Abstract
The aim of this study was to investigate the effect chitosan (Ch) porous 3D scaffolds embedded with resolvin D1 (RvD1), an endogenous pro-resolving lipid mediator, on bone tissue healing. These scaffolds previous developed by us have demonstrated to have immunomodulatory properties namely in the modulation of the macrophage inflammatory phenotypic profile in an in vivo model of inflammation. Herein, results obtained in an in vivo rat femoral defect model demonstrated that two months after Ch+RvD1 scaffolds implantation, an increase in new bone formation, in bone trabecular thickness, and in collagen type I and Coll I/Coll III ratio were observed. These results suggest that Ch scaffolds embedded with RvD1 were able to lead to the formation of new bone with improvement of trabecular thickness. This study shows that the presence of RvD1 in the acute phase of the inflammatory response to the implanted biomaterial had a positive role in the subsequent bone tissue repair, thus demonstrating the importance of innovative approaches for the control of immune responses to biomedical implants in the design of advanced strategies for regenerative medicine. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1626-1633, 2018.

Abstract
Bone injury healing is an orchestrated process that starts with an inflammatory phase followed by repair and remodelling of the bone defect. The initial inflammation is characterized by local changes in immune cell populations and molecular mediators, including microRNAs (miRNAs). However, the systemic response to bone injury remains largely uncharacterized. Thus, this study aimed to profile the changes in the plasma miRnome after bone injury and determine its biological implications. Methods: A rat model of femoral bone defect was used, and animals were evaluated at days 3 and 14 after injury. Non-operated (NO) and sham operated animals were used as controls. Blood and spleen were collected and peripheral blood mononuclear cells (PBMC) and plasma were separated. Plasma miRnome was determined by RT-qPCR array and bioinformatics Ingenuity pathway analysis (IPA) was performed. Proliferation of bone marrow mesenchymal stem/stromal cells (MSC) was evaluated by Ki67 staining and high-throughput cell imaging. Candidate miRNAs were evaluated in splenocytes by RT-qPCR, and proteins found in the IPA analysis were analysed in splenocytes and PBMC by Western blot. Results: Bone injury resulted in timely controlled changes to the miRNA expression profile in plasma. At day 3 there was a major down-regulation of miRNA levels, which was partially recovered by day 14 post-injury. Interestingly, bone injury led to a significant up-regulation of let-7a, let-7d and miR-21 in plasma and splenocytes at day 14 relative to day 3 after bone injury, but not in sham operated animals. IPA predicted that most miRNAs temporally affected were involved in cellular development, proliferation and movement. MSC proliferation was analysed and found significantly increased in response to plasma of animals days 3 and 14 post-injury, but not from NO animals. Moreover, IPA predicted that miRNA processing proteins Ago2 and Dicer were specifically inhibited at day 3 post-injury, with Ago2 becoming activated at day 14. Protein levels of Ago2 and Dicer in splenocytes were increased at day 14 relative to day 3 post-bone injury and NO animals, while in PBMC, levels were reduced at day 3 (albeit Dicer was not significant) and remained low at day 14. Ephrin receptor B6 followed the same tendency as Ago2 and Dicer, while Smad2/3 was significantly decreased in splenocytes from day 14 relative to NO and day 3 post-bone injury animals. Conclusion: Results show a systemic miRNA response to bone injury that is regulated in time and is related to inflammation resolution and the start of bone repair/regeneration, unravelling candidate miRNAs to be used as biomarkers in the monitoring of healthy bone healing and as therapeutic targets for the development of improved bone regeneration therapies.

Abstract
Inflammation is a common symptom in joint disorders such as rheumatoid arthritis, osteoarthritis (OA) and implant aseptic loosening (AL). The sympathetic nervous system is well known to play a critical role in regulating inflammatory conditions, and imbalanced sympathetic activity has been observed in rheumatoid arthritis. In AL it is not clear whether the sympathetic nervous system is altered. In this study we evaluated the systemic and local profile of neuroimmune molecules involved in the interplay between the sympathetic nervous system and the periprosthetic inflammation in hip AL. Our results showed that periprosthetic inflammation does not trigger a systemic response of the sympathetic nervous system, but is mirrored rather by the impairment of the sympathetic activity locally in the hip joint. Moreover, macrophages were identified as key players in the local regulation of inflammation by the sympathetic nervous system in a process that is implant debris-dependent and entails the reduction of both adrenergic and Neuropetide Y (NPY)-ergic activity. Additionally, our results showed a downregulation of semaphorin 3A (SEMA3A) that may be part of the mechanism sustaining the periprosthetic inflammation. Overall, the local sympathetic nervous system emerges as a putative target to mitigate the inflammatory response to debris release and extending the lifespan of orthopedic implants.

Abstract
In the last decades, the weight of renewable energies sources (RES-E) in the electricity generation mix of most European countries has considerably increased, constituting an important contribution to the transition towards a low-carbon economy. Until very recently, RES-E were supported by favorable investment mechanisms specially designed to endorse investment in RES-E. More recently, as RES-E are becoming increasingly more competitive (especially wind and solar photovoltaic), RES-E are starting to be remunerated according to market mechanisms. This has generated a lively debate on the economic pros and cons of dispatching RES-E in the market. This paper contributes to this debate by developing a game theoretical model in the context of which we analyze how the inclusion of RES-E in the electricity wholesale market affects equilibrium outcomes under demand and supply uncertainty. Then, we examine how the inclusion of RES-E in the electricity wholesale market impacts firms' incentives to invest in conventional energy sources, characterizing the optimal investment under demand and supply uncertainty. We find that, when RES-E capacity and asymmetry in firms' marginal production costs are sufficiently high, RES-E producers may strategically reduce the market price, in order to evict the less efficient conventional source in that period. Although, in the short-run, this strategy may actually favor energy consumers (since prices are lower), the expectations of inactivity periods (regardless of whether they arise for strategic or market reasons) may negatively affect investment in back-up capacity, possibly leading to an increase in future prices (since less back-up capacity is available). Finally, we provide an analytical characterization of optimal investment levels in conventional energy sources under demand and supply uncertainty.

Abstract

Abstract
It is common knowledge that history repeats itself! Maybe not literally, but patterns of behaviour likely dependent of the human nature, are probably prone to repeat themselves. So, one may wonder if looking back could help us prepare for a better future. Moreover, by looking back at the history of people and societies, we should all be able to have a better understanding of why things happen the way they do. This seldom happens, and when it does, it is happening within very limited circle of the society such as scholars and some politician circles, rarely overflowing to the whole society.The point is that, what we see today is not very different from what has happened in the past. Let us go back to November 13, 1460, the day Prince Henry the Navigator, passed away in Sagres, leaving Portugal with an enormous debt. Despite that fact, Prince Henry was the “guiding force behind Portugal’s assimilation of nautical knowledge and its vast extension of maritime exploration for nearly four decades” (Kock, 2003, p.59). It is interesting that by that time intellectual property was already being managed. (...)