Reduced dorsal fronto-striatal connectivity at rest in anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a serious psychiatric illness that remains difficult to treat. Elucidating the neural mechanisms of AN is necessary to identify novel treatment targets and improve outcomes. A growing body of literature points to a role for dorsal fronto-striatal circuitry in the pathophysiology of AN, with increasing evidence of abnormal task-based fMRI activation within this network among patients with AN. Whether these abnormalities are present at rest and reflect fundamental differences in brain organization is unclear. METHODS: The current study combined resting-state fMRI data from patients with AN (n = 89) and healthy controls (HC; n = 92) across four studies, removing site effects using ComBat harmonization. First, the a priori hypothesis that dorsal fronto-striatal connectivity strength - specifically between the anterior caudate and dlPFC - differed between patients and HC was tested using seed-based functional connectivity analysis with small-volume correction. To assess specificity of effects, exploratory analyses examined anterior caudate whole-brain connectivity, amplitude of low-frequency fluctuations (ALFF), and node centrality. RESULTS: Compared to HC, patients showed significantly reduced right, but not left, anterior caudate-dlPFC connectivity (p = 0.002) in small-volume corrected analyses. Whole-brain analyses also identified reduced connectivity between the right anterior caudate and left superior frontal and middle frontal gyri (p = 0.028) and increased connectivity between the right anterior caudate and right occipital cortex (p = 0.038). No group differences were found in analyses of anterior caudate ALFF and node centrality. CONCLUSIONS: Decreased coupling of dorsal fronto-striatal regions indicates that circuit-based abnormalities persist at rest and suggests this network may be a potential treatment target.

Dentate Gyrus Microstructure Is Associated With Resilience After Exposure to Maternal Stress Across Two Human Cohorts.

BACKGROUND: Maternal stress (MS) is a well-documented risk factor for impaired emotional development in offspring. Rodent models implicate the dentate gyrus (DG) of the hippocampus in the effects of MS on offspring depressive-like behaviors, but mechanisms in humans remain unclear. Here, we tested whether MS was associated with depressive symptoms and DG micro- and macrostructural alterations in offspring across 2 independent cohorts. METHODS: We analyzed DG diffusion tensor imaging-derived mean diffusivity (DG-MD) and volume in a three-generation family risk for depression study (TGS; n = 69, mean age = 35.0 years) and in the Adolescent Brain Cognitive Development (ABCD) Study (n = 5196, mean age = 9.9 years) using generalized estimating equation models and mediation analysis. MS was assessed by the Parenting Stress Index (TGS) and a measure compiled from the Adult Response Survey from the ABCD Study. The Patient Health Questionnaire-9 and rumination scales (TGS) and the Child Behavior Checklist (ABCD Study) measured offspring depressive symptoms at follow-up. The Schedule for Affective Disorders and Schizophrenia-Lifetime interview was used to assign depression diagnoses. RESULTS: Across cohorts, MS was associated with future symptoms and higher DG-MD (indicating disrupted microstructure) in offspring. Higher DG-MD was associated with higher symptom scores measured 5 years (in the TGS) and 1 year (in the ABCD Study) after magnetic resonance imaging. In the ABCD Study, DG-MD was increased in high-MS offspring who had depressive symptoms at follow-up, but not in offspring who remained resilient or whose mother had low MS. CONCLUSIONS: Converging results across 2 independent samples extend previous rodent studies and suggest a role for the DG in exposure to MS and offspring depression.

Maternal childhood maltreatment: associations to offspring brain volume and white matter connectivity.

The deleterious effects of adversity are likely intergenerational, such that one generation's adverse experiences can affect the next. Epidemiological studies link maternal adversity to offspring depression and anxiety, possibly via transmission mechanisms that influence offspring fronto-limbic connectivity. However, studies have not thoroughly disassociated postnatal exposure effects nor considered the role of offspring sex. We utilized infant neuroimaging to test the hypothesis that maternal childhood maltreatment (CM) would be associated with increased fronto-limbic connectivity in infancy and tested brain-behavior associations in childhood. Ninety-two dyads participated (32 mothers with CM, 60 without; 52 infant females, 40 infant males). Women reported on their experiences of CM and non-sedated sleeping infants underwent MRIs at 2.44 ± 2.74 weeks. Brain volumes were estimated via structural MRI and white matter structural connectivity (fiber counts) via diffusion MRI with probabilistic tractography. A subset of parents (n = 36) reported on children's behaviors at age 5.17 ± 1.73 years. Males in the maltreatment group demonstrated greater intra-hemispheric fronto-limbic connectivity (b = 0.96, p= 0.008, [95%CI 0.25, 1.66]), no differences emerged for females. Fronto-limbic connectivity was related to somatic complaints in childhood only for males (r = 0.673, p = 0.006). Our findings suggest that CM could have intergenerational associations to offspring brain development, yet mechanistic studies are needed.

Managing cholesteatomas with labyrinthine fistula.

Introduction: A retrospective study (2011 to 2018) was conducted to evaluate the management of cholesteatomas with labyrinthine fistulae (LFs), clinical characteristics and postoperative hearing outcomes in a hospital. Methods: Demographic data of patients with primary middle ear mastoidectomies for cholesteatoma were extracted. Preoperative high-resolution computed tomography (HRCT) temporal bone and intraoperative findings, and hearing levels preoperatively and postoperatively were evaluated. Results: Of the middle ear cholesteatomas, 15.6% (n = 14) of ears were complicated by LF. HRCT scans showed 92.9% sensitivity and 94.7% specificity in the identification of LFs. Intraoperative findings of LFs include stapes erosion (78.6%), malleus erosion (78.6%), incus erosion (92.9%), dehiscence of tegmen tympani (28.6%) and tympanic facial canal (64.3%). Compared to the non-LF group, the LF group showed significantly higher incidence of stapes erosion (P < 0.001), tegmen tympani dehiscence (P = 0.016) and semicircular canal dehiscence (P < 0.001). Matrix was removed completely in 85.7% (n = 12) and was left behind in 14.3% (n = 2) of ears. Also, 21.5% (n = 3) had preoperative dead ears. Postoperative hearing results had a mean follow-up time of 2.1 (standard deviation 1.5, range 0.14-4.84) years. In the matrix removal group (n = 9), 77.9% had unchanged hearing levels, 11.1% showed improvement and 11.1% showed decrease in hearing levels. The matrix preservation group (n = 2) had deteriorated hearing levels. Conclusion: Preservation of hearing in LFs is possible with cautious matrix removal. Despite matrix preservation to preserve hearing in large LFs, our patients' hearing deteriorated postoperatively. Longer follow-up of hearing with matrix preservation may show poorer hearing outcomes.

Management and Outcomes of Pediatric Craniopharyngioma: A 15-Year Experience in Singapore.

BACKGROUND: Craniopharyngiomas arise from the Rathke pouch and account for 1.2%-18.4% of pediatric primary brain tumors. Despite relatively good survival outcomes, patients face long-term morbidity from recurrences, visual impairment, and endocrinopathies, which reduce quality of life. We examined the management of pediatric craniopharyngiomas, their recurrences, and subsequent neuroendocrine sequelae in a tertiary center in South-East Asia. METHODS: A retrospective cohort of 12 paediatric patients (aged ≤18 years) with histologically confirmed diagnosis of craniopharyngioma treated from January 2002 to June 2017 was conducted. Data collected included demographics, clinical presentation, imaging data, treatment details, postoperative sequelae, and outcomes on mortality and recurrence. Survival analysis was conducted using Cox-proportional hazards model. RESULTS: The median follow-up time was 6.60 years (1.9-11.5 years). The mean age was 7.6 years (standard deviation 4.8) and 7 patients (58.3%) were male. The most common presenting symptoms were raised intracranial pressure (7, 58.3%), visual deficits (6, 50.0%), and preoperative endocrine abnormalities (2, 16.7%). Five patients underwent gross total resection (41.7%), and 7 underwent subtotal resection (58.3%). Overall survival was 75.0% (9 patients), and recurrence was 58.0% (7 patients). Median time-to-recurrence was 5.87 months (0.23-33.7, interquartile range 15.8), and median progression-free survival was 4.16 years (0.18-10.1, interquartile range 5.29). CONCLUSIONS: Long-term management of pediatric craniopharyngioma remains difficult, with multiple recurrences and long-term neuroendocrine sequelae impairing quality of life for patients. Further research into management of recurrences and neuroendocrine sequelae, as well as novel therapies to improve outcomes in these patients, may be warranted.

Large-Scale Exploration of Whole-Brain Structural Connectivity in Anorexia Nervosa: Alterations in the Connectivity of Frontal and Subcortical Networks.

BACKGROUND: Anorexia nervosa (AN) is characterized by disturbances in cognition and behavior surrounding eating and weight. The severity of AN combined with the absence of localized brain abnormalities suggests distributed, systemic underpinnings that may be identified using diffusion-weighted magnetic resonance imaging and tractography to reconstruct white matter pathways. METHODS: Diffusion-weighted magnetic resonance imaging data acquired from female patients with AN (n= 147) and female healthy control (HC) participants (n = 119), ages 12 to 40 years, were combined across 5 studies. Probabilistic tractography was completed, and full-cortex connectomes describing streamline counts between 84 brain regions were generated and harmonized. Graph theory methods were used to describe alterations in network organization in AN. The network-based statistic tested between-group differences in brain subnetwork connectivity. The metrics strength and efficiency indexed the connectivity of brain regions (network nodes) and were compared between groups using multiple linear regression. RESULTS: Individuals with AN, relative to HC peers, had reduced connectivity in a network comprising subcortical regions and greater connectivity between frontal cortical regions (p < .05, familywise error corrected). Node-based analyses indicated reduced connectivity of the left hippocampus in patients relative to HC peers (p < .05, permutation corrected). Severity of illness, assessed by body mass index, was associated with subcortical connectivity (p < .05, uncorrected). CONCLUSIONS: Analyses identified reduced structural connectivity of subcortical networks and regions, and stronger cortical network connectivity, among individuals with AN relative to HC peers. These findings are consistent with alterations in feeding, emotion, and executive control circuits in AN, and may direct hypothesis-driven research into mechanisms of persistent restrictive eating behavior.

PTNet3D: A 3D High-Resolution Longitudinal Infant Brain MRI Synthesizer Based on Transformers.

An increased interest in longitudinal neurodevelopment during the first few years after birth has emerged in recent years. Noninvasive magnetic resonance imaging (MRI) can provide crucial information about the development of brain structures in the early months of life. Despite the success of MRI collections and analysis for adults, it remains a challenge for researchers to collect high-quality multimodal MRIs from developing infant brains because of their irregular sleep pattern, limited attention, inability to follow instructions to stay still during scanning. In addition, there are limited analytic approaches available. These challenges often lead to a significant reduction of usable MRI scans and pose a problem for modeling neurodevelopmental trajectories. Researchers have explored solving this problem by synthesizing realistic MRIs to replace corrupted ones. Among synthesis methods, the convolutional neural network-based (CNN-based) generative adversarial networks (GANs) have demonstrated promising performance. In this study, we introduced a novel 3D MRI synthesis framework- pyramid transformer network (PTNet3D)- which relies on attention mechanisms through transformer and performer layers. We conducted extensive experiments on high-resolution Developing Human Connectome Project (dHCP) and longitudinal Baby Connectome Project (BCP) datasets. Compared with CNN-based GANs, PTNet3D consistently shows superior synthesis accuracy and superior generalization on two independent, large-scale infant brain MRI datasets. Notably, we demonstrate that PTNet3D synthesized more realistic scans than CNN-based models when the input is from multi-age subjects. Potential applications of PTNet3D include synthesizing corrupted or missing images. By replacing corrupted scans with synthesized ones, we observed significant improvement in infant whole brain segmentation.

Paediatric brain tumours in Singapore: A 15-year epidemiological and outcome study.

Paediatric brain tumours (PBTs) are the most common solid tumours in children. Previous publications reflect variations in incidence rates and frequency of histological types in different global populations. However, there are limited studies on the epidemiology of PBTs in Singapore. This study aims to summarise the epidemiology of paediatric brain tumours managed in Singapore. This is an ethics-approved retrospective study of all patients below 19 years old diagnosed with PBTs managed by Singapore's 2 tertiary paediatric neurosurgical centres, KK Women's and Children's Hospital (KKH) and the National University Hospital (NUH) over a 15-year period from 01 January 2002 to 31 December 2017. Data collected was analysed for age, gender, tumour characteristics, presenting complaints, location, treatment modalities, 1-year and 5-year overall survival (OS). A total of 396 patients were included. The mean age of diagnosis was 7.05 years (0.25-18; ± 4.83) and male-to-female ratio was 1.41:1. Top histological groups were astrocytic (30.6%), embryonal (26.0%), germ cell (11.1%), ependymoma (30, 7.58%) and craniopharyngioma (27, 6.82%). Outcomes included recurrence rate (31.2%), 1-year OS (89.5%) and 5-year OS (72.2%). Poorer 5-year OS were noted in embryonal tumours (47.0%; p < 0.001) and ependymoma (50.0%; p = 0.0074) patients. Of note, the following cohorts also had poorer OS at 5 years: supratentorial tumours (76.2%; p = 0.0426), radiotherapy (67.4%; p = 0.0467) and surgery (74.9%, HR; p < 0.001). Overall, our data reflects patient demographics, presenting complaints, treatment modalities and survival outcomes, that are comparable to other international paediatric neurosurgical centres.

ID-Seg: an infant deep learning-based segmentation framework to improve limbic structure estimates.

Infant brain magnetic resonance imaging (MRI) is a promising approach for studying early neurodevelopment. However, segmenting small regions such as limbic structures is challenging due to their low inter-regional contrast and high curvature. MRI studies of the adult brain have successfully applied deep learning techniques to segment limbic structures, and similar deep learning models are being leveraged for infant studies. However, these deep learning-based infant MRI segmentation models have generally been derived from small datasets, and may suffer from generalization problems. Moreover, the accuracy of segmentations derived from these deep learning models relative to more standard Expectation-Maximization approaches has not been characterized. To address these challenges, we leveraged a large, public infant MRI dataset (n = 473) and the transfer-learning technique to first pre-train a deep convolutional neural network model on two limbic structures: amygdala and hippocampus. Then we used a leave-one-out cross-validation strategy to fine-tune the pre-trained model and evaluated it separately on two independent datasets with manual labels. We term this new approach the Infant Deep learning SEGmentation Framework (ID-Seg). ID-Seg performed well on both datasets with a mean dice similarity score (DSC) of 0.87, a mean intra-class correlation (ICC) of 0.93, and a mean average surface distance (ASD) of 0.31 mm. Compared to the Developmental Human Connectome pipeline (dHCP) pipeline, ID-Seg significantly improved segmentation accuracy. In a third infant MRI dataset (n = 50), we used ID-Seg and dHCP separately to estimate amygdala and hippocampus volumes and shapes. The estimates derived from ID-seg, relative to those from the dHCP, showed stronger associations with behavioral problems assessed in these infants at age 2. In sum, ID-Seg consistently performed well on two different datasets with an 0.87 DSC, however, multi-site testing and extension for brain regions beyond the amygdala and hippocampus are still needed.

Impact of pain sensitisation on the quality of life of patients with knee osteoarthritis.

OBJECTIVES: We aim to evaluate the effect on different ways of classifying pain sensitisation on impact and quality of life (QoL) in knee osteoarthritis (KOA). METHODS: We used baseline data from a cohort of consecutive patients with KOA listed for arthroplasty. We collected demographics and number of painful body sites. We measured pressure pain thresholds at the right forearm (PPTarm). Pain sensitisation was classified using: (1) widespread pain, (2) lowest 10th percentile of PPTarm and (3) PainDETECT questionnaire ≥13/38. Impact and QoL were assessed using Western Ontario and McMaster Universities Osteoarthritis Index and Short Form-36. Impact and QoL scores in patients with or without pain sensitisation were compared. We evaluated the association of pain sensitisation measures with QoL scores using multivariable regression. RESULTS: 233 patients (80% female, mean age 66 years) included in the analysis; 7.3%, 11.6% and 4.7% were classified as having pain sensitisation by widespread pain, low PPTarm and PainDETECT criteria, respectively. There was minimal overlap of patients as classified as pain sensitisation phenotype by different measures. Patients with pain sensitisation had poorer QoL compared with those without. Low PPTarm identified patients with poorer general health, while widespread pain and PainDETECT identified poorer QoL in more psychological domains. There was weak correlation between number of painful body sites and PainDETECT (rho=0.23, p<0.01), but no significant correlation with PPTarm. CONCLUSION: Patients with KOA with pain sensitisation have poorer QoL compared with those without, regardless of classification method. Different criteria defined patients with different pattern of QoL impact.

Maturity of gray matter structures and white matter connectomes, and their relationship with psychiatric symptoms in youth.

Brain predicted age difference, or BrainPAD, compares chronological age to an age estimate derived by applying machine learning (ML) to MRI brain data. BrainPAD studies in youth have been relatively limited, often using only a single MRI modality or a single ML algorithm. Here, we use multimodal MRI with a stacked ensemble ML approach that iteratively applies several ML algorithms (AutoML). Eligible participants in the Healthy Brain Network (N = 489) were split into training and test sets. Morphometry estimates, white matter connectomes, or both were entered into AutoML to develop BrainPAD models. The best model was then applied to a held-out evaluation dataset, and associations with psychometrics were estimated. Models using morphometry and connectomes together had a mean absolute error of 1.18 years, outperforming models using a single MRI modality. Lower BrainPAD values were associated with more symptoms on the CBCL (pcorr  = .012) and lower functioning on the Children's Global Assessment Scale (pcorr  = .012). Higher BrainPAD values were associated with better performance on the Flanker task (pcorr  = .008). Brain age prediction was more accurate using ComBat-harmonized brain data (MAE = 0.26). Associations with psychometric measures remained consistent after ComBat harmonization, though only the association with CGAS reached statistical significance in the reduced sample. Our findings suggest that BrainPAD scores derived from unharmonized multimodal MRI data using an ensemble ML approach may offer a clinically relevant indicator of psychiatric and cognitive functioning in youth.

Impact of time to resumption of antithrombotic therapy on outcomes after surgical evacuation of chronic subdural hematoma: A multicenter cohort study.

BACKGROUND: The decision to resume antithrombotic therapy after surgical evacuation of chronic subdural hematoma (CSDH) requires judicious weighing of the risk of bleeding against that of thromboembolism. This study aimed to investigate the impact of time to resumption of antithrombotic therapy on outcomes of patients after CSDH drainage. METHODS: Data were obtained retrospectively from three tertiary hospitals in Singapore from 2010 to 2017. Outcome measures analyzed were CSDH recurrence and any thromboembolic events. Logistic and Cox regression tests were used to identify associations between time to resumption and outcomes. RESULTS: A total of 621 patients underwent 761 CSDH surgeries. Preoperative antithrombotic therapy was used in 139 patients. 110 (79.1%) were on antiplatelets and 35 (25.2%) were on anticoagulants, with six patients (4.3%) being on both antiplatelet and anticoagulant therapy. Antithrombotic therapy was resumed in 84 patients (60.4%) after the surgery. Median time to resumption was 71 days (IQR 29 - 201). Recurrence requiring reoperation occurred in 15 patients (10.8%), of which 12 had recurrence before and three after resumption. Median time to recurrence was 35 days (IQR 27 - 47, range 4 - 82 days). Recurrence rates were similar between patients that were restarted on antithrombotic therapy before and after 14, 21, 28, 42, 56, 70 and 84 days, respectively. Thromboembolic events occurred in 12 patients (8.6%), of which five had the event prior to restarting antithrombosis. CONCLUSIONS: Time to antithrombotic resumption did not significantly affect CSDH recurrence. Early resumption of antithrombotic therapy can be safe for patients with a high thromboembolic risk.

Altered Dentate Gyrus Microstructure in Individuals at High Familial Risk for Depression Predicts Future Symptoms.

BACKGROUND: Offspring of individuals with major depressive disorder (MDD) are at increased risk for developing MDD themselves. Altered hippocampal, and specifically dentate gyrus (DG), structure and function may be involved in depression development. However, hippocampal abnormalities could also be a consequence of the disease. For the first time, we tested whether abnormal DG micro- and macrostructure were present in offspring of individuals with MDD and whether these abnormalities predicted future symptomatology. METHODS: We measured the mean diffusivity of gray matter, a measure of microstructure, via diffusion tensor imaging and volume of the DG via structural magnetic resonance imaging in 102 generation 2 and generation 3 offspring at high and low risk for depression, defined by the presence or absence, respectively, of moderate to severe MDD in generation 1. Prior, current, and future depressive symptoms were tested for association with hippocampal structure. RESULTS: DG mean diffusivity was higher in individuals at high risk for depression, regardless of a lifetime history of MDD. While DG mean diffusivity was not associated with past or current depressive symptoms, higher mean diffusivity predicted higher symptom scores 8 years later. DG microstructure partially mediated the association between risk and future symptoms. DG volume was smaller in high-risk generation 2 but not in high-risk generation 3. CONCLUSIONS: Together, these findings suggest that the DG has a role in the development of depression. Furthermore, DG microstructure, more than macrostructure, is a sensitive risk marker for depression and partially mediates future depressive symptoms.

Concordance in parent and offspring cortico-basal ganglia white matter connectivity varies by parental history of major depressive disorder and early parental care.

Social behavior is transmitted cross-generationally through coordinated behavior within attachment bonds. Parental depression and poor parental care are major risks for disruptions of such coordination and are associated with offspring's psychopathology and interpersonal dysfunction. Given the key role of the cortico-basal ganglia (CBG) circuits in social communication, we examined similarities (concordance) of parent-offspring CBG white matter (WM) connections and how parental history of major depressive disorder (MDD) and early parental care moderate these similarities. We imaged 44 parent-offspring dyads and investigated WM connections between basal-ganglia seeds and selected regions in temporal cortex using diffusion tensor imaging (DTI) tractography. We found significant concordance in parent-offspring strength of CBG WM connections, moderated by parental lifetime-MDD and care. The results showed diminished neural concordance among dyads with a depressed parent and that better parental care predicted greater concordance, which also provided a protective buffer against attenuated concordance among dyads with a depressed parent. Our findings provide the first neurobiological evidence of concordance between parents-offspring in WM tracts and that concordance is diminished in families where parents have lifetime-MDD. This disruption may be a risk factor for intergenerational transmission of psychopathology. Findings emphasize the long-term role of early caregiving in shaping the neural concordance among at-risk and affected dyads.

Association of Prenatal Acetaminophen Exposure Measured in Meconium With Risk of Attention-Deficit/Hyperactivity Disorder Mediated by Frontoparietal Network Brain Connectivity.

Importance: Despite evidence of an association between prenatal acetaminophen exposure and attention-deficit/hyperactivity disorder (ADHD) in offspring, the drug is not contraindicated during pregnancy, possibly because prior studies have relied on maternal self-report, failed to quantify acetaminophen dose, and lacked mechanistic insight. Objective: To examine the association between prenatal acetaminophen exposure measured in meconium (hereinafter referred to as meconium acetaminophen) and ADHD in children aged 6 to 7 years, along with the potential for mediation by functional brain connectivity. Design, Setting, and Participants: This prospective birth cohort study from the Centre Hospitalier Université de Sherbrooke in Sherbrooke, Québec, Canada, included 394 eligible children, of whom 345 had meconium samples collected at delivery and information on ADHD diagnosis. Mothers were enrolled from September 25, 2007, to September 10, 2009, at their first prenatal care visit or delivery and were followed up when children were aged 6 to 7 years. When children were aged 9 to 11 years, resting-state brain connectivity was assessed with magnetic resonance imaging. Data for the present study were collected from September 25, 2007, to January 18, 2020, and analyzed from January 7, 2019, to January 22, 2020. Exposures: Acetaminophen levels measured in meconium. Main Outcomes and Measures: Physician diagnosis of ADHD was determined at follow-up when children were aged 6 to 7 years or from medical records. Resting-state brain connectivity was assessed with magnetic resonance imaging; attention problems and hyperactivity were assessed with the Behavioral Assessment System for Children Parent Report Scale. Associations between meconium acetaminophen levels and outcomes were estimated with linear and logistic regressions weighted on the inverse probability of treatment to account for potential confounders. Causal mediation analysis was used to test for mediation of the association between prenatal acetaminophen exposure and hyperactivity by resting-state brain connectivity. Results: Among the 345 children included in the analysis (177 boys [51.3%]; mean [SD] age, 6.58 [0.54] years), acetaminophen was detected in 199 meconium samples (57.7%), and ADHD was diagnosed in 33 children (9.6%). Compared with no acetaminophen, detection of acetaminophen in meconium was associated with increased odds of ADHD (odds ratio [OR], 2.43; 95% CI, 1.41-4.21). A dose-response association was detected; each doubling of exposure increased the odds of ADHD by 10% (OR, 1.10; 95% CI, 1.02-1.19). Children with acetaminophen detected in meconium showed increased negative connectivity between frontoparietal and default mode network nodes to clusters in the sensorimotor cortices, which mediated an indirect effect on increased child hyperactivity (14%; 95% CI, 1%-26%). Conclusions and Relevance: Together with the multitude of other cohort studies showing adverse neurodevelopment associated with prenatal acetaminophen exposure, this work suggests caution should be used in administering acetaminophen during pregnancy. Research into alternative pain management strategies for pregnant women could be beneficial.

Transparent and Flexible Electronics Assembled with Metallic Nanowire-Layered Nondrying Glycerogel.

There has been increasing demand for transparent and mechanically durable electrical conductors for their uses in wearable electronic devices. It is common to layer metallic nanowires on transparent but stiff poly(dimethylsiloxane) (PDMS) or stretchable but opaque Ecoflex-based substrates. Here, we hypothesized that layering metallic nanowires on a stretchable and hygroscopic gel would allow us to assemble a transparent, stretchable, and durable conductor. The hygroscopic property of the gel was attained by partially replacing water in the preformed polyacrylamide hydrogel with glycerol. The resulting gel, denoted as a glycerogel, could remain hydrated for over 6 months in air by taking up water molecules from the air. The glycerogel was tailored to be stretchable up to 8 times its original length by tuning the amount of the cross-linker and acrylamide. The resulting glycerogel allowed for deposition of wavy silver nanowires using the prestrain method up to 400% prestrain, without causing kinks and interfacial cracks often found with nanowires layered onto PDMS. With a prestrain of 100%, the resulting nanowire-gel conductor exhibited optical transparency (85%) and electrical conductivity (17.1 ohm/sq) even after 5000 cycles of deformation. The results of this study would broadly be useful to improve the performance of the next generation of flexible electronic devices.