubstituted allenes.
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COVID-19/complicaciones , Rasgo Drepanocítico/complicaciones , Enfermedades Vasculares/diagnóstico , COVID-19/virología , Resultado Fatal , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2/genética , SARS-CoV-2/fisiología , Enfermedades Vasculares/etiología , Enfermedades Vasculares/terapiaRESUMEN
BACKGROUND: Clinical and subclinical (covert) stroke is a cause of cognitive loss and functional impairment. In the AVERROES trial, we performed serial brain magnetic resonance imaging (MRI) scans in a subgroup to explore the effect of apixaban, compared with aspirin, on clinical and covert brain infarction and on microbleeds in patients with atrial fibrillation. METHODS: We performed brain MRI (T1, T2, fluid-attenuated inversion recovery, and T2* gradient echo sequences) in 1,180 at baseline and in 931 participants at follow-up. Mean interval from baseline to follow-up MRI scans was 1.0 year. The primary outcome was a composite of clinical ischemic stroke and covert embolic pattern infarction (defined as infarction >1.5 cm, cortical-based infarction, or new multiterritory infarction). Secondary outcomes included new MRI-detected brain infarcts and microbleeds and change in white matter hyperintensities. RESULTS: Baseline MRI scans revealed brain infarct(s) in 26.2% and microbleed(s) in 10.5%. The rate of the primary outcomes was 2.0% in the apixaban group and 3.3% in the aspirin group (hazard ratio [HR] 0.55; 0.27-1.14) from baseline to follow-up MRI scan (mean duration of follow-up: 1 year). In those who completed baseline and follow-up MRI scans, the rate of new infarction detected on MRI was 2.5% in the apixaban group and 2.2% in the aspirin group (HR 1.09; 0.47-2.52), but new infarcts were smaller in the apixaban group (P = .03). There was no difference in proportion with new microbleeds on follow-up MRI (HR 0.92; 0.53-1.60) between treatment groups. CONCLUSIONS: Apixaban treatment was associated with a nonsignificant trend toward reduction in the composite of clinical ischemic stroke and covert embolic-pattern infarction and did not increase the number of microbleeds in patients with atrial fibrillation compared with aspirin.
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Aspirina/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Infarto Encefálico/prevención & control , Hemorragia Cerebral/inducido químicamente , Inhibidores del Factor Xa/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pirazoles/uso terapéutico , Piridonas/uso terapéutico , Anciano , Fibrilación Atrial/complicaciones , Encéfalo/diagnóstico por imagen , Infarto Encefálico/diagnóstico por imagen , Infarto Encefálico/etiología , Hemorragia Cerebral/diagnóstico por imagen , Embolia/etiología , Embolia/prevención & control , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Modelos de Riesgos ProporcionalesRESUMEN
Among the different types of diazocarbonyl substrates found in the literature to date, α,ß-unsaturated diazoketones have proven to be very promising as multifunctional intermediates. Possessing a diazo group, a ketone function and a double bond all together in a single molecule, these compounds constitute versatile building blocks for synthesis. For example, double bond functionalization, followed by intramolecular insertion reactions, can be a short alternative to prepare several rings or heterocyclic compounds. Although there are many efficient methods to prepare diazoketones, very few can be extended to the synthesis of the a,ß-unsaturated diazoketones; this is likely responsible for their limited application in synthesis. Unfortunately, the classical methods to prepare saturated- or aryl-diazoketones (acylation of diazomethane with acyl chlorides or mixed anhydrides) are not suitable for preparing a,ß-unsaturated diazoketones, since pyrazolines (dipolar cycloaddition products from the reaction between diazomethane and the double bond) are formed. Although Danheiser's two-step detrifluoroacetylative procedure (starting from a,ß-unsaturated methyl ketones) is considered the best general method, it cannot be applied to the synthesis of all types of a,ß-unsaturated diazoketones. For example, the synthesis of more complex unsaturated diazoketones, as well as those with epimerizable stereocenters in the γ position, was never described before. Another point is related to the geometry of the double bond, since practically all examples described thus far refer to unsaturated diazoketones with E geometry. In recent years, our research group developed two new Horner-Wadsworth-Emmons reagents (containing a diazocarbonyl function) that could be easily applied in the one-step preparation of α,ß-unsaturated diazoketones from aldehydes. Not only were we able to selectively synthesize E- and Z-unsaturated diazoketones, but also to employ these useful platforms in the short synthesis of several nitrogen heterocycles such as indolizidines, quinolizidines, piperidines, and pyrrolidines. Our purpose in this Account is to introduce this class of diazoketone and provide a brief historical overview, culminating in how we developed a general methodology to prepare them. In continuation, we wish to call of the reader's attention to these important building blocks, showing how we could apply them to the synthesis of several nitrogen heterocycles, including the very short preparation of some popular alkaloids. The reader will also notice that the combination of these three important functions in the same molecule makes these compounds special as well as provides powerful platforms to access many important molecules in a direct fashion.
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BACKGROUND: Allograft fresh-frozen bone (FFB) is an alternative to autogenous bone for oral implantation due to bone quantity availability and lower morbidity for patients. Few specific studies about the use of FFB for reconstructing the posterior mandibular alveolar crest have been conducted. OBJECTIVE: The objective of this study was to evaluate histological, histomorphometrical, and volumetric aspects of FFB allografts used to augment atrophied posterior mandible bone ridges. MATERIALS AND METHODS: Sixteen hemi-mandibles of twelve patients presenting with critical alveolar atrophy were three-dimensionally reconstructed using corticocancellous FFB. Thirty blocks were fixed with titanium screws and covered with particulate bovine bone mineral and collagen membrane. Volumetric data were obtained by cone beam computed tomography analysis after 6 months, implants were inserted, and bone biopsies were harvested and sent for histological and histomorphometric analyses. RESULTS: The blocks were distributed between nine female and three male patients (mean age, 50.9 ± 8.3 years). Thirty implants were installed, and the implant survival rate was 96.66%. Histology demonstrated newly formed vital bone contacting residual acellular allograft bone and connective tissue. The histomorphometric analysis showed 18.9 ± 8.1% newly formed bone and 32.5 ± 14.8% allograft residual bone. Graft absorption was 45% for height and volume, and both measures were significantly different (P < 0.001). CONCLUSION: Fresh-frozen allografts are a viable alternative for reconstructing an atrophied mandible in the posterior region, allowing for new bone formation, installation of implants, and prosthetic loading.