Mapping the cellular biogeography of human bone marrow niches using single-cell transcriptomics and proteomic imaging.

Non-hematopoietic cells are essential contributors to hematopoiesis. However, heterogeneity and spatial organization of these cells in human bone marrow remain largely uncharacterized. We used single-cell RNA sequencing (scRNA-seq) to profile 29,325 non-hematopoietic cells and discovered nine transcriptionally distinct subtypes. We simultaneously profiled 53,417 hematopoietic cells and predicted their interactions with non-hematopoietic subsets. We employed co-detection by indexing (CODEX) to spatially profile over 1.2 million cells. We integrated scRNA-seq and CODEX data to link predicted cellular signaling with spatial proximity. Our analysis revealed a hyperoxygenated arterio-endosteal neighborhood for early myelopoiesis, and an adipocytic localization for early hematopoietic stem and progenitor cells (HSPCs). We used our CODEX atlas to annotate new images and uncovered mesenchymal stromal cell (MSC) expansion and spatial neighborhoods co-enriched for leukemic blasts and MSCs in acute myeloid leukemia (AML) patient samples. This spatially resolved, multiomic atlas of human bone marrow provides a reference for investigation of cellular interactions that drive hematopoiesis.

Electroencephalographic Correlates of Clinical Severity in the Natural history study of RTT and Related Disorders.

OBJECTIVE: This study was undertaken to characterize quantitative electroencephalographic (EEG) features in participants from the Natural history study of RTT and Related Disorders and to assess the potential for these features to act as objective measures of cortical function for Rett syndrome (RTT). METHODS: EEG amplitude and power features were derived from the resting EEG of 60 females with RTT (median age = 10.7 years) and 26 neurotypical females (median age = 10.6 years). Analyses focus on group differences and within the RTT group, associations between the EEG parameters and clinical severity. For a subset of participants (n = 20), follow-up data were available for assessing the reproducibility of the results and the stability in the parameters over 1 year. RESULTS: Compared to neurotypical participants, participants with RTT had greater amplitude variability and greater low-frequency activity as reflected by greater delta power, more negative 1/f slope, and lower theta/delta, alpha/delta, beta/delta, alpha/theta, and beta/theta ratios. Greater delta power, more negative 1/f slope, and lower power ratios were associated with greater severity. Analyses of year 1 data replicated the associations between 1/f slope and power ratios and clinical severity and demonstrated good within-subject consistency in these measures. INTERPRETATION: Overall, group comparisons reflected a greater predominance of lower versus higher frequency activity in participants with RTT, which is consistent with prior clinical interpretations of resting EEG in this population. The observed associations between the EEG power measures and clinical assessments and the repeatability of these measures underscore the potential for EEG to provide an objective measure of cortical function and clinical severity for RTT. ANN NEUROL 2024;96:175-186.

Foster care leads to sustained cognitive gains following severe early deprivation.

This study examined longitudinal data from the Bucharest Early Intervention Project, a randomized controlled trial of foster care as an alternative to institutional care following exposure to severe psychosocial deprivation. We report data from 135 participants assessed in early adulthood (age 18 y). We find that 16 y after randomization occurred, those who had been randomized to high-quality foster care had significantly higher IQ scores (9 points, 0.6 SD) than those randomized to care as usual. Mediation analyses provide evidence that the causal effect of the intervention on cognitive ability in early adulthood could be explained, in part, by higher-quality caregiving and attachment security. These findings indicate that early investment in family care as an alternative to institutional care leads to sustained gains in cognitive ability. Fostering caregiving relationships is a likely mechanism of the intervention. In addition, exploratory analyses indicate that stable placements throughout childhood are associated with the greatest long-term gains in cognitive ability. Whether early interventions for infants and young children lead to lasting change has significant implications for decisions to invest in programs aimed at improving children's developmental outcomes.

Perinatal inflammation, fetal growth restriction, and long-term neurodevelopmental impairment in Bangladesh.

BACKGROUND: There are limited data on the impact of perinatal inflammation on child neurodevelopment in low-middle income countries and among growth-restricted infants. METHODS: Population-based, prospective birth cohort study of 288 infants from July 2016-March 2017 in Sylhet, Bangladesh. Umbilical cord blood was analyzed for interleukin(IL)-1α, IL-1ß, IL-6, IL-8, and C-reactive protein(CRP). Child neurodevelopment was assessed at 24 months with Bayley-III Scales of Infant Development. We determined associations between cord blood inflammation and neurodevelopmental outcomes, controlling for potential confounders. RESULTS: 248/288 (86%) live born infants were followed until 24 months, among whom 8.9% were preterm and 45.0% small-for-gestational-age(SGA) at birth. Among all infants, elevated concentrations (>75%) of CRP and IL-6 at birth were associated with increased odds of fine motor delay at 24 months; elevated CRP was also associated with lower receptive communication z-scores. Among SGA infants, elevated IL-1α was associated with cognitive delay, IL-8 with language delay, CRP with lower receptive communication z-scores, and IL-1ß with lower expressive communication and motor z-scores. CONCLUSIONS: In rural Bangladesh, perinatal inflammation was associated with impaired neurodevelopment at 24 months. The associations were strongest among SGA infants and noted across several biomarkers and domains, supporting the neurobiological role of inflammation in adverse fetal development, particularly in the setting of fetal growth restriction. IMPACT: Cord blood inflammation was associated with fine motor and language delays at 24 months of age in a community-based cohort in rural Bangladesh. 23.4 million infants are born small-for-gestational-age (SGA) globally each year. Among SGA infants, the associations between cord blood inflammation and adverse outcomes were strong and consistent across several biomarkers and neurodevelopmental domains (cognitive, motor, language), supporting the neurobiological impact of inflammation prominent in growth-restricted infants. Prenatal interventions to prevent intrauterine growth restriction are needed in low- and middle-income countries and may also result in long-term benefits on child development.

Annual Research Review: Early intervention viewed through the lens of developmental neuroscience.

The overarching goal of this paper is to examine the efficacy of early intervention when viewed through the lens of developmental neuroscience. We begin by briefly summarizing neural development from conception through the first few postnatal years. We emphasize the role of experience during the postnatal period, and consistent with decades of research on critical periods, we argue that experience can represent both a period of opportunity and a period of vulnerability. Because plasticity is at the heart of early intervention, we next turn our attention to the efficacy of early intervention drawing from two distinct literatures: early intervention services for children growing up in disadvantaged environments, and children at elevated likelihood of developing a neurodevelopmental delay or disorder. In the case of the former, we single out interventions that target caregiving and in the case of the latter, we highlight recent work on autism. A consistent theme throughout our review is a discussion of how early intervention is embedded in the developing brain. We conclude our article by discussing the implications our review has for policy, and we then offer recommendations for future research.

Context-dependent approach and avoidance behavioral profiles as predictors of psychopathology.

Inhibition (a temperamental profile characterized by elevated levels of avoidance behaviors) is associated with increased likelihood for developing anxiety and depression, whereas exuberance (a temperamental profile characterized by elevated levels of approach behaviors) is associated with increased likelihood for developing externalizing conditions (e.g., attention deficit/hyperactivity disorder and conduct disorder). However, not all children who exhibit high levels of approach or avoidance behaviors develop emotional or behavioral problems. In this preregistered study, we assessed context-dependent profiles of approach and avoidance behaviors in 3-year-old children (N = 366). Using latent profile analysis, four groups were identified: nonsocial approachers, social approachers, social avoiders, and nonsocial avoiders. Analyses revealed that there were minimal differences in internalizing and externalizing symptoms across the four context-dependent groups. However, exploratory analyses assessed whether high levels of approach or avoidance combined across contexts, similar to findings reported in prior work, were related to psychopathology. Children identified as high in avoidance behavior at 3 years of age were more likely to show internalizing symptoms at 3 years of age but not at 5 years of age. Children high in approach were more likely to meet criteria for anxiety and externalizing disorders by age 5 years. These findings further our understanding of individual differences in how young children adjust their behavior based on contextual cues and may inform methods for identifying children at increased likelihood for the development of emotional and behavioral problems. RESEARCH HIGHLIGHTS: Context-dependent approach and avoidance profiles were identified in 3-year-old children using a person-centered approach. Children who were high in approach behavior, regardless of context, at age three had a higher likelihood for developing an anxiety or externalizing disorder by age five. These findings may help identify children at increased risk of developing emotional and behavioral problems.

Linking caregiving quality during infancy to brain activity in early childhood and later executive function.

There is no relationship more vital than the one a child shares with their primary caregivers early in development. Yet many children worldwide are raised in settings that lack the warmth, connection, and stimulation provided by a responsive primary caregiver. In this study, we used data from the Bucharest Early Intervention Project (BEIP), a longitudinal study of institutionally-reared and family-reared children, to test how caregiving quality during infancy is associated with average EEG power over the first 3.5 years of life in alpha, beta, and theta frequency bands, and associations with later executive function (EF) at age 8 years. The sample comprised 189 children (129 institutionally-reared; 60 family-reared) who contributed data on observed caregiving quality during infancy (baseline; average age of 22 months), resting EEG power at baseline, 30, and 42 months, and performance-based data on a series of EF tasks at 8 years. Using Bayesian estimation, observed caregiving quality at baseline was marginally linked with higher average alpha and beta power, and lower theta power, from baseline to 42 months. In turn, higher average beta power and lower average theta power were marginally associated with higher EF at 8 years. In indirect effects models, higher caregiving quality at baseline was associated with higher EF at 8 years, with a marginal indirect effect through average theta power from baseline to 42 months. Variation in the quality of the early caregiving environment may be associated with later executive function, which is partially underpinned by individual differences in brain activity during early childhood. RESEARCH HIGHLIGHTS: Examined associations between caregiving quality during infancy, brain activity during early childhood, and executive function during mid-childhood in sample of never-institutionalized and institutionally-reared children. Significant associations between higher quality caregiving during infancy and higher executive function during middle childhood. Marginal associations between caregiving quality during infancy and brain activity during early childhood. Marginal associations between brain activity during early childhood and executive function during mid-childhood.

Parental communicative input as a protective factor in Bangladeshi families living in poverty: A multi-dimensional perspective.

Studies from high-income populations have shown that stimulating, supportive communicative input from parents promote children's cognitive and language development. However, fewer studies have identified specific features of input supporting the healthy development of children growing up in low- or middle-income countries. The current study proposes and tests a multi-dimensional framework for understanding whether and how caregiver communicative input mediates the associations between socio-economic conditions and early development. We also examine how caregiver conceptual scaffolding and autonomy support uniquely and synergistically explain variation in child outcomes. Participants were 71 Bangladeshi families with five-year-olds who were exposed to a range of biological and psychosocial hazards from birth. Caregiver-child interactions during snack sharing and semi-structured play were coded for caregiver conceptual scaffolding, autonomy support, and child engagement. Findings indicate that the two dimensions of input were correlated, suggesting that caregivers who provided richer conceptual scaffolds were simultaneously more supportive of children's autonomy. Notably, conceptual scaffolding and autonomy support each mediated associations between maternal education and child verbal intelligence quotient (IQ) scores. Further, caregivers who supported greater autonomy in their children had children who participated in conversations more actively, and these children in turn had higher performance IQ scores. When considered simultaneously, conceptual scaffolding was associated with verbal IQ over and above autonomy support, whereas autonomy support related to child engagement, controlling for conceptual scaffolding. These findings shed new light on how environmental factors may support early development, contributing to the design of family-centered, culturally authentic interventions. A video abstract of this article can be viewed at https://youtu.be/9v_8sIv7ako RESEARCH HIGHLIGHTS: Studies from high-income countries have identified factors mitigating the impacts of socio-economic risks on development. Such research is scarce in low- and middle-income countries. The present study conceptualized and evaluated caregiver communicative input in Bangladeshi families along two interrelated yet distinct dimensions: conceptual scaffolding and autonomy support. Conceptual scaffolding and autonomy support individually mediated associations between maternal education and child verbal IQ, shedding light on protective factors in families living in poverty. Parents providing richer conceptual scaffolds were simultaneously more supportive of children's autonomy. However, the two dimensions each related to cognition and language through unique pathways.

Long-term measurement and characterization of boundary layer optical turbulence.

The United States Naval Academy long-term scintillation measurement campaign was a multi-year effort to characterize optical turbulence in the near-maritime atmospheric boundary layer (ABL). At its core, the field experiment consists of in situ measurements of bulk atmospheric and oceanographic parameters, as well as path-averaged measurements of the refractive index structure parameter, C n2, collected using a large-aperture scintillometer. The field experiment ran from January 1st, 2020, through September 26th, 2023, representing the most comprehensive collection of optical turbulence measurements in the near-maritime ABL to date. Long-term measurements enable researchers to evaluate existing theory and develop new models applicable to this environment. The present study characterizes some of the physical relationships that affect optical turbulence. This characterization focuses on the relationship between local optical turbulence and select atmospheric and oceanographic parameters. The impact of temperature gradients on the extent of optical turbulence was analyzed, along with its interactions with relative humidity and wind speed. The diurnal and seasonal variations in measured C n2 were examined, with comparisons drawn against other environments. Further information and the full dataset are publicly available through the optical turbulence benchmark repository [Jellen et al., GitHub, 2023].

Neural network classification of beams carrying orbital angular momentum after propagating through controlled experimentally generated optical turbulence.

We generate an alphabet of spatially multiplexed Laguerre-Gaussian beams carrying orbital angular momentum, which are demultiplexed at reception by a convolutional neural network (CNN). In this investigation, a methodology for optimizing alphabet design for best classification rates is proposed, and three 256-symbol alphabets are designed for performance evaluation in optical turbulence. The beams were propagated in three environments: through underwater optical turbulence generated by Rayleigh-Bénard (RB) convection (C n2≅10-11 m -2/3), through a simulated propagation path derived from the Nikishov spectrum (C n2≅10-13 m -2/3), and through optical turbulence from a thermal point source located in a water tank (C n2≅10-10 m -2/3). We report a classification accuracy of 93.1% for the RB environment, 99.99% in simulation, and 48.5% in the point source environment. The project demonstrates that the CNN can classify the complex alphabet symbols in a practical turbulent flow that exhibits strong optical turbulence, provided sufficient training data is available and testing data is representative of the specific environment. We find the most important factor in a high classification accuracy is a diversification in the intensity profiles of the alphabet symbols.

Temperament and sex as moderating factors of the effects of exposure to maternal depression on telomere length in early childhood.

Individual differences in sensitivity to context are posited to emerge early in development and to influence the effects of environmental exposures on a range of developmental outcomes. The goal of the current study was to examine the hypothesis that temperament characteristics and biological sex confer differential vulnerability to the effects of exposure to maternal depression on telomere length in early childhood. Telomere length has emerged as a potentially important biomarker of current and future health, with possible mechanistic involvement in the onset of various disease states. Participants comprised a community sample of children followed from infancy to age 3 years. Relative telomere length was assessed from DNA in saliva samples collected at infancy, 2 years, and 3 years. Maternal depressive symptoms and the child temperament traits of negative affectivity, surgency/extraversion, and regulation/effortful control were assessed via maternal report at each timepoint. Analyses revealed a 3-way interaction among surgency/extraversion, sex, and maternal depressive symptoms, such that higher surgency/extraversion was associated with shorter telomere length specifically among males exposed to elevated maternal depressive symptoms. These findings suggest that temperament and sex influence children's susceptibility to the effects of maternal depression on telomere dynamics in early life.

Examining the relationship between psychosocial adversity and inhibitory control: A functional magnetic resonance imaging study of children growing up in extreme poverty.

Exposure to psychosocial adversity (PA) is associated with poor behavioral, physical, and mental health outcomes in adulthood. As these outcomes are related to alterations in developmental processes, growing evidence suggests that deficits in executive functions-inhibitory control in particular-may in part explain this relationship. However, literature examining the development of inhibitory control has been based on children in higher-resource environments, and little is known how low-resource settings might exacerbate the link between inhibitory control and health outcomes. In this context, we collected functional magnetic resonance imaging data during a Go/No-Go inhibitory control task and PA variables for 68 children aged 5 to 7 years living in Dhaka, Bangladesh, an area with a high prevalence of PA. The children's mothers completed behavioral questionnaires to assess the children's PA and their own PA. Whole-brain activation underlying inhibitory control was examined using the No-Go versus Go contrast, and associations with PA variables were assessed using whole-brain regressions. Childhood neglect was associated with weaker activation in the right posterior cingulate, whereas greater family conflict, economic stress, and maternal PA factors were associated with greater activation in the left medial frontal gyrus, right superior and middle frontal gyri, and left cingulate gyrus. These data suggest that neural networks supporting inhibitory control processes may vary as a function of exposure to different types of PA, particularly between those related to threat and deprivation. Furthermore, increased activation in children with greater PA may serve as a compensatory mechanism, allowing them to maintain similar behavioral task performance.

Early Family Experiences and Neural Activity in Rural Pakistani Children: The Differential Role of Gender.

Adversity within low- and middle-income countries (LMICs) poses severe threats to neurocognitive development, which can be partially mitigated by high-quality early family experiences. Specifically, maternal scaffolding and home stimulation can buffer cognitive development in LMIC, possibly by protecting underlying neural functioning. However, the association between family experiences and neural activity remains largely unexplored in LMIC contexts. This study explored the relation of early family experiences to later cognitive skills and absolute gamma power (21-45 Hz), a neural marker linked to higher-order cognitive skills. Drawing data from the PEDS trial, a longitudinal study in rural Pakistan, we examined maternal scaffolding at 24 months and home stimulation quality at 18 months as predictors of verbal IQ, executive functions, and absolute gamma at 48 months for 105 mother-child dyads (52 girls). Maternal scaffolding interacted with gender to predict absolute gamma power, such that higher maternal scaffolding was related to higher gamma more strongly for girls. Maternal scaffolding also interacted with absolute gamma to predict executive functions, such that higher gamma was related to better executive functions only when maternal scaffolding was average to high. Individual differences in early family experiences may partially buffer the neural underpinnings of cognitive skills from adversity in LMIC.

Acute Total Hip Arthroplasty Following Acetabular Fracture is Associated With a High Risk of Revision, Dislocation, and Periprosthetic Fracture.

BACKGROUND: The aim of this study was to compare outcomes between acute, subacute, and delayed arthroplasty for acetabular fractures occurring within 1 week, from 1 week to 6 months, or more than 6 months before the index total hip arthroplasty (THA), versus THA without a history of acetabular fracture as a control. METHODS: We analyzed the records of patients undergoing primary THA who were enrolled in a national database for at least 2 years before and after the index procedure. Patients who had an initial diagnostic code for acetabular fracture occurring less than 1 week, from 1 week to 6 months, or at least more than 6 months before the THA were classified as acute THA (aTHA), subacute THA (saTHA), or delayed THA (dTHA), respectively. The control group was patients undergoing THA who did not have a history of acetabular fracture. There were 430,349 control primary THAs, 462 aTHAs, 675 saTHAs, and 1,162 dTHAs. RESULTS: After adjusting for age, sex, region, and comorbidities, patients who had an aTHA and saTHA experienced statistically significant increased odds of revision, dislocation, and periprosthetic fracture compared to primary THA without a history of acetabular fracture. Similarly, dTHA was associated with increased odds of revision, dislocation, and periprosthetic fractures compared to primary THA. In the multivariate analysis, aTHA had statistically significant higher rates of dislocation when compared to dTHA. CONCLUSIONS: Patients who had a history of acetabular fractures undergoing aTHA, saTHA, or dTHA have significantly increased rates of revision, periprosthetic fracture, and dislocation compared to primary THA in those who did not have a history of acetabular fractures.

Diversity of Backgrounds and Academic Accomplishments for Presidents Elected to Hip and Knee Arthroplasty Societies in the United States.

BACKGROUND: Academic accomplishments and demographics for presidents of hip and knee arthroplasty societies are poorly understood. This study compares the characteristics of presidents nominated to serve the Hip Society, Knee Society, and American Association of Hip and Knee Surgeons. METHODS: This was a cross-sectional study of arthroplasty presidents in the United States (1990 to 2022). Curriculum vitae and academic websites were analyzed for demographic, training, bibliometric, and National Institutes of Health (NIH) funding data. Comparisons were made between organizations and time periods (1990 to 2005 versus 2006 to 2022). RESULTS: There were 97 appointments of 78 unique arthroplasty presidents (80%). Most presidents were male (99%) and Caucasian (95%). There was 1 woman (1%) and 5 non-Caucasian presidents (2% Asian, 3% Hispanic). There were no differences in demographics between the 3 arthroplasty organizations and the 2 time periods (P > .05). Presidents were appointed at 55 ± 10 years old, which was on average 24 years after completion of residency training. Most presidents had arthroplasty fellowship training (68%), and the most common were the Hospital for Special Surgery (21%) and Massachusetts General Hospital (8%). The median h-index was 53 resulting from 191 peer-reviewed publications, which was similar between the 3 organizations (P > .05). There were 2 presidents who had NIH funding (2%), and there were no differences in NIH funding between the 3 organizations (P > .05). CONCLUSIONS: Arthroplasty society presidents have diverse training pedigrees, high levels of scholarly output, and similar demographics. There may be future opportunities to promote diversity and inclusion among the highest levels of leadership in total joint arthroplasty.

Impact of Chronic Opioid Use on Postoperative Mobility Recovery and Patient-Reported Outcomes: A Propensity-Matched Study.

BACKGROUND: Opioid use prior to total joint arthroplasty may be associated with poorer postoperative outcomes. However, few studies have reported the impact on postoperative recovery of mobility. We hypothesized that chronic opioid users would demonstrate impaired objective and subjective mobility recovery compared to nonusers. METHODS: A secondary data analysis of a multicenter, prospective observational cohort study in which patients used a smartphone-based care management platform with a smartwatch for self-directed rehabilitation following hip or knee arthroplasty was performed. Patients were matched 2:1 based on age, body mass index, sex, procedure, Charnley class, ambulatory status, orthopedic procedure history, and anxiety. Postoperative mobility outcomes were measured by patient-reported ability to walk unassisted at 90 days, step counts, and responses to the 5-level EuroQol-5 dimension 5-level, compared by Chi-square and student's t-tests. Unmatched cohorts were also compared to investigate the impact of matching. RESULTS: A total of 153 preoperative chronic opioid users were matched to 306 opioid-naïve patients. Age (61.9 ± 10.5 versus 62.1 ± 10.3, P = .90) and sex (53.6 versus 53.3% women, P = .95) were similar between groups. The proportion of people who reported walking unassisted for 90 days did not vary in the matched cohort (87.8 versus 90.7%, P = .26). Step counts were similar preoperatively and 1-month postoperatively but were lower in opioid users at 3 and 6 months postoperatively (4,823 versus 5,848, P = .03). More opioid users reported moderate to extreme problems with ambulation preoperatively on the 5-level EuroQol-5 dimension 5-level (80.6 versus 69.0%, P = .02), and at 6 months (19.2 versus 9.3%, P = .01). CONCLUSIONS: Subjective and objective measures of postoperative mobility were significantly reduced in patients who chronically used opioid medications preoperatively. Even after considering baseline factors that may affect ambulation, objective mobility metrics following arthroplasty were negatively impacted by preoperative chronic opioid use.

Longitudinal interactions between maternal depression symptoms and familial stressful life events on child anxiety symptoms at 5 years of age.

In the current study we identified salient parental factors for child anxiety symptoms by considering the role of stressful life events, maternal anxiety symptoms, maternal depressive symptoms, and maternal neuroticism. Families (N = 399) in an urban area in the United States were participants in a longitudinal study beginning in infancy. Mothers completed measures of stressful life events (Revised Life Events Questionnaire at all visits), maternal anxiety and depressive symptoms (State-Trait Anxiety Inventory and Beck Depression Inventory, respectively, at infancy between 5 and 12 months, at 2 years, and at 3 years), maternal neuroticism (NEO Five-Factor Inventory at infancy), and child anxiety symptoms (Child Behavior Checklist 1.5-5 at 5 years). Linear mixed models (LMMs) were used in analyses. Maternal depressive symptoms from infancy through 3 years were associated with child anxiety symptoms; other main effects modeled (stressful life events, maternal anxiety symptoms, maternal neuroticism) were not associated with child anxiety symptoms. There was a significant interaction effect between stressful life events and maternal depression. Stressful events from infancy through 5 years of age increased risk for child anxiety symptoms at 5 years if the child's mother had a mild mood disturbance or depression, but not for children with non-depressed mothers.

Caregiving stress and maternal mental health during the COVID-19 pandemic.

It has now been extensively documented that parental mental health has deteriorated since the beginning of the COVID-19 pandemic. Although pandemic-related stress has been widespread, parents faced the unique challenge of navigating remote schooling. Parental oversight of children's education, loss of access to school supportive resources, and the challenges of remote learning may have been most problematic for parents of children with or at elevated risk for mental health difficulties. In the current study, we examined interactive effects of parent-reported pandemic-related caregiving stress and child internalizing and externalizing problems on parental depressive symptoms in a community-based cohort (N = 115) in the Northeast of the United States. Results indicated that parents experiencing higher levels of pandemic-related caregiving stress whose children exhibited elevated externalizing behaviors reported heightened levels of depressive symptoms. Greater child internalizing problems were associated with higher parental depressive symptoms independent of caregiving stress. These findings point to conditions that might heighten risk for parent mental health challenges in the context of ongoing remote or hybrid learning and pandemic-associated restrictions. Further, the findings point to conditions and characteristics that may be screened to identify and intervene with vulnerable families to mitigate mental health problems.

Patient satisfaction and patient-reported outcomes do not vary by BMI class in total hip arthroplasty.

PURPOSE: Obesity has been identified as a risk factor for postoperative complications in patients undergoing total hip arthroplasty (THA). This study aimed to investigate patient-reported outcomes, pain, and satisfaction as a function of body mass index (BMI) class in patients undergoing THA. METHODS: 1736 patients within a prospective observational study were categorized into BMI classes. Pre- and postoperative Hip disability and Osteoarthritis Outcome Score for Joint Replacement (HOOS JR), satisfaction, and pain scores were compared by BMI class using one-way ANOVA. RESULTS: Healthy weight patients reported the highest preoperative HOOS JR (56.66 ± 13.35) compared to 45.51 ± 14.45 in Class III subjects. Healthy weight and Class III patients reported the lowest (5.65 ± 2.01) and highest (7.06 ± 1.98, p < 0.0001) preoperative pain, respectively. Changes in HOOS JR scores from baseline suggest larger improvements with increasing BMI class, where Class III patients reported an increase of 33.7 ± 15.6 points at 90 days compared to 26.1 ± 17.1 in healthy weight individuals (p = 0.002). Fewer healthy weight patients achieved the minimal clinically important difference (87.4%) for HOOS JR compared to Class II (96.5%) and III (94.7%) obesity groups at 90 days postoperatively. Changes in satisfaction and pain scores were largest in the Class III patients. Overall, no functional outcomes varied by BMI class postoperatively. CONCLUSION: Patients of higher BMI class reported greater improvements following THA. While risk/benefit shared decision-making remains a personalized requirement of THA, this study highlights that utilization of BMI cutoff may not be warranted based on pain and functional improvement.

Linking specific biological signatures to different childhood adversities: findings from the HERO project.

BACKGROUND: Although investigations have begun to differentiate biological and neurobiological responses to a variety of adversities, studies considering both endocrine and immune function in the same datasets are limited. METHODS: Associations between proximal (family functioning, caregiver depression, and anxiety) and distal (SES-D; socioeconomic disadvantage) early-life adversities with salivary inflammatory biomarkers (IL-1ß, IL-6, IL-8, and TNF-α) and hair HPA markers (cortisol, cortisone, and dehydroepiandrosterone) were examined in two samples of young U.S. children (N = 142; N = 145). RESULTS: Children exposed to higher SES-D had higher levels of TNF-α (B = 0.13, p = 0.011), IL-1ß (B = 0.10, p = 0.033), and DHEA (B = 0.16, p = 0.011). Higher family dysfunction was associated with higher cortisol (B = 0.08, p = 0.033) and cortisone (B = 0.05, p = 0.003). An interaction between SES-D and family dysfunction was observed for cortisol levels (p = 0.020) whereby children exposed to lower/average levels of SES-D exhibited a positive association between family dysfunction and cortisol levels, whereas children exposed to high levels of SES-D did not. These findings were partially replicated in the second sample. CONCLUSIONS: Our results indicate that these biological response systems may react differently to different forms of early-life adversity. IMPACT: Different forms of early-life adversity have varied stress signatures, and investigations of early-life adversities with inflammation and HPA markers are lacking. Children with higher socioeconomic disadvantage had higher TNF-α, IL-1ß, and DHEA. Higher family dysfunction was associated with higher hair cortisol and cortisone levels, and the association between family dysfunction and cortisol was moderated by socioeconomic disadvantage. Biological response systems (immune and endocrine) were differentially associated with distinct forms of early-life adversities.