Genetically engineered-MSC therapies for non-unions, delayed unions and critical-size bone defects

The normal bone regeneration process is a complex and coordinated series of events involving different cell types and molecules. However, this process is impaired in critical-size/large bone defects, with non-unions or delayed unions remaining a major clinical problem. Novel strategies are needed to aid the current therapeutic approaches. Mesenchymal stem/stromal cells (MSCs) are able to promote bone regeneration. Their beneficial effects can be improved by modulating the expression levels of specific genes with the purpose of stimulating MSC proliferation, osteogenic differentiation or their immunomodulatory capacity. In this context, the genetic engineering of MSCs is expected to further enhance their pro-regenerative properties and accelerate bone healing. Herein, we review the most promising molecular candidates (protein-coding and non-coding transcripts) and discuss the different methodologies to engineer and deliver MSCs, mainly focusing on in vivo animal studies. Considering the potential of the MSC secretome for bone repair, this topic has also been addressed. Furthermore, the promising results of clinical studies using MSC for bone regeneration are discussed. Finally, we debate the advantages and limitations of using MSCs, or genetically-engineered MSCs, and their potential as promoters of bone fracture regeneration/repair.This project is supported by Fundação para a Ciência e a Tecnologia (FCT)—in the framework of the project POCI-01-0145-FEDER-031402-R2Bone, under the PORTUGAL 2020 Partnership Agreement, through ERDF, co-funded by FEDER/FNR, and national funding (through FCT – Fundação para a Ciência e a Tecnologia, I.P., provided by the contract-program and according to numbers 4, 5 and 6 of art. 23 of Law No. 57/2016 of 29 August 2016, as amended by Law No. 57/2017 of 19 July 2017). RG, JHT, and MIA are supported by FCT, through the FCT Investigator Program (IF/00638/2014), SFRH/BD/112832/2015, and DL 57/2016/CP1360/CT0008, respectively

Mesenchymal Stromal Cell Secretome: Influencing Therapeutic Potential by Cellular Pre-conditioning

Mesenchymal stromal cells (MSCs) are self-renewing, culture-expandable adult stem cells that have been isolated from a variety of tissues, and possess multipotent differentiation capacity, immunomodulatory properties, and are relatively non-immunogenic. Due to this unique set of characteristics, these cells have attracted great interest in the field of regenerative medicine and have been shown to possess pronounced therapeutic potential in many different pathologies. MSCs' mode of action involves a strong paracrine component resulting from the high levels of bioactive molecules they secrete in response to the local microenvironment. For this reason, MSCs' secretome is currently being explored in several clinical contexts, either using MSC-conditioned media (CM) or purified MSC-derived extracellular vesicles (EVs) to modulate tissue response to a wide array of injuries. Rather than being a constant mixture of molecular factors, MSCs' secretome is known to be dependent on the diverse stimuli present in the microenvironment that MSCs encounter. As such, the composition of the MSCs' secretome can be modulated by preconditioning the MSCs during in vitro culture. This manuscript reviews the existent literature on how preconditioning of MSCs affects the therapeutic potential of their secretome, focusing on MSCs' immunomodulatory and regenerative features, thereby providing new insights for the therapeutic use of MSCs' secretome.We would like to acknowledge Norte Portugal Regional Operational Programme (NORTE 2020) in the framework of the project “Bioengineered Therapies for Infectious Diseases and Tissue Regeneration” (NORTE-01-0145-FEDER-000012). We also acknowledge Fundação para a Ciência e a Tecnologia (FCT) and Fundo Europeu de Desenvolvimento Regional (FEDER) funds through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020-in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). We also acknowledge EUROSPINE TRF for the funded project “Disc Regeneration, Immuno, and Neuro Modulation” , ref. 2017_05 . In addition, JF and RG also acknowledge FCT for funding the BiotechHealth Ph.D. fellowship (PD/BD/135486/2018) and the FCT Investigator Grant (IF/00638/2014), respectively

A Dashboard for Security Forces Data Visualization and Storytelling

Neto, M. D. C., Nascimento, M., Sarmento, P., Ribeiro, S., Rodrigues, T., & Painho, M. (2019). A Dashboard for Security Forces Data Visualization and Storytelling. In I. Ramos, R. Quaresma, P. R. D. Silva, & T. Oliveira (Eds.), Information Systems for Industry 4.0: Proceedings of the 18th Conference of the Portuguese Association for Information Systems (pp. 47-62). (Lecture Notes in Information Systems and Organisation; Vol. 31). Springer International Publishing. https://doi.org/10.1007/978-3-030-14850-8_4Being security assumed as a basic right of citizens in the current model of democratic rule of law, optimal resources allocation altogether with budgetary constraints are a key component. In fact optimal resources allocation and budgetary constraints oblige an increasingly careful strategic management, adapted to demographic reality. The SIM4SECURITY project aims to build a technological solution to support decision making regarding security, based on the development of a GIS model and in the implementation of demographic scenarios. This model will allow policy makers, leaders and forces of command units and services in the planning and rational affectation of resources adjusted to local dynamics in crime prevention and crime fighting. To communicate the SIM4SECURITY results and support decision making, a data visualization and storytelling approach was adopted by creating dashboards containing the various dimensions and perspectives of the information were elaborated and are presented. The obtained outcomes show that dashboards are an important visual tool in the decision-making process by providing meaningful insights regarding security and in the location-allocation of security forces.authorsversionpublishe

Towards understanding startup product development as effectual entrepreneurial behaviors

Software startups face with multiple technical and business challenges, which could make the startup journey longer, or even become a failure. Little is known about entrepreneurial decision making as a direct force to startup development outcome. In this study, we attempted to apply a behaviour theory of entrepreneurial firms to understand the root-cause of some software startup s challenges. Six common challenges related to prototyping and product development in twenty software startups were identified. We found the behaviour theory as a useful theoretical lens to explain the technical challenges. Software startups search for local optimal solutions, emphasise on short-run feedback rather than long-run strategies, which results in vague prototype planning, paradox of demonstration and evolving throw-away prototypes. The finding implies that effectual entrepreneurial processes might require a more suitable product development approach than the current state-of-practice.Comment: This is the author's version of the work. Copyright owner's version can be accessed at https://doi.org/10.1007/978-3-319-69191-6_15, 8th ICSOB 2017, Essen, German

In the beginning: Role of autonomy support on the motivation, mental health and intentions of participants entering an exercise referral scheme

Self-determination theory (Deci & Ryan, 2000, Intrinsic motivation and self-determination in human behaviour. New York: Plenum Publishing) highlights the impact autonomy supportive environments can have on exercise motivation and positive health outcomes. Yet little is known about whether differential effects occur as a function of which significant other is providing this support. Further, no research has examined the relationship between motivation and the social environment with participants’ mental health and intentions to be physically active before entering an exercise intervention. Study participants were 347 British adults who were about to start an exercise referral scheme. Regression analyses revealed that the effects of autonomy support on mental health and physical activity intentions differed as a function of who provided the support (offspring, partner or physician), with the offspring having the weakest effects. A structural model was supported, indicating that autonomy support and more autonomous regulations led to more positive mental health outcomes and stronger intentions to be physically active. Knowledge of the social environmental and personal motivation of those about to commence an exercise programme can provide important insights for professionals supporting such efforts

Sex and body mass index impact on digit circumference for Leeds Dactylitis Index calculation

Objectives: To estimate digit circumference and the impact of sex and body mass index (BMI) for the calculation of the Leeds Dactylitis Index (LDI) in psoriatic arthritis (PsA) patients with bilateral dactylitis. Methods: Digit circumference of the hands and the foot were measured with a dactylometer and were studied according to sex and BMI (divided in 4 weight categories) in healthy Portuguese subjects, using Student's t-test and One-way ANOVA, respectively. The effect size of sex and BMI were calculated using Cohen's d test and Eta squared, respectively. Multiple linear regression was used to calculate the effect of sex and BMI, as well as their interaction, to create a formula to predict digit circumference. Results: Fifty-nine participants (33 women, 26 men) with a mean BMI of 24.8 were included. Men's mean digit circumferences were statistically higher than those of women (p<0.001), with a large sex effect size in most of the digits. Differences in the mean circumference between the four BMI categories were statistically significant (p<0.05) for all digits, with a large BMI effect size. Sex and BMI were independent variables to predict mean digit circumference (p<0.001). A new tool (based on regression analysis) allowing to estimate the circumference of digits for males and females of different BMIs is presented. Conclusions: Our data allows the calculation of digit circumference for males and females of different BMIs in the Portuguese population; and shows that BMI influences digital circumference supporting BMI inclusion in LDI references tablesinfo:eu-repo/semantics/publishedVersio

Caracterização dos Hábitos de Sono na Primeira Infância numa População Clínica

Introdução: Os problemas de sono fazem parte das queixas mais referidas, nomeadamente as dificuldades para as crianças se tranquilizarem e adormecerem na hora de dormir e os despertares noturnos frequentes. O objectivo deste estudo foi caracterizar os hábitos de sono na primeira infância. Materiais e Métodos: Construção de questionário sobre os hábitos de sono na primeira infância, aplicando-o a uma população de crianças atendidas em primeira consulta de pedopsiquiatria no Centro de Estudos do Bebé e da Criança / Unidade da Primeira Infância (n=93), dos 0 aos 3 anos de idade, durante o ano de 2014. Resultados: A média de idades é de 27 meses, variando entre 1 e 36 meses. Não existem diferenças estatisticamente significativas entre sexos e idades relativamente ao ambiente em que dormem. 77% das crianças têm rotinas antes de adormecer. As crianças que têm rotinas, têm menor dificuldade em adormecer (p=0,028). 38,04% dos pais considera que existem problemas de sono. A média do número total de horas de sono entre os 3 e os 11 meses foi de 12h e entre os 12 e os 35 meses de 11h. Discussão: Concordante com a literatura, a maioria das crianças acorda durante a noite (61,3%), o número e a duração de sestas diminui ao longo da vida e os problemas de sono são frequentes (38,04%), apesar de neste estudo terem uma prevalência ligeiramente superior. A duração de sono das crianças é inferior ao recomendado. Conclusão: Verifica-se uma associação significativa entre a inexistência de rotinas e a dificuldade em adormecer e uma associação significativa entre crianças que dormem sozinhas e ausência de problemas de sono.info:eu-repo/semantics/publishedVersio

Primary resistance of HIV to antiretrovirals among individuals recently diagnosed at voluntary counselling and testing centres in the metropolitan region of Recife, Pernambuco

Determining the prevalence and type of antiretroviral (ARV) resistance among ARV-naïve individuals is important to assess the potential responses of these individuals to first-line regimens. The prevalence of primary resistance and the occurrence of recent infections among individuals with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) were identified among recently diagnosed patients at five sexually transmitted disease/AIDS testing and counselling centres in the metropolitan region of Recife (RMR), Pernambuco, Brazil, between 2007-2009. One-hundred and eight samples were analysed using the Calypte® BED assay. Males predominated (56%), as did patients aged 31-50 years. Twenty-three percent presented evidence of a recent HIV infection. The median CD4+ T lymphocyte count was 408 cells/mm³ and the median viral load was 3.683 copies/mL. The prevalence of primary resistance was 4.6% (confidence interval 95% = 1-8.2%) based on criteria that excluded common polymorphisms in accordance with the surveillance drug resistance mutation criteria. The prevalence of resistance to non-nucleoside reverse transcriptase, nucleoside/nucleotide reverse transcriptase and protease inhibitors were 3.8%, 1.5% and 0.8%, respectively. Fifty-seven percent of strains were from clade B, 37.7% were clade F and 3.1% were clade C; there were no statistically significant differences with respect to resistance between clades. Recent infection tended to be more common in men (p = 0.06) and in municipalities in the south of the RMR (Jaboatão dos Guararapes and Cabo de Santo Agostinho) (p = 0.046). The high prevalence of recent infection and the high prevalence of non-B strains in this poor Brazilian region merit further attention.Laboratório Central de Saúde Pública de Pernambuco Setor de VirologiaUniversidade Federal de Pernambuco Programa de Pós-Graduação em Medicina TropicalFiocruz Centro de Pesquisa Aggeu MagalhãesCentro de Testagem e Aconselhamento Herbert de SouzaUniversidade Federal de São Paulo (UNIFESP) Laboratório de RetrovirologiaUNIFESP, Laboratório de RetrovirologiaSciEL