Bike Model District “Alte Neustadt” in Bremen

How to transform existing urban structures into zero emission cities by 2050 - especially if money is rare? The School of Architecture Bremen (SoAB) at the City’s University of Applied Science have initiated an innovative and collaborative project for the further development of the university’s neighbourhood, the “Alte Neustadt”. SoAB participated in the national climate protection by bicycle traffic competition and was granted funding for the transformation of the district into Germany’s first bicycle zone. In cooperation with the city district, NGO's, cultural institutions, and other neighbourhood organisations, a network of bicycle streets in connection with new bicycle highways will be installed. By 2020 comprehensive new bicycle parking areas will be finished, as well as new cyclist and pedestrian friendly crossings over the main roads. The campus’ main street will be transformed into an “Open Campus” for the university and the neighbourhood. A multifunctional “Bike Repair Café” with cargo bike sharing and bike rental facilities will enhance the district’s transformation even further, thus creating a space to reflect environmental problems to be solved. The bike model district “Alte Neustadt“ is just a small step in the right direction, but a huge improvement of the district’s quality of life.323

Gonadotrophin stimulation in IVF alters the immune cell profile in follicular fluid and the cytokine concentrations in follicular fluid and serum.

Study question Are the immune cell profiles and the cytokine concentrations in follicular fluid (FF) and serum at the preovulatory stage different in conventional exogenous gonadotrophin stimulated IVF (c-IVF) compared with natural cycle IVF (NC-IVF)? Summary answer The cell counts of CD45+ leucocytes and T cell subpopulations and the cytokine concentrations in FF and serum are different in c-IVF compared to NC-IVF. What is known already FF-derived cells are heterogeneous. Immune cells are involved in intra-ovarian processes and cytokines are required for normal follicular development. Gonadotrophins stimulate the regulatory intrafollicular system and influence the local distribution of immune cells and the intrafollicular release of cytokines. Administration of exogenous gonadotrophins may have a significant effect on this local regulatory system, which then in turn could influence oocyte quality. Study design, size, duration The study included 105 patients, 69 undergoing c-IVF and 36 undergoing NC-IVF. c-IVF was performed by exogenous ovarian stimulation with hMG and GnRH antagonists. Participants/materials, setting, methods FF samples were collected from the first dominant follicle in c-IVF without pooling and from single leading preovulatory follicles in NC-IVF. Three different approaches were used to analyze FF samples: (i) microscopic investigation of CD45+ leucocytes, (ii) fluorescence-activated cell sorting to determine CD19+ B cells and CD3+ T cells including T cell subpopulations (CD4+, CD8+), and (iii) evaluation of tumour necrosis factor-alpha (TNF-α), interferon-gamma (INF-γ), interleukins (IL)-2, -6, -8, -10 and vascular endothelial growth factor (VEGF) levels in matched FF and serum samples using the Bio-Plex® platform. Main results and the role of chance FF obtained from c-IVF contained proportionally more CD45+ leucocytes (P = 0.0384), but fewer CD8+ cytotoxic T cells than FF from NC-IVF. CD3+ T lymphocytes were the most common type of lymphocytes, and the number thereof was comparable in the two study groups. In c-IVF, serum VEGF levels were higher (P = 0.007) than in NC-IVF while FF contained marginally decreased concentrations of IL-8 in c-IVF in comparison to NC-IVF. The cytokine concentration gradient between FF and serum in c-IVF was 10-fold for IL-8 and 8-fold for VEGF and thereby markedly lower than in NC-IVF, where the differences were 32-fold and 30-fold, respectively. Strong positive correlations were determined between FF- IL-10 and FF- VEGF in c-IVF (r = 0.85, P < 0.0001) and in NC-IVF (r = 0.81, P < 0.0001). Large scale data N/A. Limitations, reasons for caution The ovulation of NC-IVF follicles was induced by the exogenous administration of hCG, which means that the environment did not fully correspond to the physiological situation. Wider implications of the findings The differences in the immune profile and the cytokine concentrations in c-IVF and NC-IVF follicles support the hypothesis that conventional ovarian stimulation affects indirectly and heterogeneously the intrafollicular milieu, and thereby possibly affects the oocyte quality and the IVF outcome. However, further studies are needed to confirm our findings and to refine stimulation protocols in the context of optimizing the intrafollicular environment during oocyte maturation. Study funding/competing interest(s) The study was supported by a research grant from IBSA Institut Biochimique SA and MSD Merck Sharp & Dohme GmbH. The authors are clinically involved in low dose mono-follicular stimulation and IVF-therapies, using gonadotrophins from all gonadotrophins distributors on the Swiss market, including Institut Biochimique SA and MSD Merck Sharp & Dohme GmbH

Feasibility of a Mobile Phone–Based Data Service for Functional Insulin Treatment of Type 1 Diabetes Mellitus Patients

Reviewer: Franklin, VReviewer: Sullivan-Bolyai, Susan[This item is a preserved copy and is not necessarily the most recent version. To view the current item, visit http://www.jmir.org/2007/5/e36/ ] Background: Patients with type 1 diabetes mellitus (DM1) have to be active participants in their treatment because they are inevitably responsible for their own day-to-day-care. Availability of mobile Internet access is advancing rapidly and mobile phones are now widely available at low cost. Thus, mobile phones have the potential to assist in daily diabetes management and to enable a telemedical interaction between patients and health care professionals. Objective: The aim of the study was to evaluate the feasibility and user acceptance of a mobile phone–based data service to assist DM1 patients on intensive insulin treatment. Methods: A software application called Diab-Memory (based on Java 2 Mobile Edition) has been developed to support patients when entering diabetes-related data with synchronization to the remote database at the monitoring center. The data were then processed to generate statistics and trends, which were provided for the patient and his/her health care professional via a Web portal. The system has been evaluated in the course of a clinical before-after pilot trial. Outcome measures focused on patients’ adherence to the therapy, availability of the monitoring system, and the effects on metabolic status. General user acceptance of the system was evaluated using a questionnaire. Results: Ten patients (four female) with DM1 participated in the trial. Mean age was 36.6 years (± 11.0 years) and prestudy glycated hemoglobin (HbA1c) was 7.9% (± 1.1%). A total of 3850 log-ins were registered during the 3 months of the study. The total number of received datasets was 13003, which equates to an average of 14 transmitted parameters per patient per day. The service was well accepted by the patients (no dropouts), and data transmission via mobile phone was successful on the first attempt in 96.5% of cases. Upon completion of the study, a statistically significant improvement in metabolic control was observed (HbA1c: prestudy 7.9% ± 1.1% versus poststudy 7.5% ± 0.9%;P= .02). While there was a slight decrease in average blood glucose level (prestudy 141.8 mg/dL ± 22.5 mg/dL vs poststudy 141.2 mg/dL ± 23.1 mg/dL;P= .69), the difference was not statistically significant. Conclusion: The results of the clinical pilot trial indicate that this proposed diabetes management system was well accepted by the patients and practical for daily usage. Thus, using the mobile phone as patient terminal seems to provide a ubiquitous, easy-to-use, and cost efficient solution for patient-centered data acquisition in the management of DM1. To confirm the promising results of the pilot trial further research has to be done to study long-term effects on glycemic control and cost-effectiveness

Cdk4 and Cdk6 cooperate in counteracting the INK4 family of inhibitors during murine leukemogenesis.

Cdk4 and Cdk6 are related protein kinases that bind d-type cyclins and regulate cell-cycle progression. Cdk4/6 inhibitors are currently being used in advanced clinical trials and show great promise against many types of tumors. Cdk4 and Cdk6 are inhibited by INK4 proteins, which exert tumor-suppressing functions. To test the significance of this inhibitory mechanism, we generated knock-in mice that express a Cdk6 mutant (Cdk6 R31C) insensitive to INK4-mediated inhibition. Cdk6(R/R) mice display altered development of the hematopoietic system without enhanced tumor susceptibility, either in the presence or absence of p53. Unexpectedly, Cdk6 R31C impairs the potential of hematopoietic progenitors to repopulate upon adoptive transfer or after 5-fluorouracil-induced damage. The defects are overcome by eliminating sensitivity of cells to INK4 inhibitors by introducing the INK4-insensitive Cdk4 R24C allele, and INK4-resistant mice are more susceptible to hematopoietic and endocrine tumors. In BCR-ABL-transformed hematopoietic cells, Cdk6 R31C causes increased binding of p16(INK4a) to wild-type Cdk4, whereas cells harboring Cdk4 R24C and Cdk6 R31C are fully insensitive to INK4 inhibitors, resulting in accelerated disease onset. Our observations reveal that Cdk4 and Cdk6 cooperate in hematopoietic tumor development and suggest a role for Cdk6 in sequestering INK4 proteins away from Cdk4.This work was supported by grants from the Austrian Science Foundation (FWF) (SFB47 and P24297) (V.S.), fellowships from the Spanish Ministerio de Economia y Competitividad (MINECO) (E.R.-D., V.Q.), and grants from MINECO (SAF2012-38215), Fundacion Ramon Areces, the OncoCycle Programme (S2010/BMD-2470) from the Comunidad de Madrid, the OncoBIO Consolider-Ingenio 2010 Programme (CSD2007-00017) from MINECO, and the European Union Seventh Framework Programme (MitoSys project; HEALTH-F5-2010-241548) (M.M.).S

Revaccination with Bacille Calmette-Guérin (BCG) is associated with an increased risk of abscess and lymphadenopathy

The reported frequency and types of adverse events following initial vaccination and revaccination with Bacille Calmette-Guérin (BCG) varies worldwide. Using active surveillance in a randomised controlled trial of BCG vaccination (the BRACE trial), we determined the incidence and risk factors for the development of BCG injection site abscess and regional lymphadenopathy. Injection site abscess occurred in 3% of 1387 BCG-vaccinated participants; the majority (34/41, 83%) resolved without treatment. The rate was higher in BCG-revaccinated participants (OR 3.6, 95% CI 1.7-7.5), in whom abscess onset was also earlier (median 16 vs. 27 days, p = 0.008). No participant with an abscess had a positive interferon-gamma release assay. Regional lymphadenopathy occurred in 48/1387 (3%) of BCG-vaccinated participants, with a higher rate in revaccinated participants (OR 2.1, 95% CI 1.1-3.9). BCG-associated lymphadenopathy, but not injection site abscess, was influenced by age and sex. A previous positive tuberculin skin test was not associated with local reactions. The increased risk of injection site abscess or lymphadenopathy following BCG revaccination is relevant to BCG vaccination policy in an era when BCG is increasingly being considered for novel applications

The safety of co-administration of Bacille Calmette-Guérin (BCG) and influenza vaccines

Background: With the emergence of novel vaccines and new applications for older vaccines, co-administration is increasingly likely. The immunomodulatory effects of BCG could theoretically alter the reactogenicity of co-administered vaccines. Using active surveillance in a randomised controlled trial, we aimed to determine whether co-administration of BCG vaccination changes the safety profile of influenza vaccination. Methods: Participants who received influenza vaccine alone (Influenza group) were compared with those who also received BCG-Denmark vaccine in the contralateral arm (Influenza+BCG group). Data on the influenza vaccination site were collected using serial questionnaires and active follow-up for 3 months post vaccination. Results: Of 1351 participants in the Influenza+BCG group and 1418 participants in the Influenza group, 2615 (94%) provided influenza vaccine safety data. There was no significant difference in the proportion of participants with any local adverse reaction between the Influenza+BCG group and the Influenza group (918/1293 [71.0%] versus (906/1322 [68.5%], p = 0.17). The proportion of participants reporting any pain, erythema and tenderness at the influenza vaccination site were similar in both groups. Swelling was less frequent (81/1293 [6.3%] versus 119/1322 (9.0%), p = 0.01) and the maximal diameter of erythema was smaller (mean 1.8 cm [SD 2.0] versus 3.0 cm [SD 2.5], p&lt;0.001) in the Influenza+BCG group. Sixteen participants reported serious adverse events: 9 participants in the Influenza+BCG group and 7 in the Influenza group. Conclusions: Adverse events following influenza vaccination are not increased when BCG is co-administered.</p

CDK6 as a key regulator of hematopoietic and leukemic stem cell activation

The cyclin-dependent kinase 6 (CDK6) and CDK4 have redundant functions in reg- ulating cell-cycle progression. We describe a novel role for CDK6 in hematopoietic and leukemic stem cells (hematopoietic stem cells [HSCs] and leukemic stem cells [LSCs]) that exceeds its function as a cell-cycle regulator. Although hematopoiesis appears normal under steady-state conditions, Cdk62/2 HSCs do not efficiently repopulate upon competitive transplantation, and Cdk6-deficient mice are significantly more sus- ceptible to 5-fluorouracil treatment. We find that activation of HSCs requires CDK6, which interferes with the transcription of key regulators, including Egr1. Transcrip- tional profiling of HSCs is consistent with the central role of Egr1. The impaired repopulation capacity extends to BCR-ABLp2101 LSCs. Transplantation with BCR- ABLp2101–infected bone marrow from Cdk62/2 mice fails to induce disease, although recipient mice do harbor LSCs. Egr1 knock-down in Cdk62/2 BCR-ABLp2101 LSKs significantly enhances the potential to form colonies, underlining the importance of the CDK6-Egr1 axis. Our findings define CDK6 as an important regulator of stem cell activation and an essential component of a transcriptional complex that suppresses Egr1 in HSCs and LSCs.Depto. de Bioquímica y Biología MolecularFac. de Ciencias BiológicasTRUEpu

Cdk6 contributes to cytoskeletal stability in erythroid cells

Mice lacking Cdk6 kinase activity suffer from mild anemia accompanied by elevated numbers of Ter119(+) cells in the bone marrow. The animals show hardly any alterations in erythroid development, indicating that Cdk6 is not required for proliferation and maturation of erythroid cells. There is also no difference in stress erythropoiesis following hemolysis in vivo. However, Cdk6(-/-) erythrocytes have a shortened lifespan and are more sensitive to mechanical stress in vitro, suggesting differences in cytoskeletal architecture. Erythroblasts contain both Cdk4 and Cdk6, while mature erythrocytes apparently lack Cdk4 and their Cdk6 is partly associated with the cytoskeleton. We used mass spectrometry to show that Cdk6 interacts with a number of proteins involved in cytoskeleton organization. Cdk6(-/-) erythroblasts show impaired F-actin formation and lower levels of gelsolin, which interacts with Cdk6. We also found that Cdk6 regulates the transcription of a panel of genes involved in actin (de-) polymerization. Cdk6-deficient cells are sensitive to drugs that interfere with the cytoskeleton, suggesting that our findings are relevant to the treatment of patients with anemia - and may be relevant to cancer patients treated with the new generation of CDK6 inhibitor