Impact of corticosteroids on late growth of radiofrequency lesions in infant pigs: histopathological and electroanatomical findings

Aims Corticosteroids attenuate late growth of radiofrequency (RF) lesions in the thigh muscle of infant rats. We sought to assess the impact of these drugs on the late growth of RF lesions in immature swine myocardium and to determine the electroanatomical mapping (EAM) characteristics of these lesions.Methods and results Radiofrequency (60 degrees C; 60 s) lesions were created in the right atrium (n = 2) and ventricle (n = 2) of 14 piglets (age 65 days; weight 5 kg) and 3 adults. Piglets were divided into: controls (n 7) and treated (n 7), receiving hydrocortisone (10 mg/kg iv after RF) and prednisone (1 mg/kg/day) for 29 days. After 8 months, animals were sacrificed for histological analysis. in four piglets, endocardial and epicardial voltage EAM were performed.In infant groups, the dimensions of atrial (11 +/- 5 vs. 13 +/- 7 mm) and ventricular (12 +/- 3 vs. 11 +/- 3 mm) lesions were similar. in adults, atrial (6 +/- 1 mm) and ventricular (6 +/- 1 mm) lesions were smaller. in controls, ventricular lesions depicted dense fibrosis and multiple strands of fibrous tissue extending from the lesion into normal muscle. Treated piglets revealed scars exhibiting less dense fibrosis with predominance of fibroadipose tissue and less collagen proliferation. Large atrial and ventricular low-voltage areas corresponding to the macroscopic lesions were identified in all animals.Conclusion Radiofrequency lesions in infant pigs reveal late growth and invasion of normal muscle by intense collagen proliferation. Corticosteroids do not prevent late enlargement of the lesions but modulate the fibrotic proliferation. the expressive growth of the lesion may generate low-voltage areas detectable by EAM.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Discipline Cardiol, Paulista Sch Med, BR-04039030 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pathol, Paulista Sch Med, BR-04039030 São Paulo, BrazilUniversidade Federal de São Paulo, Discipline Cardiol, Paulista Sch Med, BR-04039030 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pathol, Paulista Sch Med, BR-04039030 São Paulo, BrazilWeb of Scienc

Métodos ativos de ensino de Física e medidas de autoeficácia discente

Parte da comunidade de pesquisa em ensino de Física tem devotado atenção ao estudo de métodos ativos de ensino que primam pela centralização do processo de ensino-aprendizagem no aluno. Além da aprendizagem conceitual, tais métodos buscam favorecer o desenvolvimento de habilidades associadas ao trabalho colaborativo, à argumentação de ideias e diminuir a evasão estudantil. Contudo, o sucesso de tais iniciativas depende do quanto os alunos se julgam capazes de realizar as atividades propostas pelo professor: depende do nível de autoeficácia dos alunos em realizar determinadas ações. Pesquisas apontam para uma baixa mudança em níveis de autoeficácia em função do uso de métodos ativos. Através de um estudo de caso, argumentamos que um reajuste importante nos níveis de autoeficácia pode estar ocorrendo, despercebido em função do modo como os níveis estão sendo medidos

Prognostic implications of the ID1 expression in acute myeloid leukemia patients treated in a resource-constrained setting

Introduction: The aberrant expression of the inhibitor of DNA binding (ID1) gene has been frequently associated with the leukemogenesis and prognostication acute myeloid leukemia (AML), although its clinical importance has never been investigated in patients treated outside well-controlled clinical trials. Methods: Using quantitative real-time polymerase chain reaction, we investigated the role of the ID1 expression in the clinical outcomes of non-selected patients with acute myeloid leukemia treated in a real-life setting. Results: Overall, 128 patients were enrolled. Patients with high ID1 expression had a lower 3-year overall survival (OS) rate of 9%, with the 95% confidence interval (95%CI) at 3 to 20%, compared to patients with a low ID1 expression (22%, 95%CI: 11 - 34%) (p = 0.037), although these findings did not retain significance after adjustment (hazard ratio (HR): 1.5, 95%CI: 0.98 - 2.28; p = 0.057). The ID1 expression had no impact on post-induction outcomes (disease-free survival, p = 0.648; cumulative incidence of relapse, p = 0.584). Conclusions: Although we are aware thar our data are confronted with many variables that cannot be fully controlled, including drug unavailability, risk-adapted treatment, comorbidities and the time from diagnosis to treatment initiation, we are firm believers that such an initiative can provide more realistic data on understudied populations, in particular those from low- and middle-income countries.</p

The partial inhibition of hypothalamic IRX3 exacerbates obesity

The Iroquois homeobox 3 (Irx3) gene has been identified as a functional long-range target of obesity-associated variants within the fat mass and obesity-associated protein (FTO) gene. It is highly expressed in the hypothalamus, and both whole-body knockout and hypothalamic restricted abrogation of its expression results in a lean phenotype, which is mostly explained by the resulting increased energy expenditure in the brown adipose tissue. Because of its potential implication in the pathogenesis of obesity, we evaluated the hypothalamic cell distribution of Irx3 and the outcomes of inhibiting its expression in a rodent model of diet-induced obesity. Methods: Bioinformatics tools were used to evaluate the correlations between hypothalamic Irx3 and neurotransmitters, markers of thermogenesis and obesity related phenotypes. Droplet-sequencing analysis in >20,000 hypothalamic cells was used to explore the types of hypothalamic cells expressing Irx3. Lentivirus was used to inhibit hypothalamic Irx3 and the resulting phenotype was studied. Findings: IRX3 is expressed predominantly in POMC neurons. Its expression is inhibited during prolonged fasting, as well as when mice are fed a high-fat diet. The partial inhibition of hypothalamic Irx3 using a lentivirus resulted in increased diet-induced body mass gain and adiposity due to increased caloric intake and reduced energy expenditure. Interpretation: Contrary to the results obtained when lean mice are submitted to complete inhibition of Irx3, partial inhibition of hypothalamic Irx3 in obese mice causes an exacerbation of the obese phenotype. These data suggest that at least some of the Irx3 functions in the hypothalamus are regulated according to a hormetic pattern, and modulation of its expression can be a novel approach to modifying the body's energy-handling regulation.39448460FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2013/07607-8; 2017/02983-

ULEEN: A Novel Architecture for Ultra Low-Energy Edge Neural Networks

The deployment of AI models on low-power, real-time edge devices requires accelerators for which energy, latency, and area are all first-order concerns. There are many approaches to enabling deep neural networks (DNNs) in this domain, including pruning, quantization, compression, and binary neural networks (BNNs), but with the emergence of the "extreme edge", there is now a demand for even more efficient models. In order to meet the constraints of ultra-low-energy devices, we propose ULEEN, a model architecture based on weightless neural networks. Weightless neural networks (WNNs) are a class of neural model which use table lookups, not arithmetic, to perform computation. The elimination of energy-intensive arithmetic operations makes WNNs theoretically well suited for edge inference; however, they have historically suffered from poor accuracy and excessive memory usage. ULEEN incorporates algorithmic improvements and a novel training strategy inspired by BNNs to make significant strides in improving accuracy and reducing model size. We compare FPGA and ASIC implementations of an inference accelerator for ULEEN against edge-optimized DNN and BNN devices. On a Xilinx Zynq Z-7045 FPGA, we demonstrate classification on the MNIST dataset at 14.3 million inferences per second (13 million inferences/Joule) with 0.21 $\mu$s latency and 96.2% accuracy, while Xilinx FINN achieves 12.3 million inferences per second (1.69 million inferences/Joule) with 0.31 $\mu$s latency and 95.83% accuracy. In a 45nm ASIC, we achieve 5.1 million inferences/Joule and 38.5 million inferences/second at 98.46% accuracy, while a quantized Bit Fusion model achieves 9230 inferences/Joule and 19,100 inferences/second at 99.35% accuracy. In our search for ever more efficient edge devices, ULEEN shows that WNNs are deserving of consideration.Comment: 14 pages, 14 figures Portions of this article draw heavily from arXiv:2203.01479, most notably sections 5E and 5F.

Active vitamin D (1,25-dihydroxyvitamin D) and bone health in middle-aged and elderly men: the European male aging study (EMAS)

&lt;p&gt;Context: There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] on bone health including turnover.&lt;/p&gt; &lt;p&gt;Objective: The objective of the study was to determine the influence of 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men.&lt;/p&gt; &lt;p&gt;Design, Setting, and Participants: Men aged 40–79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)2D, 25(OH)D, and PTH were measured. 1,25(OH)2D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers.&lt;/p&gt; &lt;p&gt;Main Outcome Measure(s): QUS of the heel, bone markers P1NP and β-cTX, and DXA of the hip and lumbar spine were measured.&lt;/p&gt; &lt;p&gt;Results: A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)2D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)2D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)2D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)2D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels.&lt;/p&gt; &lt;p&gt;Conclusions: Serum 1,25(OH)2D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health.&lt;/p&gt

Pathophysiology of major depression by clinical stages

The comprehension of the pathophysiology of the major depressive disorder (MDD) is essential to the strengthening of precision psychiatry. In order to determine the relationship between the pathophysiology of the MDD and its clinical progression, analyzed by severity of the depressive symptoms and sleep quality, we conducted a study assessing different peripheral molecular biomarkers, including the levels of plasma C-reactive protein (CRP), serum mature brain-derived neurotrophic factor (mBDNF), serum cortisol (SC), and salivary cortisol awakening response (CAR), of patients with MDD (n = 58) and a control group of healthy volunteers (n = 62). Patients with the first episode of MDD (n = 30) had significantly higher levels of CAR and SC than controls (n = 32) and similar levels of mBDNF of controls. Patients with treatment-resistant depression (TRD, n = 28) presented significantly lower levels of SC and CAR, and higher levels of mBDNF and CRP than controls (n = 30). An increased severity of depressive symptoms and worse sleep quality were correlated with levels low of SC and CAR, and with high levels of mBDNF. These results point out a strong relationship between the stages clinical of MDD and changes in a range of relevant biological markers. This can assist in the development of precision psychiatry and future research on the biological tests for depression

Active vitamin D (1,25-dihydroxyvitamin D) and bone health in middle-aged and elderly men: the European male aging study (EMAS)

&lt;p&gt;Context: There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] on bone health including turnover.&lt;/p&gt; &lt;p&gt;Objective: The objective of the study was to determine the influence of 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men.&lt;/p&gt; &lt;p&gt;Design, Setting, and Participants: Men aged 40–79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)2D, 25(OH)D, and PTH were measured. 1,25(OH)2D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers.&lt;/p&gt; &lt;p&gt;Main Outcome Measure(s): QUS of the heel, bone markers P1NP and β-cTX, and DXA of the hip and lumbar spine were measured.&lt;/p&gt; &lt;p&gt;Results: A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)2D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)2D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)2D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)2D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels.&lt;/p&gt; &lt;p&gt;Conclusions: Serum 1,25(OH)2D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health.&lt;/p&gt

One-pot isothermal DNA amplification Hybridisation and detection by a disc-based method

[EN] An integrated sensor comprising isothermal DNA amplification and in situ detection is presented. The method principle is based on recombinase polymerase amplification (RPA) and detection in the microarray format by compact disc technology as a high-throughput sensing platform. Primers were immobilised on the polycarbonate surface of digital versatile discs (DVD) and, after hemi-nested amplification, multiplexing identification of each tethered product was achieved by optical scanning with a 650 nm-laser of the DVD drive. The efficiency of one-pot hybridisation/elongation/detection depended strongly on probedensity and other factors such as the concentration of the unbound primers present in solution. The optimised conditions provided equivalent amplification factors (7.3 x 10(8) -8.9 x 10(8) fold) to those obtained by conventional reactions performed in vials. The proposed method was applied to Salmonella detection (generic by hns and oriC genes, and specific for subspecies I by STM4507 gene). A triplex assay was satisfactorily compared to the non-integrated protocols. Food and vaccine samples were analysed in a shorter time with less handling. The results indicate that the multiplex DVD assay is a simple, competitive, isothermal, portable system that is particularly useful for microbiological routine analysis. (C) 2014 Elsevier B.V. All rights reserved.This research has been funded through Projects GVA-PROMETEO/2010/008 (Generalitat Valenciana) and CTQ/2013/ 45875-R (MINECO). The Spanish Ministry of Education and Science provided S.S.F. with a grant for her PhD studies.Santiago Felipe, S.; Tortajada-Genaro, LA.; Morais, S.; Puchades, R.; Maquieira Catala, Á. (2014). One-pot isothermal DNA amplification Hybridisation and detection by a disc-based method. Sensors and Actuators B: Chemical. 204:273-281. https://doi.org/10.1016/j.snb.2014.07.073S27328120