Fate of Bone Marrow-Derived Stromal Cells after Intraperitoneal Infusion or Implantation into Femoral Bone Defects in the Host Animal

The fate of intraperitoneally injected or implanted male rat bone marrow-derived stromal cells inside female sibling host animals was traced using Y-chromosome-sensitive PCR. When injected intraperitoneally, Y-chromosome-positive cells were found in all studied organs: heart muscle, lung, thymus, liver, spleen, kidney, skin, and femoral bone marrow with a few exceptions regardless of whether they had gone through osteogenic differentiation or not. In the implant experiments, expanded donor cells were seeded on poly(lactide-co-glycolide) scaffolds and grown under three different conditions (no additives, in osteogenic media for one or two weeks) prior to implantation into corticomedullar femoral defects. Although the impact of osteogenic in vitro cell differentiation on cell migration was more obvious in the implantation experiments than in the intraperitoneal experiments, the donor cells stay alive when injected intraperitoneally or grown in an implant and migrate inside the host. However, when the implants contained bioactive glass, no signs of Y-chromosomal DNA were observed in all studied organs including the implants indicating that the cells had been eliminated

Signature of circulating small non-coding RNAs during early fracture healing in mice

Fracture healing is a complex process with multiple overlapping metabolic and differentiation phases. Small non-coding RNAs are involved in the regulation of fracture healing and their presence in circulation is under current interest due to their obvious value as potential biomarkers. Circulating microRNAs (miRNAs) have been characterized to some extent but the current knowledge on tRNA-derived small RNA fragments (tsRNAs) is relatively scarce, especially in circulation.In this study, the spectrum of circulating miRNAs and tsRNAs was analysed by next generation sequencing to show their differential expression during fracture healing in vivo. Analysed tsRNA fragments included stress-induced translation interfering tRNA fragments (tiRNAs or tRNA halves) and internal tRNA fragments (i-tRF), within the size range of 28–36 bp. To unveil the expression of these non-coding RNAs, genome-wide analysis was performed on two months old C57BL/6 mice on days 1, 5, 7, 10, and 14 (D1, D5, D7, D10, and D14) after a closed tibial fracture.Valine isoacceptor tRNA-derived Val-AAC 5′end and Val-CAC 5′end fragments were the major types of 5′end tiRNAs in circulation, comprising about 65 % of the total counts. Their expression was not affected by fracture. After a fracture, the levels of two 5′end tiRNAs Lys-TTT 5′ and Lys-CTT 5′ were decreased and His-GTG 5′ was increased through D1-D14. The level of miR-451a was decreased on the first post-fracture day (D1), whereas miR-328-3p, miR-133a-3p, miR-375-3p, miR-423-5p, and miR-150-5p were increased post-fracture. These data provide evidence on how fracture healing could provoke systemic metabolic effects and further pinpoint the potential of small non-coding RNAs as biomarkers for tissue regeneration.</p

Psychosocial risk factors for impaired health‑related quality of life in living kidney donors: results from the ELIPSY prospective study

Living kidney donors' follow-up is usually focused on the assessment of the surgical and medical outcomes. Whilst the psychosocial follow-up is advocated in literature. It is still not entirely clear which exact psychosocial factors are related to a poor psychosocial outcome of donors. The aim of our study is to prospectively assess the donors' psychosocial risks factors to impaired health-related quality of life at 1-year post-donation and link their psychosocial profile before donation with their respective outcomes. The influence of the recipient's medical outcomes on their donor's psychosocial outcome was also examined. Sixty donors completed a battery of standardized psychometric instruments (quality of life, mental health, coping strategies, personality, socio-economic status), and ad hoc items regarding the donation process (e.g., motivations for donation, decision-making, risk assessment, and donor-recipient relationship). Donors' 1-year psychosocial follow-up was favorable and comparable with the general population. So far, cluster-analysis identified a subgroup of donors (28%) with a post-donation reduction of their health-related quality of life. This subgroup expressed comparatively to the rest, the need for more pre-donation information regarding surgery risks, and elevated fear of losing the recipient and commitment to stop their suffering

Multiple targets identified with genome wide profiling of small RNA and mRNA expression are linked to fracture healing in mice

Long-bone fracture is a common injury and its healing process at the fracture site involves several overlapping phases, including inflammation, migration of mesenchymal progenitors into the fracture site, endochondral ossification, angiogenesis and finally bone remodelling. Increasing evidence shows that small noncoding RNAs are important regulators of chondrogenesis, osteogenesis and fracture healing. MicroRNAs are small single-stranded, non-coding RNA-molecules intervening in most physiological and biological processes, including fracture healing. Angiogenin-cleaved 5' tRNA halves, also called as tiRNAs (stress-induced RNAs) have been shown to repress protein translation. In order to gain further understanding on the role of small noncoding RNAs in fracture healing, genome wide expression profiles of tiRNAs, miRNAs and mRNAs were followed up to 14 days after fracture in callus tissue of an in vivo mouse model with closed tibial fracture and, compared to intact bone and articular cartilage at 2 months of age. Total tiRNA expression level in cartilage was only approximately one third of that observed in control D0 bone. In callus tissue, 11 mature 5'end tiRNAs out of 191 tiRNAs were highly expressed, and seven of them were differentially expressed during fracture healing. When comparing the control tissues, 25 miRNAs characteristic to bone and 29 miRNAs characteristic to cartilage tissue homeostasis were identified. Further, a total of 54 out of 806 miRNAs and 5420 out of 18,700 mRNAs were differentially expressed (DE) in callus tissue during fracture healing and, in comparison to control bone. They were associated to gene ontology processes related to mesenchymal tissue development and differentiation. A total of 581 miRNA-mRNA interactions were identified for these 54 DE miRNAs by literature searches in PubMed, thereby linking by Spearman correlation analysis 14 downregulated and 28 upregulated miRNAs to 164 negatively correlating and 168 positively correlating miRNA-mRNA pairs with chondrogenic and osteogenic phases of fracture healing. These data indicated that tiRNAs and miRNAs were differentially expressed in fracture callus tissue, suggesting them important physiological functions during fracture healing. Hence, the data provided by this study may contribute to future clinical applications, such as potential use as biomarkers or as tools in the development of novel therapeutic approaches for fracture healing.</p

(O)motiverad Invandrarpolitik : en studie om motiven att frångå invandrarpolitik och införa integrationspolitik

An effective Integration policy is important in Sweden while our government has decided and committed to be a country where everybody will be given the same opportunities. There is a greater awareness in today’s society of integration policy goals such as equal rights, responsibilities and opportunities for all. In a number of areas, however, the disparities between immigrants and Swedish-born citizens are still too large. The Swedish Riksdag decided on integration policy in 1997. The main task for this thesis will be to examine the motive behind the Government's decision to revoke immigrations policy and introduce integration policy. This task will be completed with two questions at issue; • Which were the obvious pronounced and underlying, extern- and intern sectorial motives and which immigrant policies could be identified during the three periods; 1, 2 and 3? • In what way have the extern- and intern sectorial motives, that where expressed in 1997, affected the douting in 2006 years integrationspolicy? The questions will be examined by using Lindbloms muddling through theory and Dahlströms “eigth faces of immigration politics” and for identifying motives a model inspired by Hadenius will be used. The empirical material has brought forward that the decision to introduce integrationpolicy was based on the central motive that earlier immigration policy produced assimilationpolitics. Which futher on caused the “perverse effect” – segregationpolitics. The adjustments have been clarifying of words sooner than improvement of concrete measures. The Swedish government has applied seven different immigrationpolitics during the periods 1, 2 and 3. Becides Dahlströms “eight faces of immigration politics” two more have been identified; “demanding politics and condition politics”. Seven of the ten different types have been noticed; assimilation-, segregation-, diversity-, demanding, condition-, residual-, universial politics. The motives that where observed during period 2 didn´t improve the conditions for the immigrant which were discriminated in society especially on the labourmarket. The motives from period 2 have therefore affected the motives for period 3. The recently appointed government will during it´s runningperiod try to leave the muddling through theory by the motives in creating conditions for a “self earned living” and participation. By doing this the esscense of diversity and integration policy will hopefully be reached

Översikt av indikatorer för hållbart boende - Del av förstudie om användbara kriterier för hållbart boende i Stockholms län

Denna rapport gör en översiktlig inventering över indikatorer för miljömässig och social hållbarhet för byggande och boende. Meningen med inventeringen är att ge kunskapsunderlag för diskussioner kring hur hållbarhetskriterier kan konstrueras och användas av kommunerna i Storstockholm för att driva på hållbarhetsarbetet i stadsutvecklingen. Det finns många indikatorsystem utarbetade av olika aktörer. Indikatorer finns på olika nivåer, från byggnader till hela städer. Rapporten går igenom åtta miljöcertifieringssystem som finns på den svenska marknaden, sex uppföljningssystem som används bland kommuner i Storstockholm och 14 internationella indikatorsystem för hållbara städer. Sammanfattningsvis listas 189 indikatorer inom social-, miljömässig och ekonomisk hållbarhet samt inom förvaltning och styrning. Att välja lämpliga indikatorer beror till stor del på vilka mål man vill styra mot, samt arbetsbördan som krävs för att ta fram underlagsdata, redovisa resultat och eventuellet låter verifiera detta. Datatillgänglighet är en viktig aspekt för att välja lämpligt indikatorsystem. Uppföljnings- och rankingsystem för städer kan även handla om att redovisa strategier och planer för att uppnå mål kopplade till Agenda 2030 och nationella miljökvalitetsmål. Då jämförs inte nyckeltal utan en bedömning görs till vilken grad utvalda områden uppfylls. Rapporten ger på så vis underlag för en diskussion kring vilka hållbarhetskriterier som bäst skulle driva på stadsutvecklingen i Storstockholm.Denna rapport gör en översiktlig inventering över indikatorer för miljömässig och social hållbarhet för byggande och boende. Rapporten går igenom åtta miljöcertifieringssystem som finns på den svenska marknaden, sex uppföljningssystem som används bland kommuner i Storstockholm och 14 internationella indikatorsystem för hållbara städer. Sammanfattningsvis listas 189 indikatorer inom social-, miljömässig och ekonomisk hållbarhet samt inom förvaltning och styrning

Delningens potential, kortversion

Detta är en kortversion av rapporten från projektet Delningens potential, där vi bedömt potentialen för att delning av transporter, verktyg och yta ökar och samtidigt bidrar till ekonomiska, sociala och miljömässiga vinster. I Sverige finns en lång tradition och vana av att dela på resurser. Delning har potential att ge både ekologiska, sociala och ekonomiska vinster under vissa förutsättningar

Delningens potential

This project investigates the potential increasing resource efficiency and reducing environmental impact and how the potential can be achieved for premises, transports and tools. The driving forces and obstacles for sharing have been studied, methodology for sustainability assessments and potential rebound effects have been investigated and ten success factors have been identified for upscaling sharing solutions: 1. Trust. For the sharing platform, the quality of the goods and for other users. 2. Accessibility. Geographically, temporally and in terms of access to systems and spaces. 3. Managed risk. Sharing is associated with risk, which needs to be managed and facilitated by existing regulations and which can be mitigated by commercial insurance. 4. Quality. The quality of the goods and services need to be at least as good as those the consumer would otherwise have bought for them to switch to sharing. 5. Simple and smooth transactions. By making it easier to share than to buy new, the interest in sharing solutions can increase. 6. Visibility. The fact that the knowledge and habit of sharing are so low means that the critical mass of users and objects is still too low. 7. Belonging. In several of the product categories, like transport and space, there is a need to feel that you belong - a sense of ”this is my space”. For sharing to scale up, design, business models and policy need to relate to that need. 8. Negative effects. The ability to limit and manage the negative effects of the sharing economy on conventional companies is an important factor for upscaling. 9. Access to capital is in many cases critical to growth, both to achieve a critical mass and long-term economic sustainability. 10. Regulation. Sharing requires regulations and policy support for better conditions with clear rules and tailor-made policy instruments for sharing. Several actors play an important role in building sharing potential; the role of the business sector to create new business models and good working conditions, the role of the financial sector to improve the conditions for sharing initiatives to be able to upscale, the role of national decision makers to both regulate and create conditions for sharing and manage the consequences of sharing, the role of the cities to create infrastructure, coordinate and be a driving force in itself to shape the development of sharing so that it contributes to sustainability and the role of research to develop innovative forms of sharing, continue to follow the development of sharing and develop ways to measure effects and prevent rebound effects.Delning av underutnyttjade resurser kan vara en viktig pusselbit i omställningen till en mer hållbar konsumtion. Projektet Delningens potential har tittat på potentialen att dela transporter, lokaler och verktyg. Projektet har finansierats genom det strategiska innovationsprogrammet RE:Source och genomförts av IVL Svenska Miljöinstitutet i samverkan med KTH och Lunds universitet

Multiple targets identified with genome wide profiling of small RNA and mRNA expression are linked to fracture healing in mice

Long-bone fracture is a common injury and its healing process at the fracture site involves several overlapping phases, including inflammation, migration of mesenchymal progenitors into the fracture site, endochondral ossification, angiogenesis and finally bone remodelling. Increasing evidence shows that small noncoding RNAs are important regulators of chondrogenesis, osteogenesis and fracture healing. MicroRNAs are small singlestranded, non-coding RNA-molecules intervening in most physiological and biological processes, including fracture healing. Angiogenin-cleaved 5' tRNA halves, also called as tiRNAs (stress-induced RNAs) have been shown to repress protein translation. In order to gain further understanding on the role of small noncoding RNAs in fracture healing, genome wide expression profiles of tiRNAs, miRNAs and mRNAs were followed up to 14 days after fracture in callus tissue of an in vivo mouse model with closed tibial fracture and, compared to intact bone and articular cartilage at 2 months of age. Total tiRNA expression level in cartilage was only approximately one third of that observed in control D0 bone. In callus tissue, 11 mature 5 ' end tiRNAs out of 191 tiRNAs were highly expressed, and seven of them were differentially expressed during fracture healing. When comparing the control tissues, 25 miRNAs characteristic to bone and 29 miRNAs characteristic to cartilage tissue homeostasis were identified. Further, a total of 54 out of 806 miRNAs and 5420 out of 18,700 mRNAs were differentially expressed (DE) in callus tissue during fracture healing and, in comparison to control bone. They were associated to gene ontology processes related to mesenchymal tissue development and differentiation. A total of 581 miRNA-mRNA interactions were identified for these 54 DE miRNAs by literature searches in PubMed, thereby linking by Spearman correlation analysis 14 downregulated and 28 upregulated miRNAs to 164 negatively correlating and 168 positively correlating miRNA-mRNA pairs with chondrogenic and osteogenic phases of fracture healing. These data indicated that tiRNAs and miRNAs were differentially expressed in fracture callus tissue, suggesting them important physiological functions during fracture healing. Hence, the data provided by this study may contribute to future clinical applications, such as potential use as biomarkers or as tools in the development of novel therapeutic approaches for fracture healing.Peer reviewe