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Gender Inequality in Managing Childhood Sleep: Which Parent Gets up at Night?
No full textInternational audienceObjective: Parental responsibilities for childcare remain unequally distributed between mothers and fathers. This study investigates whether such gender disparity also applies to night-time care, particularly when children experience sleep disorders.Methods: We conducted a cross-sectional survey study including 882 clinical files from sleep consultations for children aged 0 to 5 years, completed by one parent (98% mothers). To assess inter-rater reliability, 112 father–mother dyads outside the clinical setting were also surveyed. Additionally, 1409 mothers from the general population formed a control group.Results: In the clinical group, 60% of children were cared for exclusively by their mother at night, versus 9% by the father. In the control group, the figures were 64% and 6%, respectively. Gender disparities persisted even when both parents worked full-time or when the child was no longer breastfed. Inter-rater reliability was strong (r > 0.70). Factors such as number of night awakenings, child’s age, and maternal education influenced caregiving distribution. Greater maternal involvement was associated with increased psychological distress and lower relationship satisfaction.Conclusions: Mothers remain the primary caregivers at night, even in dual-earner families. This unequal distribution can affect maternal well-being and couple dynamics. Promoting paternal involvement may reduce maternal overload and improve child sleep outcomes
Comorbid Insomnia and Sleep Apnea Across the Pediatric Age: A Polysomnographic Study
No full textInternational audienceBackground/Objectives: Comorbid insomnia and sleep apnea (COMISA) in children is poorly documented. This study aimed to evaluate the frequency of COMISA and to explore its clinical and polysomnographic characteristics in children referred for polysomnography (PSG) for any sleep complaint. Methods: All patients with a complete insomnia sub-score on the Sleep Disturbance Scale for Children (SDSC; for children from 6 months to 16 years old) who underwent a night PSG in a pediatric sleep unit (2018–2024) were included in this retrospective study. Pathological SDSC insomnia sub-score defined insomnia and obstructive apnea-hypopnea index ≥ 2/h on PSG defined OSA. Questionnaires regarding sleepiness, depression, anxiety, and hyperactivity were also collected. Results: Children had isolated insomnia in 11.5% of cases, isolated OSA in 37.5%, and COMISA in 13.5%. Insomnia frequency was not different between patients with and those without OSA (26.5% vs. 23.5%). COMISA was more frequent in patients under 4 years old than in older ones (39.1% vs. 5.8%). No polysomnographic or clinical characteristic of COMISA was identified, except that OAHI was higher in children with isolated OSA. Patients with COMISA or isolated insomnia were more anxious than those with isolated OSA. Conclusions: Unlike in adults, the present findings do not support a mutual association between OSA and insomnia in children. OSA severity was lower in children with COMISA. Anxiety levels were higher in children with insomnia, regardless of the presence of OSA, suggesting that anxiety should be assessed in all children with OSA
Phase IV international prospective validation of the EORTC patient satisfaction core questionnaire (EORTC PATSAT-C33) and outpatient module (EORTC OUT-PATSAT7)
No full textInternational audienceAbstractBackground Advances in cancer care require ongoing monitoring of patient satisfaction using rigorousquestionnaires. The EORTC Quality of Life Group has cross-culturally developed a patient satisfaction corequestionnaire (PATSAT-C33) to be used in any hospital cancer care settings and an outpatient satisfaction module(OUT-PATSAT7) to address specific aspects of ambulatory care. This multi-center international prospective study aimedto validate the PATSAT-C33 and OUT-PATSAT7, including assessing its acceptability.Methods Patients (N = 690) affected by any cancer site or stage equally distributed by age and gender, were enrolledin in- and out-patient cancer settings from 20 institutions, 12 countries and 5 geographic/cultural areas. Amongthem, 675 completed the PATSAT-C33 alongside the EORTC QLQ-C30, Oberst’s perception of care quality 5-item,and ‘intention to recommend the hospital’ 1-item. Among the 532 outpatients, 526 also completed the OUT-PATSAT7.A subset completed a two-week retest (N = 120 & 96 for the PATSAT-C33 & OUT-PATSAT7, respectively) or one-yearresponsiveness-to-change assessment (RCA) (N = 166 & 155). Comprehensive psychometric testing was performed.Results Full item completion was high (85% & 88%), 83% of patients took ≤ 20 min to complete both questionnaires(40 items); 5% of patients required help with understanding questionnaire items. Confirmatory factor analysesevidenced satisfactory fit on the eleven PATSAT-C33 and two OUT-PATSAT7 multi-item scales (CFI/TLI > 0.90;RMSEA < 0.10 and = 0.108, respectively). Internal consistency was good to excellent (all ≥ 0.80); test–retest reliabilitywas fair (0.48, 1 scale), good (0.60–0.74, 11 scales) to excellent (≥ 0.75, 7 scales). Convergent validity was supported bycorrelations of ≥ 0.40 with related Oberst’s scales and < 0.30 with unrelated QLQ-C30 scales. Known-groups differenceswas shown for comorbidity, toxicity, global health, care expectations and intention to recommend the hospital
Structural mutations set an equilibrium non-coding genome fraction
No full textInternational audienceNon-coding genome size evolution is poorly understood. While some fraction of non-coding DNA has arguably a regulatory function, a large part does not seem to have a detectable impact on any phenotypic trait. The abundance of non-functional DNA in genomes, observed across the Tree of Life, challenges a purely adaptationist explanation. Several non-adaptive theories have been proposed to explain its presence and identify its determinants, emphasizing either the mutational processes or the mutational hazard entailed by non-coding and non-functional DNA. However, those theories have not yet been integrated into a single framework, and the exact nature of the mutational hazard is not yet fully understood. In this work, we propose a simple mathematical model of genome size evolution. The model shows how the non-coding fraction of the genome is shaped by two factors: unavoidable biases in the neutrality of the different mutation types (adding base pairs is more likely to be neutral than removing some), and the robustness selection imposed by the mere existence of structural mutations (larger genomes are more prone to double-strand breaks that can initiate structural mutations, imposing a second-order selection on robustness). Together, these two factors ensure the existence of an equilibrium non-coding fraction. We show that this equilibrium depends solely on mutation biases and the product of population size and mutation rate
High-resolution electrophysiological mapping of effective connectivity of lateral prefrontal cortex
No full textInternational audienceAbstract The lateral prefrontal cortex (LPFC) serves as a critical hub for higher-order cognitive and executive functions in the human brain, coordinating brain networks whose disruption has been implicated in many neurological and psychiatric disorders. While transcranial brain stimulation treatments often target the LPFC, our current understanding of connectivity profiles guiding these interventions based on electrophysiology remains limited. Here, we present a high-resolution probabilistic map of bidirectional effective connectivity between the LPFC and widespread cortical and subcortical regions. This map is derived from intracranial evoked potential analysis of 48,797 intracranial direct electrical stimulation runs across 759 implantations in 724 patients with refractory epilepsy (368 male, 354 female, two unspecified; mean age 24±13.5 years). We mapped probabilistic connectivity between brain parcels with adaptive resolution – higher resolution in the LPFC in the hemisphere of interest and lower elsewhere – maintaining statistical power while achieving 95% average confidence interval of ∼0.03 for connectivity probability estimates. In addition, the significance threshold (p-value) for probabilistic connectivity was obtained from surrogate distributions. Overall, we observed remarkable symmetry between afferent and efferent connectivity patterns of the LPFC, with a slight preference for efferent connections (mean slope = 0.92±0.09, mean R² = 0.93±0.025). For example, connections between the inferior frontal gyrus (IFG) and anterior cingulate showed notable directional asymmetry. The IFG strongly projected to most brain networks compared to other LPFC regions, with the strongest connectivity to the ventral attention network (0.26±0.01 compared to values between 0.15 and 0.21 in other LPFC regions). Posterior DLPFC demonstrated stronger connectivity to brain networks compared to anterior DLPFC regions (eg. 0.21±0.01 vs 0.15±0.01 for connectivity to ventral attention network), with the exception of the limbic cortex. All LPFC subregions strongly projected to the fronto-parietal (greater than 0.17) and ventral attention (greater than 0.15) networks, with moderate connections to the default network (between 0.1 and 0.15, with the maximum corresponding to superior DLPFC). Finally, latency analysis suggested that the left LPFC's influence on ipsilateral emotion-related regions is primarily polysynaptic, with particularly strong pathways from IFG to amygdala (0.16±0.02) and hippocampus (0.12±0.01). Taken together, these comprehensive connectivity maps provide a new detailed electrophysiological foundation for understanding the functional anatomy of LPFC and guiding targeted brain stimulation protocols
Des variants faux-sens du gène DPYSL5, associés à des troubles neurodéveloppementaux et à des malformations cérébrales, entraînent une maturation neuronale altérée in vitro.
No full textInternational audienceNeurodevelopmental disorders (NDD) with brain malformations have recently been associated with de novo variants in the DPYSL5 gene, which encodes a member of the dihydropyrimidinase-like proteins family. Here, we aimed to understand its role in NDD by characterizing novel or recurrent de novo variants at the molecular and cellular levels. We collected clinical data on individuals in whom DPYSL5 missense variants were identified through clinical genetic assessment of NDD or following the identification of brain malformations in fetuses. Functional analyses of wild-type and variant DPYSL5 proteins were performed to evaluate their impact on in vitro neuronal development and maturation, using primary neuronal cultures from mouse embryonic brains or hiPSC-derived human neural stem cells. We describe six different missense variants in DPYSL5 in nine individuals (including three fetuses), including the previously identified p.(Glu41Lys) recurrent mutation (in 2 individuals), a novel recurrent missense p.(Glu25Lys) de novo variant (in 3 individuals including 2 fetuses), and 3 novel candidates. Common features were developmental delay, intellectual disability, as well as brain malformations including agenesis of the corpus callosum for the N-terminal variants. Functional assays in differentiating mouse or human neuronal cultures revealed impairments in dendritic arborization, axonal elongation, and synaptic density. We thus expanded the functional characterization of DPYSL5 variants in NDD with brain malformations, including at the fetal stage, highlighting a fundamental role of the DPYSL5 gene in brain formation and functioning.Les troubles neurodéveloppementaux (TND) avec malformations cérébrales ont récemment été associés à des variants de novo du gène DPYSL5, qui code pour une protéine de la famille des dihydropyrimidinases. Dans l'étude que nous rapportons ici, nous avons cherché à comprendre le rôle de ce gène dans les TND en caractérisant une série de variants de novo, nouveaux ou récurrents, aux niveaux moléculaire et cellulaire. Nous avons recueilli des données cliniques d'individus chez lesquels des variants faux-sens de DPYSL5 ont été identifiés lors d'un bilan génétique clinique de TND ou suite à la détection de malformations cérébrales chez le fœtus. Des analyses fonctionnelles des variants protéiques de DPYSL5 ont été réalisées afin d'évaluer leur impact sur le développement et la maturation neuronaux in vitro, à l'aide de cultures neuronales primaires issues de cerveaux d'embryons de souris ou de cellules souches neurales humaines dérivées de cellules hiPSC. Nous décrivons six variants faux-sens du gène DPYSL5 chez neuf individus (dont trois fœtus), incluant la mutation récurrente p.(Glu41Lys) déjà décrite (chez deux individus), un nouveau variant faux-sens récurrent de novo p.(Glu25Lys) (chez trois individus, dont deux fœtus), et trois nouveaux candidats. Les caractéristiques communes observées sont un retard de développement, une déficience intellectuelle, ainsi que des malformations cérébrales, notamment une agénésie du corps calleux pour les variants N-terminaux. Des analyses fonctionnelles sur des cultures neuronales de souris ou humaines en différenciation ont révélé des altérations de l'arborisation dendritique, de l'élongation axonale et de la densité synaptique. Nous avons ainsi élargi la caractérisation fonctionnelle des variants de DPYSL5 dans les troubles neurodéveloppementaux associés à des malformations cérébrales, y compris au stade fœtal, soulignant le rôle fondamental du gène DPYSL5 dans la formation et le fonctionnement du cerveau
Tripartite ER-Mitochondria-Lipid Droplets contact sites control adipocyte metabolic flexibility
No full textInternational audienceAbstract Obesity is a major risk factor for cardiometabolic diseases, with adipocyte dysfunction playing a central role. In individuals living with obesity, adipose tissue (AT) enters a state of metabolic inertia, reducing its capacity to store excess lipids and promoting ectopic lipid accumulation in non-adipose tissues—thereby contributing to cardiometabolic complications. Understanding the mechanisms that regulate lipid storage and mobilization in adipocytes—and how these are disrupted in obesity—is critical for addressing these complications. Generalized lipodystrophy, the most severe form of primary adipocyte dysfunction, is caused in approximately 50% of cases by mutations in the BSCL2 gene encoding Seipin, an endoplasmic reticulum (ER) protein essential for lipid droplet (LD) biogenesis and maintenance. Seipin also localizes to ER/mitochondria contact sites (MAM), where it regulates calcium exchange and mitochondrial function. This study aimed to determine whether Seipin’s recruitment to MAM and ER/LD contact sites overlaps and to assess the consequences of Seipin dysfunction on membrane contact site (MCS) dynamics and adipocyte metabolism. Using in situ proximity ligation assays (PLA) and transmission electron microscopy (TEM), we observed altered MCS involving the ER, LDs, and mitochondria in Seipin-deficient models. Functional assays revealed that Seipin knockdown impairs triglyceride transfer to LDs, an effect that was rescued by the MAM-reinforcing synthetic peptide, the Linker-ER-Mi. Further, we investigated how MCS remodeling influences adipocyte metabolic flexibility. Using TEM and PLA in both mouse AT and 3T3-L1 adipocytes, here, we show that lipid loading increases contacts involving the lipid droplet (LD), specifically ER/LD and mitochondria/LD (Mi/LD) contacts. However, lipid loading exerts opposite effects on MAM subtypes: oleic acid increases the MAM involving mitochondria in close contact with the LD, the MAM-LD, while decreasing the MAM involving cytosolic mitochondria, the “classical” MAM-CM contacts. Notably, this adaptive MCS remodeling was blunted in the AT of diet-induced obese mice. Genetic disruption of MCS in 3T3-L1 adipocytes led to altered lipid flux, impaired lipolysis, and reduced insulin signaling. Collectively, our findings demonstrate that MAM-LD contacts are central to adipocyte metabolic flexibility and lipid handling, and that their dysregulation in obesity may underlie the metabolic inflexibility characteristic of this condition
IntegrAlign: a comprehensive tool for multi-immunofluorescence panel integration through image alignment
No full textInternational audienceMotivationTyramide-based multiplex-immunofluorescence (mIF) enables the simultaneous analysis of up to seven protein markers on a whole slide, providing a comprehensive approach to study the tumor microenvironment. Integrating multiple mIF panels through image alignment of serial slide significantly expands the number of cell populations analysed in a single space. IntegrAlign was developed to optimize this integration on serial whole slides, enhancing the value and applicability of -mIF for comprehensive spatial analyses and enabling biomarker discovery at scale.ResultsIntegrAlign, leveraging the SimpleITK toolkit, applies a two-step alignment using rigid and B-spline transformations to integrate serial mIF whole slides. Validation on simulated and real datasets demonstrated alignment accuracy below the diameter of a cell nucleus (∼6 µm), outperforming existing methods. This precision enhances spatial analyses by combining extended phenotypic data, supporting novel insights into tissue architecture and cellular interactions.Availability and implementionIntegrAlign is open-source, implemented in Python, and freely available under the MIT license at https://github.com/CAUXlab/IntegrAlign
Collaboration is our most powerful resistance in an increasingly fragmented world: Science is the light that reveals the unity beneath our differences
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Évaluation du risque fracturaire de l’os tumoral
No full textInternational audienceThere has been significant therapeutic progress in the management of cancer patients, with marked improvements in survival rates, including for those with stage IV bone metastases. Against this backdrop, locomotor health is becoming a central issue in preserving patients' autonomy and quality of life. A key element of the decision-making strategy is assessing the risk of fracture in patients with bone metastases, as this guides prescriptions for anti-resorptive agents, recommendations for physical activity, and local interventions such as radiotherapy, surgery, and interventional radiology. Due to the often asymptomatic and diffuse nature of bone metastases, the systematic mapping of bone locations, particularly within load-bearing bones, is essential. Currently, fracture risk assessment for each identified location is based on qualitative imaging approaches supported by scores such as Mirels or SINS. However, these tools have significant limitations, which justify the development of new methods for assessing fracture risk in bone metastases and myeloma. One of the emerging tools for personalised estimation of tumour bone strength and better assessment of pathological fracture risk at the femoral and vertebral levels is numerical simulation based on quantitative computed tomography (qCT) scans. Future generations of numerical simulations, enriched by artificial intelligence, will incorporate multiple loading conditions linked to movement, providing a more accurate reflection of real-life constraints. This approach aims to guide patients' rehabilitation and physical activity within a personalized medicine framework.D'importants progrès thérapeutiques ont été réalisés dans la prise en charge des patients atteints de cancer, avec une amélioration notable de la survie, y compris chez les patients porteurs de métastases osseuses de stade IV. Dans ce contexte, la santé locomotrice devient un enjeu central pour préserver l'autonomie et la qualité de vie des patients. L'évaluation du risque fracturaire des métastases osseuses constitue l'élément pivot de la stratégie décisionnelle, guidant les prescriptions d'agents anti-résorptifs, les recommandations d'activité physique et les interventions locales telles que la radiothérapie, la chirurgie ou la radiologie interventionnelle. Une étape incontournable, du fait du caractère souvent asymptomatique et diffus des métastases osseuses, est la cartographie systématique des localisations osseuses, notamment au sein des os porteurs. Pour chaque localisation identifiée, l'évaluation du risque fracturaire repose actuellement sur des approches qualitatives par imagerie, appuyées par des scores comme ceux de Mirels ou SINS. Ces outils présentent néanmoins des limites importantes, justifiant le développement de nouvelles méthodes d'évaluation du risque fracturaire dans les métastases osseuses et le myélome. La simulation numérique à partir d'images quantitatives scanographiques qCT constitue l'un des outils émergents permettant d'estimer, de façon personnalisée, la résistance osseuse tumorale et de mieux évaluer le risque de fracture pathologique au niveau fémoral et vertébral. Les générations futures de simulations numériques, enrichies par l'intelligence artificielle, intégreront des conditions de charge multiples liées au mouvement afin de refléter au mieux les contraintes de la vie réelle. Cette approche vise à guider la réhabilitation et l'activité physique des patients dans une logique de médecine personnalisée