Search

Diêgo dos Santos Ferreira,1,2 Samilla Dornelas Faria,1 Sávia Caldeira de Araújo Lopes,1 Cláudia Salviano Teixeira,1 Angelo Malachias,3 Rogério Magalhães-Paniago,3 José Dias de Souza Filho,4 Bruno Luis de Jesus Pinto Oliveira,2 Alexander Ramos Guimarães,2 Peter Caravan,2 Lucas Antônio Miranda Ferreira,1 Ricardo José Alves,1 Mônica Cristina Oliveira1 1Department of Pharmaceutical Products, Faculty of Pharmacy,Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 2Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 3Department of Physics, 4Department of Chemistry, Institute of Exact Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Background: Despite recent advances in cancer therapy, the treatment of bone tumors remains a major challenge. A possible underlying hypothesis, limitation, and unmet need may be the inability of therapeutics to penetrate into dense bone mineral, which can lead to poor efficacy and high toxicity, due to drug uptake in healthy organs. The development of nanostructured formulations with high affinity for bone could be an interesting approach to overcome these challenges.Purpose: To develop a liposomal formulation with high affinity for hydroxyapatite and the ability to release doxorubicin (DOX) in an acidic environment for future application as a tool for treatment of bone metastases.Materials and methods: Liposomes were prepared by thin-film lipid hydration, followed by extrusion and the sulfate gradient-encapsulation method. Liposomes were characterized by average diameter, ζ-potential, encapsulation percentage, X-ray diffraction, and differential scanning calorimetry. Release studies in buffer (pH 7.4 or 5), plasma, and serum, as well as hydroxyapatite-affinity in vitro analysis were performed. Cytotoxicity was evaluated by MTT assay against the MDA-MB-231 cell line, and biodistribution was assessed in bone metastasis-bearing animals.Results: Liposomes presented suitable diameter (~170 nm), DOX encapsulation (~2 mg/mL), controlled release, and good plasma and serum stability. The existence of interactions between DOX and the lipid bilayer was proved through differential scanning calorimetry and small-angle X-ray scattering. DOX release was faster when the pH was in the range of a tumor than at physiological pH. The bone-targeted formulation showed a strong affinity for hydroxyapatite. The encapsulation of DOX did not interfere in its intrinsic cytotoxicity against the MDA-MB-231 cell line. Biodistribution studies demonstrated high affinity of this formulation for tumors and reduction of uptake in the heart.Conclusion: These results suggest that bone-targeted pH-sensitive liposomes containing DOX can be an interesting strategy for selectively delivering this drug into bone-tumor sites, increasing its activity, and reducing DOX-related toxicity. Keywords: hydroxyapatite-targeted formulations, bisphosphonates, pH-responsive nanostructures, bone-tumor treatment

Objetivos: Avaliar a relação entre grau de hemólise, resultado do doppler transcraniano (DTC) e risco para acidente vascular cerebral isquêmico (AVCi) em pacientes de 2 a 16 anos portadores de doença falciforme (DF) atendidos no ambulatório de Hematologia Pediátrica. Material e métodos: Coleta de dados em prontuários eletrônicos após assinatura de TCLE e TALE. O N foi de 116 e os dados eram referentes ao período de fev/2021 a fev/2022. Definiu-se risco de AVCi como o resultado de fluxo de artéria cerebral média ao DTC igual ou superior a 170 cm/s. Definiu-se grau de hemólise em 4 subvariáveis: Hemoglobina (Hb), Bilirrubina Indireta (BI), Reticulócitos (%) e Desidrogenase Láctica (DHL), obtidas a partir da média dos resultados de todos os exames ambulatoriais do período. Outras variáveis foram valor de plaquetas e de leucócitos (também a partir das médias), idade, raça e diagnóstico genético. Análise realizada em duas etapas: 1. Analisar como cada uma das variáveis se relacionava com a variável Risco de AVCi através de Testes Exatos de Fisher ou de Wilcoxon, onde valores de p < 0,05 indicam relação estatisticamente significativa entre variáveis. 2. Modelos de Regressão Logística para estudo da relação entre o risco de AVCi e as variáveis estatisticamente significativas na seção anterior, através de Razão de Chances com intervalo de confiança de 95%. Resultados: Foi demonstrada relação estatisticamente significativa entre Risco de AVCi e Hemoglobina (p = 0.01), DHL (p = 0.01), Reticulócitos (p = 0.013), Leucograma (p = 0.025) e Plaquetograma (p = 0.045). Ademais, obteve-se que quando a Hb aumenta em uma unidade, o risco de AVCi diminui em 42%; quando o DHL aumenta em 100 unidades, o risco aumenta em 37% e quando reticulócitos aumentam em uma unidade, o risco aumenta em 18%. Discussão: DF é uma hemoglobinopatia que através de hemólise, inflamação e vasoclusão, propicia a ocorrência de eventos isquêmicos cerebrovasculares especialmente na infância. HbSS é o tipo mais prevalente relacionado ao AVCi. Fatores de risco para AVCi são principalmente baixo valor de Hb e alto valor de leucócitos. Valores baixos de Hb estão relacionados a maior grau de hemólise, que propicia vasculopatia, estreitamento arterial e maior grau de lesão endotelial por aumento de fluxo arterial cerebral. Leucocitose se relaciona ao maior risco de AVCi por gerar inflamação, adesão ao endotélio e vasoclusão. Depois dela, maior ativação e adesão plaquetárias propiciadas pelo estado de hemólise também geram vasoclusão. Outros indicadores de hemólise envolvidos seriam DHL acima de 240 e reticulocitose, dado que reticulócitos falciformes estimulam ativação e agregação de leucócitos e plaquetas, provocam maior dano endotelial e possuem maior adesividade, contribuindo para ocorrência de AVCi. Medidas de controle e seguimento são realização de DTC periódico, transfusões crônicas para redução de HbS < 30%, uso de hidroxiuréia para aumento de Hb fetal, controle de processos envolvidos na vasoclusão e redução de leucócitos e plaquetas. Conclusão: Baixo valor de Hb, alto valor de DHL, reticulocitose, leucocitose e plaquetose possuem relação estatisticamente significativa com o risco de AVCi em pacientes pediátricos portadores de DF. A vigilância destes parâmetros se faz necessária no seguimento destes pacientes e seu controle é fator relevante na prevenção de AVCi.

Abstract Background The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020. Methods The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications. The panel searched for evidence on antidiabetic therapy in people with T2D without cardiorenal disease and in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or diabetic kidney disease (DKD). The degree of recommendation and the level of evidence were determined using predefined criteria. Results and conclusions All people with T2D need to have their cardiovascular (CV) risk status stratified and HbA1c, BMI, and eGFR assessed before defining therapy. An HbA1c target of less than 7% is adequate for most adults, and a more flexible target (up to 8%) should be considered in frail older people. Non-pharmacological approaches are recommended during all phases of treatment. In treatment naïve T2D individuals without cardiorenal complications, metformin is the agent of choice when HbA1c is 7.5% or below. When HbA1c is above 7.5% to 9%, starting with dual therapy is recommended, and triple therapy may be considered. When HbA1c is above 9%, starting with dual therapyt is recommended, and triple therapy should be considered. Antidiabetic drugs with proven CV benefit (AD1) are recommended to reduce CV events if the patient is at high or very high CV risk, and antidiabetic agents with proven efficacy in weight reduction should be considered when obesity is present. If HbA1c remains above target, intensification is recommended with triple, quadruple therapy, or even insulin-based therapy. In people with T2D and established ASCVD, AD1 agents (SGLT2 inhibitors or GLP-1 RA with proven CV benefit) are initially recommended to reduce CV outcomes, and metformin or a second AD1 may be necessary to improve glycemic control if HbA1c is above the target. In T2D with HF, SGLT2 inhibitors are recommended to reduce HF hospitalizations and mortality and to improve HbA1c. In patients with DKD, SGLT2 inhibitors in combination with metformin are recommended when eGFR is above 30 mL/min/1.73 m2. SGLT2 inhibitors can be continued until end-stage kidney disease.

Abstract A method to determine the effects of the geometry and lateral ordering on the electronic properties of an array of one-dimensional self-assembled quantum dots is discussed. A model that takes into account the valence-band anisotropic effective masses and strain effects must be used to describe the behavior of the photoluminescence emission, proposed as a clean tool for the characterization of dot anisotropy and/or inter-dot coupling. Under special growth conditions, such as substrate temperature and Arsenic background, 1D chains of In0.4Ga0.6 As quantum dots were grown by molecular beam epitaxy. Grazing-incidence X-ray diffraction measurements directly evidence the strong strain anisotropy due to the formation of quantum dot chains, probed by polarization-resolved low-temperature photoluminescence. The results are in fair good agreement with the proposed model.

Hyperbolic phonon polaritons have recently attracted considerable attention in nanophotonics mostly due to their intrinsic strong electromagnetic field confinement, ultraslow polariton group velocities, and long lifetimes. Here we introduce tin oxide (SnO2) nanobelts as a photonic platform for the transport of surface and volume phonon polaritons in the mid- to far-infrared frequency range. This report brings a comprehensive description of the polaritonic properties of SnO2 as a nanometer-sized dielectric and also as an engineered material in the form of a waveguide. By combining accelerator-based IR-THz sources (synchrotron and free-electron laser) with s-SNOM, we employed nanoscale far-infrared hyper-spectral-imaging to uncover a Fabry-Perot cavity mechanism in SnO2 nanobelts via direct detection of phonon-polariton standing waves. Our experimental findings are accurately supported by notable convergence between theory and numerical simulations. Thus, the SnO2 is confirmed as a natural hyperbolic material with unique photonic properties essential for future applications involving subdiffractional light traffic and detection in the far-infrared range.

O artigo objetiva contribuir para com a compreensão do conceito interseccionalidade (CRENSHAW, 2009), como conhecimento também produzido por mulheres negras intelectuais brasileiras. Para tanto, como estratégia metodológica, a narrativa apresenta as interfaces da História, Comunicação e Educação e, a despeito dos diferentes tempos históricos estabelece diálogos reflexivos, transculturais e educomunicativos (MALACHIAS, 2018), identificados como “Ação educativa de combate ao racismo” - terceiro princípio das Diretrizes Curriculares Nacionais para a Educação Étnico-racial Ensino de História e Cultura Afro-brasileira e Africana (BRASIL, 2004). Como resultado, identifica o protagonismo das mulheres negras na criação de uma agenda política interseccional, na perspectiva de classe, raça-etnia e gênero. Entretanto, embora seja inegável, a participação ativa das Mulheres Negras nem sempre é conhecida e/ou desvelada.

Abstract Uncontrolled hypertension has a high prevalence and is related to numerous negative health outcomes. This study aimed to investigate the factors associated with the lack of blood pressure control in hypertensive Brazilians treated in public and private services. This is an analytical, multicentric, and national cross‐sectional study, carried out with adult hypertensive patients, monitored in 45 outpatient clinics (September 2013 to October 2015) in a prospective record interview, clinical, and anthropometric assessment. Outcome variables included uncontrolled pressure (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg). Simple and multiple logistic regression analyses were performed. Two thousand six hundred forty‐three participants were assessed with a mean age of 61.6 ± 11.9 years, 55.7% of women, and 46.4% with uncontrolled blood pressure (BP). The following were associated with uncontrolled BP: age over 60 years (OR: 1.31 [1.11–1.55]); practice of irregular physical activity (OR: 1.28 [1.06–1.55]); attending the emergency room for hypertensive crises in the last six months (OR: 1.80 [1.46–2.22]); increased body mass index (OR: 1.02 [1.01–1.04]); low adherence to drug treatment (OR: 1.22 [1.04–1.44]) and menopause (OR: 1.36 [1.07–1.72]). The following were negatively associated: fruit consumption (OR: 0.90 [0.85–0.94]); presence of dyslipidemia (OR: 0.75 [0.64–0.89]), acute myocardial infarction (OR: 0.59 [0.46–0.76]), and peripheral arterial disease (OR: 0.52 [0.34‐0.78]). Factors associated with difficult‐to‐control blood pressure are the same that increase the risk for hypertension, while the presence of atherosclerotic disease and its outcomes were associated with better control.

Background: One approach to enhancing the pedagogy of science education is to employ academics who are not only science-trained but also engaged in education research. As some academics begin their Scholarship of Teaching and Learning research careers with a pure science background, shifting in disciplinary perspectives can be a source of professional tension. The pedagogic frailty model provides a framework that helps us to integrate institutional efforts to enhance teaching improvements by maintaining a simultaneous focus on critical areas that are thought to impede academic development. Purpose: This paper draws attention to the importance of disciplinary crossover by uncovering and comparing academics' teaching perspectives, views and beliefs from three disciplines: natural science (chemistry), social science (education) and science education. Method: Through a case study design using the pedagogic frailty model and concept map-mediated interviews as a tool, three academics engaged in a non-linear discourse in which their conceptions could be visualised and analysed. Findings and Discussion: Analysis of the case study interviews indicated that the academics' conceptions of teaching were highly individualised. The discourse surrounding the curriculum, and the embeddedness of and connection between pedagogy and discipline, were both subject-sensitive and influenced by professional backgrounds and research areas. On the other hand, because they operated under the same institutional values and regulations, we found a considerable overlap in terms of how the academics perceived the tensions between research and teaching and academic leadership. By comparing three academics who were at a different stage in the journey from disciplinary experts (chemistry) to teaching expert (education), we were able to uncover and understand more about the ways that the teaching environment impacted upon their practices. The science educator shared aspects of the other two perspectives, which suggests that his profile was a transitory state in comparison with the chemist and the educationist. Conclusion: The findings provide a glimpse of the distinctive nature of the values that underpin teaching and offer insights that can be used to promote dialogue about quality enhancement in science education.

Abstract More stringent blood pressure (BP) goals have led to greater prevalence of apparent resistant hypertension (ARH), yet the long‐term prognostic impact of ARH diagnosed according to these goals in the general population remains unknown. We assessed the prognostic impact of ARH according to contemporary BP goals in 9612 participants of the Atherosclerosis Risk in Communities (ARIC) study without previous cardiovascular disease. ARH, defined as BP above goal (traditional goal

Aim: Postresuscitation hemodynamics are associated with hospital mortality/functional outcome. We sought to determine whether low-dose steroids started during and continued after cardiopulmonary resuscitation (CPR) affect postresuscitation hemodynamics and other physiological variables in vasopressor-requiring, in-hospital cardiac arrest. Methods: We conducted a two-center, randomized, double-blind trial of patients with adrenaline (epinephrine)-requiring cardiac arrest. Patients were randomized to receive either methylprednisolone 40 mg (steroids group) or normal saline-placebo (control group) during the first CPR cycle post-enrollment. Postresuscitation shock was treated with hydrocortisone 240 mg daily for 7 days maximum and gradual taper (steroids group), or saline-placebo (control group). Primary outcomes were arterial pressure and central-venous oxygen saturation (ScvO2) within 72 hours post-ROSC. Results: Eighty nine of 98 controls and 80 of 86 steroids group patients with ROSC were treated as randomized. Primary outcome data were collected from 100 patients with ROSC (control, n = 54; steroids, n = 46). In intention-to-treat mixed-model analyses, there was no significant effect of group on arterial pressure, marginal mean (95% confidence interval) for mean arterial pressure, steroids vs. control: 74 (68–80) vs. 72 (66–79) mmHg] and ScvO2 [71 (68–75)% vs. 69 (65–73)%], cardiac index [2.8 (2.5–3.1) vs. 2.9 (2.5–3.2) L/min/m2], and serum cytokine concentrations [e.g. interleukin-6, 89.1 (42.8–133.9) vs. 75.7 (52.1–152.3) pg/mL] determined within 72 hours post-ROSC (P = 0.12–0.86). There was no between-group difference in body temperature, echocardiographic variables, prefrontal blood flow index/cerebral autoregulation, organ failure-free days, and hazard for poor in-hospital/functional outcome, and adverse events (P = 0.08–>0.99). Conclusions: Our results do not support the use of low-dose corticosteroids in in-hospital cardiac arrest.Trial Registration: ClinicalTrials.gov number: NCT02790788 (https://www.clinicaltrials.gov).