Vascularization in skin wound healing: where do we stand and where do we go?

Cutaneous healing is a highly complex process that, if altered due to, for example, impaired vascularization, results in chronic wounds or repaired neotissue of poor quality. Significant progress has been achieved in promoting neotissue vascularization during tissue repair/regeneration. In this review, we discuss the strategies that have been explored and how each one of them contributes to regulate vascularization in the context of cutaneous wound healing from two different perspectives â biomaterial-based and a cell-based approaches. Finally, we discuss the implications of these findings on the development of the â next generationâ approaches to target vascularization in wound healing highlighting the importance of going beyond its contribution to regulate vascularization and take into consideration the temporal features of the healing process and of different types of wounds.The authors thank the financial support given by the European Research Council through the consolidator grant ‘ECM_INK’ (ERC-2016-COG 726061) and to the FSE/POCH (Fundo Social Europeu através do Programa Operacional do Capital Humano) under the scope of the PD/169/2013, NORTE-08-5369-FSE-000037. Authors would also like to acknowledge BioRender.com as a platform for image creation

STE(A)M aprroach: distinguishing and discussing meanings

The STE(A)M approach has been recognized by several authors for its potential in assisting teaching and learning, and several curriculum standards already value its application in the classroom [1]. This approach is based on the articulation between different areas, the clarification, and the deepening of the concepts being studied. Although there are different approaches, according to the fields involved, STEM and STEAM are two among the most often mentioned in the literature. STEM is based on learning that integrates the following areas of knowledge: Science, Technology, Engineering, and Mathematics. The conceptualization of the STE(A)M approach is not consensual and uniform. There are different models focusing on problem-solving based learning, project-based-learning, design-based learning, and engineering models. Still, different authors [3] [4] [5] present different conceptualizations of this approach. In this paper, we relied on the existing literature to discuss the different understandings of the STE(A)M approach. We will also pay attention to mathematics and how different authors see the disciplines’ role within a STE(A)M approach and discuss the evolution of the mentioned authors’ positions throughout time. Thus, methodologically, we undertook the following steps: (i) literature search based on the selected keywords; (ii) selection of the texts, considering the authors and time gap, in order to analyze the evolution of the research and (iii) collection and organization of the relevant topics for the study. This study aims to present the meanings, conceptualizations, and possible influences present in different models and for understand the evolution of the STEM and STEAM approaches over time. The main findings suggest a focus on the interdisciplinary or transdisciplinary approach as opposed to the primeval years of investigations in STEM and STEAM when many authors advocated a multidisciplinary approach. This change in thinking is due to the need to train students in an integral and holistic manner, developing citizens with transversal knowledge and skills prepared for the current societal challenges.This work has been supported by FCT – Fundação para a Ciência e Tecnologia within the Project Scope: UIDB/05777/2020. Research Centre in Basic Education (CIEB), Instituto Politécnico de Bragança, Portugal.info:eu-repo/semantics/publishedVersio

Influence of the presence of biofilms on the biotribocorrosion of titanium

Even though titanium (Ti) has the ability to develop a highly stable passive oxide layer (TiO2) that provides an excellent corrosion resistance; it’s not inert to corrosive attack. Under in vivo conditions, such as in orthopedic and dental implants, a tribological contact may be formed in association with a chemical aggressive environment. Consequently, wear debris and corrosion products or ions can lead to inflammatory reactions, such as osteolysis (bone resorption), provoking peri-prosthetic bone loss and subsequent loosening of the implant/prosthesis [1]. The microbial effect on the corrosion of metallic biomaterials remains unknown. Chang et al. [2] reported an increase on the corrosion behaviour of dental metallic materials in the presence of Streptococcus mutans and its growth byproducts. Moreover, brushing can lead to the production of wear debris, which together with the attachment of microbes can disturb the passivity of the metal oxide. In addition, the organic acids produced by bacteria may reduce the pH, favoring the corrosion and tribocorrosion of implants. The aim of this work was to study the influence of mixed biofilms on the biotribocorrosion behaviour of commercially pure (cp) Ti for dental implants, and the consequent effect of fluoride

Tribological behaviour of oral mixed biofilms

The use of dental implants has been increasing even though failures do occur. The presence of wear debris and oral microorganisms can contribute to infections and jeopardize implant integration. The aim of this work was to study the influence of mixed biofilms in the tribological behaviour of commercially pure titanium for dental implants under different concentrations of fluoride. Samples of titanium with two different surface topographies were used. Mixed biofilms of Candida albicans and Streptococcus mutans were formed on both surfaces at 37 °C in a tryptic soy broth containing mucin, peptone, yeast extract and sucrose. After 8 days, biofilm biomass was analysed by crystal violet staining method. Biofilm biomass was significantly higher for the samples with higher roughness. Some samples with biofilms were analysed under friction (using a force of 100 mN) in an artificial saliva solution (Fusayama) without or with different concentrations of fluoride (30 and 227 ppm). It was verified that the coefficient of friction (COF) decreased in the presence of biofilms. Moreover, samples with more biomass (0.4 μm of roughness) presented the lowest values of COF. Concerning the effect of the presence of fluoride, although there were no significant differences on the COF for 30 ppm, for 227 ppm a transition regimen was observed. These results were confirmed by sample observation under scanning electron microscopy. In conclusion, it can be highlighted that biofilm formation on dental implants can significantly affect the tribological behaviour of titanium, namely, the presence of biofilms reduces the release of wear debris

Unravelling the path to create a cell sheet-based model of skin scar-like tissue

Regardless of the advances in understanding the mechanisms and the pathophysiology behind skin deformities, scaring continues to be an unsolved clinical problem. The underlying wound healing process involves a series of key cells which play different key roles. Fibroblasts are known to suffer the influence of local biochemical (e.g TGF-B1) and biomechanical signaling upon a wound scenario leading to a phenotypical change into myofibroblasts. The latter enhance immature extracellular matrix (ECM) synthesis and generate tensional forces that leads to ECM reorganization. Certain skin pathologies (e.g hypertrophic scars) rise from a dysfunction of this underlying regulatory mechanism which in turn drives myofibroblast persistence in the wound. When trying to study the mechanisms behind scarring human ex vivo samples are many times scarce and most of the current in vitro systems rely on standard 2D cultures of keloid/hypertrophic scar fibroblasts. Taking all of this into consideration we propose the use of cell sheet technology to create an in vitro 3D scar model. Herein we report the effect of TGF-B1 in human dermal fibroblast cell sheets as the first step to attain cell sheets with a myofibroblast-like phenotype in which cells are embedded in a scar-like ECM. To further strengthen our concept we performed the stacking of pre-formed cell sheets generating a cohesive 3D scar-like tissue. Human dermal fibroblast (hDFbs) cell sheets were produced as previously described1, and stimulated with TGF-B1 (10ng/ml) over 7, 14 and 21 days. Following phenotype and ECM characterization, cell sheets were stacked in order to obtain a 3D structure composed of 2 or 3 cell-sheets. The analysis of key genes (q-PCR) and proteins (Western blot and immunocytochemistry) showed that hDFbs cell sheets, when stimulated with TGF-B1 present an increased expression of a-SMA, fibronectin (FN) ED- A and FN ED-B, characteristic of a myofibroblast-like phenotype. When looking into the expression of scar ECM-associated proteins, hDFbs cell sheets obtained in the presence of TGF-B1 produced higher amounts of fibronectin and collagen I. Stable 3D constructs with a noticeable level of integration after a total of 21 days of culture, were further created upon stacking of the cell sheets obtained after 7days of culture in the presence of TGF-B1. In conclusion, this work suggested that it is possible to promote the secretion of scar-like ECM in hDFbs cell sheets due to phenotypic changes into myofibroblast-like cells when stimulated with TGF-B1. Cohesive 3D scar-like tissue structures were obtained which opens the possibility to develop a highly accurate in vitro 3D scar model to study underlying cellular mechanisms involved in the wound healing deregulation. Grant IF/00945/2014 funded by FCT/MCTES, Project “NORTE-08-5369-FSE-000044”, funded by Programa Operacional Norte 2020 Fundo Social Europeu, and GENE2SKIN Twinning Project, Horizon 2020, funded by the European Commissioninfo:eu-repo/semantics/publishedVersio

In vitro 3D cell sheet-based model for unraveling scar pathophysiology

Fibroblasts are key players in the scarring process. In hypertrophic scars, fibroblasts suffer phenotypical changes into myofibroblasts persisting in the wound under the influence of local biochemical (TGFb1) and biomechanical signaling leading to enhanced immature extracellular matrix (ECM) synthesis. Benchtop models of hypertrophic scars rely on scarce human ex vivo samples or standard 2D cultures of hypertrophic scar fibroblasts. We therefore propose the use of human dermal fibroblast cell sheets (hDFbsCS) as the first step to attain cell sheets with a myofibroblast-like phenotype to generate cohesive in vitro 3D scar-like tissues. hDFbsCS were produced as previously described (Cerqueira, 2014), and stimulated with TGFb1 up to 21 days. Following phenotype and ECM characterization, 3 hDFbsCS were stacked to obtain a 3D structure. Gene and protein analysis showed that upon TGFb1 stimulation, hDFbsCS present a higher expression of aSMA, fibronectin EDA and EDB, characteristic of amyofibroblast-like phenotype. Regarding the expression of scar ECM-associated proteins, TGFb1 stimulated hDFbsCS produced increased fibronectin and collagen I. Upon stacking of hDFbsCS obtained after 7 days of culture in the presence of TGFb1, stable and integrated 3D constructs were obtained. This work suggests that it is possible to create cohesive 3D scar-like tissue structures from hDFbsCS opening the possibility to develop in vitro 3D scar models to study wound healing deregulation pathophysiology. Acknowledgments: Grant IF.00945.2014 and SFRH.BD. 119756.2016 (FCT MCTES), NORTE.08.5369.FSE.000044 (funded by Programa Operacional Norte 2020 Fundo Social Europeu), GENE2SKIN Twinning Project, Horizon 2020 (European Commission).Grant IF.00945.2014 and SFRH.BD.119756.2016 (FCT_MCTES), NORTE.08.5369.FSE.000044 (funded by Programa_Operacional_Norte_2020 Fundo Social Europeu), GENE2SKIN Twinning Project, Horizon_2020 (European Commission).info:eu-repo/semantics/publishedVersio

IT-REHAB : Integral Telerehabilitation System

The main functionalities of the physical rehabilitation module of IT-REHAB are briefly described in this paper. IT-REHAB is a telerehabilitation system under development for patients with physical or cognitive rehabilitation needs. It supports wireless biomechanical and physiological data collection and includes advanced functionalities based on a custom-designed Medium Access (MAC) protocol for improved bandwidth utilization and an immersive user interface that incorporates virtual reality elements for a motivating experience. Moreover, it includes affective computing technologies for pain intensity estimation, wearables for easy sensor devices setting up, and real-time communication between patients and therapists

Los papeles y funciones del enfermero de salud laboral en Brasil y en los Estados Unidos de America

Cross-sectional exploratory research developed to outline the roles and functions of occupational health nurses (OHNs) in Brazil and compare them with those in the United States. The sample consisted of 154 Brazilian occupational health nurses. First, the instrument Job Analysis Survey of Occupational Health Nursing Practice was translated into Portuguese, followed by data collection and data analysis, comparing the results of the proposed study in Brazil with the findings of a job delineation study conducted in the United States. It was found that most were women, white, between 41 and 50 years of age and working primarily at hospitals or medical centers as clinicians and managers/administrators. Besides, it was found that most Brazilian OHNs spend more time in managerial roles, followed by consultant and educator responsibilities while, in the United States, OHNs spend significantly more time in education/advisory roles.Investigación transversal realizada con el objetivo de definir los papeles y funciones de los enfermeros de salud laboral (ESLs) en Brasil y compararles con los de los Estados Unidos de América (EUA). La muestra fue compuesta por ciento cincuenta y cuatro enfermeros de salud laboral brasileños. Primero, fue realizada la traducción de lo instrumento Job Analysis Survey of Occupational Health Nursing Practice para el Portugués, seguido de la recolecta y análisis de los datos, comparándolos con los hallazgos de un estudio conducido en los EUA. Se encontró que la mayoría eran mujeres, blancas, entre 41 y 50 años e trabajan en hospitales y centros médicos como enfermeros clínicos y administradores. También se encontró que ESLs brasileños dedican más tiempo en funciones administrativas, seguidas de responsabilidades de consultoría y educador, mientras en los EUA los ESLs dedican significativamente más tiempo en funciones educativas y de asesoría.Estudo transversal desenvolvido com o objetivo de delinear as responsabilidades e funções das enfermeiras do trabalho no Brasil e compará-las às atribuições das enfermeiras de saúde ocupacional nos Estados Unidos. A amostra foi composta por 154 enfermeiras do trabalho. Inicialmente, foi realizada a tradução para a língua portuguesa do instrumento de coleta de dados Job Analysis Survey of Occupational Health Nursing Practice, seguido da coleta e análise dos resultados, comparando-os aos dados obtidos num estudo realizado nos EUA. Foi constatado que a maioria das enfermeiras eram mulheres, brancas, com faixa etária entre 41 e 50 anos e trabalhavam em hospitais e centros médicos como enfermeiras clínicas ou administradoras. Além disso, observou-se que as enfermeiras brasileiras despendem maior tempo em funções administrativas, atividades de consultoria e ações educativas, enquanto que as enfermeiras norte-americanas gastam um tempo significativamente maior desenvolvendo papéis educativos e de consultoria

Histopathological features of organs in a rat model of mamamry carcinogenesis: a reference database

Mammary tumors’ development was induced through the intraperioneal administration of the carcinogen N-methyl-N-nitrosourea (MNU). Animals from group control were injected with the vehicle (saline solution). Animals were sacrificed at 25 weeks-old and the organs were histopathologically evaluated. A higher number of lesions was observed in the organs of animals from group MNU. The animals from group control did not present any lesion in lymph nodes. Independently of the experimental group, the internal organs presented hemodynamic alterations, degenerative and inflammatory changes. Hemodynamic changes may be consequence of euthanasia method. As expected, the higher number and the higher grade of the lesions in group MNU were due to the carcinogen administration.info:eu-repo/semantics/publishedVersio

6-Amidinopurines as convenient precursors to pyrimido[5,4-d]pyrimidines for sar studies on Mycobacterium tuberculosis

Thanks are due to University of Minho and Fundação para a Ciência e Tecnologia for financial support (project nºF-COMP-01-0124-FEDER-022716 (ref. FCT PEst-/QUI/UI0686/2011) FEDER-COMPETE, FCT-Portugal and PhD grant awarded to Ana Bacelar SRFH/BD/24959/2005). The NMR spectrometer (Bruker 400 Avance III) is part of the National NMR Network supported with funds from FCT.nºF-COMP-01-0124-FEDER-02271