NIS expression in thyroid tumors, relation with prognosis clinicopathological and molecular features

Thyroid cancer therapy is based on surgery followed by radioiodine treatment. The incorporation of radioiodine by cancer cells is mediated by sodium iodide symporter (NIS) (codified by the SLC5A5 gene), that is functional only when targeted to the cell membrane. We aimed to evaluate if NIS expression in thyroid primary tumors would be helpful in predicting tumor behavior, response to therapy and prognosis. NIS expression was addressed by qPCR and immunohistochemistry. In order to validate our data, we also studied SLC5A5 expression on 378 primary papillary thyroid carcinomas from The Cancer Genome Atlas (TCGA) database. In our series, SLC5A5 expression was lower in carcinomas with vascular invasion and with extrathyroidal extension and in those harboring BRAFV600E mutation. Analysis of SLC5A5 expression from TCGA database confirmed our results. Furthermore, it showed that larger tumors, with locoregional recurrences and/or distant metastases or harboring RAS, BRAF and/or TERT promoter (TERTp) mutations presented significantly less SLC5A5 expression. Regarding immunohistochemistry, 12/211 of the cases demonstrated NIS in the membrane of tumor cells, those cases showed variable outcomes concerning therapy success, prognosis and all but one were wild type for BRAF, NRAS and TERTp mutations. SLC5A5 mRNA lower expression is associated with features of aggressiveness and with key genetic alterations involving BRAF, RAS and TERTp. Mutations in these genes seem to decrease protein expression and its targeting to the cell membrane. SLC5A5 mRNA expression is more informative than NIS immunohistochemical expression regarding tumor aggressiveness and prognostic features.This study was supported by FCT (‘Portuguese Foundation for Science and Technology’) through PhD grants to Catarina Tavares (SFRH/BD/87887/2012), Ana Pestana (SFRH/BD/110617/2015), Rui Batista (SFRH/BD/111321/2015) and by a CNPq PhD grant (‘National Counsel of Technological and Scientific Development’, Brazil), Science without Borders, Process n# 237322/2012-9 for Luciana Ferreira. Miguel Melo received a grant from Genzyme for the research project ‘Molecular biomarkers of prognosis and response to therapy in differentiated thyroid carcinomas’. Further funding was obtained from FEDER – Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 – Operational Program for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT – Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia e Inovação in the framework of the project ‘Institute for Research and Innovation in Health Sciences’ (POCI-01-0145-FEDER-007274) and by the project ‘Advancing cancer research: from basic knowledgement to application’; NORTE-01-0145-FEDER-000029; ‘Projetos Estruturados de I&D&I’, funded by Norte 2020-Programa Operacional Regional do Norte. This work was also financed by Sociedade Portuguesa de Endocrinologia Diabetes e Metabolismo through a grant ‘Prof. E Limbert Sociedade Portuguesa de Endocrinologia Diabetes e Metabolismo/Sanofi-Genzyme in thyroid pathology’

Isometry of Potential Attachment Sites for the Iliotrochanteric Suture in Dogs: an ex vivo Study

Background: Coxofemoral luxation is the most common traumatic luxation in dogs and the iliotrochanteric suture is one of the surgical treatment options. The orthopedic suture aimed at surgically restoring joint movement should be employed in an isometric manner in order to maintain adequate tension throughout the arc of motion. This study aimed to determine the isometric points for the iliotrochanteric suture in dogs during the joint extension and flexion movements. This evaluation was performed both in the intact hip joint and in the luxation model, establishing the best combination, among the determined points, for the reestablishment of normal joint movement.Materials, Methods & Results: Radiographic analyses of 12 canine cadaveric hips, both intact and in craniodorsal luxation model, were performed in a neutral position, flexion at 50°, and extension at 150°. In the trochanteric segment, two parallel lines were drawn, creating the central vertical axis and the secondary vertical axis. Three points were then determined on each axis, from proximal to distal, corresponding to 25, 50, and 75% of the height of the axis, and were labelled as T1, T2, and T3 and T4, T5, and T6, respectively. In the iliac segment, a line perpendicular to the longitudinal axis of the ilium was drawn, and 25, 50, and 75% of this height corresponded to points I1, I2, and I3, respectively. The lengths between the points were measured, with the objective of evaluating which combination of points presented less variation in the joint positions. The central location of the iliac and trochanteric segments, determined respectively by I2 and T2, provided smaller variations during the maximal movements of hip flexion and extension.Discussion: The surgical techniques of iliotrochanteric suture target to maintain the internal rotation of the femoral head inside the acetabulum and abduction of the femur until the soft tissues have healed. The described techniques for the iliotrochanteric suture present a great anatomical variety in the arrangement of the anchor points of the suture. It is known that if during motion, the attachment sites move closer to one another, the suture will become lax and, if the attachment sites move away from one another, the suture will tighten. Therefore, the implantation in isometric sites assists in reducing the variation of the distance between the points of origin and insertion of the suture during joint movement, keeping the suture tension constant and allowing the functional recovery of the joint. This study demonstrates that there are some locations for the origin and insertion of an iliotrochanteric suture that are associated with less length change than others. I2-T2 combination is the point closest to isometry for the iliotrochanteric suture during hip extension and flexion, so that, T2 is the most central point of the greater trochanter, corresponding to 50% of the height of its central vertical axis, as well as I2, which corresponds to the most central point of the ilium, representing 50% of the height of the most caudal portion of its body. The isometric point found by us details the exact location of perforation in all aspects (height and length), both in the ilium and the trochanter. In addition, it is a personalized point created for each patient from its radiographic examination and taking into consideration its anatomical variations, so that there is no damage to the suture during hip extension and flexion movements

Impacto de um curso de informática para trabalhadores mais velhos : análise de um caso

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Histórias e memórias : ressignificando as lembranças escolares de trabalhadores mais velhos

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Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Development of sweeteners microcapsules produced by double emulsion followed by complex coacervation and study of their functionality un chewing gum

Orientadores: Helena Maria Andre Bolini, Carmen Silvia Favaro TrindadeTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de AlimentosResumo: Em todo o mundo, tem-se observado o aumento do interesse da população em ingerir produtos isentos de açúcar e com menor teor calórico. Esse interesse tem impulsionado o mercado dos produtos chamados diet/light e as gomas de mascar desempenham importante papel neste setor. Os edulcorantes utilizados nesse segmento podem ser microencapsulados, com o objetivo de reduzir a higroscopicidade desses compostos e prolongar a sensação de doçura. A microencapsulação é uma tecnologia que vem se mostrando viável para diversas aplicações industriais. O prolongamento do gosto doce é bastante desejado em alguns produtos, especialmente as gomas de mascar, que permanecem um período maior na boca antes da ingestão. Nesse contexto, os objetivos deste trabalho foram desenvolver e caracterizar microcápsulas com diferentes tipos de edulcorantes, aplicá-las em gomas de mascar e determinar o perfil tempo-intensidade de doçura, além da aceitação dos produtos em relação à aparência, aroma, sabor, textura e impressão global. Mesmo sendo compostos hidrofílicos, foi possível encapsular os edulcorantes aspartame, sucralose e estévia por meio da adição da técnica de dupla emulsão ao processo de encapsulação por coacervação complexa. As microcápsulas formadas eram esféricas, multinucleadas e apresentaram baixos valores de solubilidade e higroscopicidade. As gomas de mascar produzidas com edulcorante microencapsulado apresentaram um perfil de liberação do gosto doce mais duradouro em relação às amostras produzidas com edulcorante na forma livre, sem perda da aceitação pelos consumidores, o que indica a potencialidade do uso desse tipo de microcápsulas em gomas de mascar visando aumentar o tempo de duração do gosto doceAbstract: In recent years, the interest of the population in consuming lower-calorie sugar-free products has grown. This interest has driven the market of light and diet products, and chewing gums play an important role in this sector. Microencapsulation is a technology that has proven viable for several industrial applications. With regard to sweeteners, the process may reduce the hygroscopicity of such compounds and extend the sensation of sweetness. Extending the sweet taste is quite interesting for some products, especially chewing gums, which remain a longer period in the mouth during consumption. In this context, this study aimed at developing and characterizing microcapsules containing different types of sweeteners, applying the microcapsules in chewing gum and determining the time-intensity sweetness profile and acceptance of products, concerning the parameters appearance, aroma, flavor, texture and overall impression. Although sweeteners are hydrophilic compounds, it was possible to encapsulate aspartame, sucralose and stevia using double emulsion stage prior to complex coacervation process. The microcapsules formed were spherical, multinucleated and exhibited low values of solubility and hygroscopicity. The chewing gum produced with microencapsulated sweetener showed a more prolonged sweetness release profile than the samples containing sweetener in free form, without affecting consumer acceptance, indicating the potential use of such microcapsules in chewing gum aimed at extending sweetness durationDoutoradoConsumo e Qualidade de AlimentosDoutora em Alimentos e Nutriçã

Morphology, Stability, and Application of Lycopene Microcapsules Produced by Complex Coacervation

The interest in lycopene has increased in recent years due to studies that associate it with the reduction in risk of developing cardiovascular diseases and cancer. However, due to its high degree of unsaturation, this carotenoid is inclined to isomerize and oxidize during processing and storage, making it difficult to use in the food industry. Microencapsulation can improve this situation, increasing its stability and making incorporation into food formulations possible. Thus, the aim of this study was to microencapsulate lycopene by complex coacervation using gelatin and gum Arabic as the encapsulating agents. The microcapsules were evaluated based on the encapsulation efficiency and their morphology and then submitted to a stability test and applied in cake making. Most of the systems studied presented spherical microcapsules with defined walls. The encapsulation efficiency values were above 90%, and the average diameter of the capsules ranged from 61 to 144 μm. The stability test showed that microencapsulation offered greater protection to the lycopene as compared to its free form. The application of nonfreeze dried coacervated microcapsules in cake making was satisfactory, but the color transference was low when freezedried coacervated microcapsules were used