Showing papers by "Paris Descartes University published in 2022"

Antifungal Drugs TDM: Trends and Update

Abstract: The increasing burden of invasive fungal infections results in growing challenges to antifungal (AF) therapeutic drug monitoring (TDM). This review aims to provide an overview of recent advances in AF TDM.We conducted a PubMed search for articles during 2016-2020 using "TDM" or "pharmacokinetics" or "drug-drug-interaction" with "antifungal," consolidated for each AF. Selection was limited to English language articles with human data on drug exposure.More than 1000 articles matched the search terms. We selected 566 publications. The latest findings tend to confirm previous observations in real-life clinical settings. The pharmacokinetic variability related to special populations is not specific but must be considered. AF benefit-to-risk ratio, drug-drug interaction (DDI) profiles, and minimal inhibitory concentrations for pathogens must be known to manage at-risk situations and patients. Itraconazole has replaced ketoconazole in healthy volunteers DDI studies. Physiologically based pharmacokinetic modeling is widely used to assess metabolic azole DDI. AF prophylactic use was studied more for Aspergillus spp. and Mucorales in oncohematology and solid organ transplantation than for Candida (already studied). Emergence of central nervous system infection and severe infections in immunocompetent individuals both merit special attention. TDM is more challenging for azoles than amphotericin B and echinocandins. Fewer TDM requirements exist for fluconazole and isavuconazole (ISZ); however, ISZ is frequently used in clinical situations in which TDM is recommended. Voriconazole remains the most challenging of the AF, with toxicity limiting high-dose treatments. Moreover, alternative treatments (posaconazole tablets, ISZ) are now available.TDM seems to be crucial for curative and/or long-term maintenance treatment in highly variable patients. TDM poses fewer cost issues than the drugs themselves or subsequent treatment issues. The integration of clinical pharmacology into multidisciplinary management is now increasingly seen as a part of patient care.

Periodic attention operates faster during more complex visual search

Abstract: Attention has been found to sample visual information periodically, in a wide range of frequencies below 20 Hz. This periodicity may be supported by brain oscillations at corresponding frequencies. We propose that part of the discrepancy in periodic frequencies observed in the literature is due to differences in attentional demands, resulting from heterogeneity in tasks performed. To test this hypothesis, we used visual search and manipulated task complexity, i.e., target discriminability (high, medium, low) and number of distractors (set size), while electro-encephalography was simultaneously recorded. We replicated previous results showing that the phase of pre-stimulus low-frequency oscillations predicts search performance. Crucially, such effects were observed at increasing frequencies within the theta-alpha range (6-18 Hz) for decreasing target discriminability. In medium and low discriminability conditions, correct responses were further associated with higher post-stimulus phase-locking than incorrect ones, in increasing frequency and latency. Finally, the larger the set size, the later the post-stimulus effect peaked. Together, these results suggest that increased complexity (lower discriminability or larger set size) requires more attentional cycles to perform the task, partially explaining discrepancies between reports of attentional sampling. Low-frequency oscillations structure the temporal dynamics of neural activity and aid top-down, attentional control for efficient visual processing.

Infectious Agents as Potential Drivers of α‐Synucleinopathies

Abstract: α-synucleinopathies, encompassing Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, are devastating neurodegenerative diseases for which available therapeutic options are scarce, mostly because of our limited understanding of their pathophysiology. Although these pathologies are attributed to an intracellular accumulation of the α-synuclein protein in the nervous system with subsequent neuronal loss, the trigger(s) of this accumulation is/are not clearly identified. Among the existing hypotheses, interest in the hypothesis advocating the involvement of infectious agents in the onset of these diseases is renewed. In this article, we aimed to review the ongoing relevant factors favoring and opposing this hypothesis, focusing on (1) the potential antimicrobial role of α-synuclein, (2) potential entry points of pathogens in regard to early symptoms of diverse α-synucleinopathies, (3) pre-existing literature reviews assessing potential associations between infectious agents and Parkinson's disease, (4) original studies assessing these associations for dementia with Lewy bodies and multiple system atrophy (identified through a systematic literature review), and finally (5) potential susceptibility factors modulating the effects of infectious agents on the nervous system. © 2022 International Parkinson and Movement Disorder Society.

RNA-Seq is not required to determine stable reference genes for qPCR normalization

Abstract: Assessment of differential gene expression by qPCR is heavily influenced by the choice of reference genes. Although numerous statistical approaches have been proposed to determine the best reference genes, they can give rise to conflicting results depending on experimental conditions. Hence, recent studies propose the use of RNA-Seq to identify stable genes followed by the application of different statistical approaches to determine the best set of reference genes for qPCR data normalization. In this study, however, we demonstrate that the statistical approach to determine the best reference genes from commonly used conventional candidates is more important than the preselection of 'stable' candidates from RNA-Seq data. Using a qPCR data normalization workflow that we have previously established; we show that qPCR data normalization using conventional reference genes render the same results as stable reference genes selected from RNA-Seq data. We validated these observations in two distinct cross-sectional experimental conditions involving human iPSC derived microglial cells and mouse sciatic nerves. These results taken together show that given a robust statistical approach for reference gene selection, stable genes selected from RNA-Seq data do not offer any significant advantage over commonly used reference genes for normalizing qPCR assays.

Wasl is crucial to maintain microglial core activities during glioblastoma initiation stages

Abstract: Microglia actively promotes the growth of high-grade gliomas. Within the glioma microenvironment an amoeboid microglial morphology has been observed, however the underlying causes and the related impact on microglia functions and their tumor promoting activities is unclear. Using the advantages of the larval zebrafish model, we identified the underlying mechanism and show that microglial morphology and functions are already impaired during glioma initiation stages. The presence of pre-neoplastic HRasV12 expressing cells induces an amoeboid morphology of microglia, increases microglial numbers and decreases their motility and phagocytic activity. RNA sequencing analysis revealed lower expression levels of the actin nucleation promoting factor wasla in microglia. Importantly, a microglia specific rescue of wasla expression restores microglial morphology and functions. This results in increased phagocytosis of pre-neoplastic cells and slows down tumor progression. In conclusion, we identified a mechanism that de-activates core microglial functions within the emerging glioma microenvironment. Restoration of this mechanism might provide a way to impair glioma growth.

Challenges in Comparative Meta-Analysis of the Accuracy of Multiple Diagnostic Tests.

Abstract: The rapid increase in diagnostic and screening techniques has urged the need to choose among multiple diagnostic tests. For the majority of diseases, there is more than a single test available, and studies usually compare a subset of these tests. In such cases, a separate meta-analysis of each test cannot provide a reliable answer on the relative accuracy of the multiple available tests. Extensions of standard (hierarchical) meta-analysis to network meta-analysis (NMA) models for the comparison of at least three diagnostic tests have been the subject of methodological research in recent years. NMA can be used to jointly analyze the totality of evidence in order to provide estimates of relative accuracy (sensitivity and specificity ), to compare tests that have not been compared head-to-head, and to obtain a ranking of all competing tests in order to further facilitate the decision-making process.In this chapter, we illustrate current methodology for meta-analysis of multiple test comparisons, introduce NMA methods of diagnostic tests as an extension to the standard meta-analysis of diagnostic test accuracy (DTA) studies, and present existing approaches to rank tests according to their accuracy, specificity , and sensitivity . We also describe the basic concepts, underlying assumptions, and challenges in NMA of multiple diagnostic tests.

Pembrolizumab-induced cyclic ACTH-dependent Cushing's syndrome treated by a block-and-replace approach with osilodrostat

Abstract: Community-Directed Treatment with Ivermectin (CDTI) is the strategy of choice to fight onchocerciasis in Africa. In areas where loiasis is endemic, onchocerciasis control and/or elimination is hindered by severe adverse events (SAEs) occurring after ivermectin mass treatments. This study aimed at (i) investigating the impact of two decades of CDTI on L. loa clinical and parasitological indicators in the Ndikinimeki Health District, and (ii) assessing the risk of SAEs after this long-term preventive chemotherapy. A cluster-based cross-sectional survey was conducted in the six Health Areas of the Ndikinimeki Health District. All volunteers underwent day-time calibrated thick blood smears to search for L. loa microfilariae, as well as an interview to assess the history of migration of eye worm and Calabar swelling. The overall prevalence of L. loa microfilaraemia was 2.2 % (95% CI: 1.3–3.7%), and the proportions of individuals who had already experienced eye worm and/or Calabar swelling were 1.0% and 0.5%, respectively. The mean microfilarial density was 63.55 (SD: 559.17; maximum: 9220.0) mf/mL. These findings indicate that (i) the long-term ivermectin-based preventive chemotherapy against onchocerciasis significantly reduced L. loa clinical and parasitological indicators, and (ii) the risk of developing neurologic and potentially fatal SAE after ivermectin mass treatment is zero in the Ndikinimeki Health District.

3D nanoparticle superlocalization with a thin diffuser

Abstract: We report on the use of a thin diffuser placed in the close vicinity of a camera sensor as a simple and effective way to superlocalize plasmonic nanoparticles in 3D. This method is based on holographic reconstruction via quantitative phase and intensity measurements of a light field after its interaction with nanoparticles. We experimentally demonstrate that this thin diffuser can be used as a simple add-on to a standard bright-field microscope to allow the localization of 100 nm gold nanoparticles at video rate with nanometer precision (1.3 nm laterally and 6.3 nm longitudinally). We exemplify the approach by revealing the dynamic Brownian trajectory of a gold nanoparticle trapped in various pockets within an agarose gel. The proposed method provides a simple but highly performant way to track nanoparticles in 3D.

Ethical challenges in palliative sedation of adults: protocol for a systematic review of current clinical practice guidelines

Abstract: This study aims to identify the full spectrum of ethical challenges of all forms of palliative sedation for adults as presented in current clinical practice guidelines (CPGs) and to determine whether CPGs specify ethical challenges of this therapy for patients with cancer and non-cancer and, if so, how exactly they do this. To the best of our knowledge, no studies have yet investigated this topic. The purpose is purely descriptive; our aim is not to make any kind of normative judgements on these challenges. Nor is our aim to assess the quality of the CPGs.We will perform a systematic review of CPGs on palliative sedation for adults via five electronic databases, grey literature search tools, citation tracking and contact with palliative care experts. Current CPGs accredited by an international, national or regional authority, published in English, German, French, Italian or Polish, from 2000 to the date of the search, will be subjected to content analysis at the textual, linguistic and thematic levels.This is a protocol for a systematic review and no human will be involved in this research. Therefore, ethics approval and consent to participate are not applicable to this context. This study protocol is reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis for Protocols criteria and registered on PROSPERO. Moreover, the integral version of this study protocol is published as a preprint on Research Square. The results of this study will be actively disseminated through peer-reviewed journals and books, international, national and local conference presentations, social media and media in general.

Rheumatoid arthritis, as a clinical disease, but not rheumatoid arthritis-associated autoimmunity, is linked to cardiovascular events

Abstract: Rheumatoid arthritis (RA) is characterized by increased cardiovascular (CV) mortality. CV events are particularly high in patients with RA-specific autoimmunity, including rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), raising the question whether RA-specific autoimmunity itself is associated with CV events.New CV events (myocardial infarction, stroke or death by CV cause) were recorded in 20,625 subjects of the Electricité de France - Gaz de France (GAZEL) cohort. Self-reported RA cases in the GAZEL cohort were validated by phone interview on the basis of a specific questionnaire. In 1618 subjects, in whom plasma was available, RF and ACPA were measured. A piecewise exponential Poisson regression was used to analyze the association of CV events with presence of RA as well as RA-specific autoimmunity (without RA).CV events in GAZEL were associated with age, male sex, smoking, hypertension, hyperlipidemia, and diabetes mellitus (HR from 1.06 to 1.87, p < 0.05). Forty-two confirmed RA cases were identified. Confirmed RA was significantly associated with CV risk increase (HR of 3.03; 95% CI: 1.13-8.11, p = 0.03) independently of conventional CV risk factors. One hundred seventy-eight subjects showed RF or ACPA positivity without presence of RA. CV events were not associated with ACPA positivity (HR: 1.52, 95% CI: 0.47-4.84, p = 0.48) or RF positivity (HR: 1.15, 95% CI: 0.55-2.40, p = 0.70) in the absence of RA.RA, as a clinical chronic inflammatory disease, but not mere positivity for RF or ACPA in the absence of clinical disease is associated with increased CV risk.

Modeling Multicomponent Interventions in Network Meta-Analysis.

Abstract: There is a rapid increase in trials assessing healthcare interventions consisting of a combination of drugs (polytherapies) or multiple components. In the latter type of interventions (also known as complex interventions), the aspect of complexity is of paramount importance. For example, nonpharmacological interventions, such as psychological interventions or self-management interventions, usually share common components that relate to the nature of intervention, who delivers it, or where and how. In a network of trials, there is often the need to identify the most effective (or safest) component and/or combination of components. Four key meta-analytical approaches have been presented in the literature to handle complex interventions. These include (a) the single-effect model, (b) the full interaction model, (c) the additive main effects model, and (d) the two-way interaction model. In this chapter, we present and discuss the advantages and limitations of these approaches. We illustrate these methods using a network that assesses the relative effects of self-management interventions on waist size in patients with type 2 diabetes.

Methodological guidelines to estimate population-based health indicators using linked data and/or machine learning techniques

Abstract: The capacity to use data linkage and artificial intelligence to estimate and predict health indicators varies across European countries. However, the estimation of health indicators from linked administrative data is challenging due to several reasons such as variability in data sources and data collection methods resulting in reduced interoperability at various levels and timeliness, availability of a large number of variables, lack of skills and capacity to link and analyze big data. The main objective of this study is to develop the methodological guidelines calculating population-based health indicators to guide European countries using linked data and/or machine learning (ML) techniques with new methods.We have performed the following step-wise approach systematically to develop the methodological guidelines: i. Scientific literature review, ii. Identification of inspiring examples from European countries, and iii. Developing the checklist of guidelines contents.We have developed the methodological guidelines, which provide a systematic approach for studies using linked data and/or ML-techniques to produce population-based health indicators. These guidelines include a detailed checklist of the following items: rationale and objective of the study (i.e., research question), study design, linked data sources, study population/sample size, study outcomes, data preparation, data analysis (i.e., statistical techniques, sensitivity analysis and potential issues during data analysis) and study limitations.This is the first study to develop the methodological guidelines for studies focused on population health using linked data and/or machine learning techniques. These guidelines would support researchers to adopt and develop a systematic approach for high-quality research methods. There is a need for high-quality research methodologies using more linked data and ML-techniques to develop a structured cross-disciplinary approach for improving the population health information and thereby the population health.

White-Coat Free Genome-Wide Epigenetics of Human Blood Pressure

Abstract: HomeHypertensionVol. 79, No. 4White-Coat Free Genome-Wide Epigenetics of Human Blood Pressure Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessEditorialPDF/EPUBWhite-Coat Free Genome-Wide Epigenetics of Human Blood Pressure Daniel Vaiman Daniel VaimanDaniel Vaiman Correspondence to: Daniel Vaiman, Institut Cochin, U1016 INSERM-UMR8104 CNRS, Université de Paris, France. Email E-mail Address: [email protected] https://orcid.org/0000-0002-1915-0717 Institut Cochin, U1016 INSERM-UMR8104 CNRS, Université de Paris, France. Search for more papers by this author Originally published9 Mar 2022https://doi.org/10.1161/HYPERTENSIONAHA.121.18852Hypertension. 2022;79:773–774This article is a commentary on the followingUnique Associations of DNA Methylation Regions With 24-Hour Blood Pressure Phenotypes in Black ParticipantsBlood pressure (BP) is one of the most common measures practiced in medicine from >100 years. Despite extremely classical procedures, the 2 values generally obtained through plethysmography (systolic blood pressure and diastolic blood pressure) mask an incredibly complex reality. In fact, the final result depends on many biological parameters that are at least genetic, endocrinologic, behavioral, and probably stochastics.See related article, pp 761–772The history of BP started probably in 1733 when the experimental works of Sir Stephen Hales revealed a blood column of >2.50 meters above the left heart ventricle when a catheter was plunged in the vein of a horse leg.1 This interesting history of BP was recently summarized by Rader and Victor,2 as a comment of an article describing a cuff-free photoplethysmograph,3 allowing ambulatory measurement of BP. With perspective, it seems that clinical measures are often flawed by cues that may be visual (white-coat hypertension4), lability (orthostatic hypotension, in elderly patients5), or masked hypertension, often found in young stressed male patients.6 These flaws may be overturned when BP is measured continuously.The topic of the article published in this issue by Roberts et al7 deals with the possible connection between methylation measures in blood cells (potential biomarkers of the pathophysiology of BP) and continuous variables linked to blood pressure (systolic blood pressure, diastolic blood pressure, pulse pressure and mean arterial pressure). Two major originalities distinguish the article from previous studies, especially from the data acquired by Richard et al,8 which identified 13 differentially methylated CpGs linked to BP, starting with 17 010 individuals; one is the methylation analysis methodology based upon Reduced Representative Bisulphite Sequencing, rather than methylation arrays with the Illumina Technology. Another relevant difference is that in the 2017 study, classical clinical measures of BP were analyzed (with a potential white-coat effect) while here, the correlation with genome wide methylation is attempted on classical BP measurements, but also on a continuous measure in the same individuals (potentially white-coat free). Only the latter allowed to find significantly differentially methylated regions associated to BP. Also, in the 2017 article, mathematical adjustment to the use of antihypertensive medication was used, while in the present study, the treatments (as well as antilipidic treatment) were interrupted 1 week before the measures (may not be sufficient to abolish the medication effects).Technical InnovationThe results obtained were strongly supported by additional samples from 117 individuals using a novel and independent method called bisulfite/bisulfite-specific PCR ULtrapLEx targeted sequencing (BULLET-Seq). This procedure per se, albeit complex, might be an interesting alternative to other quantitative approaches such as pyrosequencing when multiple regions have to be validated. The principle is based upon the analysis of a controlled mix between 2 samples:Sample 1: a reference panel prepared by mixing, in various ratios, 2 preparations of the same DNA: a bisulphite prePCR treatment, followed by a Bisulphite-specific PCR (thus allowing a transformation only of unmethylated Cytosines in Uracil) on the one hand, and a PCR followed by bisulphite treatment (where methylation will be lost completely, thus inducing a transformation of all the Cytosines in Uracil by bisulphite treatment) on the other hand.Sample 2: the experimental sample that is treated by bisulphite and then by PCR (Bisulphite specific) and thus where the remaining Cytosines correspond to nucleotides that were previously methylatedThese 2 samples are mixed and used to create a NGS library, by classical means, and sequenced. It makes it possible to count the Cytosine that resisted Bisulphite by reading the sequences at a given position, and thus evaluate the methylation level. The authors conclude that the technique is reliable for differences in methylation levels >10%. The approach was successful in validating a methylated region located on chr19, nearby the gene ZC3H4. It would be necessary to extend the approach to other regions, or other topics.Major Biological ObservationsOne striking observation of the authors is the fact that while they did not find statistically significant differentially methylated regions when the correlation was searched with the classical measurement (one-shot clinical measurement), they did identify 72 significantly altered regions in terms of methylation when continuous measures were performed over 24-hour time windows.The article used exclusive samples from the Black population (281 in the discovery cohort and 117 in the replication cohort, as mentioned), and one relevant question is the applicability of the findings to other populations. As such, the comparison with the data obtained by Richards and coworkers by Infinium HumanMethylation450 BeadChip (2017) is enlightening.8 Four CpGs were found in common between the 2 studies, despite the method of detection, which is completely different, located in the genes ZNF283 (chr7), ZMIZ1 (chr10), PRDM16 (chr1), and GNLY (chr2); 3 of these genes are encoding Zinc-finger containing proteins. This relatively limited overlap might be because of several differences: (1) the fact that only a small part of the CpG analyzed (5.85%) are in common between the 2 studies, (2) the larger multiethnic sample of the Richard and coworkers study, (3) the 24-hour measure of the present study that erases the possible limits of a mere single or double clinical measurement. Until now, ethnic specificities were mostly detected at the genetic level (SNPs that differ between ethnicities), while pure epigenetic differences (such as methylation) might be less systematically influenced by ethnicity. This is one of the reasons why in a vast majority of papers making use of methylation arrays (Illumina 450K or the more recent EPIC-arrays), the CpG corresponding also to genetic variants (SNP, about 10% of the CpG positions present in these microarrays), are removed before proceeding to the analysis. Maintaining these SNPs in the analysis could probably separate predominantly the ethnic backgrounds rather than the methylation effects induced by the pathophysiological conditions. Overall, these considerations suggest that (1) the methylation alterations found in common between the Richard study and the present one are extremely robust, since they are common to different populations and are based upon different detection techniques. On the other hand (2), since the discoveries of the present article are based upon a different phenotypic assessment, and upon different sets of CpGs, the findings may be extremely relevant to understand the environmental impact on human blood pressure, in a broad sense.One conclusion put forward by the authors is the calculation that the part of cumulated variance explained by the methylation differences reaches 14%, suggesting that genome methylation marks present on blood cells, partake per se a striking part of the blood pressure variance existing in human populations. Nevertheless, one limit could be the fact that known possible confounding factors in BP measurement (body mass index, waist circumference, chronic diseases) were not clearly considered in the study, several of these factors being well-known as correlated to DNA methylation differences.Disclosures None.FootnotesThe opinions expressed in this article are not necessarily those of the American Heart Association.For Disclosures, see page 774.Correspondence to: Daniel Vaiman, Institut Cochin, U1016 INSERM-UMR8104 CNRS, Université de Paris, France. Email daniel.[email protected]frReferences1. Booth J. A short history of blood pressure measurement.Proc R Soc Med. 1977; 70:793–799.MedlineGoogle Scholar2. Rader F, Victor RG. The slow evolution of blood pressure monitoring: but wait, not so fast!JACC Basic Transl Sci. 2017; 2:643–645. doi: 10.1016/j.jacbts.2017.11.001CrossrefMedlineGoogle Scholar3. Watanabe N, Bando YK, Kawachi T, Yamakita H, Futatsuyama K, Honda Y, Yasui H, Nishimura K, Kamihara T, Okumura T, et al.. Development and validation of a novel cuff-less blood pressure monitoring device.JACC Basic Transl Sci. 2017; 2:631–642. doi: 10.1016/j.jacbts.2017.07.015CrossrefMedlineGoogle Scholar4. Siegel WC, Blumenthal JA, Divine GW. Physiological, psychological, and behavioral factors and white coat hypertension.Hypertension. 1990; 16:140–146. doi: 10.1161/01.hyp.16.2.140LinkGoogle Scholar5. Ricci F, De Caterina R, Fedorowski A. Orthostatic hypotension: epidemiology, prognosis, and treatment.J Am Coll Cardiol. 2015; 66:848–860. doi: 10.1016/j.jacc.2015.06.1084CrossrefMedlineGoogle Scholar6. Pickering TG, Eguchi K, Kario K. Masked hypertension: a review.Hypertens Res. 2007; 30:479–488. doi: 10.1291/hypres.30.479CrossrefMedlineGoogle Scholar7. Roberts ML, Kotchen TA, Pan X, Li Y, Yang C, Liu P, Wang T, Laud PWChelius TH, Munyura Y, et al.. Unique associations of DNA methylation regions with 24-hour blood pressure phenotypes in blacks.Hypertension. 2022; 79:761–772. doi: 10.1161/HYPERTENSIONAHA.121.18584Google Scholar8. Richard MA, Huan T, Ligthart S, Gondalia R, Jhun MA, Brody JA, Irvin MR, Marioni R, Shen J, Tsai PC, et al.; BIOS Consortium. DNA methylation analysis identifies loci for blood pressure regulation.Am J Hum Genet. 2017; 101:888–902. doi: 10.1016/j.ajhg.2017.09.028CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesUnique Associations of DNA Methylation Regions With 24-Hour Blood Pressure Phenotypes in Black ParticipantsMichelle L. Roberts, et al. Hypertension. 2022;79:761-772 April 2022Vol 79, Issue 4Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/HYPERTENSIONAHA.121.18852PMID: 35263160 Originally publishedMarch 9, 2022 PDF download Advertisement SubjectsBiomarkersEpigeneticsHigh Blood Pressure

Study on the use practices and knowledges of French practitioners about the use of intra-uterine devices in early post-partum contraception in France.

Abstract: Objectives Intra-Uterine Device (IUD) insertion is possible in early postpartum. Although this contraception method is recognized and used in lots of country, it seems infrequent and poorly known in France. Our study aims to assess the barriers to the application of this method in France. Methods A questionnaire was sent to obstetricians-gynaecologist professionals and midwives in France, through the affiliation to CNGOF (French National College of Obstetricians and Gynecologists) and to CNSF (French National College of Midwives). Questions were focused on the practices and knowledge about the insertion of IUD in early postpartum. Results four hundred eight practitioners responded. Amongst them, 63% knew about the possibility to use IUDs after a vaginal delivery and 31% knew it could be inserted during cesarean section. Ten percent of them used this method. Most of these practitioners (80% of them) would like to discuss the insertion of an IUD in early postpartum with their patients and 71% would like to perform the insertion themselves after training. Besides, this study shows that contraception is rarely addressed by physicians during the follow-up of pregnancies. Less than 15% of respondents report discussing the topic systematically with the patient during the pregnancy follow during pregnancy follow. Conclusion insertion of IUDs in early postpartum is uncommon in France. The main limitation seems to be a lack of knowledge, but practitioners seem to be interested in this practice. Training courses could be created in order to rase up the adoption of this practice.

Intrathymic SIRPa cDC subsets organization in normal and stress conditions reveal another level of cDCs heterogeneity

Abstract: Three major subsets constitute the dendritic cells (DCs) pool in the thymus. They play key roles in self-antigen-specific thymocyte deletion and in the development of immunoregulatory T cells. Resident SIRPa- conventional DCs (cDCs, CD11c+ PDCA1lo ) are derived from intrathymic progenitors, whereas migratory SIRPa+ cDCs and plasmacytoid DCs (pDCs, CD11c+ PDCA1+ ) originate from extrathymic sites. Here, we describe the organization and the shaping of cDC populations at the steady state and under stress conditions in wild-type and mutant mice (CD3eKO, IL7RaKO, and Flt3LKO). In neonates, the thymus is mainly composed of SIRPa- -resident cDCs, whereas both cDC subsets are present in equal proportions in the adult. Upon thymus colonization, migratory SIRPa+ cDCs gain expression of phenotypic markers in a microenvironment dependent way. Here, we show that both processes are deeply impacted by mutations affecting T cell development. Under stress conditions such as sublethal irradiation, intrathymic resident SIRPa- cDCs are the first to regenerate the thymic cDC pool. Upon bone marrow transplantation, migratory SIRPa+ cDCs become the main source of thymic cDCs. These successive waves of regeneration eventually lead to a balance between resident and migratory DCs within the newly colonized thymus. These findings highlight an unrevealed division of labor between resident and migratory subsets for the organization/establishment of the thymic cDC compartment.

[Transplantation cardiaque pédiatrique : quel futur ?]

Abstract: The future of pediatric heart transplantation. Pediatric heart transplantation developed in the 1980s, following the introduction of cyclosporine. The International Registry includes more than 14 000 patients (10 % of the whole). The results improved progressively. However, two drawbacks persist : a shortage of donors, particularly in infants and a high morbi-mortality on the long term. The rapid achievement of a pediatric artificial heart is unlikely. The future offers two directions. Firsly xenotransplantation : the production of genetically-modified pigs and new immuno-suppressive modalities allow long-term survival in heterologous pig/primate transplantation. Human clinical trials may begin soon, particularly in neonates. Secondly tissue engineering : constant advances (scaffolds, cells lines, growth factors) may make possible the production of a functional heart from the receivor's own stem-cells.Transplantation cardiaque pédiatrique : quel futur ? La transplantation cardiaque pédiatrique s’est développée dans les années 1980, avec l’avènement de la ciclosporine. Le Registre International compte plus de 14 000patients (10 % de l’ensemble). Les résultats se sont progressivement améliorés, mais deux écueils persistent : la pénurie de donneurs, en particulier chez le nourrisson, et la morbi-mortalité élevée à très long terme. Le développement rapide d’un coeur artificiel adapté à l’enfant est peu probable et l’avenir s’oriente dans deux directions. D’une part la xénotransplan¬tation, la production de porcs génétiquement modifiés et des trai¬tements immunosuppresseurs innovants ayant permis la survie prolongée de greffons cardiaques entre porc et primate. Les essais cliniques semblent proches, en particulier chez le nouveau-né. D’autre part l’ingénierie tissulaire ; en effet des progrès constants (matrices, lignées cellulaires, facteurs de croissance) laissent en¬trevoir la possibilité de créer un coeur fonctionnel à partir des propres cellules du receveur.