Consenso Técnico para a determinação do status da proteína HER2 por imunocitoquímica em carcinoma da mama

A determinação do status da proteína HER2 por imunocitoquímica é uma metodologia fundamental para o diagnóstico, prognóstico e indicação terapêutica no carcinoma da mama, nomeadamente para o encaminhamento terapêutico com Herceptin®/trastuzumab. O estabelecimento desta terapêutica nas vertentes adjuvante ou neoadjuvante, e até em doença metastática, tem vindo a acentuar a importância da determinação do referido status de modo a melhor responder às necessidades dos doentes. Sendo a imunocitoquímica o método validado para determinação do status HER2 em carcinoma da mama, é de extrema importância definir linhas de orientação para a sua correta performance como tem sido estabelecido em diversos países em todo o mundo. A área científica de Anatomia Patológica, Citológica e Tanatológica da Escola Superior de Tecnologia da Saúde de Lisboa (APCT-ESTeSL) e a Associação Portuguesa de Técnicos de Anatomia Patológica (APTAP) reuniram um painel de especialistas para a construção e estabelecimento de linhas de orientação técnica para a determinação do status HER2 em carcinoma da mama para a realidade portuguesa. Pretende-se com este consenso criar linhas de orientação técnicas para a construção, validação e manutenção do teste imunocitoquímico para determinação do status HER2 em carcinoma da mama, no que diz respeito à realidade portuguesa. Todas as orientações aqui descritas têm em conta o estado da arte atual no que diz respeito à determinação do status HER2 por imunocitoquímica em carcinoma da mama, bem como a experiência pessoal e académica de cada um dos membros do painel de especialistas que a subscrevem

Social capital and self-rated health among adolescents in Brazil: an exploratory study

<p>Abstract</p> <p>Background</p> <p>Social capital may influence health and the patterns of association differ according its dimension such as cognitive, behavioral, bridging or bonding. There is a few numbers of studies in Latin America which comprise these aspects of social capital and health. The aim of this study was to examine the association between social capital and self-rated health among youth, and distinguish between the different forms of social capital - cognitive versus behavioral, and bonding versus bridging.</p> <p>Findings</p> <p>A cross-sectional study was conducted in 2009 among working adolescents supported by a Brazilian NGO. The sample comprised 363 individuals and data were collected using a validated structured questionnaire. The outcome, self-rated health, was measured as a dichotomous variable (poor/good health) and fourteen social capital indicators were investigated (cognitive, behavioral and bonding/bridging). Data were analyzed using multivariate logistic regression. Cognitive (social support and trust), behavioral (civic participation) and bridging social capital were associated with good self-rated health after adjustment of all the other social capital indicators and confounders (sex, age, skin color and educational background).</p> <p>Conclusions</p> <p>Social capital was associated with self-rated health and the patterns of association differed according its specific dimensions. Cognitive, behavioral and bridging social capitals were protective for adolescents health living in a developing country context..</p

Fatigue survival and damage modes of lithium disilicate and resin nanoceramic crowns

Polymer-based composite materials have been proposed as an alternative for single unit restorations, due to their resilient and shock absorbing behavior, in contrast to the brittleness of ceramic materials that could result in failure by fracture. Objective: To evaluate the fatigue strength and damage modes of monolithic posterior resin nanoceramic and lithium disilicate glass ceramic crowns.&nbsp;Methodology: Twenty-six resin nanoceramic (RNC) and lithium disilicate glass ceramic (LD) 2 mm monolithic crowns (n=13) were cemented on composite resin replicas of a prepared tooth and subjected to cyclic load with lithium disilicate indenters for 2 million cycles. Specimens and indenters were inspected every 500,000 cycles and suspended when presenting fractures or debonding. Surviving specimens were embedded in epoxy resin, polished and subsurface damage was analyzed. Specimens presenting fractures or severe subsurface damage were considered as failures. Survival data was subjected to Fisher's exact test; damage modes were subjected to Mann-Whitney test (p&lt;0.05).&nbsp;Results: There were no debonding, cohesive or catastrophic failures. Considering subsurface damage, 53.8% of RNC and 46.2% of LD crowns survived the fatigue test, presenting no statistical difference. Chief damage modes were radial cracks for RNC and inner cone cracks for LD, presenting no statistical difference.&nbsp;Conclusions: The results suggest that if debonding issues can be resolved, resin nanoceramic figures can be an alternative to posterior crowns. Although distinct, damage modes revealed potential to cause bulk fracture in both glass ceramic and resin nanoceramic crowns

Effect of Training in Peripheral Blood Lymphocytes and Cytokine Levels in Elite Kayakers

Prolonged strenuous exercise has been associated with impaired immune function. The objective of this study was to investigate the differences in the peripheral blood cell counts and cytokynes in kayakers at different moments of training. The sample consisted of eight elite male kayakers, 22± 4 years old, 77.2 kg±6.7 body mass and 177.5±5.6 cm stature. The initial VO2max was 61.2±5.5 mL.kg.min-1. The control group consisted of six healthy males, 18±1 years old, 81.3± 13.8 kg body mass and 171.9±4.5cm stature. Blood samples were collected, at rest, from the kayakers at 4 time points of the training season: t0 early November (beginning of the training season), t1 late February (after an increased volume in training load), t2 early April (after an increase in training intensity) and t4 in June (after a major competition). Blood samples from the controls were taken at 3 equivalent time-points. Lymphocyte subpopulations were determined by flow cytometry. Cytokine concentrations were determined by ELISA. Statistical analysis was done using Friedman\u27s ANOVA- Repeated measures and the Mann-Whitney test for comparing the kaykers and control groups. The total nº of lymphocytes decreased and the natural killer (NK) CD3+CD56+CD8+ cells increased at t2 when compared to baseline (t0). No changes between time points for the lymphocyte subpopulations were found in the control group. When comparing both groups lower levels of NK cells were found at baseline and througth out the season in the kayakers. When looking at plasma cytokine concentration an increase in intensity training and the competitive period were able to elevate the concentrations of pro and anti-inflammatory cytokines (IL1-Ra, IL-6, Il-1beta and IL-18), even after 24hours of rest. However IFN-Υ, TNF-α and IL-10 were not significantly affected in the kayakers. When comparing both groups at t0, kayakers showed lower levels of IL-1β, IL-18, IL-1ra and IFN-γ. Changes in training load intensity were able to affect the number of lymphocytes and their subpopulations in the circulation periphery. Significant reductions in circulating NK CD3-CD56+ and CD3-CD56+CD8+, appears to be associated with increased risk of URS. In spite of the increase of cytokines after the competition period, the kayakers maintained lower levels of pro and anti-inflammatory cytokines when compared with the control group. Despite extreme levels of exercise being associated with reduced immune function and increased susceptibility to infections, a reduction in inflammation due to training may represent a beneficial effect of the long term exercise practice

Projecting future climate change-mediated impacts in Three Paralytic Shellfish Toxins-Producing dinoflagellate species

Simple Summary Harmful algal blooms present a particular risk for marine ecosystems and human health alike. In this sense, it is important to accurately predict how toxin-producing microalgae could be affected by future climate change. The present study applied species distribution models (SDMs) to project the potential changes in the habitat suitability and distribution of three key paralytic shellfish toxin (PST)-producing dinoflagellate species (i.e., Alexandrium catenella, A. minutum, and Gymnodinium catenatum), up to 2040/50 and 2090/2100, across four different greenhouse gas emission scenarios, and using four abiotic predictors (i.e., sea surface temperature, salinity, current velocity, and bathymetry). In general, considerable contractions were observed for all three species in the lower latitudes of their distribution, together with projected expansions into higher latitudes, particularly in the Northern Hemisphere. This study aims to entice further research on the future biogeographical impacts of climate change in toxin-producing microalgae species while, at the same time, helping to advise the correct environmental management of coastal habitats and ecosystems. Toxin-producing microalgae present a significant environmental risk for ecosystems and human societies when they reach concentrations that affect other aquatic organisms or human health. Harmful algal blooms (HAB) have been linked to mass wildlife die-offs and human food poisoning episodes, and climate change has the potential to alter the frequency, magnitude, and geographical extent of such events. Thus, a framework of species distribution models (SDMs), employing MaxEnt modeling, was used to project changes in habitat suitability and distribution of three key paralytic shellfish toxin (PST)-producing dinoflagellate species (i.e., Alexandrium catenella, A. minutum, and Gymnodinium catenatum), up to 2050 and 2100, across four representative concentration pathway scenarios (RCP-2.6, 4.5, 6.0, and 8.5; CMIP5). Despite slightly different responses at the regional level, the global habitat suitability has decreased for all the species, leading to an overall contraction in their tropical and sub-tropical ranges, while considerable expansions are projected in higher latitudes, particularly in the Northern Hemisphere, suggesting poleward distributional shifts. Such trends were exacerbated with increasing RCP severity. Yet, further research is required, with a greater assemblage of environmental predictors and improved occurrence datasets, to gain a more holistic understanding of the potential impacts of climate change on PST-producing species.info:eu-repo/semantics/publishedVersio

Preparation of well-dispersed chitosan/alginate hollow multilayered microcapsules for enhanced cellular internalization

Hollow multilayered capsules have shown massive potential for being used in the biomedical and biotechnology fields, in applications such as cellular internalization, intracellular trafficking, drug delivery, or tissue engineering. In particular, hollow microcapsules, developed by resorting to porous calcium carbonate sacrificial templates, natural-origin building blocks and the prominent Layer-by-Layer (LbL) technology, have attracted increasing attention owing to their key features. However, these microcapsules revealed a great tendency to aggregate, which represents a major hurdle when aiming for cellular internalization and intracellular therapeutics delivery. Herein, we report the preparation of well-dispersed polysaccharide-based hollow multilayered microcapsules by combining the LbL technique with an optimized purification process. Cationic chitosan (CHT) and anionic alginate (ALG) were chosen as the marine origin polysaccharides due to their biocompatibility and structural similarity to the extracellular matrices of living tissues. Moreover, the inexpensive and highly versatile LbL technology was used to fabricate core-shell microparticles and hollow multilayered microcapsules, with precise control over their composition and physicochemical properties, by repeating the alternate deposition of both materials. The microcapsules' synthesis procedure was optimized to extensively reduce their natural aggregation tendency, as shown by the morphological analysis monitored by advanced microscopy techniques. The well-dispersed microcapsules showed an enhanced uptake by fibroblasts, opening new perspectives for cellular internalization.publishe

Trigger and Target of Renal Functions

This work was supported by “Fundação para a Ciência e a Tecnologia” – FCT to AP (PD/BD/136887/2018); MJM (PD/BD/114256/2016), MPM (PTDC/DTP-EPI/0207/2012), DOB e MPM (PTDC/BIM-MET/2115/2014); iNOVA4Health (UIDB/Multi/04462/2020), by the European Commission Marie Skłodowska -Curie Actions H2020 (grant agreements nos. 722619 and 734719), and by the Sociedade Portuguesa de Diabetologia.Kidney function in metabolism is often underestimated. Although the word “clearance” is associated to “degradation”, at nephron level, proper balance between what is truly degraded and what is redirected to de novo utilization is crucial for the maintenance of electrolytic and acid–basic balance and energy conservation. Insulin is probably one of the best examples of how diverse and heterogeneous kidney response can be. Kidney has a primary role in the degradation of insulin released in the bloodstream, but it is also incredibly susceptible to insulin action throughout the nephron. Fluctuations in insulin levels during fast and fed state add another layer of complexity in the understanding of kidney fine-tuning. This review aims at revisiting renal insulin actions and clearance and to address the association of kidney dysmetabolism with hyperinsulinemia and insulin resistance, both highly prevalent phenomena in modern society.publishersversionpublishe

Fabrication, Structural and Biological Characterization of Zinc-Containing Bioactive Glasses and Their Use in Membranes for Guided Bone Regeneration

Funding Information: The authors extend their appreciation to the FEDER funds through the COMPETE 2020 Program and National Funds through FCT—Portuguese Foundation for Science and Technology under the project LISBOA-01-0247-FEDER-039985/POCI-01-0247-FEDER-039985, LA/P/0037/2020, UIDP/50025/2020, and UIDB/50025/2020 of the Associate Laboratory Institute of Nanostructures, Nanomodelling, and Nanofabrication—i3N., UCIBIO (UIDP/04378/2020 and UIDB/04378/2020) and Associate Laboratory i4HB (LA/P/0140/2020). S.R. Gavinho and A. Sofia Pádua acknowledge FCT—Portuguese Foundation for Science and Technology for the PhD grant (SFRH/BD/148233/2019 and UI/BD/151287/2021, respectively). Funding Information: FEDER funds through the COMPETE 2020 Program and National Funds through FCT—Portuguese Foundation for Science and Technology under the project LISBOA-01-0247-FEDER-039985/POCI-01-0247-FEDER-039985 LA/P/0037/2020, UIDP/50025/2020, and UIDB/50025/2020 of the Associate Laboratory Institute of Nanostructures, Nanomodelling, and Nanofabrication—i3N, UCIBIO (UIDP/04378/2020 and UIDB/04378/2020), and Associate Laboratory i4HB (LA/P/0140/2020). S.R. Gavinho and A. Sofia Pádua acknowledges FCT—Portuguese Foundation for Science and Technology for the PhD grant (SFRH/BD/148233/2019 and UI/BD/151287/2021, respectively). Publisher Copyright: © 2023 by the authors.Polymeric membranes are widely used in guided bone regeneration (GBR), particularly in dentistry. In addition, bioactive glasses can be added to the polymers in order to develop a matrix that is osteoconductive and osteoinductive, increasing cell adhesion and proliferation. The bioactive glasses allow the insertion into its network of therapeutic ions in order to add specific biological properties. The addition of zinc into bioactive glasses can promote antibacterial activity and induce the differentiation and proliferation of the bone cells. In this study, bioactive glasses containing zinc (0.25, 0.5, 1 and 2 mol%) were developed and structurally and biologically characterized. The biological results show that the Zn-containing bioactive glasses do not present significant antibacterial activity, but the addition of zinc at the highest concentration does not compromise the bioactivity and promotes the viability of Saos-2 cells. The cell culture assays in the membranes (PCL, PCL:BG and PCL:BGZn2) showed that zinc addition promotes cell viability and an increase in alkaline phosphatase (ALP) production.publishersversionpublishe

Biocompatibility, Bioactivity, and Antibacterial Behaviour of Cerium-Containing Bioglass®

Funding Information: The authors extend their appreciation to the FEDER funds through the COMPETE 2020 Program and National Funds through FCT—Portuguese Foundation for Science and Technology under the project LISBOA-01-0247-FEDER-039985/POCI-01-0247-FEDER-039985, UIDP/50025/2020, and UIDB/50025/2020 of the Associate Laboratory Institute of Nanostructures, Nanomodelling, and Nanofabrication—i3N., UCIBIO (UIDP/04378/2020 and UIDB/04378/2020) and Associate Laboratory i4HB (LA/P/0140/2020). S.R. Gavinho and A. Sofia Pádua acknowledge FCT—Portuguese Foundation for Science and Technology for the PhD grant (SFRH/BD/148233/2019 and UI/BD/151287/2021, respectively). Publisher Copyright: © 2022 by the authors.The main reason for the increased use of dental implants in clinical practice is associated with aesthetic parameters. Implants are also presented as the only technique that conserves and stimulates natural bone. However, there are several problems associated with infections, such as peri-implantitis. This disease reveals a progressive inflammatory action that affects the hard and soft tissues surrounding the implant, leading to implant loss. To prevent the onset of this disease, coating the implant with bioactive glasses has been suggested. In addition to its intrinsic function of promoting bone regeneration, it is also possible to insert therapeutic ions, such as cerium. Cerium has several advantages when the aim is to improve osseointegration and prevent infectious problems with dental implant placement. It promotes increased growth and the differentiation of osteoblasts, improves the mechanical properties of bone, and prevents bacterial adhesion and proliferation that may occur on the implant surface. This antibacterial effect is due to its ability to disrupt the cell wall and membrane of bacteria, thus interfering with vital metabolic functions such as respiration. In addition, its antioxidant effect reverses oxidative stress after implantation in bone. In this work, Bioglass 45S5 with CeO2 with different percentages (0.25, 0.5, 1, and 2 mol%) was developed by the melt-quenching method. The materials were analyzed in terms of morphological, structural, and biological (cytotoxicity, bioactivity, and antibacterial activity) properties. The addition of cerium did not promote structural changes to the bioactive glass, which shows no cytotoxicity for the Saos-2 cell line up to 25 mg/mL of extract concentration for all cerium contents. For the maximum cerium concentration (2 mol%) the bioactive glass shows an evident inhibitory effect for Escherichia coli and Streptococcus mutans bacteria. Furthermore, all samples showed the beginning of the deposition of a CaP-rich layer on the surface of the material after 24 h.publishersversionpublishe