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Stressful early-life experiences increase the risk of developing an alcohol use disorder. We had previously found that male C57BL/6J mice reared under limited bedding and nesting (LBN) conditions, a model of early-life adversity, escalate their ethanol intake in limited-access two-bottle choice (2BC) sessions faster than control (CTL)-reared counterparts when exposed to chronic intermittent ethanol (CIE) vapor inhalation. However, the alcohol consumption of female littermates was not affected by LBN or CIE. In the present study, we sought to determine whether this phenotype reflected a general insensitivity of female mice to the influence of early life stress on alcohol responses.In a first experiment, CTL and LBN females with a history of 2BC combined or not with CIE were tested in affective and nociceptive assays during withdrawal. In a second group of CTL and LBN females, ethanol-induced antinociception, sedation, plasma clearance, and c-Fos induction were examined.In females withdrawn from chronic 2BC, CIE increased digging, reduced grooming, and increased immobility in the tail suspension test regardless of early-life history. In contrast, LBN rearing lowered mechanical nociceptive thresholds regardless of CIE exposure. In females acutely treated with ethanol, LBN rearing facilitated antinociception and delayed the onset of sedation without influencing ethanol clearance rate or c-Fos induction in the paraventricular nucleus of the hypothalamus, paraventricular nucleus of the thalamus, central nucleus of the amygdala, or auditory cortex.CIE withdrawal produced multiple indices of negative affect in C57BL/6J females, suggesting that their motivation to consume alcohol may differ from air-exposed counterparts despite equivalent intake. Contrasted with our previous findings in males, LBN-induced mechanical hyperalgesia in chronic alcohol drinkers was specific to females. Lower nociceptive thresholds combined with increased sensitivity to the acute antinociceptive effect of ethanol may contribute to reinforcing ethanol consumption in LBN females but are not sufficient to escalate their intake.

Fetal growth restriction (FGR) is a risk factor for neurodevelopmental problems, yet remains poorly understood. We sought to examine the relationship between intrauterine development and neonatal neurobehavior in pregnancies diagnosed with antenatal FGR.We recruited women with singleton pregnancies diagnosed with FGR and measured placental and fetal brain volumes using MRI. NICU Network Neurobehavioral Scale (NNNS) assessments were performed at term equivalent age. Associations between intrauterine volumes and neurobehavioral outcomes were assessed using generalized estimating equation models.We enrolled 44 women diagnosed with FGR who underwent fetal MRI and 28 infants underwent NNNS assessments. Placental volumes were associated with increased self-regulation and decreased excitability; total brain, brainstem, cortical and subcortical gray matter (SCGM) volumes were positively associated with higher self-regulation; SCGM also was positively associated with higher quality of movement; increasing cerebellar volumes were positively associated with attention, decreased lethargy, non-optimal reflexes and need for special handling; brainstem volumes also were associated with decreased lethargy and non-optimal reflexes; cerebral and cortical white matter volumes were positively associated with hypotonicity.Disrupted intrauterine growth in pregnancies complicated by antenatally diagnosed FGR is associated with altered neonatal neurobehavior. Further work to determine long-term neurodevelopmental impacts is warranted.Fetal growth restriction is a risk factor for adverse neurodevelopment, but remains difficult to accurately identify. Intrauterine brain volumes are associated with infant neurobehavior. The antenatal diagnosis of fetal growth restriction is a risk factor for abnormal infant neurobehavior.

Sex-based differences in brain structure and function are observable throughout development and are thought to contribute to differences in behavior, cognition, and the presentation of neurodevelopmental disorders. Using multiple support vector machine (SVM) models as a data-driven approach to assess sex differences, we sought to identify regions exhibiting sex-dependent differences in functional connectivity and determine whether they were robust and sufficiently reliable to classify sex even prior to birth. To accomplish this, we used a sample of 110 human fetal resting state fMRI scans from 95 fetuses, performed between 19 and 40 gestational weeks. Functional brain connectivity patterns classified fetal sex with 73% accuracy. Across SVM models, we identified features (functional connections) that reliably differentiated fetal sex. Highly consistent predictors included connections in the somatomotor and frontal areas alongside the hippocampus, cerebellum, and basal ganglia. Moreover, high consistency features also implicated a greater magnitude of cross-region connections in females, while male weighted features were predominately within anatomically bounded regions. Our findings indicate that these differences, which have been observed later in childhood, are present and reliably detectable even before birth. These results show that sex differences arise before birth in a manner that is consistent and reliable enough to be highly identifiable.

The parasubthalamic nucleus (PSTN) is responsive to refeeding after food deprivation and PSTN subpopulations can suppress feeding. However, no study directly addressed the role of PSTN neurons activated upon food access resumption. Here we show that the ensemble of refeeding-activated PSTN neurons drastically increases the latency to initiate refeeding with both familiar and novel food but exerts limited control over the amount of food consumed by hungry mice. This ensemble also delays sucrose consumption but accelerates water consumption in thirsty mice. We next sought to identify which subpopulations of PSTN neurons might be driving these effects. We discovered that PSTNTac1neurons projecting to the CeA selectively suppress feeding initiation while PSTNCrhneurons surprisingly promote the consumption of novel, palatable substances. Our results demonstrate the key role of endogenous PSTN activity in the control of feeding initiation and identify PSTN subpopulations counteracting each other’s influence on consummatory behaviors.

The subplate is a transient brain structure which plays a key role in the maturation of the cerebral cortex. Altered brain growth and cortical development have been suggested in fetuses with complex congenital heart disease (CHD) in the third trimester. However, at an earlier gestation, the putative role of the subplate in altered brain development in CHD fetuses is poorly understood. This study aims to examine subplate growth (i.e., volume and thickness) and its relationship to cortical sulcal development in CHD fetuses compared with healthy fetuses by using 3D reconstructed fetal magnetic resonance imaging. We studied 260 fetuses, including 100 CHD fetuses (22.3–32 gestational weeks) and 160 healthy fetuses (19.6–31.9 gestational weeks). Compared with healthy fetuses, CHD fetuses had 1) decreased global and regional subplate volumes and 2) decreased subplate thickness in the right hemisphere overall, in frontal and temporal lobes, and insula. Compared with fetuses with two-ventricle CHD, those with single-ventricle CHD had reduced subplate volume and thickness in right occipital and temporal lobes. Finally, impaired subplate growth was associated with disturbances in cortical sulcal development in CHD fetuses. These findings suggested a potential mechanistic pathway and early biomarker for the third-trimester failure of brain development in fetuses with complex CHD. Significance Statement Our findings provide an early biomarker for brain maturational failure in fetuses with congenital heart disease, which may guide the development of future prenatal interventions aimed at reducing neurological compromise of prenatal origin in this high-risk population.

Background Due to random motion of fetuses and maternal respirations, image quality of fetal brain MRIs varies considerably. To address this issue, visual inspection of the images is performed during acquisition phase and after 3D-reconstruction, and the images are re-acquired if they are deemed to be of insufficient quality. However, this process is time-consuming and subjective. Multi-instance (MI) deep learning methods (DLMs) may perform this task automatically. Purpose To propose an MI count-based DLM (MI-CB-DLM), an MI vote-based DLM (MI-VB-DLM), and an MI feature-embedding DLM (MI-FE-DLM) for automatic assessment of 3D fetal-brain MR image quality. To quantify influence of fetal gestational age (GA) on DLM performance. Study type Retrospective. Subjects Two hundred and seventy-one MR exams from 211 fetuses (mean GA ± SD = 30.9 ± 5.5 weeks). Field strength/sequence T2 -weighted single-shot fast spin-echo acquired at 1.5 T. Assessment The T2 -weighted images were reconstructed in 3D. Then, two fetal neuroradiologists, a clinical neuroscientist, and a fetal MRI technician independently labeled the reconstructed images as 1 or 0 based on image quality (1 = high; 0 = low). These labels were fused and served as ground truth. The proposed DLMs were trained and evaluated using three repeated 10-fold cross-validations (training and validation sets of 244 and 27 scans). To quantify GA influence, this variable was included as an input of the DLMs. Statistical tests DLM performance was evaluated using precision, recall, F-score, accuracy, and AUC values. Results Precision, recall, F-score, accuracy, and AUC averaged over the three cross validations were 0.85 ± 0.01, 0.85 ± 0.01, 0.85 ± 0.01, 0.85 ± 0.01, 0.93 ± 0.01, for MI-CB-DLM (without GA); 0.75 ± 0.03, 0.75 ± 0.03, 0.75 ± 0.03, 0.75 ± 0.03, 0.81 ± 0.03, for MI-VB-DLM (without GA); 0.81 ± 0.01, 0.81 ± 0.01, 0.81 ± 0.01, 0.81 ± 0.01, 0.89 ± 0.01, for MI-FE-DLM (without GA); and 0.86 ± 0.01, 0.86 ± 0.01, 0.86 ± 0.01, 0.86 ± 0.01, 0.93 ± 0.01, for MI-CB-DLM with GA. Data conclusion MI-CB-DLM performed better than other DLMs. Including GA as an input of MI-CB-DLM improved its performance. MI-CB-DLM may potentially be used to objectively and rapidly assess fetal MR image quality. Evidence level 4 TECHNICAL EFFICACY: Stage 3.

Recent advances in brain imaging have enabled non-invasive in vivo assessment of the fetal brain. Characterizing brain development in healthy fetuses provides baseline measures for identifying deviations in brain function in high-risk clinical groups. We examined 110 resting state MRI data sets from fetuses at 19 to 40 weeks’ gestation. Using graph-theoretic techniques, we characterized global organizational features of the fetal functional connectome and their prenatal trajectories. Topological features related to network integration (i.e., global efficiency) and segregation (i.e., clustering) were assessed. Fetal networks exhibited small-world topology, showing high clustering and short average path length relative to reference networks. Likewise, fetal networks’ quantitative small world indices met criteria for small-worldness (σ > 1, ω = [−0.5 0.5]). Along with this, fetal networks demonstrated global and local efficiency, economy, and modularity. A right-tailed degree distribution, suggesting the presence of central areas that are more highly connected to other regions, was also observed. Metrics, however, were not static during gestation; measures associated with segregation—local efficiency and modularity—decreased with advancing gestational age. Altogether, these suggest that the neural circuitry underpinning the brain’s ability to segregate and integrate information exists as early as the late 2nd trimester of pregnancy and reorganizes during the prenatal period. Significance statement. Mounting evidence for the fetal origins of some neurodevelopmental disorders underscores the importance of identifying features of healthy fetal brain functional development. Alterations in prenatal brain connectomics may serve as early markers for identifying fetal-onset neurodevelopmental disorders, which in turn provide improved surveillance of at-risk fetuses and support the initiation of early interventions.

Objectives:Women carrying a fetus diagnosed with congenital heart disease often experience significant distress because of their medical diagnosis. Given the well-documented impact associated with elevated prenatal stress and critical importance of developing targeted interventions, this study aims to examine stressors, coping and resilience resources, and mental health treatment preferences in pregnant women receiving a congenital heart disease diagnosis to inform the development of a psychological intervention to reduce maternal distress prenatally.Methods:Three groups of participants were included consisting of two pregnant women carrying a fetus with congenital heart disease, five women of children (4−16 months) with congenital heart disease, and five paediatric cardiology medical providers. Responses were gathered via semi-structured interviews and analysed using qualitative thematic analysis.Results:Information regarding four broad areas were analysed of emotional distress during pregnancy; experience of initial diagnosis; coping and resilience; and perspectives on a mental health intervention in pregnancy. Anxiety regarding baby’s future, guilt following diagnosis, and various coping strategies emerged as primary themes among the participant sample. Medical staff corroborated mothers’ heightened anxiety and viewed a psychotherapeutic intervention during the prenatal period as essential and complimentary to standard of care.Conclusion:We identified salient themes and preferred components for a future psychological intervention delivered prenatally.Practice Implications:Patients’ and providers’ perspectives regarding the nature of maternal distress, resilience and treatment preferences can inform the development of interventions to support the emotional well-being of pregnant women carrying a fetus with congenital heart disease to optimise care and potentially improve outcomes for fetal brain development.

Background Elevated maternal psychological distress during pregnancy is linked to adverse outcomes in offspring. The potential effects of intensified levels of maternal distress during the COVID-19 pandemic on the developing fetal brain are currently unknown. Methods We prospectively enrolled 202 pregnant women: 65 without known COVID-19 exposures during the pandemic who underwent 92 fetal MRI scans, and 137 pre-pandemic controls who had 182 MRI scans. Multi-plane, multi-phase single shot fast spin echo T2-weighted images were acquired on a GE 1.5 T MRI Scanner. Volumes of six brain tissue types were calculated. Cortical folding measures, including brain surface area, local gyrification index, and sulcal depth were determined. At each MRI scan, maternal distress was assessed using validated stress, anxiety, and depression scales. Generalized estimating equations were utilized to compare maternal distress measures, brain volume and cortical folding differences between pandemic and pre-pandemic cohorts. Results Stress and depression scores are significantly higher in the pandemic cohort, compared to the pre-pandemic cohort. Fetal white matter, hippocampal, and cerebellar volumes are decreased in the pandemic cohort. Cortical surface area and local gyrification index are also decreased in all four lobes, while sulcal depth is lower in the frontal, parietal, and occipital lobes in the pandemic cohort, indicating delayed brain gyrification. Conclusions We report impaired fetal brain growth and delayed cerebral cortical gyrification in COVID-19 pandemic era pregnancies, in the setting of heightened maternal psychological distress. The potential long-term neurodevelopmental consequences of altered fetal brain development in COVID-era pregnancies merit further study.

Objectives:Prenatal maternal stress is associated with adverse offspring outcomes, which may be mediated by maternal stress hormones. However, evidence supporting the association between maternal stress and cortisol levels in high-risk pregnancies is limited. This study aims to determine the relationship between self-reported maternal mental distress and maternal salivary cortisol levels in pregnancies complicated by foetal CHD compared with healthy pregnancies.Methods:We recruited women with pregnancies complicated by foetal CHD and healthy pregnancies. Maternal saliva was collected between 22 and 40 gestational weeks. Standardized questionnaires measuring stress, depression, and anxiety were completed by patients. Generalized estimating equation was used to evaluate associations between maternal mental distress scales and cortisol levels.Results:We studied 165 women (55 CHD, 110 controls) and collected 504 cortisol samples (160 CHD, 344 controls). Women carrying CHD foetuses had higher stress, anxiety, and depression scores compared to women carrying healthy foetuses. However, maternal cortisol levels did not significantly differ in CHD and controls. Cortisol levels were higher in women carrying foetuses with functionally single-ventricle versus two-ventricle CHD. In both CHD and controls, there was no significant association between maternal stress, depression or anxiety scores and cortisol levels.Conclusion:Our data suggest that self-reported maternal stress, anxiety, and depression are not associated with maternal salivary cortisol levels in CHD and healthy pregnancies. The impact of maternal mental distress on foetal health may be through other mediating pathways other than maternal cortisol concentrations.

BACKGROUND AND PURPOSE: Gamma-aminobutyric acid and glutamate system disruptions may underlie neonatal brain injury. However, in vivo investigations are challenged by the need for special 1H-MR spectroscopy sequences for the reliable measurement of the neurotransmitters in this population. We used J-edited 1H-MR spectroscopy (Mescher-Garwood point-resolved spectroscopy) to quantify regional in vivo gamma-aminobutyric acid and glutamate concentrations during the early postnatal period in healthy neonates. MATERIALS AND METHODS: We prospectively enrolled healthy neonates and acquired Mescher-Garwood point-resolved spectroscopy spectra on a 3T MR imaging scanner from voxels located in the cerebellum, the right basal ganglia, and the right frontal lobe. CSF-corrected metabolite concentrations were compared for regional variations and cross-sectional temporal trends with advancing age. RESULTS: Fifty-eight neonates with acceptable spectra acquired at postmenstrual age of 39.1 (SD, 1.3) weeks were included for analysis. Gamma-aminobutyric acid (+ macromolecule) (2.56 [SD, 0.1]) i.u., glutamate (3.80 [SD, 0.2]), Cho, and mIns concentrations were highest in the cerebellum, whereas NAA (6.72 [SD, 0.2]), NAA/Cho, Cr/Cho, and Glx/Cho were highest in the basal ganglia. Frontal gamma-aminobutyric acid (1.63 [SD, 0.1]), Glx (4.33 [SD, 0.3]), Cr (3.64 [SD, 0.2]), and Cho concentrations were the lowest among the ROIs. Glx, NAA, and Cr demonstrated a significant adjusted increase with postmenstrual age (β = 0.2–0.35), whereas gamma-aminobutyric acid and Cho did not. CONCLUSIONS: We report normative regional variations and temporal trends of in vivo gamma-aminobutyric acid and glutamate concentrations reflecting the functional and maturational status of 3 distinct brain regions of the neonate. These measures will serve as important normative values to allow early detection of subtle neurometabolic alterations in high-risk neonates.

Brain injury is a serious and common complication of critical congenital heart disease (CHD). Impaired autonomic development (assessed by heart rate variability (HRV)) is associated with brain injury in other high-risk neonatal populations.To determine whether impaired early neonatal HRV is associated with pre-operative brain injury in CHD.In infants with critical CHD, we evaluated HRV during the first 24 h of cardiac ICU (CICU) admission using time-domain (RMS 1, RMS 2, and alpha 1) and frequency-domain metrics (LF, nLF, HF, nHF). Pre-operative brain magnetic resonance imaging (MRI) was scored for injury using an established system. Spearman's correlation coefficient was used to determine the association between HRV and pre-operative brain injury.We enrolled 34 infants with median birth gestational age of 38.8 weeks (IQR 38.1-39.1). Median postnatal age at pre-operative brain MRI was 2 days (IQR 1-3 days). Thirteen infants had MRI evidence of brain injury. RMS 1 and RMS 2 were inversely correlated with pre-operative brain injury.Time-domain metrics of autonomic function measured within the first 24 h of admission to the CICU are associated with pre-operative brain injury, and may perform better than frequency-domain metrics under non-stationary conditions such as critical illness.Autonomic dysfunction, measured by heart rate variability (HRV), in early transition is associated with pre-operative brain injury in neonates with critical congenital heart disease. These data extend our earlier findings by providing further evidence for (i) autonomic dysfunction in infants with CHD, and (ii) an association between autonomic dysfunction and brain injury in critically ill neonates. These data support the notion that further investigation of HRV as a biomarker for brain injury risk is warranted in infants with critical CHD.

Background: Elevated maternal psychological distress during pregnancy is linked to adverse short- and long-term outcomes in the offspring. The potential deleterious effects of intensified levels of maternal distress during the COVID-19 pandemic on the developing fetal brain are currently unknown. Methods: We prospectively enrolled 202 pregnant women: 65 with negative COVID-19 diagnoses during the pandemic who underwent 92 fetal MRI scans, and 137 pre-pandemic controls who had 182 MRI scans. Multi-plane, multi-phase single shot fast spin echo T2-weighted images were acquired on a GE 1.5T MRI Scanner. High-resolution 3D models of the fetal brains were reconstructed, and volumes of six brain tissue types were calculated: cortical gray matter (CGM), white matter (WM), cerebellum, deep gray matter (DGM), brainstem, and hippocampus. Cortical folding measures, including brain surface area, local gyrification index (LGI), and sulcal depth were determined. At each MRI scan, maternal distress was assessed using validated stress, anxiety and depression scales. Generalized estimating equations (GEEs) were utilized to compare maternal distress measures, brain volume and cortical folding differences between pandemic and pre-pandemic cohorts. Findings: Stress and depression scores were significantly higher in the pandemic cohort (14.2 vs. 10.4 for stress; 5.9 vs. 4.2 for depression; p

Introduction: Studies have shown that maternal stress and anxiety during pregnancy have been associated with a higher incidence of preterm birth and low birth weight. However, the relationship between prenatal maternal mental distress and placental development in fetuses with congenital heart disease (CHD) is unknown. Hypothesis: We tested the hypothesis that elevated maternal anxiety is associated with altered placental morphology in fetuses with CHD. Methods: A total of 141 pregnant women were recruited prospectively (control: 91; two-ventricle/2V CHD: 29; single-ventricle/SV CHD: 21), in which 228 fetal MR scans were performed (gestational age: 31.8±4.5 weeks). Single shot fast spin echo T2-weighted images were acquired on a 1.5 Tesla GE MRI scanner. Placenta tissue was manually segmented, and slice-to-volume registration was used for motion correction and 3D reconstruction. Six placental features were calculated: volume, thickness, elongation, surface area, mean diameter, and umbilical cord centricity. We completed the Spielberger State (SSAI) and Trait (SSAI) Anxiety Inventory at each study visit. Linear mixed models were utilized to analyze the placental features predicted by maternal anxiety. Results: Placental volume, surface area, and mean diameter were decreased with elevated SSAI in 2V CHD fetuses, while volume and cord centricity were increased with higher SSAI in SV CHD fetuses. Lower cord centricity was associated with elevated STAI in 2V CHD fetuses, and elongation was positively associated with STAI in SV CHD fetuses. There were no associations between anxiety measures and placental features in control fetuses. Conclusions: We report for the first time that elevated prenatal maternal anxiety is associated with altered in vivo placental structures in pregnancies complicated by fetal CHD. Our data suggest that disturbances in placental structure vary based on the type of fetal CHD (SV vs. 2V) in the setting of elevated prenatal maternal anxiety.

Introduction: Neurodevelopmental disabilities are common among infants with complex congenital heart disease (CHD). While hemispheric asymmetries in normal fetal brain size and shape have been reported, the effect of CHD on hemispheric development of the developing fetal brain remains unknown. Hypothesis: We hypothesized that emerging cerebral hemispheric asymmetries of the fetal CHD brain would differ compared to healthy controls using in vivo MRI tools. Methods: A total of 252 pregnant women were recruited (164 controls; 88 CHD fetuses), in which 328 fetal MRI scans were performed. Single shot fast spin echo T2-weighted images were acquired on a 1.5T GE MRI scanner. High-resolution 3D models of the fetal brain were reconstructed using slice-to-volume registration method for motion correction and Draw-EM algorithm for automatic segmentation. Volumetric analysis of brain tissues was conducted, and cortical folding measures of brain lobes were evaluated. Mixed effects regression was utilized to compare the brain features between right and left hemispheres for healthy controls and CHD fetuses. Results: The mean gestational age of all fetal MRI studies was 32.1±3.7 weeks (range: 24.0-39.4). For healthy fetuses, the volume of cortical gray matter was higher in the left hemisphere; however, this pattern was diminished in CHD fetuses. Gyrification indices were higher in the parietal and occipital lobes of the right hemisphere for controls, but not for CHD fetuses. Similarly, Gaussian curvature was higher in the right frontal lobe for controls only. Conversely, the surface area of the left occipital lobe was lower in CHD fetuses, but not in healthy fetuses. Conclusions: We report for the first time early disturbances in emerging hemispheric asymmetric patterns of the fetal brain in CHD compared to controls. The extent to which these lateralization differences reflect genetic, epigenetic and/or hemodynamic disturbances in CHD fetuses is under investigation.

Introduction: Brain injury and delayed brain development have been reported in fetuses with congenital heart disease (CHD). While reduced volumes of fetal brain structures have been discovered, the shape alternations of the brainstem affected by CHD were not fully investigated. Hypothesis: We assessed the hypothesis that the morphology of the brainstem in CHD fetuses was altered when compared to healthy controls. Methods: A total of 146 pregnant women were recruited for this longitudinal observational study (99 controls and 47 CHD; median gestational age (GA) and range: 33.4 [24.4-39.1] weeks), in which 207 MRI scans were performed. Single shot fast spin echo T2-weighted images were acquired on a 1.5T GE MRI scanner. Anatomical landmarks of brainstem were manually identified on 1 mm 3 isotropic 3D reconstructed images using RView software. Anterior-posterior and transverse diameters of mesencephalon, pons, and medullary were determined based on 12 landmarks on the midsagittal and coronal planes correspondingly. The inter-landmark distances and 2D areas enclosed by landmarks on the midsagittal plane of the two groups were analyzed using generalized estimating equations, adjusting for GA and fetal gender. Results: Results indicated lower regional anterior-posterior diameters of the pons in CHD fetuses [landmarks 2-3, 2-6, 3-4, and 4-6 ( p-values 2 ; CHD: 175±10 mm 2 ; p =0.016). No differences in transverse diameters were observed between control and CHD fetuses on the three coronal planes. All measured diameters and areas were significantly increased with advancing GA ( p-values Conclusions: We report for the first time impaired regional growth of the pons in fetuses with CHD. The pons may play a role in altered emerging cerebral-cerebellar structure and functional connections in fetal CHD.

Prenatal maternal psychological distress is associated with disturbances in fetal brain development. However, the association between altered fetal brain development, prenatal maternal psychological distress, and long-term neurodevelopmental outcomes is unknown.To determine the association of fetal brain development using 3-dimensional magnetic resonance imaging (MRI) volumes, cortical folding, and metabolites in the setting of maternal psychological distress with infant 18-month neurodevelopment.Healthy mother-infant dyads were prospectively recruited into a longitudinal observational cohort study from January 2016 to October 2020 at Children's National Hospital in Washington, DC. Data analysis was performed from January 2016 to July 2021.Prenatal maternal stress, anxiety, and depression.Prenatal maternal stress, anxiety, and depression were measured using validated self-report questionnaires. Fetal brain volumes and cortical folding were measured from 3-dimensional, reconstructed T2-weighted MRI scans. Fetal brain creatine and choline were quantified using proton magnetic resonance spectroscopy. Infant neurodevelopment at 18 months was measured using Bayley Scales of Infant and Toddler Development III and Infant-Toddler Social and Emotional Assessment. The parenting stress in the parent-child dyad was measured using the Parenting Stress Index-Short Form at 18-month testing.The cohort consisted of 97 mother-infant dyads (mean [SD] maternal age, 34.79 [5.64] years) who underwent 184 fetal MRI visits (87 participants with 2 fetal studies each) with maternal psychological distress measures between 24 and 40 gestational weeks and completed follow-up infant neurodevelopmental testing. Prenatal maternal stress was negatively associated with infant cognitive performance (β = -0.51; 95% CI, -0.92 to -0.09; P = .01), and this association was mediated by fetal left hippocampal volume. In addition, prenatal maternal anxiety, stress, and depression were positively associated with all parenting stress measures at 18-month testing. Finally, fetal cortical local gyrification index and sulcal depth were negatively associated with infant social-emotional performance (local gyrification index: β = -54.62; 95% CI, -85.05 to -24.19; P .001; sulcal depth: β = -14.22; 95% CI, -23.59 to -4.85; P = .002) and competence scores (local gyrification index: β = -24.01; 95% CI, -40.34 to -7.69; P = .003; sulcal depth: β = -7.53; 95% CI, -11.73 to -3.32; P .001).In this cohort study of 97 mother-infant dyads, fetal cortical local gyrification index and sulcal depth were associated with infant 18-month social-emotional and competence outcomes, and fetal left hippocampal volume mediated the association between prenatal maternal stress and infant cognitive outcome. These findings suggest that altered prenatal brain development in the setting of elevated maternal distress has adverse infant sociocognitive outcomes, and identifying early biomarkers associated with long-term neurodevelopment may assist in early targeted interventions.

Large conductance potassium (BK) channels are among the most sensitive molecular targets of ethanol and genetic variations in the channel-forming α subunit have been nominally associated with alcohol use disorders. However, whether the direct action of ethanol at BK α influences the motivation to drink alcohol remains to be determined. In the present study, we sought to investigate the behavioral relevance of this molecular interaction by introducing in the mouse genome a point mutation known to render BK channels insensitive to ethanol while preserving their physiological function. The BK α K361N substitution prevented ethanol from reducing spike threshold in medial habenula neurons. However, it did not alter acute responses to ethanolin vivo, including ataxia, sedation, hypothermia, analgesia, and conditioned place preference.Furthermore, the mutation did not have reproducible effects on alcohol consumption in limited, continuous, or intermittent access home cage two-bottle choice paradigms conducted in both males and females. Notably, in contrast to previous observations made in mice missing BK channel auxiliary β subunits, the BK α K361N substitution had no significant impact on ethanol intake escalation induced by chronic intermittent alcohol vapor inhalation. It also did not affect the metabolic and locomotor consequences of chronic alcohol exposure. Altogether, these data suggest that the direct interaction of ethanol with BK α does not mediate the alcohol-related phenotypes examined here in mice.

Purpose This paper describes the approach used to develop the Adolescent Family Life Program (AFLP) Positive Youth Development (PYD) Model within the structure of an existing state government-run program. Description The California Department of Public Health, Maternal, Child and Adolescent Health (CDPH/MCAH) Division undertook an innovative approach to develop a program model to help expectant and parenting youth build resilience. CDPH/MCAH started by assessing existing program efforts and theory to develop and test new strategies in the field, structure a program model, and build toward broader expansion and sustainability. CDPH/MCAH engaged local organizations from across the state, their staff and enrolled youth, experts, and evaluators in an iterative program development process to standardize an effective model that could be replicated and evaluated. Assessment Key lessons for program developers and administrators are to ensure adequate staffing with diverse expertise related to the topic and content to support the multiple components of program development and implementation, evaluation, and training; identify the guiding theory and framework early and link them with clearly articulated core components to ensure the final model reflects the intended purpose and is structured to support implementation; engage implementation staff on the ground and focus early and often on processes for supporting people through change. Conclusion The lessons learned can guide others working with existing programs to develop standardized program models or translate new science and theory into practice.

Selon une enquete 2019 du BTPST menee aupres de 35 grutiers, l’accessibilite a des toilettes est un probleme prioritaire pour la quasi-unanimite des salaries interroges. Pourtant, le sujet explore en 2015 par la MSA Ain-Rhone pour les paysagistes reste tabou, par pudeur, resignation, habitude. Il est peu aborde en entreprises, y compris par les preventeurs, alors qu’il touche a la dignite des salaries et peut avoir des repercussions sur leur sante, la securite et l’organisation des chantiers. Rappelons le principe de la pyramide de Maslow qui modelise la hierarchie entre les differents besoins humains : chaque niveau ne peut etre atteint que si les precedents le sont. Ainsi, pouvoir assouvir ses besoins physiologiques dont eliminer, constitue la condition prealable a toute mesure destinee a ameliorer la qualite de vie au travail (QVT) et donc sa realisation. Le code du travail prevoit pour le secteur du BTP les conditions de mise a disposition de WC sur les chantiers. Le grutier ne peut y acceder librement sous peine de desorganiser la bonne marche des travaux. La recommandation R 498 adoptee en 2016 par le Comite Technique National des industries du Bâtiment et des Travaux Publics, vise a ameliorer les conditions de travail dans les grues a tour et permettre aux salaries d’intervenir dans de meilleures conditions de securite et de protection de leur sante. Elle fait etat de mesures de prevention mais ne prend pas en compte cette problematique specifique. Plus de 2/3 des grutiers urinent comme ils peuvent, dans des bouteilles qu’ils transportent sur leur dos en montant et descendant de la grue. Des entreprises mettent a disposition des sacs a urine gelifiants qui ne donnent pas entiere satisfaction. Le besoin de defequer est oublie. Les enjeux sont pourtant majeurs : – Sante et securite des salaries : douleur abdominale, retention urinaire et/ou fecale volontaire, limitation de l’hydratation, hygiene defectueuse – Performance globale de l’entreprise : productivite et securite affectees pour les grutiers mis en situation d’inconfort pouvant nuire a l’attention soutenue necessaire a la bonne execution de leur travail ; QVT, image de l’entreprise ; exclusion de facto des femmes de la profession. Cette question doit donc sortir de l’ombre, etre prise en compte de facon systematique dans l’organisation des chantiers : integration de toilettes aux cabines par les fabricants de grues, occasion d’echanger sur le contenu du travail reel en CSE, mise a disposition systematique de toilettes seches portatives…Ces actions concretes de prevention primaire visant a ameliorer les conditions de travail, atout inconteste de performance, articulent les problematiques individuelles et collectives.

This cohort study examines the association between parental socioeconomic status measures and brain volume and cortical features among fetuses., Key Points Question Is parental socioeconomic status associated with fetal brain development? Findings In this cohort study of 144 healthy pregnant women and their fetuses, low parental socioeconomic status was associated with decreased regional fetal brain tissue volume and increased brain gyrification. Meaning This cohort study found that parental socioeconomic status was associated with altered fetal brain morphology as measured by quantitative magnetic resonance imaging techniques, which may serve as an early biomarker associated with childhood neurodevelopmental disorders., Importance Children raised in settings with lower parental socioeconomic status are at increased risk for neuropsychological disorders. However, to date, the association between socioeconomic status and fetal brain development remains poorly understood. Objective To determine the association between parental socioeconomic status and in vivo fetal brain growth and cerebral cortical development using advanced, 3-dimensional fetal magnetic resonance imaging. Design, Setting, and Participants This cohort study of fetal brain development enrolled 144 healthy pregnant women from 2 low-risk community obstetrical hospitals from 2012 through 2019 in the District of Columbia. Included women had a prenatal history without complications that included recommended screening laboratory and ultrasound studies. Exclusion criteria were multiple gestation pregnancy, known or suspected congenital infection, dysmorphic features of the fetus, and documented chromosomal abnormalities. T2-weighted fetal brain magnetic resonance images were acquired. Each pregnant woman was scanned at up to 2 points in the fetal period. Data were analyzed from June through November 2020. Exposures Parental education level and occupation status were documented. Main Outcomes and Measures Regional fetal brain tissue volume (for cortical gray matter, white matter, cerebellum, deep gray matter, and brainstem) and cerebral cortical features (ie, lobe volume, local gyrification index, and sulcal depth) in the frontal, parietal, temporal, and occipital lobes were calculated. Results Fetal brain magnetic resonance imaging studies were performed among 144 pregnant women (median [interquartile range] age, 32.5 [27.0-36.1] years) with gestational age from 24.0 to 39.4 weeks; 75 fetuses (52.1%) were male, and 69 fetuses (47.9%) were female. Higher parental education level was associated with significantly increased volume in the fetal white matter (mothers: β, 2.86; 95% CI, 1.26 to 4.45; P = .001; fathers: β, 2.39; 95% CI, 0.97 to 3.81; P = .001), deep gray matter (mothers: β, 0.16; 95% CI, 0.002 to 0.32; P = .048; fathers: β, 0.16; 95% CI, 0.02 to 0.31; P = .02), and brainstem (mothers: β, 0.06; 95% CI, 0.02 to 0.10; P = .01; fathers: β, 0.04; 95% CI, 0.004 to 0.08; P = .03). Higher maternal occupation status was associated with significantly increased volume in the fetal white matter (β, 2.07; 95% CI, 0.88 to 3.26; P = .001), cerebellum (β, 0.17; 95% CI, 0.04 to 0.29; P = .01), and brainstem (β, 0.03; 95% CI, 0.001 to 0.07; P = .04), and higher paternal occupation status was associated with significantly increased white matter volume (β, 1.98; 95% CI, 0.71 to 3.25; P

Importance Maternal psychological distress during pregnancy is associated with adverse obstetric outcomes and neuropsychiatric deficits in children. Currently unavailable in vivo interrogation of fetal brain function could provide critical insights into the onset and timing of altered neurodevelopmental trajectories. Objective To investigate the association between prenatal maternal stress, anxiety, and depression and in vivo fetal brain resting state functional connectivity. Design, Setting, and Participants This cohort study included pregnant women scanned between January 2016 and April 2019. A total of 50 pregnant women with healthy pregnancies were prospectively recruited from low-risk obstetric clinics in the Washington DC area and were scanned at Children’s National in Washington DC. Exposures Maternal stress, anxiety, and depression. Main Outcomes and Measures The association of prenatal maternal stress, anxiety, and depression with whole-brain connectivity was analyzed using multivariate distance matrix regression. Prenatal maternal stress, anxiety, and depression were assessed using the Perceived Stress Scale, Spielberger State Anxiety Inventory and Spielberger Trait Anxiety Inventory, and the Edinburgh Postnatal Depression Scale, respectively. Whole-brain connectivity was measured from 100 functionally defined regions of interest. Results This study analyzed 59 resting-state functional connectivity magnetic resonance image data sets from the fetuses (mean [SD] gestational age, 33.52 [4 weeks]) of 50 healthy pregnant women (mean [SD] age, 33.77 [5.51]). Mean (SD) scores for the questionnaires were as follows: Spielberger State Anxiety Inventory, 26.66 (6.72) (range, 20-48); Spielberger Trait Anxiety Inventory, 28.09 (6.62) (range, 20-50); Perceived Stress Scale, 9.27 (5.13) (range, 1-25); and Edinburgh Postnatal Depression Scale 3.24 (2.84) (range, 0-14). Prenatal maternal anxiety scores measured using the Spielberger Trait and State Anxiety Inventories were associated with differences in fetal connectivity (Spielberger State Anxiety Inventory: pseudo-R2 = 0.019,P = .04; Spielberger Trait Anxiety Inventory: pseudo-R2 = 0.021,P = .007). Interhemispheric connections, such as those involving the parietofrontal and occipital association cortices, were associated with reduced maternal prenatal anxiety, and those between the brainstem and sensorimotor areas were associated with higher anxiety scores. Conclusions and Relevance In this cohort study, an association was found between prenatal maternal anxiety and disturbances in fetal brain functional connectivity, suggesting altered fetal programming. Early onset of functional deviations suggests the need for more widespread screening of pregnant women for symptoms of anxiety.

Proton magnetic resonance spectroscopy (1H-MRS) of the fetal brain can be used to study emerging metabolite profiles in the developing brain. Identifying early deviations in brain metabolic profiles in high-risk fetuses may offer important adjunct clinical information to improve surveillance and management during pregnancy. Objective To investigate the normative trajectory of the fetal brain metabolites during the second half of gestation, and to determine the impact of using different Cramer-Rao Lower Bounds (CRLB) threshold on metabolite measurements using magnetic resonance spectroscopy. Study design We prospectively enrolled 219 pregnant women with normal fetal ultrasound and biometric measures. We performed a total of 331 fetal 1H-MRS studies with gestational age in the rage of 18–39 weeks with 112 of the enrolled participants scanned twice. All the spectra in this study were acquired on a GE 1.5 T scanner using long echo-time of 144 ​ms and analyzed in LCModel. Results We successfully acquired and analyzed fetal 1H-MRS with a success rate of 93%. We observed increases in total NAA, total creatine, total choline, scyllo inositol and total NAA-to-total choline ratio with advancing GA. Our results also showed faster increases in total NAA and total NAA-to-total choline ratio during the third trimester compared to the second trimester. We also observed faster increases in total choline and total NAA in female fetuses. Increasing the Cramer-Rao lower bounds threshold progressively from 100% to 40%–20% increased the mean metabolite concentrations and decreased the number of observations available for analysis. Conclusion We report serial fetal brain biochemical profiles in a large cohort of health fetuses studied twice in gestation with a high success rate in the second and third trimester of pregnancy. We present normative in-vivo fetal brain metabolite trajectories over a 21-week gestational period which can be used to non-invasively measure and monitor brain biochemistry in the healthy and high-risk fetus.

International audience; The neuronal population of the subthalamic nucleus (STN) has the ability to prolong incoming cort-ical excitation. This could result from intra-STN feedback excitation. The combination of inducible genetic fate mapping techniques with in vitro targeted patch-clamp recordings, allowed identifying a new type of STN neurons that possess a highly collateralized intrinsic axon. The time window of birth dates was found to be narrow (E10.5-E14.5) with very few STN neurons born at E10.5 or E14.5. The fate mapped E11.5-12.5 STN neuronal population included 20% of neurons with profuse axonal branching inside the nucleus and a dendritic arbor that differed from that of STN neurons without local axon collaterals. They had intrinsic electrophysiological properties and in particular, the ability to generate plateau potentials, similar to that of STN neurons without local axon collaterals and more generally to that of classically described STN neurons. This suggests that a subpopulation of STN neurons forms a local glutamatergic network, which together with plateau potentials, allow amplification of hyperdirect cortical inputs and synchronization of the STN neuronal population.

L’idee de ce travail part du constat de nombreuses situations de travail adverses en lien avec des erreurs de conception ou d’amenagement qui compliquent la vie des operateurs et generent troubles musculosquelettiques, accidents de travail. Les entreprises, en constante evolution, conduisent des projets de differentes natures et enjeux : d’un changement de machine a la construction d’un nouveau bâtiment. La reussite des projets d’amenagements de locaux ou d’investissements passe par l’integration des besoins en sante securite des la conception. L’objectif de l’accompagnement est la fluidite dans la realisation de la production. C’est une action de prevention primaire qui interroge le travail reel. L’employeur dans son role de maitre d’ouvrage valide la presence des operateurs autant que necessaire a chaque phase du projet. Methode Apres une premiere journee d’observation, le chef d’entreprise recoit une proposition d’intervention. L’ergonome et les preventeurs : medecin du travail, conseiller en prevention, au cote du maitre d’ouvrage, utilisent la methode d’instruction a chaque phase du projet. Ils accompagnent pour la mise en mots des besoins et la transcription sur des documents adaptes a chacune des cinq phases du projet : – la phase d’intention aboutit a la redaction d’un etat des lieux qui aide le chef d’entreprise a identifier les atouts et les faiblesses de son projet d’investissement ; – la phase de programmation aboutit a la redaction d’un cahier des charges qui recense les besoins en termes de circulation des engins, des personnes, des animaux autour et dans le futur bâtiment, les flux entrants, les flux sortants, les modalites d’entretien et de reparation du materiel. Le cahier des charges, ainsi etabli, permet la transmission des exigences claires et precises a la maitrise d’œuvre ; – la phase de conception permet d’aider a valider les plans sur la base de simulations prenant en compte les besoins formalises au depart ; – la phase de realisation permet le reperage des phases cles essentielles lors de la progression du chantier et prepare la reception des travaux ; – la phase de rodage est une observation du demarrage du travail pour les derniers ajustements avant la mise en route. Resultats et conclusions Depuis trois ans, les vingt et un projets accompagnes ont permis la mise en place de conditions de travail favorables. Le maitre d’ouvrage ayant vecu l’experience de cet accompagnement devient temoin aupres des professionnels de sa filiere. L’experience de cette methode de conduite de projet induit des changements de comportements de l’employeur pour des projets ulterieurs et change le positionnement des operateurs qui voient leur contribution a la reussite du projet.

L’EP (epuisement professionnel) interroge les professionnels de sante. La MSA Ain-Rhone a mis en place et finance un protocole d’accompagnement avec intervention d’un PT (psychologue du travail). Methode Les MT (medecins du travail) incluent les salaries en EP apres realisation d’un test d’inventaire du Burnout (MBI) et identification d’indicateurs listes dans le protocole. Le PT realise des entretiens individuels et participe a une rencontre conjointe de l’employeur avec le MT et le SI (salarie inclus) si le retour dans l’entreprise est envisage. Une plaquette « Prevenir l’epuisement professionnel » a ete realisee et est transmise aux SI et aux employeurs. Le SI est acteur de son accompagnement : il contacte le PT, declenche les examens de pre-reprise necessaires, sollicite son employeur pour organiser la rencontre. Le PT accompagne le SI dans la reconstruction de son identite professionnelle pour lui permettre d’etablir un nouvel equilibre entre sa vie professionnelle et sa vie privee dans le temps contraint de 5 a 7 seances (si pas de rencontre de l’employeur). Le but de la rencontre avec l’employeur est de favoriser le retour dans l’emploi du SI et d’informer plus largement l’employeur sur les signes d’alerte et la prevention de l’EP. Resultats de la premiere annee d’inclusion En 1 an, 22 salaries ont ete inclus dont 18 femmes, l’âge moyen est de 43 ans. La decision d’inclusion a ete prise dans 57 % des cas en visite a la demande, donc pour des salaries en activite. Le secteur du tertiaire (essentiellement activites financieres et d’assurance) represente 86 % des cas inclus et 27 % sont des managers. Le MBI d’inclusion est en faveur d’un EP severe a modere. Dans 86 % des cas, on identifie au moins 8 indicateurs de risque. En fin de protocole, 50 % des SI ont repris une activite professionnelle dans leur entreprise, le plus souvent a temps partiel therapeutique. La duree moyenne des arrets de travail est de 259 jours pour les cas conclus. Le protocole beneficie d’une evaluation qualitative realisee aupres des SI et des employeurs a distance de la reprise. Celle-ci est en cours et les premiers resultats sont favorables. Discussion La prise en charge collaborative MT-PT apparait comme un atout pour accompagner les salaries en EP. Acteurs de la demarche, ils retrouvent la capacite de repenser leur lien au travail, de faire des choix. La rencontre avec l’employeur est un facteur de prevention tertiaire mais aussi primaire pour le collectif de travail incluant l’employeur. Conclusion Ces premiers resultats ont valides la poursuite du protocole. L’evaluation tant quantitative que qualitative est incluse dans chaque phase du protocole. Son resultat sera mis a jour au cours des prochains mois et donc d’ici le congres.

Selon une enquete realisee par la MSA Ain-Rhone en 2015, l’accessibilite a des toilettes est une problematique prioritaire pour 80 % des paysagistes interroges. Et pourtant, le sujet est tabou et peu aborde en entreprise alors qu’il touche a la dignite des salaries et peut avoir des repercussions sur leur sante. La pyramide de Maslow modelise la hierarchie entre les differents besoins humains : chaque niveau ne peut etre atteint que si les precedents sont satisfaits. Ainsi, pouvoir assouvir ses besoins physiologiques, dont eliminer, constitue la condition prealable a toute action destinee a ameliorer la qualite de vie au travail (QVT) et donc sa bonne execution. Ni le code du travail, ni le code rural (pour les salaries affilies au regime agricole que nous suivons) ne creent d’obligation pour l’employeur en ce qui concerne la mise a disposition de toilettes en dehors des locaux de l’entreprise. Cependant, la miction sur la voie publique, pratique recurrente, est passible d’une contravention, voire peut constituer un delit d’exhibition sexuelle. Dans ce contexte, les enjeux pour l’entreprise sont majeurs. Ils concernent son image, sa productivite, et, au-dela de sa performance economique, sa performance sociale par l’attention que deploie l’employeur en vue d’ameliorer la qualite de vie au travail de ses salaries. La MSA Ain-Rhone a ainsi pris le parti de communiquer aupres des chefs d’entreprise en terme de performance globale (economique et sociale) via divers canaux : salon national Paysalia®, presse professionnelle, plaquette dediee adressee aux entreprises qui lui sont affiliees, evocation de la problematique a l’occasion de CHSCT et de visite d’entreprises. Il s’agit de passer du tabou a la prevention integree a la performance, en mettant en evidence cette problematique et en montrant qu’il est possible d’agir a divers niveaux pour la prendre en compte. Ainsi, des mesures generales a l’echelon de la filiere, une evolution du code rural sont envisageables. De plus, dans les entreprises, l’organisation et la planification des chantiers peuvent integrer l’accessibilite des toilettes a condition d’y penser en amont de leur realisation… Les salaries sont egalement en premiere ligne pour faire evoluer les mentalites.

Contexte Les risques professionnels « traditionnels » identifies dans la filiere du paysage (manutention, positions contraignantes, vibrations…) sont bien documentes et font deja l’objet de mesures de prevention adaptees. Notre etude se positionne en amont de cette evaluation. Elle prend en compte les caracteristiques communes aux differents chantiers (entretien, creation, elagage) et impliquees par un travail nomade, en exterieur, en milieu urbain ou periurbain le plus souvent. En effet, les besoins physiologiques fondamentaux d’uriner et de defequer sont loin d’etre pris en compte habituellement dans l’organisation des chantiers du paysage. C’est pourtant une base inalienable a la satisfaction de toute autre exigence selon la theorie des besoins, explicitee par la Pyramide de Maslow ! Etude L’impossibilite d’acceder a des toilettes pendant des journees entieres de travail est deniee, porte a sourire ou est consideree comme une fatalite. L’objectif de notre etude est donc de demontrer que c’est une reelle problematique. La methode 91 salaries ont repondu a un questionnaire durant l’echange en consultation medicale ou en entretien infirmier sur une periode de 6 mois. Les resultats montrent que l’acces aux toilettes est un probleme plutot ou tout a fait prioritaire pour 79 % d’entre eux ! On note des pratiques : – indignes : hygiene de base compromise, mictions sur la voie publique (delit), defecation dans la benne du camion… – alarmantes : limitation volontaire de s’hydrater, retention urinaire (13 %) et fecale (36 %) necessaire et frequente… Les consequences sur la sante et la securite sont reelles : – constipation ou douleur abdominale (14 %) ; – troubles de la concentration favorisant les risques sur le chantier et sur la route par la necessite de trouver des toilettes en urgence… Perspectives L’interet de cette etude est d’apporter des arguments quantitatifs et qualitatifs aux entreprises du paysage afin d’ouvrir le dialogue entre decideurs et ouvriers pour la prise en compte de cette problematique. En l’absence d’une legislation adaptee (code du travail et code rural) ou d’accords de branche, des solutions propres aux activites pourront etre experimentees : – organiser et prevoir des moyens sur place (toilettes chimiques ou seches…) ; – permettre d’acceder a des WC exterieurs : localisation des toilettes les plus proches des la conception des chantiers, couverture en AT si accident au cours du deplacement necessaire, financement des frais… Conclusion La prise en compte des besoins physiologiques des travailleurs est une composante oubliee et pourtant fondamentale de la qualite de vie au travail, s’integrant de fait au souci de performance globale de l’entreprise, tant economique que sociale.

M.H. est embauche en 2001,a 36 ans, comme ouvrier paysagiste. Une hospitalisation, 4 ans plus tard, revele une psychose ancienne justifiant la prise de neuroleptiques. La vie professionnelle de M.H est emaillee de nombreux arrets (AT, maladie) indicateurs de moments critiques. Il rencontre 5 medecins du travail differents et 2 internes au gre des reorganisations du service de sante au travail. En 2010, la RQTH est obtenue, l’utilisation des machines dangereuses est contre-indiquee. Mais en 2012, la prise en charge s’egare : une surdite va accaparer l’attention car presentee par le salarie comme responsable exclusive de difficultes professionnelles (incomprehension des consignes, prises de risques objet d’une alerte du CHSCT et de l’employeur…). Pourtant 18 mois plus tard, rien ne va plus malgre le port d’appareils auditifs (apres aide financiere de l’AGEFIPH). Ses collegues refusent de travailler avec lui. Il est au bord du licenciement pour faute. Il signale un mal etre au travail. Les arrets se multiplient. En 2014, une prestation ponctuelle specifique du handicap psychique est prescrite par le SAMETH. Debut 2015, une reunion est organisee avec M.H., son employeur, sa curatrice, la psychologue de l’ADAPT (association pour l’insertion sociale et professionnelle des personnes handicapees), le conseiller du SAMETH et le medecin du travail. Apres l’accord du medecin conseil pour la mise en place d’une invalidite partielle, une reduction du temps de travail et une revision profonde des missions sont mises en place. Depuis l’employeur et le salarie sont satisfaits malgre la perte des appareils auditifs depuis plus de 6 mois ! Cette histoire met en evidence des points d’alerte : repetition d’arrets a des moments critiques, invisibilite du handicap psychique souvent cache par le salarie,role d’alerte du CHSCT et de l’employeur, expression par le salarie d’un mal etre au travail. Elle permet de cibler : – des leviers : obligation d’emploi pour les entreprises de plus de 20 salaries, necessite d’une bonne connaissance des dispositifs et des partenaires par le medecin du travail, role du SAMETH et aides financieres de l’AGEFIPH, implication du salarie et de l’employeur… – des freins : maintien dans l’emploi chronophage, multiplicite des intervenants et de dispositifs complexes, instabilite des equipes de medecins du travail, particularites du handicap psychiques et du polyhandicap, remise en question de l’organisation du travail… De facon plus generale, on peut rappeler que la meilleure facon de favoriser l’employabilite reste la prevention primaire voire secondaire, qui permet la mise en place de mesures collectives et individuelles de lutte contre la penibilite au travail, les TMS et les RPS, en particulier.

The classic zigzagged chain structure of orthorhombic plumbocene, [Pb(η-C 5 H 5 ) 2 ] ∞ , is obtained by crystal growth from the vapour phase; however, crystallisation from toluene results in modification of the conformation of the polymer chain, as observed in the solvate [Pb(η-C 5 H 5 )·C 6 H 5 Me ] ∞ 1, and cyclisation into hexamers, as seen in the new hexagonal phase [Pb(η-C 5 H 5 ) 2 ] 6 2.