Oskar Bordeaux
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Alzheimers Dement
Get PDFINTRODUCTION: White matter hyperintensities (WMHs), a major cerebral small vessel disease (cSVD) marker, may arise from different pathologies depending on their location. We explored clinical and genetic correlates of agnostically derived spatial WMH patterns in two longitudinal population-based cohorts (Three-City Study [3C]-Dijon, LIFE-Adult). METHODS: We derived seven WMH spatial patterns using Bullseye segmentation in 2878 individuals aged 65+ and explored their associations with vascular and genetic risk factors, cognitive performance, dementia and stroke incidence. RESULTS: WMHs in the frontoparietal and anterior periventricular region were associated with blood pressure traits, WMH genetic risk score (GRS), baseline and decline in general cognitive performance, incident all-cause dementia, and ischemic stroke. Juxtacortical-deep occipital WMHs were not associated with vascular risk factors and WMH GRS, but with incident all-cause dementia and intracerebral hemorrhage. DISCUSSION: Accounting for WMH spatial distribution is key to deciphering mechanisms underlying cSVD subtypes, an essential step towards personalized therapeutic approaches. HIGHLIGHTS: We studied spatial patterns of WMHs in 2878 participants. Blood pressure was associated with frontoparietal and anterior PV WMHs. Anterior PV WMHs predicted dementia and stroke risk. Juxtacortical-deep occipital WMH burden was not associated with blood pressure or WMH genetic risk. Juxtacortical-deep occipital WMH burden predicted dementia and intracerebral hemorrhage.Stopping cognitive decline and dementia by fighting covert cerebral small vessel diseaseVaincre les maladies vasculaires cérébrales par un nouveau paradigme de prévention de précision et d'innovation thérapeutiqu
Generation of metabolomic-informed models of metabolism for microbial communities
No full textLa génération de réseaux métaboliques à l'échelle du génome est devenue une analyse de routine pour des organismes individuels ou des communautés. Cependant, ces réseaux métaboliques générés automatiquement sont incomplets car ils sont construits sur la base de la combinaison de l'annotation des gènes et des réactions disponibles dans des bases de données génériques (Metacyc, BIGG, ModelSEED...). Ces bases de données sont orientées vers des organismes bien connus ou des organismes modèles et passent à côté de fonctions importantes du métabolisme secondaire. Nous proposons de combiner l'analyse de données métabolomiques, la modélisation métabolique et l'annotation métabolique et la modélisation métabolique et l'annotation minière pour construire des modèles de haute qualité du métabolisme microbien avec l'objectif à long terme d'une meilleure compréhension des communautés microbiennes. En termes d'application des méthodes aux communautés microbiennes végétales, nous espérons que les modèles nouvellement développés permettront de mieux comprendre le processus de recrutement microbien par la plante : fonctions métaboliques impliquées, micro-organismes associés à ces fonctions.The generation of genome-wide metabolic networks has become a routine analysis for individual organisms or communities communities. However, these automatically generated metabolic networks are incomplete because they are constructed by based on the combination of gene annotation and reactions available in generic available in generic databases (Metacyc, BIGG, ModelSEED...). These are oriented towards well-known organisms or organisms or model organisms and miss out on important functions secondary metabolism. We propose to combine metabolomic data analysis, metabolic modelling and annotation metabolic modelling and annotation mining to build high-quality models of high quality models of microbial metabolism with the long-term aim of better understanding of microbial communities. In terms of application of the methods to plant microbial communities, we hope that the plant microbial communities, we hope that the newly developed models will provide a better understanding of the process of microbial recruitment by the plant: metabolic functions involved, micro-organisms associated with these functions.Computationel models of crop plant microbial biodiversit
Front Public Health
No full textBackground Female sex workers (FSWs) are at high risk of contracting STIs, in particular in Sub-Saharan Africa. The implementation of oral HIV pre-exposure prophylaxis provided an opportunity to draw attention to the sexual health needs of FSWs. Innovative strategies to screen for and reduce the burden of STIs is thus a priority. This study describes STI screening among FSWs enrolled in the PRINCESSE project in Côte d’Ivoire. Methods The PRINCESSE project (2019–2023) was an interventional cohort of FSWs ≥18 years, evaluating a comprehensive, community-based sexual and reproductive health care package, including the management of STIs, offered through mobile clinics operating on prostitution sites in San Pedro area. HIV testing and syndromic STI testing were offered at baseline and every 3 months. Biological testing of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) was offered annually. Clinical forms included sociodemographic, behavioral and sex-work-related characteristics. We describe baseline characteristics, coverage of clinical examination, and vaginal, anal swab collection. Social, behavioral and sex work-related factors associated with an STI syndromic diagnosis were explored. A multivariable logistic regression model was used to identify factors associated with diagnosing a symptomatic STI. Results 489 FSWs were included in the PRINCESSE cohort. Median age was 29 years (24–35 years), 28.6% had had sex without a condom in the last 7 days. The prevalence of HIV at baseline was 10.5%. Only one case of HIV seroconversion was observed during the project. The most frequent symptom was ano-vaginal discharge (19.1%). The prevalence of STI based on clinical symptoms was 26.6%. The proportion of vaginal swab samples for which the PCR result was positive was 8.0% for CT and 4.0% for NG. Only age remained significantly associated with diagnosing a symptomatic STI in the multivariable analysis. Conclusion This study revealed a high prevalence of HIV and STIs, similar to national estimates among FSWs enrolled in a sexual health cohort. Screening for these generically asymptomatic bacterial STIs must be combined with the syndromic approach used in key populations, especially with the introduction of new PrEP programs, to reduce the exposure of individuals in these populations to STIs
Host specialisation or generalism? Population genetics of the aphid Myzus persicae reveals dominance of superclones across diverse host plants
No full textMost phytophagous insect species are specialized to feed on a narrow range of host plants, typically within the same genus or family, and sometimes even on a single plant species. However, some insect taxa are able to feed on plants from different families and are therefore considered to be generalists. Nevertheless, these generalist species can sometimes form cryptic species complexes or differentiate into host-based populations or races. Moreover, the host breadth of generalists is often measured under laboratory conditions, which may not accurately reflect the more challenging natural environments they encounter, and thus may lead to an overestimation of generalism. In this study, we used a population genetics approach to test whether Myzus persicae, a highly polyphagous aphid, is composed of hostspecialized populations or clones, or whether generalism is an intrinsic characteristic of the species as a whole. We sampled M. persicae over four consecutive years in northern France from a variety of host plants belonging to different botanical families. We found that populations of M. persicae in northern France were predominantly composed of superclones, namely multilocus genotypes identified in many copies. In particular, four superclones dominated M. persicae populations, occurring in high proportions on a broad range of unrelated host plants in each year of the study. Moreover, the array of characterized genotypes of M. persicae formed distinct genetic clusters, but with no clear association to specific host plants. This study shows that under natural conditions and at the very fine genetic level of a single clone, the generalist characteristic of M. persicae holds. Thus, M. persicae remains an exceptional example of a true generalist species
En‐échelon Rifting and Origin of the Volcanism in the Comoros
Get PDFAbstractTwo volcanic provinces have been recently discovered during the SISMAORE oceanographic cruise in the Comoros archipelago in the North Mozambique Channel between Madagascar and East Africa: N’Droundé, along the North‐eastern insular slopes of Grande Comores Island and Mwezi, in the abyssal plain, north‐east of Mayotte and Anjouan islands. By combining bathymetry and backscatter data, high‐resolution seismic reflection and sub‐bottom profiles, we have identified and mapped various tectonic (faults, forced folds) and volcanic structures (lava flows, edifices, sills, dykes) at several spatial scales on the seabed and in cross‐section within the sedimentary cover. We have characterized the volcano‐tectonic structures (geometry, segmentation, and kinematics) to better understand the link (geometry, chronology) between tectonic and volcanic processes. We show that volcanic and tectonic features are controlled by tectonic processes and vice‐versa. Ridges, volcanic cones and lava flows are set up along fissures and dikes during main rifting events to accommodate a N40°E regional extension within an E‐W right lateral shear transfer zone. The volcano tectonic features are Plio‐Pleistocene. This transfer zone lies between the offshore branch of the East African rift system and Malagasy grabens and may have formed when the East African rifts propagated offshore. We evidence a major rifting episode in the last Ma. The estimated volume and flux of extruded lavas show that the volcanism of the Comoros could be related to shallow tectonic processes.COmores & maYotte : vOlcanisme, TEctonique et Sismicit
Diagn Interv Imaging
No full textPelvic congestion syndrome (PCS) is a major cause of chronic pelvic pain in women of reproductive age. It is often associated with pelvic venous insufficiency and venous dilatation of the ovarian and uterine veins, resulting in a variety of symptoms exacerbated by venous hypertension. Despite its prevalence, PCS lacks standardized diagnostic and management protocols, making effective treatment challenging. The purpose of this expert consensus statement was to summarize the opinions of French radiologists and gynecologists regarding the diagnosis, imaging, treatment, and management of PCS. A working group of 14 expert radiologists and gynecologists from various French medical centers used a Delphi panel approach with several rounds of remote and face-to-face meetings to formulate and refine expert opinions based on the current literature and clinical expertise. These opinions were categorized according to diagnostic criteria, imaging techniques, therapeutic options, and follow-up protocols. The group formulated 72 initial opinions, and 65 were retained after rigorous evaluation for consensus. Key diagnostic tools include Doppler ultrasound for detection of venous reflux and magnetic resonance imaging for detailed assessment of venous anatomy. Endovascular embolization was highlighted as the primary treatment approach and recommended after thorough imaging evaluation. Noninvasive treatments and multidisciplinary care were also emphasized for comprehensive management. The expert opinion also included post-treatment follow-up to assess quality of life and symptom resolution. This structured consensus approach helped develop standardized expert opinions on management of, providing clear guidelines for diagnosis, treatment, and follow-up. These guidelines should improve clinical practice and patient care in the management of PCS
Pharmacoepidemiol Drug Saf
No full textPURPOSE: This study assesses success and methodological implications of linking IQVIA's Electronic Medical Records (EMR) of type 2 diabetes (T2D) patients with the National Health Data System (SNDS) database, a cornerstone process in healthcare research. METHODS: The OREOT cohort was constituted by T2D patients identified in the IQVIA EMR from 2014 to 2018 and linked indirectly to SNDS database. The EMR database contains clinical records from general practitioner consultations, representing ~2.8% of the French population and the SNDS claims database covers over 99% of the French population's healthcare activities. Linkage success was evaluated by the linkage rate. Baseline patients' characteristics were described for both linked and non-linked patients. RESULTS: Of the 291 408 T2D patients identified in the EMR, 244 656 (84%) were successfully linked. After technical data cleaning, 239 141 (82%) were finally linked. Linked and non-linked patients (n = 52,267) were aged 65 years and more frequently male (57% and 59%); half were obese, and most of comorbidities were consistent. Linked patients had more EMR consultations (median 32 vs 16), and more cardiovascular events (12% vs 7%) or chronic kidney disease (10% vs 7%). CONCLUSIONS: The successful linkage of EMR and SNDS databases provides valuable insights for future research in T2D and other chronic diseases requiring clinical data. This study demonstrates the feasibility of such data alignments, particularly in patients with complex health profiles or extensive medical records, and linkage potential to enhance real-world research quality. Despite higher prevalence of baseline comorbidities among linked patients, patients' characteristics were consistent with French T2D population
Small nucleolar RNAs promote the restoration of muscle differentiation defects in cells from myotonic dystrophy type 1
No full textAbstract Recently, the repertoire of human small nucleolar noncoding RNAs (snoRNAs) and their potential functions has expanded with the discovery of new snoRNAs and messenger RNA (mRNA) targets, for which snoRNA-guided modifications may influence their stability, translatability, and splicing. We previously identified snoRNAs that are abundant in healthy human muscle progenitor cells. In this study, we demonstrated that SNORA40 and SNORA70 loss-of-function impairs myogenic differentiation. Interestingly, gain-of-function can rescue impaired differentiation muscle progenitor cells in myotonic dystrophy type 1 (DM1). We identified cyclin D3 (CCND3) mRNA, which is partially located in the nucleolus, as a target for SNORA40 and SNORA70, which are required for its pseudouridylated status. Expression of the CCND3 protein is required for muscle progenitors to exit the cell-cycle when they are induced to differentiate. We revealed that this switch requires SNORA40/70. Finally, we observed that DM1 cells show reduced levels of SNORA40/70 and undetectable CCND3 protein. However, restoring normal levels of SNORA40/70 partially restored CCND3 protein expression, coinciding with improved cell fusion capacity in DM1 muscle progenitors. Collectively, these data suggest that this effect may stem from SNORA40/70-dependent pseudouridylation of CCND3 mRNA, emphasizing snoRNAs as key players in normal and pathological muscle differentiation