The multinational second Diabetes, Attitudes, Wishes and Needs study: results of the French survey

International audienceAIM:The second Diabetes, Attitudes, Wishes and Needs (DAWN2™) multinational cross-sectional study was aimed at generating insights to facilitate innovative efforts by people with diabetes (PWD), family members (FMs), and health care professionals (HCPs) to improve self-management and psychosocial support in diabetes. Here, the French data from the DAWN2™ study are described.METHODS:In France, 500 PWD (80 with type 1 diabetes [T1] and 420 with type 2 diabetes [T2]), 120 FMs, and 288 HCPs were recruited. The questionnaires assessed the impact of diabetes on quality of life and mood, self-management, attitudes/beliefs, and care/support.RESULTS:Diabetes negatively impacted the emotional well-being of 59% of people with T1 versus 45% of people with T2 (P<0.05) and about half of FMs. A high level of distress was felt by about half of PWD and FMs. About half of HCPs reported assessing depression in their patients. Sixty-two percent of FMs considered managing diabetes to be a burden. Hypoglycemia was a source of concern for 64% of people with T1 and 73% of FMs of insulin users. About two-thirds of non-insulin-medicated people with T2 agreed to start insulin if prescribed, while half of HCPs preferred to delay insulin initiation. A discrepancy between HCPs' perceptions of their interactions with their patients and PWD's recollection of these interactions with regard to patients' personal needs and distress was also observed.CONCLUSION:While distress remains under-assessed by HCPs, the negative impact of diabetes on the lives of PWD and FMs clearly induces distress on both groups. These findings provide new understanding of barriers precluding optimal management of diabetes. Developing strategies to overcome these barriers is now warranted

Implantable SDF-1α-loaded silk fibroin hyaluronic acid aerogel sponges as an instructive component of the glioblastoma ecosystem: between chemoattraction and tumor shaping into resection cavities

In view of inevitable recurrences despite resection, glioblastoma (GB) is still an unmet clinical need. Dealing with the stromal-cell derived factor 1-alpha (SDF-1α)/CXCR4 axis as a hallmark of infiltrative GB tumors and with the resection cavity situation, the present study described the effects and relevance of a new engineered micro-nanostructured SF-HA-Hep aerogel sponges, made of silk fibroin (SF), hyaluronic acid (HA) and heparin (Hep) and loaded with SDF-1α, to interfere with the GB ecosystem and residual GB cells, attracting and confining them in a controlled area before elimination. 70 µm-pore sponges were designed as an implantable scaffold to trap GB cells. They presented shape memory and fit brain cavities. Histological results after implantation in brain immunocompetent Fischer rats revealed that SF-HA-Hep sponges are well tolerated for more than 3 months while moderately and reversibly colonized by immuno-inflammatory cells. The use of human U87MG GB cells overexpressing the CXCR4 receptor (U87MG-CXCR4+) and responding to SDF-1α allowed demonstrating directional GB cell attraction and colonization of the device in vitro and in vivo in orthotopic resection cavities in Nude rats. Not modifying global survival, aerogel sponge implantation strongly shaped U87MG-CXCR4+ tumors in cavities in contrast to random infiltrative growth in controls. Overall, those results support the interest of SF-HAHep sponges as modifiers of the GB ecosystem dynamics acting as “cell meeting rooms” and biocompatible niches whose properties deserve to be considered toward the development of new clinical procedures

Carcinome épidermoide sur mal perforant lépreux (2 cas)

PARIS6-Bibl. St Antoine CHU (751122104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Implication of BRG1 and cdk9 in the STAT3-mediated activation of the p21waf1 gene

STAT transcription factors (signal transducers and activators of transcription) are cytoplasmic proteins that induce gene activation in response to cytokine receptor stimulation. Following tyrosine phosphorylation, STAT proteins translocate into the nucleus and activate specific target genes. We have previously reported that STAT3 activates the expression of the p21waf1 gene through its association with the NcoA/SRC1a and CBP coactivators. In this study, we explore the role of BRG1, a component of the SWI/SNF chromatin-remodeling complex, and the role of cdk9, a component of the elongation factor P-TEFb, in the STAT3-mediated expression of p21waf1. We found using pull-down experiments and co-immunoprecipitation assays that both proteins associate with STAT3. Chromatin immunoprecipitation (ChIP) experiments indicate that STAT3 DNA binding results in histone H3 acetylation and BRG1 recruitment. Using Southern blot analysis, we found that the loading of BRG1 is followed by an increased accessibility of the proximal p21waf1 promoter and by the association of RNA polymerase II. As a next step, STAT3 then recruits the cdk9 kinase to phosphorylate the carboxy-terminal domain of the RNA polymerase at serine 2. Accordingly, the elongating form of the polymerase can be detected by ChIP experiments on the coding region of the gene, probably initiating mRNA synthesis. Therefore, STAT3 not only promotes the initiation of transcription but also regulates chromatin remodeling and transcription elongation through its interaction with BRG1 and cdk9

Transcriptional Regulation by a DNA-associated Form of Cyclin D1

International audienceBesides its function as a cell cycle regulator, cyclin D1 interacts with transcription factors to regulate gene activation. In this study, we show that cyclin D1 is recruited to the p21waf1 promoter by a STAT3-NcoA complex. The association of cyclin D1 with DNA prevented the recruitment of the CBP histone acetylase and RNA polymerase II, leading to an inhibition of the p21waf1 gene. Confirming the transcriptional function of the protein, the expression of the p21waf1 gene was enhanced in cyclin D1؊/؊ fibroblasts or upon siRNA-mediated down-regulation of the cyclin. Moreover, the STAT3-mediated activation of p21waf1 was also inhibited in breast cancer cells containing elevated levels of cyclin D1. Altogether, these results suggest that the transcriptional activities of cyclin D1 might play an important role in the regulation of cell-cycle regulatory genes and that these functions are probably involved in cell transformation

Patient perceptions and understanding of treatment instructions for ovarian stimulation during infertility treatment

International audienceThe impact of patient-physician communication and levels of understanding of treatment on patient knowledge and compliance has been studied in patients undergoing their first cycle of infertility treatment. This observational, real-life, longitudinal study involved 488 patients from 28 infertility centres in France. Data on communication quality, understanding of treatment instructions, patient knowledge and compliance to treatment protocol were collected through questionnaires administered before treatment initiation (V1) and at oocyte retrieval (V2). At V1, patients were very satisfied with their levels of understanding of the injection and monitoring schedules, the information given by the medical team, and the way of receiving instructions, with average ratings on a scale of 0-100% of > 75%. They rated their understanding of possible treatment side-effects as satisfactory (average score 71.1%). Gaps in patient knowledge about their treatment, revealed by discrepancies between physician and patient reports, were observed in 20.5% of patients (n = 79/386), and most commonly resulted from confusion about the units and dose of gonadotropin. Anxiety about performing self-injections and a lack of confidence in their ability to self-inject correctly were each observed in approximately one-third of patients. Patient self-assessment of compliance at V2 revealed that 27% of patients (n = 83/305) did not comply with or had doubts about the injection schedule or dose injected. Meanwhile physicians reported high levels of patient compliance (94.3%; n = 350/371). In conclusion, even when patient-physician relationships appear to be satisfactory, patient miscomprehension and non-compliance during infertility treatment may be underestimated. Further interventions are required to improve these outcomes

Silencing of miR-21 and miR-210 by LNA-lipid nanocapsules complexes sensitize human glioblastoma cells to radiation-induced cell death

National audienc

Why synchrony matters during mother-child interactions: a systematic review.

BACKGROUND:Assessment of mother-child interactions is a core issue of early child development and psychopathology. This paper focuses on the concept of "synchrony" and examines (1) how synchrony in mother-child interaction is defined and operationalized; (2) the contribution that the concept of synchrony has brought to understanding the nature of mother-child interactions. METHOD:Between 1977 and 2013, we searched several databases using the following key-words: "synchrony" "interaction" and "mother-child". We focused on studies examining parent-child interactions among children aged 2 months to 5 years. From the 63 relevant studies, we extracted study description variables (authors, year, design, number of subjects, age); assessment conditions and modalities; and main findings. RESULTS:The most common terms referring to synchrony were mutuality, reciprocity, rhythmicity, harmonious interaction, turn-taking and shared affect; all terms were used to characterize the mother-child dyad. As a consequence, we propose defining synchrony as a dynamic and reciprocal adaptation of the temporal structure of behaviors and shared affect between interactive partners. Three main types of assessment methods for studying synchrony emerged: (1) global interaction scales with dyadic items; (2) specific synchrony scales; and (3) micro-coded time-series analyses. It appears that synchrony should be regarded as a social signal per se as it has been shown to be valid in both normal and pathological populations. Better mother-child synchrony is associated with familiarity (vs. unknown partner), a healthy mother (vs. pathological mother), typical development (vs. psychopathological development), and a more positive child outcomes. DISCUSSION:Synchrony is a key feature of mother-infant interactions. Adopting an objective approach in studying synchrony is not a simple task given available assessment tools and due to its temporality and multimodal expression. We propose an integrative approach combining clinical observation and engineering techniques to improve the quality of synchrony analysis