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This work reports that synchronization of Mott material-based nanoscale coupled spiking oscillators can be drastically different from that in conventional harmonic oscillators. We investigated the synchronization of spiking nanooscillators mediated by thermal interactions due to the close physical proximity of the devices. Controlling the driving voltage enables in-phase 1:1 and 2:1 integer synchronization modes between neighboring oscillators. Transition between these two integer modes occurs through an unusual stochastic synchronization regime instead of the loss of spiking coherence. In the stochastic synchronization regime, random length spiking sequences belonging to the 1:1 and 2:1 integer modes are intermixed. The occurrence of this stochasticity is an important factor that must be taken into account in the design of large-scale spiking networks for hardware-level implementation of novel computational paradigms such as neuromorphic and stochastic computing.
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FOXP1 syndrome caused by haploinsufficiency of the forkhead box protein P1 (FOXP1) gene is a neurodevelopmental disorder that manifests motor dysfunction, intellectual disability, autism, and language impairment. In this study, we used a Foxp1+/- mouse model to address whether cognitive and motor deficits in FOXP1 syndrome are associated with mitochondrial dysfunction and oxidative stress. Here, we show that genes with a role in mitochondrial biogenesis and dynamics (e.g., Foxo1, Pgc-1α, Tfam, Opa1, and Drp1) were dysregulated in the striatum of Foxp1+/- mice at different postnatal stages. Furthermore, these animals exhibit a reduced mitochondrial membrane potential and complex I activity, as well as decreased expression of the antioxidants superoxide dismutase 2 (Sod2) and glutathione (GSH), resulting in increased oxidative stress and lipid peroxidation. These features can explain the reduced neurite branching, learning and memory, endurance, and motor coordination that we observed in these animals. Taken together, we provide strong evidence of mitochondrial dysfunction in Foxp1+/- mice, suggesting that insufficient energy supply and excessive oxidative stress underlie the cognitive and motor impairment in FOXP1 deficiency.
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Fatores de Transcrição Forkhead/genética , Deficiência Intelectual/genética , Transtornos Motores/genética , Proteínas Repressoras/genética , Animais , Transtorno do Espectro Autista/genética , Transtorno Autístico/metabolismo , Cognição/fisiologia , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/deficiência , Fatores de Transcrição Forkhead/metabolismo , Haploinsuficiência/genética , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/genética , Mitocôndrias/metabolismo , Atividade Motora/genética , Transtornos Motores/metabolismo , Transtornos do Neurodesenvolvimento/metabolismo , Neurogênese , Estresse Oxidativo/fisiologia , Proteínas Repressoras/deficiência , Proteínas Repressoras/metabolismoRESUMO
OBJECTIVES: Our goal was to compare the chest computed tomography (CT) imaging findings of COVID-19 in lung transplant recipients (LTR) and a group of non-transplanted controls (NTC). METHODS: This retrospective study included 51 consecutive LTR hospitalized with COVID-19 from two centers. A total of 75 NTC were included for comparison. Images were classified regarding the standardized RSNA category, main pattern of lung attenuation, and longitudinal and axial distribution. Quantitative CT (QCT) analysis was performed to evaluate percentage of high attenuation areas (%HAA, threshold -250 to -700 HU). CT scoring was used to measure severity of parenchymal abnormalities. RESULTS: The imaging findings of COVID-19 in LTR were significantly different from controls regarding the RSNA classification and pattern of lung attenuation. LTR had a significantly higher proportion of patients with an indeterminate pattern on CT (0.31 vs. 0.11, p = 0.014). The most frequent pattern of attenuation in LTR was predominantly consolidation (0.39 vs. 0.22, p = 0.144) followed by a mixed pattern of ground-glass opacities (GGO) and consolidation (0.37 vs. 0.20, adjusted p = 0.102). On the other hand, the most common pattern in NTC was GGO predominant (0.58 vs. 0.24 of LTR, p = 0.001). LTR had significantly more severe parenchymal disease measured by CT score and %HAA by QCT (0.372 ± 0.08 vs. 0.148 ± 0.06, p < 0.001). CONCLUSION: The most frequent finding of COVID-19 in LTR is a predominant pattern of consolidation. Compared to NTC, LTR more frequently demonstrated an indeterminate pattern according to the RSNA classification and more extensive lung abnormalities on QCT and semi-quantitative scoring. KEY POINTS: ⢠The most common CT finding of COVID-19 in LTR is a predominant pattern of consolidation followed by a mixed pattern of GGO and consolidation, while controls more often have a predominant pattern of GGO. ⢠LTR more often presents with an indeterminate pattern of COVID-19 by RSNA classification than controls; therefore, molecular testing for COVID-19 is essential for LTR presenting with lower airway infection independently of imaging findings. ⢠LTR had more extensive disease by semi-quantitative CT score and increased percentage areas of high attenuation on QCT.
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COVID-19 , Humanos , Teste para COVID-19 , Estudos Retrospectivos , Transplantados , SARS-CoV-2 , Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodosRESUMO
The long-term success of forest restoration programs can be improved using climate-based species distribution models (SDMs) to predict which tree species will tolerate climate change. However, as SDMs cannot estimate if species will recruit at these habitats, determining whether their predictions apply to early life-cycle stages of trees is critical to support such a usage. For this, we propose sowing seeds of the focal tree species under the current climate and simulated climate change conditions in target restoration sites. Thus, using of SDMs to design climate-adaptive forest restoration programs would be supported if the differences in habitat occupancy probabilities of species they predict between the current and future climate concurs with the observed differences in recruitment rates of species when sowed under the current climate and simulated climate change conditions. To test this hypothesis, we calibrated SDMs for Vachellia pennatula and Prosopis laevigata, two pioneer tree species widely recommended to restore human-degraded drylands in Mexico, and transferred them to climate change scenarios. After that, we applied the experimental approach proposed above to validate the predictions of SDMs. These models predicted that V. pennatula will decrease its habitat occupancy probabilities across Mexico, while P. laevigata was predicted to keep out their current habitat occupancy probabilities, or even increase them, in climate change scenarios. The results of the field experiment supported these predictions, as recruitment rates of V. pennatula were lower under simulated climate change than under the current climate, while no differences were found for the recruitment rates of P. laevigata between these environmental conditions. These findings demonstrate that SDMs provide meaningful insights for designing climate-adaptive forest restoration programs but, before applying this methodology, predictions of these models must be validated with field experiments to determine whether the focal tree species will recruit under climate change conditions. Moreover, as the pioneer trees used to test our proposal seem to be differentially sensitive to climate change, this approach also allows establishing what species must be prescribed to restore forests with a view to the future and what species must be avoided in these practices.
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Mudança Climática , Florestas , Árvores , Humanos , Ecossistema , Previsões , MéxicoRESUMO
Slow-wave sleep cortical brain activity, conformed by slow-oscillations and sleep spindles, plays a key role in memory consolidation. The increase of the power of the slow-wave events, obtained by auditory sensory stimulation, positively correlates with memory consolidation performance. However, little is known about the experimental protocol maximizing this effect, which could be induced by the power of slow-oscillation, the number of sleep spindles, or the timing of both events' co-occurrence. Using a mean-field model of thalamocortical activity, we studied the effect of several stimulation protocols, varying the pulse shape, duration, amplitude, and frequency, as well as a target-phase using a closed-loop approach. We evaluated the effect of these parameters on slow-oscillations (SO) and sleep-spindles (SP), considering: (i) the power at the frequency bands of interest, (ii) the number of SO and SP, (iii) co-occurrences between SO and SP, and (iv) synchronization of SP with the up-peak of the SO. The first three targets are maximized using a decreasing ramp pulse with a pulse duration of 50 ms. Also, we observed a reduction in the number of SO when increasing the stimulus energy by rising its amplitude. To assess the target-phase parameter, we applied closed-loop stimulation at 0°, 45°, and 90° of the phase of the narrow-band filtered ongoing activity, at 0.85 Hz as central frequency. The 0° stimulation produces better results in the power and number of SO and SP than the rhythmic or random stimulation. On the other hand, stimulating at 45° or 90° change the timing distribution of spindles centers but with fewer co-occurrences than rhythmic and 0° phase. Finally, we propose the application of closed-loop stimulation at the rising zero-cross point using pulses with a decreasing ramp shape and 50 ms of duration for future experimental work.
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Consolidação da Memória/fisiologia , Modelos Neurológicos , Sono de Ondas Lentas/fisiologia , Sono/fisiologia , Tálamo/fisiologia , Estimulação Acústica , Córtex Cerebral/fisiologia , Biologia Computacional , Eletroencefalografia , HumanosRESUMO
BACKGROUND. Current guidelines recommend visual evaluation of coronary artery calcium (CAC) on all nongated noncontrast chest CT examinations. However, chest CT examinations are often performed with contrast material administration. OBJECTIVE. The purpose of our study was to evaluate diagnostic performance, prognostic utility, and interobserver agreement of visual CAC assessment on chest CT performed for other indications. METHODS. This retrospective study included 260 patients (158 men, 102 women; mean age, 60 ± 11 [SD] years) who underwent both nongated chest CT (contrast-enhanced in 116 patients; noncontrast in 144 patients) and cardiac calcium score CT within a 12-month interval. A cardiothoracic radiologist visually assessed CAC on chest CT using an ordinal scale (absent, mild, moderate, or severe). Cardiac CT Agatston calcium scores were quantified according to established guidelines and were categorized as CAC absent (0), mild CAC (1-99), moderate CAC (100-299), or severe CAC (≥ 300). The diagnostic performance of chest CT for the presence of CAC was assessed using cardiac CT as the reference standard. Major adverse cardiac events (MACE) were assessed as a composite of cardiovascular death and myocardial infarction and were evaluated using Cox proportional hazards models. A second cardiothoracic radiologist performed visual CAC assessments in a random subset of 50 chest CT examinations to assess interob-server agreement. RESULTS. For the presence of any CAC on cardiac CT, contrast-enhanced and non-contrast chest CT had sensitivity of 83% (62/75) and 89% (85/95) (p = .20) and specificity of 100% (41/41) and 100% (49/49) (p = .99). CAC present on cardiac CT was misclassified as absent on 13 contrast-enhanced and 10 noncontrast chest CT examinations; Agatston score was less than 30 in all such patients, and none experienced any MACE. The visual ordinal CAC score was associated with MACE for contrast-enhanced chest CT (hazard ratio [HR] = 4.5 [95% CI, 1.2-16.4], p = .02) and noncontrast chest CT (HR = 3.4 [95% CI, 1.5-7.8], p = .003). Interobserver agreement was excellent for contrast-enhanced (κ = 0.89) and noncontrast (κ = 0.95) chest CT. CONCLUSION. Visual ordinal CAC assessment on both contrast-enhanced and non-contrast chest CT has high diagnostic performance, prognostic utility, and interobserver agreement. CLINICAL IMPACT. Routine reporting of CAC on all chest CT examinations regardless of clinical indication and contrast material administration could identify a large number of patients with previously unknown CAC who might benefit from preventive treatment.
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Doença da Artéria Coronariana , Calcificação Vascular , Idoso , Cálcio , Meios de Contraste , Angiografia Coronária/métodos , Doença da Artéria Coronariana/complicações , Vasos Coronários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X/métodos , Calcificação Vascular/complicaçõesRESUMO
The use of substances or conditions as elicitors can significantly increase the production of secondary metabolites. In this research, the effects of different elicitors on the production of antioxidant secondary metabolites were evaluated in a strain of Ganoderma sp. The elicitors tested were pH changes in different growth phases of the fungus (pH 3, 5.5 and 8), different concentrations of peptone as a nitrogen source (1 g/L and 10 g/L), and the addition of chemical agents to the culture medium (ethanol, growth regulators, and salts). The alkaline pH during the stationary phase and the high availability of nitrogen were effective elicitors, producing cultures with higher antioxidant activity (37.87 g/L and 43.13 g/L dry biomass) although there were no significant differences with other treatments.
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Antioxidantes , Ganoderma , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Costa Rica , Ganoderma/metabolismo , NitrogênioRESUMO
Peer learning is a quality initiative used to identify potential areas of practice improvement, both on a patient level and on a systemic level. Opportunities for peer learning include review of prior imaging studies, evaluation of cases from multidisciplinary case conferences, and review of radiology trainees' call cases. Peer learning is non-punitive and focuses on promoting life-long learning. It seeks to identify and disseminate learning opportunities and areas for systems improvement compared to traditional peer review. Learning opportunities arise from peer learning through both individual communication of cases reviewed for routine work, as well as through anonymous presentation of aggregate cases in an educational format. In conjunction with other tools such as root cause analysis, peer learning can be used to guide future practice improvement opportunities. This guide provides definitions of terms and a synthetic evidence review regarding peer review and peer learning, as well as medicolegal and jurisdictional considerations. Important aspects of what makes an effective peer learning program and best practices for implementing such a program are presented. The guide is intended to be a living document that will be updated regularly as new data emerges and peer learning continues to evolve in radiology practices.
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Radiologia , Humanos , Aprendizagem , Revisão por Pares , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The cardiothoracic ratio (CTR) is commonly assessed on chest radiography for detection of cardiac chamber enlargement, but the traditional cutpoint of 0.5 has low specificity. We sought to evaluate the diagnostic accuracy of new measurement techniques for the detection of cardiac enlargement on chest radiographs. METHODS: We obtained retrospective cross-sectional data on consecutive patients who underwent both chest radiography and cardiac magnetic resonance imaging (MRI) within a 14-day interval between 2006 and 2016 at a large academic hospital network. We established the presence of cardiac chamber enlargement using cardiac MRI as the reference standard. We evaluated the diagnostic performance of different techniques for measuring heart size and CTR on frontal chest radiographs. RESULTS: Of 152 patients included, 81 (53%) were men and the mean age was 52 years. Maximum heart diameter had the highest area under the receiver operating characteristic curve for detection of cardiac enlargement (0.827, 95% confidence interval 0.760-0.894). In the subgroup of posteroanterior chest radiography studies (n = 101), a CTR cutpoint of 0.50 had only moderate sensitivity (72%) and specificity (72%). In men, a maximum heart diameter cutpoint of 15 cm had a sensitivity of 86% and a negative likelihood ratio of 0.24, and a cutpoint of 19 cm had a specificity of 100% and a positive likelihood ratio of infinity. In women, a maximum heart diameter cutpoint of 13 cm had a sensitivity of 91% and a negative likelihood ratio of 0.15, and a cutpoint of 17 cm had a specificity of 91% and a positive likelihood ratio of 3.5. INTERPRETATION: A traditional CTR cutpoint of 0.5 has limited diagnostic value. Simple heart diameter measurements have higher diagnostic performance measures than CTR.
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Cardiomegalia/diagnóstico por imagem , Coração/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética/normas , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Radiografia Torácica/métodos , Radiografia Torácica/normas , Padrões de Referência , Estudos Retrospectivos , Sensibilidade e Especificidade , Método Simples-Cego , Adulto JovemRESUMO
BACKGROUND: Abiraterone is a medication frequently used for metastatic castrate-resistant prostate cancer. We report a case of non-sustained episodes of TdP associated with severe hypokalemia due to androgen-deprivation therapy. Few case presentations describe this association; the novelty lies in the potentially lethal cardiovascular events among cancer patients receiving hormonal therapy. CASE PRESENTATION: A 70-year-old male presented with recurrent syncope without prodrome. ECG revealed frequent ventricular ectopy, non-sustained episodes of TdP, and severe hypomagnesemia and hypokalemia. During potassium and magnesium infusion for repletion, the patient underwent temporary transvenous atrial pacing. As part of the work-up, coronary angiography revealed a mild coronary artery disease, and transthoracic echocardiogram showed a moderately depressed ejection fraction. After electrolyte disturbances were corrected, the QT interval normalized, and transvenous pacing was no longer necessary. Abiraterone was discontinued during the admission, and the patient returned to baseline. CONCLUSIONS: Cancer treatment is complex and requires a multidisciplinary approach. We presented a case of non-sustained TdP associated with androgen-deprivation therapy in an elderly patient with mild coronary artery disease and moderately reduced ejection fraction. Close follow-up and increased awareness are required in patients with hormonal treatment, especially in the setting of other cardiovascular risk factors.
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Acetato de Abiraterona/efeitos adversos , Antineoplásicos/efeitos adversos , Frequência Cardíaca/efeitos dos fármacos , Síndrome do QT Longo/induzido quimicamente , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Inibidores da Síntese de Esteroides/efeitos adversos , Síncope/induzido quimicamente , Torsades de Pointes/induzido quimicamente , Idoso , Estimulação Cardíaca Artificial , Hidratação , Humanos , Síndrome do QT Longo/diagnóstico por imagem , Síndrome do QT Longo/fisiopatologia , Síndrome do QT Longo/terapia , Masculino , Síncope/diagnóstico , Síncope/fisiopatologia , Síncope/terapia , Torsades de Pointes/diagnóstico , Torsades de Pointes/fisiopatologia , Torsades de Pointes/terapia , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate quantitative chest computed tomography (CT) methods for the detection of air trapping (AT) and to assess its diagnostic performance for the diagnosis of bronchiolitis obliterans syndrome (BOS) in single lung transplant (SLT) patients. METHODS: Adult patients who had a SLT at a single transplant center and underwent CT scan after transplantation were retrospectively included. CT findings of air trapping were measured by three different methods: expiratory air-trapping index (ATIexp), mean lung density on expiratory acquisition (MLDexp) and expiratory to inspiratory ratio of mean lung density (E/I-ratio(MLD). Sensitivity, specificity and diagnostic accuracy of the three methods for the detection of BOS status evaluated by serial routine measures of pulmonary function tests (gold standard) were assessed. RESULTS: Forty-six SLT patients (52.2% females, mean age 58 ± 6 years) were included in the analysis, 12 (26%) patients with a diagnosis of BOS. Quantitative CT diagnosis of AT ranged from 26 to 35%. Sensitivity, specificity and accuracy of each method for the detection of BOS were 85.7%, 84.7% and 85.0% for ATIexp, 78.5%, 93.4% and 90.0% for MLD and 64.2%, 89.1% and 83.3% E/I-ratio(MLD), respectively. CONCLUSION: Quantitative measures of AT obtained from standard CT are feasible and show high specificity and accuracy for the detection of BOS in SLT patients.
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Bronquiolite Obliterante/diagnóstico por imagem , Transplante de Pulmão/efeitos adversos , Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Antimicrobial compounds are associated with a wide range of adverse events (AE) and some of them can be potentially preventable. AIM: To characterize AE associated with antimicrobial compounds. PATIENTS AND METHODS: Retrospective analysis of AEs reported to the National Pharmacological Surveillance System from 2014 to 2017 in a regional hospital. Severity, causality and preventability were analyzed. RESULTS: Sixty events were observed in 56 patients aged 2 months to 96 years. Cases were registered mostly in hospitalized patients. The most frequent AEs were skin disorders (56.7%), followed by hepatobiliary (13.3%), and CNS events (10%). Blood, kidney, respiratory gastrointestinal and immunological disorders were less frequently registered, including cases with anaphylactic shock and Stevens-Johnson syndrome (SJS). Causal analysis indicated a definitive association in 8.3%, probable in 70% and possible in 22%. Skin lesions were mostly associated with beta-lactams, hepatobiliary disorders with antituberculosis drugs and CNS manifestations with carbapenems. Cutaneous, neurological, and hepatobiliary events appeared at a median of 4, 2.5 and 10.5 days after starting the medication, respectively. AEs were managed with withdrawal of the suspected drug (83.3%) and other auxiliary therapies. AEs were categorized as severe in 22% and one case with SJS had a fatal outcome (1.7%). Preventability analysis revealed 25% of potentially avoidable events. CONCLUSIONS: Antimicrobial AE involved a wide diversity of compounds, occurred in different hospitalization units, affected patients of a wide age range and attacked different systems or organs. An important fraction was potentially avoidable.
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Anti-Infecciosos , Hospitais Gerais , Chile/epidemiologia , Hospitalização , Humanos , Estudos RetrospectivosRESUMO
Two types of spawning strategy have been described for ommastrephid squids: coastal and oceanic. It has been suggested that ancestral ommastrephids inhabited coastal waters and expanded their distribution into the open ocean during global changes in ocean circulation in the Oligocene. This hypothesis could explain the different reproductive strategies in oceanic squids, but has never been tested in a phylogenetic context. In the present study, we assess the coastal-to-open-ocean hypothesis through inferring the evolution of reproductive traits (spawning type) of ommastrephid squids using the phylogenetic comparative method to estimate ancestral states and divergence times. This analysis was performed using a robust molecular phylogeny with three mitochondrial genes (COI, CYTB and 16S) and two nuclear genes (RHO and 18S) for nearly all species of ommastrephid squid. Our results support dividing the Ommastrephidae into the three traditional subfamilies, plus the monotypic subfamily Todaropsinae as proposed previously. Divergence times were found to be older than those suggested. Our analyses strongly suggest that early ommastrephid squids spawned in coastal areas, with some species subsequently switching to spawn in oceanic areas, supporting previous non-tested hypotheses. We found evidence of gradual evolution change of spawning type in ommastrephid squids estimated to have occurred since the Cretaceous.
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Decapodiformes/classificação , Evolução Molecular , Animais , Teorema de Bayes , Citocromos b/classificação , Citocromos b/genética , Decapodiformes/genética , Complexo IV da Cadeia de Transporte de Elétrons/classificação , Complexo IV da Cadeia de Transporte de Elétrons/genética , Filogenia , RNA Ribossômico 16S/classificação , RNA Ribossômico 16S/genética , RNA Ribossômico 18S/classificação , RNA Ribossômico 18S/genéticaRESUMO
Optimizing radiologists' performance is a major priority for managers of health services/systems, since the radiologists' reporting activity imposes a severe constraint on radiology productivity. Despite that, methods to optimize radiologists' reporting workplace layout are scarce in the literature. This study was performed in the Radiology Division (RD) of an 850-bed University-based general hospital. The analysis of the reporting workplace layout was carried out using the systematic layout planning (SLP) method, in association with cluster analysis as a complementary tool in early stages of SLP. Radiologists, architects, and hospital managers were the stakeholders consulted for the completion of different stages of the layout planning process. A step-by-step description of the proposed methodology to plan an RD reporting layout is presented. Clusters of radiologists were defined using types of exams reported and their frequency of occurrence as clustering variables. Sectors with high degree of interaction were placed in proximity in the new RD layout, with separation of noisy and quiet areas. Four reporting cells were positioned in the quiet area, grouping radiologists by subspecialty, as follows: cluster 1-abdomen; cluster 2-musculoskeletal; cluster 3-neurological, vascular and head & neck; cluster 4-thoracic and cardiac. The creation of reporting cells has the potential to limit unplanned interruptions and enhance the exchange of knowledge and information within cells, joining radiologists with the same expertise. That should lead to improvements in productivity, allowing managers to more easily monitor radiologists' performance.
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Competência Clínica/normas , Eficiência Organizacional/normas , Radiologistas/normas , Sistemas de Informação em Radiologia/organização & administração , Brasil , Eficiência , Humanos , Radiologia/organização & administração , Radiologia/normas , Sistemas de Informação em Radiologia/normasRESUMO
AIM: To describe daily displacements when using fiducial markers as surrogates for the target volume in patients with prostate cancer treated with IGRT. BACKGROUND: The higher grade of conformity achieved with the use of modern radiation technologies in prostate cancer can increase the risk of geographical miss; therefore, an associated protocol of IGRT is recommended. MATERIALS AND METHODS: A single-institution, retrospective, consecutive study was designed. 128 prostate cancer patients treated with daily on-line IGRT based on 2D kV orthogonal images were included. Daily displacement of the fiducial markers was considered as the difference between the position of the patient when using skin tattoos and the position after being relocated using fiducial markers. Measures of central tendency and dispersion were used to describe fiducial displacements. RESULTS: The implant itself took a mean time of 15 min. We did not detect any complications derived from the implant. 4296 sets of orthogonal images were identified, 128 sets of images corresponding to treatment initiation were excluded; 91 (2.1%) sets of images were excluded from the analysis after having identified that these images contained extreme outlier values. If IGRT had not been performed 25%, 10% or 5% of the treatments would have had displacements superior to 4, 7 or 9 mm respectively in any axis. CONCLUSIONS: Image guidance is required when using highly conformal techniques; otherwise, at least 10% of daily treatments could have significant displacements. IGRT based on fiducial markers, with 2D kV orthogonal images is a convenient and fast method for performing image guidance.
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BACKGROUND: Vasodilator stress perfusion cardiovascular magnetic resonance imaging is a clinically useful tool for detection of clinically significant myocardial ischaemia in adults. We report our 5-year retrospective experience with perfusion cardiovascular magnetic resonance in a large, quarternary adult congenital heart disease centre. METHODS: We reviewed all cases of perfusion cardiovascular magnetic resonance in patients referred from the adult congenital heart disease service. Dipyridamole stress perfusion cardiovascular magnetic resonance was undertaken on commercially available 1.5 and 3 T cardiovascular magnetic resonance scanners. Late gadolinium enhancement imaging was performed 8-10 minutes after completion of the rest perfusion sequence. Navigator whole-heart coronary magnetic resonance angiography was also performed where feasible. RESULTS of stress cardiovascular magnetic resonance were correlated with complementary imaging studies, surgery, and clinical outcomes. RESULTS: Over 5 years, we performed 34 stress perfusion cardiovascular magnetic resonance examinations (11 positive). In all, 84% of patients had further investigations for ischaemia in addition to cardiovascular magnetic resonance. Within a subgroup of 19 patients who had definitive alternative assessment of their coronary arteries, stress perfusion cardiovascular magnetic resonance demonstrated a sensitivity of 82% and specificity of 100%. Of the 34 studies, two were false negatives, in which the aetiology of ischaemia was extrinsic arterial compression rather than intrinsic coronary luminal narrowing. Coronary abnormalities were identified in 71% of cases who had coronary magnetic resonance angiography. CONCLUSION: Stress perfusion cardiovascular magnetic resonance is a useful and accurate tool for investigation of myocardial ischaemia in an adult congenital heart disease population with suspected non-atherosclerotic coronary abnormalities.
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Teste de Esforço , Cardiopatias Congênitas/diagnóstico , Hospitais Gerais , Imagem Cinética por Ressonância Magnética/métodos , Isquemia Miocárdica/diagnóstico , Imagem de Perfusão/métodos , Vasodilatadores , Adulto , Diagnóstico Diferencial , Feminino , Seguimentos , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/fisiopatologia , Humanos , Infusões Intravenosas , Masculino , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/fisiopatologia , Ontário , Reprodutibilidade dos Testes , Estudos Retrospectivos , Vasodilatadores/administração & dosagemRESUMO
Worldwide climate-driven shifts in the distribution of species is of special concern when it involves habitat-forming species. In the coastal environment, large Laminarian algae-kelps-form key coastal ecosystems that support complex and diverse food webs. Among kelps, Macrocystis pyrifera is the most widely distributed habitat-forming species and provides essential ecosystem services. This study aimed to establish the main drivers of future distributional changes on a global scale and use them to predict future habitat suitability. Using species distribution models (SDM), we examined the changes in global distribution of M. pyrifera under different emission scenarios with a focus on the Southeast Pacific shores. To constrain the drivers of our simulations to the most important factors controlling kelp forest distribution across spatial scales, we explored a suite of environmental variables and validated the predictions derived from the SDMs. Minimum sea surface temperature was the single most important variable explaining the global distribution of suitable habitat for M. pyrifera. Under different climate change scenarios, we always observed a decrease of suitable habitat at low latitudes, while an increase was detected in other regions, mostly at high latitudes. Along the Southeast Pacific, we observed an upper range contraction of -17.08° S of latitude for 2090-2100 under the RCP8.5 scenario, implying a loss of habitat suitability throughout the coast of Peru and poleward to -27.83° S in Chile. Along the area of Northern Chile where a complete habitat loss is predicted by our model, natural stands are under heavy exploitation. The loss of habitat suitability will take place worldwide: Significant impacts on marine biodiversity and ecosystem functioning are likely. Furthermore, changes in habitat suitability are a harbinger of massive impacts in the socio-ecological systems of the Southeast Pacific.
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Obesity, a burgeoning global health crisis, has tripled in prevalence over the past 45 years, necessitating innovative research methodologies. Adipocytes, which are responsible for energy storage, play a central role in obesity. However, most studies in this field rely on animal models or adipocyte monolayer cell cultures, which are limited in their ability to fully mimic the complex physiology of a living organism, or pose challenges in terms of cost, time consumption, and ethical considerations. These limitations prompt a shift towards alternative methodologies. In response, here we show a 3D in vitro model utilizing the 3T3-L1 cell line, aimed at faithfully replicating the metabolic intricacies of adipocytes in vivo. Using a workable cell line (3T3-L1), we produced adipocyte spheroids and differentiated them in presence and absence of TNF-α. Through a meticulous proteomic analysis, we compared the molecular profile of our adipose spheroids with that of adipose tissue from lean and obese C57BL/6J mice. This comparison demonstrated the model's efficacy in studying metabolic conditions, with TNF-α treated spheroids displaying a notable resemblance to obese white adipose tissue. Our findings underscore the model's simplicity, reproducibility, and cost-effectiveness, positioning it as a robust tool for authentically mimicking in vitro metabolic features of real adipose tissue. Notably, our model encapsulates key aspects of obesity, including insulin resistance and an obesity profile. This innovative approach has the potential to significantly impact the discovery of novel therapeutic interventions for metabolic syndrome and obesity. By providing a nuanced understanding of metabolic conditions, our 3D model stands as a transformative contribution to in vitro research, offering a pathway for the development of small molecules and biologics targeting these pervasive health issues in humans.
Assuntos
Células 3T3-L1 , Adipócitos , Obesidade , Esferoides Celulares , Animais , Camundongos , Obesidade/metabolismo , Adipócitos/metabolismo , Adipócitos/citologia , Esferoides Celulares/metabolismo , Camundongos Endogâmicos C57BL , Redes e Vias Metabólicas , Diferenciação Celular , Fator de Necrose Tumoral alfa/metabolismo , Proteômica/métodosRESUMO
Glutamate concentration at the synaptic level must be kept low in order to prevent excitotoxicity. Astrocytes play a key role in brain energetics, and also astrocytic glutamate transporters are responsible for the vast majority of glutamate uptake in CNS. Experiments with primary astrocytic cultures suggest that increased influx of glutamate cotransported with sodium at astrocytes favors its flux to the tricarboxylic acid cycle instead of the glutamate-glutamine cycle. Although metabolic coupling can be considered an emergent field of research with important recent discoveries, some basic aspects of glutamate metabolism still have not been characterized in brain tissue. Therefore, the aim of this study was to investigate whether the presence of extracellular glutamate is able to modulate the use of glutamate and glucose as energetic substrates. For this purpose, isolated hippocampi of mice were incubated with radiolabeled substrates, and CO2 radioactivity and extracellular lactate were measured. Our results point to a diminished oxidation of glucose with increasing extracellular glutamate concentration, glutamate presumably being the fuel, and might suggest that oxidation of glutamate could buffer excitotoxic conditions by high glutamate concentrations. In addition, these findings were reversed when glutamate uptake by astrocytes was impaired by the presence of (3S)-3-[[3-[[4-(trifluoromethyl)benzoyl]amino]phenyl]methoxy]-L-aspartic acid (TFB-TBOA). Taken together, our findings argue against the lactate shuttle theory, because glutamate did not cause any detectable increase in extracellular lactate content (or, presumably, in glycolysis), because the glutamate is being used as fuel instead of going to glutamine and back to neurons.
Assuntos
Glucose/metabolismo , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Sistema X-AG de Transporte de Aminoácidos/metabolismo , Animais , Ácido Aspártico/análogos & derivados , Ácido Aspártico/farmacologia , Líquido Extracelular/química , Hipocampo/efeitos dos fármacos , Masculino , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Técnicas de Cultura de Órgãos , OxirreduçãoRESUMO
OBJECTIVE: This article reviews the role of coronary calcium quantification in symptomatic patients and the pros and cons of acquiring an unenhanced coronary calcium scan in every patient with suspected coronary artery disease referred for coronary CT angiography. CONCLUSION: The acquisition of a coronary calcium scan in every symptomatic patient referred for coronary CT angiography requires a case-by-case approach.