Decreased spermatogonial quantity in prepubertal boys with leukaemia treated with alkylating agents

Non peer reviewe

Serum 25-Hydroxyvitamin D Concentrations at Birth in Children Screened for HLA-DQB1 Conferred Risk for Type 1 Diabetes

Vitamin D has several effects on the immune system that might be of relevance for the pathogenesis of type 1 diabetes (T1D).To evaluate whether umbilical cord serum concentrations of 25-hydroxy-vitamin D (25[OH]D) differ in children developing either islet autoimmunity (IA) or overt T1D during childhood and adolescence.Umbilical cord serum samples from 764 children born from 1994 to 2004 with HLA-DQB1 conferred risk for T1D participating in the Type 1 Diabetes Prediction and Prevention Study were analyzed for 25(OH)D using an enzyme immunoassay.DIPP clinics in Turku, Oulu, and Tampere University Hospitals, Finland.Two hundred fifty children who developed T1D diabetes at a median age of 6.7 years (interquartile range [IQR] 4.0 to 10.1 years) and 132 additional case children who developed IA, i.e., positivity for multiple islet autoantibodies. Cases were matched for date of birth, gender, and area of birth with 382 control children who remained autoantibody negative. The median duration of follow up was 9.8 years (IQR 5.7 to 13.1 years).The median 25(OH)D concentrations.The median 25(OH)D concentration in cord serum was low [31.1 nmol/L (IQR 24.0 to 41.8); 88% <50 nmol/L], but not statistically different between children who developed T1D or IA and their control groups (P = 0.70). The levels were associated mainly with geographical location, year and month of birth, age of the mother, and maternal intake of vitamin D during pregnancy.The 25(OH)D concentrations at birth are not associated with the development of T1D during childhood.Peer reviewe

Serum 25-Hydroxyvitamin D Concentrations at Birth in Children Screened for HLA-DQB1 Conferred Risk for Type 1 Diabetes

Context: Vitamin D has several effects on the immune system that might be of relevance for the pathogenesis of type 1 diabetes (T1D).Objective: To evaluate whether umbilical cord serum concentrations of 25-hydroxy-vitamin D (25[OH]D) differ in children developing either islet autoimmunity (IA) or overt T1D during childhood and adolescence.Design: Umbilical cord serum samples from 764 children born from 1994 to 2004 with HLA-DQB1 conferred risk for T1 D participating in the Type 1 Diabetes Prediction and Prevention Study were analyzed for 25(OH)D using an enzyme immunoassay.Setting: DIPP clinics in Turku, Oulu, and Tampere University Hospitals, Finland.Participants: Two hundred fifty children who developed T1D diabetes at a median age of 6.7 years (interquartile range [IQR] 4.0 to 10.1 years) and 132 additional case children who developed IA, i.e., positivity for multiple islet autoantibodies. Cases were matched for date of birth, gender, and area of birth with 382 control children who remained autoantibody negative. The median duration of follow up was 9.8 years (IQR 5.7 to 13.1 years).Main Outcome Measure: The median 25(OH)D concentrations.Results: The median 25(OH)D concentration in cord serum was low [31.1 nmol/L (IQR 24.0 to 41.8); 88% Conclusions: The 25(OH)D concentrations at birth are not associated with the development of T1D during childhood.</div

Executing circular economy strategies in practice in Finland. Results and experiences from Circwaste project

A Europe-wide circular economy policy was launched in 2014 when the European Commission published the first strategic policy programme for circular economy. It was compiled to provide very comprehensive impacts and dimensions of sustainable development: sustainable growth and a climate neutral, resource efficient and competitive economy. The targets of a circular economy are that the value of products, materials and resources is maintained in the economy for as long as possible, economic growth is decoupled from resource use, generation of waste and environmental loads are minimised, and pressure on the Earth’s resources and biodiversity is minimised. The European Union is supporting the sustainability transition with research and development funding. In Finland, Circwaste – Towards Circular Economy is one of the biggest development projects accelerating the transition to a circular economy. During the period 2016–2020, the project has produced monitoring data on the development of circular economy and the sustainability of waste management, highlighted the circular economy concept, promoted stakeholder collaboration, supported strategic national processes, strengthened know-how and mainstreamed and concretised circular economy thinking. This interim report presents all the relevant results so far. It is crucial that data is produced from different angles on implementing the circular economy. More information is needed both to support decision making and on connections between and reflections on different factors. The key figures for Finland show quite clear coupling of the use of natural resources, waste amounts and economic growth. The circular material use rate is ca. 7%, which can be considered quite modest. Quantitative national targets for decreasing the use of natural resources are needed. Instead of country comparisons, the focus should be on trends in order to learn from the past and to identify the policy instruments needed to achieve the level aspired to. One of the key findings is the need for regional indicators and data for decisionmaking. The work done within Circwaste is the first effort towards a systematic monitoring scheme for monitoring circular economy regionally. The study showed that the production of regional waste data is challenging, that the estimated recycling rates have not increased adequately to reach the EU targets and that there could therefore be a need for municipallevel recycling targets. The transition to a circular economy also causes fundamental social changes in society. In the project, new indicators were developed for measuring social impacts: circular economy employment, education and employment for vulnerable groups, publicly shared resources, accessibility of recycling services and sustainable vehicle fuels. The first baseline data show advances towards the circular economy: the accessibility of waste management services has improved, the Finnish educational system has been able to respond quickly to the need for circular economy education, circular economy activities have potential for the employment of vulnerable groups and economic activities related to recycling, repair and reuse have grown. The regions and municipalities emerge as key actors in facilitating a socially just transition towards a circular economy. The study on innovative material processing technologies gathered data on technologies for elemental recycling, especially for plastic waste but also for making new fibres from textiles waste. Financial issues are key to the survival of these technologies and there is a need for governmental financial support. Public procurers can be considered key players in the circular economy, creating demand for more sustainable products and services. Implementing circular economy in municipalities requires commitment, financial planning, interaction with regional actors and inclusion of circular economy in financial rules. The construction sector is a major consumer of natural resources, but the municipalities can make construction more sustainable through public procurements and planning. As buyers, they can require the use of recycled raw materials and soils in construction projects. Obligations for ecological compensation and goals of no net loss of biodiversity would decrease the pressure on natural resources. To support municipalities in their work, a national organisation for providing municipal auditing, development, education and business support services could be established. Employing circular economy experts in each municipality to work as crossadministrative coordinators could enhance the transition. The project has created a lot of political, theoretical and practical content on the concept and field of circular economy. The next steps are to further develop and widen, as well as deepen, the results and to provide national support in searching for answers and solutions for decreasing the use of natural resources, achieving the MSW recycling targets and creating a more sustainable society

Retinoblastoma protein (RB) interacts with E2F3 to control terminal differentiation of Sertoli cells

The retinoblastoma protein (RB) is essential for normal cell cycle control. RB function depends, at least in part, on interactions with the E2F family of DNA-binding transcription factors (E2Fs). To study the role of RB in the adult testis, a Sertoli cell (SC)-specific Rb knockout mouse line (SC-RbKO) was generated using the Cre/loxP recombination system. SC-RbKO mice exhibited an age-dependent testicular atrophy, impaired fertility, severe SC dysfunction, and spermatogenic defects. Removal of Rb in SC induced aberrant SC cycling, dedifferentiation, and apoptosis. Here we show that E2F3 is the only E2F expressed in mouse SCs and that RB interacts with E2F3 during mouse testicular development. In the absence of RB, the other retinoblastoma family members p107 and p130 began interacting with E2F3 in the adult testes. In vivo silencing of E2F3 partially restored the SC maturation and survival as well as spermatogenesis in the SC-RbKO mice. These results point to RB as a key regulator of SC function in adult mice and that the RB/E2F3 pathway directs SC maturation, cell cycle quiescence, and RB protects SC from apoptosis

Developmental effects of imatinib mesylate on follicle assembly and early activation of primordial follicle pool in postnatal rat ovary

Imatinib mesylate is an anti-cancer agent that competitively inhibits several receptor tyrosine kinases (RTKs). RTKs play important roles in the regulation of primordial follicle formation, the recruitment of primordial follicles into the pool of growing follicles and maturation of the follicles. In the present study, we investigated the effects of the tyrosine kinase inhibitor imatinib on primordial follicle assembly and early folliculogenesis in postnatal rats. Female Sprague-Dawley rats were treated with either imatinib (150mg/kg) or placebo (water) on postnatal days 2-4. Bilateral ovariectomy was performed on postnatal day 2 and 5. Histology, immunohistochemistry, and mRNA analysis were performed. Imatinib treatment was associated with increased density of the multi-oocyte follicles (P<0.01), oogonia (p<0.01) and germline clusters (P<0.05), decreased activation of primordial follicles, increased expression of c-Kit and AMH, and decreased protein expression of Kit-ligand and GDF9 when compared to age-matched controls. In conclusion, imatinib affects folliculogenesis in postnatal rat ovaries by delaying the cluster breakdown, follicular assembly and early activation of the primordial follicle pool

Developmental effects of imatinib mesylate on follicle assembly and early activation of primordial follicle pool in postnatal rat ovary

Imatinib mesylate is an anti-cancer agent that competitively inhibits several receptor tyrosine kinases (RTKs). RTKs play important roles in the regulation of primordial follicle formation, the recruitment of primordial follicles into the pool of growing follicles and maturation of the follicles. In the present study, we investigated the effects of the tyrosine kinase inhibitor imatinib on primordial follicle assembly and early folliculogenesis in postnatal rats. Female Sprague-Dawley rats were treated with either imatinib (150mg/kg) or placebo (water) on postnatal days 2-4. Bilateral ovariectomy was performed on postnatal day 2 and 5. Histology, immunohistochemistry, and mRNA analysis were performed. Imatinib treatment was associated with increased density of the multi-oocyte follicles (P<0.01), oogonia (p<0.01) and germline clusters (P<0.05), decreased activation of primordial follicles, increased expression of c-Kit and AMH, and decreased protein expression of Kit-ligand and GDF9 when compared to age-matched controls. In conclusion, imatinib affects folliculogenesis in postnatal rat ovaries by delaying the cluster breakdown, follicular assembly and early activation of the primordial follicle pool