Predicted impact of banning nonessential, energy-dense food and beverages in schools in Mexico: A microsimulation study.

BACKGROUND: Childhood obesity is a growing concern worldwide. School-based interventions have been proposed as effective means to improve nutritional knowledge and prevent obesity. In 2023, Mexico approved a reform to the General Education Law to strengthen the ban of sales and advertising of nonessential energy-dense food and beverages (NEDFBs) in schools and surroundings. We aimed to predict the expected one-year change in total caloric intake and obesity prevalence by introducing the ban of NEDFBs sales in schools, among school-aged children and adolescents (6 to 17 years old) in Mexico. METHODS AND FINDINGS: We used age-specific equations to predict baseline fat-free mass (FFM) and fat mass (FM) and then estimated total energy intake (TEI) per day. The TEI after the intervention was estimated under 4 scenarios: (1) using national data to inform the intervention effect; (2) varying law compliance; (3) using meta-analytic data to inform the intervention effect size on calories; and (4) using national data to inform the intervention effect by sex and socioeconomic status (SES). We used Hall's microsimulation model to estimate the potential impact on body weight and obesity prevalence of children and adolescents 1 year after implementing the intervention in Mexican schools. We found that children could reduce their daily energy intake by 33 kcal/day/person (uncertainty interval, UI, [25, 42] kcal/day/person), reducing on average 0.8 kg/person (UI [0.6, 1.0] kg/person) and 1.5 percentage points (pp) in obesity (UI [1.1, 1.9] pp) 1 year after implementing the law. We showed that compliance will be key to the success of this intervention: considering a 50% compliance the intervention effect could reduce 0.4 kg/person (UI [0.3, 0.5] kg/person). Our sensitivity analysis showed that the ban could reduce body weight by 1.3 kg/person (UI [0.8, 1.8] kg/person) and up to 5.4 kg/person (UI [3.4, 7.5] kg/person) in the best-case scenario. Study limitations include assuming that obesity and the contribution of NEDFBs consumed at school remain constant over time, assuming full compliance, and not considering the potential effect of banning NEDFBs in stores near schools. CONCLUSIONS: Even in the most conservative scenario, banning sales of NEDFBs in schools is expected to significantly reduce obesity, but achieving high compliance will be key to its success. WHY WAS THIS STUDY DONE?: - School-based interventions have been recognized as effective means to improve nutritional knowledge and prevent obesity-related diseases.- In December 2023, the Chamber of Representatives of Mexico approved an amendment that strengthens and updates the General Education Law (Article 75) and nutritional guidelines to ban the sales and advertising of nonessential energy-dense food and beverages (NEDFBs) in schools. WHAT DID THE RESEARCHERS DO AND FIND?: - We used age-specific equations to predict baseline fat-free mass (FFM) and fat mass (FM) and total energy intake (TEI) per day.- We used microsimulation modeling to predict body weight and obesity prevalence of children and adolescents 1 year after implementing the intervention in Mexican schools.- Our modeling study suggests that an important impact on obesity prevalence can be expected if the law is implemented and enforced as intended. WHAT DO THESE FINDINGS MEAN?: - If successful, this law could serve as an example beyond Mexico on how to achieve changes in body weight through school food regulation.- An important limitation of our main scenario is that we assumed full compliance of schools with the law, yet lower compliance will reduce its impact. We also did not consider historical trends on obesity or NEDFBs consumed in schools during our 1 year simulation, and we considered only the ban impact inside schools, excluding effects near and outside schools.

Illusions of Self-Motion during Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Tremor.

OBJECTIVE: Brain networks mediating vestibular perception of self-motion overlap with those mediating balance. A systematic mapping of vestibular perceptual pathways in the thalamus may reveal new brain modulation targets for improving balance in neurological conditions. METHODS: Here, we systematically report how magnetic resonance-guided focused ultrasound surgery of the nucleus ventralis intermedius of the thalamus commonly evokes transient patient-reported illusions of self-motion. In 46 consecutive patients, we linked the descriptions of self-motion to sonication power and 3-dimensional (3D) coordinates of sonication targets. Target coordinates were normalized using a standard atlas, and a 3D model of the nucleus ventralis intermedius and adjacent structures was created to link sonication target to the illusion. RESULTS: A total of 63% of patients reported illusions of self-motion, which were more likely with increased sonication power and with targets located more inferiorly along the rostrocaudal axis. Higher power and more inferiorly targeted sonications increased the likelihood of experiencing illusions of self-motion by 4 and 2 times, respectively (odds ratios = 4.03 for power, 2.098 for location). INTERPRETATION: The phenomenon of magnetic vestibular stimulation is the most plausible explanation for these illusions of self-motion. Temporary unilateral modulation of vestibular pathways (via magnetic resonance-guided focused ultrasound) unveils the central adaptation to the magnetic field-induced peripheral vestibular bias, leading to an explicable illusion of motion. Consequently, systematic mapping of vestibular perceptual pathways via magnetic resonance-guided focused ultrasound may reveal new intracerebral targets for improving balance in neurological conditions. ANN NEUROL 2024.

BeatProfiler: Multimodal In Vitro Analysis of Cardiac Function Enables Machine Learning Classification of Diseases and Drugs.

Goal: Contractile response and calcium handling are central to understanding cardiac function and physiology, yet existing methods of analysis to quantify these metrics are often time-consuming, prone to mistakes, or require specialized equipment/license. We developed BeatProfiler, a suite of cardiac analysis tools designed to quantify contractile function, calcium handling, and force generation for multiple in vitro cardiac models and apply downstream machine learning methods for deep phenotyping and classification. Methods: We first validate BeatProfiler's accuracy, robustness, and speed by benchmarking against existing tools with a fixed dataset. We further confirm its ability to robustly characterize disease and dose-dependent drug response. We then demonstrate that the data acquired by our automatic acquisition pipeline can be further harnessed for machine learning (ML) analysis to phenotype a disease model of restrictive cardiomyopathy and profile cardioactive drug functional response. To accurately classify between these biological signals, we apply feature-based ML and deep learning models (temporal convolutional-bidirectional long short-term memory model or TCN-BiLSTM). Results: Benchmarking against existing tools revealed that BeatProfiler detected and analyzed contraction and calcium signals better than existing tools through improved sensitivity in low signal data, reduction in false positives, and analysis speed increase by 7 to 50-fold. Of signals accurately detected by published methods (PMs), BeatProfiler's extracted features showed high correlations to PMs, confirming that it is reliable and consistent with PMs. The features extracted by BeatProfiler classified restrictive cardiomyopathy cardiomyocytes from isogenic healthy controls with 98% accuracy and identified relax90 as a top distinguishing feature in congruence with previous findings. We also show that our TCN-BiLSTM model was able to classify drug-free control and 4 cardiac drugs with different mechanisms of action at 96% accuracy. We further apply Grad-CAM on our convolution-based models to identify signature regions of perturbations by these drugs in calcium signals. Conclusions: We anticipate that the capabilities of BeatProfiler will help advance in vitro studies in cardiac biology through rapid phenotyping, revealing mechanisms underlying cardiac health and disease, and enabling objective classification of cardiac disease and responses to drugs.

Developmental characteristics and accuracy of autism screening among two-year-old toddlers in the ECHO program.

BACKGROUND: The Modified Checklist for Autism in Toddlers (M-CHAT) is a common pediatric screening tool with mixed accuracy findings. Prior evidence supports M-CHAT screening for developmental concerns, especially in toddlers born preterm. This study examined M-CHAT accuracy in a large, nationwide sample. METHODS: 3393 participants from the Environmental influences on Child Health Outcomes (ECHO) program were included. Harmonized M-CHAT (M-CHAT-H) results were compared with parent-reported autism diagnosis and autism-related characteristics to assess accuracy for term and preterm children, together and separately. Generalized estimating equations, clustering for ECHO cohort and controlling for demographic covariates, were used to examine associations between developmental and behavioral characteristics with M-CHAT-H accuracy. RESULTS: Sensitivity of the M-CHAT-H ranged from 36 to 60%; specificity ranged from 88 to 99%. Positive M-CHAT-H was associated with more developmental delays and behavior problems. Children with severe motor delays and more autism-related problems were more likely to have a false-negative M-CHAT-H. Children with fewer behavior problems and fewer autism-related concerns were more likely to have a false-positive screen. CONCLUSION: The M-CHAT-H accurately detects children at low risk for autism and children at increased risk with moderate accuracy. These findings support use of the M-CHAT-H in assessing autism risk and developmental and behavioral concerns in children. IMPACT: Previous literature regarding accuracy of the Modified Checklist for Autism in Toddlers (M-CHAT) is mixed but this study provides evidence that the M-CHAT performs well in detecting children at low risk for autism and consistently detects children with developmental delays and behavioral problems. The M-CHAT moderately detects children at increased risk for autism and remains a useful screening tool. This study examines M-CHAT accuracy in a large-scale, nationwide sample, examining associations between screening accuracy and developmental outcomes. These findings impact pediatric screening for autism, supporting continued use of the M-CHAT while further elucidating the factors associated with inaccurate screens.

The criminalization of women with postpartum psychosis: "a call for action" for judicial change.

PURPOSE: To prevent the incarceration and influence outcomes when criminal culpability is linked to postpartum psychosis. METHODS: Infanticide, neonaticide and filicide are most often linked with postpartum psychosis, which affects 1-2 women per 1,000 births or 4,000 women each year in the United States. Multiple genetic, hormonal and psychosocial factors surrounding childbirth result in a 1 to 4% risk of infanticide in women with postpartum psychosis. The authors seek to increase awareness of postpartum psychosis and postpartum depression in state legislatures. Others are working to have it recognized in the Diagnostic and Statistical Manual of Mental Disorders (DSM) as a specific illness. Specific postpartum legislation for those charged with crimes related to maternal mental illness is necessary. RESULTS: In Illinois, the very first criminal law in the nation recognizing the pernicious effects of this illness went into effect in 2018. The authors and others are attempting to cause similar or broader legislation to be brought in other states. Several women have been released from extended incarceration utilizing this law. CONCLUSIONS: This temporary mental illness can lead to tragic outcomes when hospitalization and crisis intervention is delayed or the illness is misdiagnosed. The legal/judicial system has not utilized the growing body of scientific developments that medical researchers have discovered in recent decades. The lack of a unique diagnostic classification in the DSM and the lack of postpartum criminal laws, lead to mentally ill mothers in the U.S. receiving excessively harsh sentences when prosecuted, evidenced both in trial and sentencing.

Epigenetic associations in HPA axis genes related to bronchopulmonary dysplasia and antenatal steroids.

BACKGROUND: Bronchopulmonary dysplasia (BPD), a common morbidity among very preterm infants, is associated with chronic disease and neurodevelopmental impairments. A hypothesized mechanism for these outcomes lies in altered glucocorticoid (GC) activity. We hypothesized that BPD and its treatments may result in epigenetic differences in the hypothalamic-pituitary-adrenal (HPA) axis, which is modulated by GC, and could be ascertained using an established GC risk score and DNA methylation (DNAm) of HPA axis genes. METHODS: DNAm was quantified from buccal tissue (ECHO-NOVI) and from neonatal blood spots (ELGAN ECHO) via the EPIC microarray. Prenatal maternal characteristics, pregnancy complication, and neonatal medical complication data were collected from medical record review and maternal interviews. RESULTS: The GC score was not associated with steroid exposure or BPD. However, six HPA genes involved in stress response regulation demonstrated differential methylation with antenatal steroid exposure; two CpGs within FKBP5 and POMC were differentially methylated with BPD severity. These findings were sex-specific in both cohorts; males had greater magnitude of differential methylation within these genes. CONCLUSIONS: These findings suggest that BPD severity and antenatal steroids are associated with DNAm at some HPA genes in very preterm infants and the effects appear to be sex-, tissue-, and age-specific. IMPACT: This study addresses bronchopulmonary dysplasia (BPD), an important health outcome among preterm neonates, and interrogates a commonly studied pathway, the hypothalamic-pituitary-adrenal (HPA) axis. The combination of BPD, the HPA axis, and epigenetic markers has not been previously reported. In this study, we found that BPD itself was not associated with epigenetic responses in the HPA axis in infants born very preterm; however, antenatal treatment with steroids was associated with epigenetic responses.

Toward a more holistic approach to the study of exposures and child outcomes.

Aim: The current work was designed to demonstrate the application of the exposome framework in examining associations between exposures and children's long-term neurodevelopmental and behavioral outcomes. Methods: Longitudinal data were collected from birth through age 6 from 402 preterm infants. Three statistical methods were utilized to demonstrate the exposome framework: exposome-wide association study, cumulative exposure and machine learning models, with and without epigenetic data. Results: Each statistical approach answered a distinct research question regarding the impact of exposures on longitudinal child outcomes. Findings highlight associations between exposures, epigenetics and executive function. Conclusion: Findings demonstrate how an exposome-based approach can be utilized to understand relationships between internal (e.g., DNA methylation) and external (e.g., prenatal risk) exposures and long-term developmental outcomes in preterm children.

Change Over Time in Pre-End-Stage Renal Disease 24-Hour Urine Creatinine as Muscle Mass Surrogate and Post-End-Stage Renal Disease Mortality.

OBJECTIVE: Loss of muscle mass and sarcopenia are common in chronic kidney disease (CKD) and end-stage renal disease (ESRD), and sarcopenia can worsen insidiously in patients with advancing CKD. The temporal dynamics of sarcopenia in patients with progressive loss of kidney function, and its association with future outcomes, is unclear. METHODS: In a contemporary national cohort of incident ESRD US veterans, we selected 661 patients who had at least 2 24-hour urine creatinine (24hrUC) measurements, a surrogate of muscle mass, performed during the 3-year prelude period prior to ESRD transition. We estimated 24hrUC slopes in mixed effects models. To assess the temporal dynamics of pre-ESRD changes in 24hrUC and its association with changing eGFR, we separately fitted in mixed effects models a penalized spline regression of 24hrUC on time and on eGFR. We examined the association of 24hrUC slopes with postdialysis all-cause mortality using Cox models adjusted for confounders. RESULTS: The mean slope of 24hrUC versus time was -78 mg/year (95% confidence interval: -102 to -54), with a steeper decline noted in the last year prior to ESRD. More severe decreases in 24hrUC were associated with higher all-cause mortality: a 100 mg/year decrease in 24hrUC was associated with a multivariable adjusted death hazard ratio of 1.41 (95% confidence interval: 1.00-1.98, P = .05). CONCLUSION: Patients with advanced CKD lose a substantial proportion of their muscle mass each year during pre-ESRD prelude. Loss of muscle mass accelerates near ESRD transition, and more loss of muscle mass is associated with higher mortality after ESRD transition.

Associations between neighborhood characteristics and child well-being before and during the COVID-19 pandemic: A repeated cross-sectional study in the Environmental influences on Child Health Outcomes (ECHO) program.

The corona virus disease (COVID-19) pandemic disrupted daily life worldwide, and its impact on child well-being remains a major concern. Neighborhood characteristics affect child well-being, but how these associations were affected by the pandemic is not well understood. We analyzed data from 1039 children enrolled in the Environmental influences on Child Health Outcomes Program whose well-being was assessed using the Patient-Reported Outcomes Measurement Information System Global Health questionnaire and linked these data to American Community Survey (ACS) data to evaluate the impacts of neighborhood characteristics on child well-being before and during the pandemic. We estimated the associations between more than 400 ACS variables and child well-being t-scores stratified by race/ethnicity (non-Hispanic white vs. all other races and ethnicities) and the timing of outcome data assessment (pre-vs. during the pandemic). Network graphs were used to visualize the associations between ACS variables and child well-being t-scores. The number of ACS variables associated with well-being t-scores decreased during the pandemic period. Comparing non-Hispanic white with other racial/ethnic groups during the pandemic, different ACS variables were associated with child well-being. Multiple ACS variables representing census tract-level housing conditions and neighborhood racial composition were associated with lower well-being t-scores among non-Hispanic white children during the pandemic, while higher percentage of Hispanic residents and higher percentage of adults working as essential workers in census tracts were associated with lower well-being t-scores among non-white children during the same study period. Our study provides insights into the associations between neighborhood characteristics and child well-being, and how the COVID-19 pandemic affected this relationship.

Real-life management of psoriasis with biological agents during pregnancy.

BACKGROUND: French guidelines recommend stopping biologic treatment of psoriasis between 3 and 24 weeks before conception in accordance with the relevant Summary of Product Characteristics (SmPC). The aim of this study was to evaluate the real-life practice of dermatologists in the management of pregnant women with psoriasis previously treated with biologic agents. We wished to assess the level of practitioner adherence to the relevant SmPCs. MATERIAL AND METHODS: We conducted a study in collaboration with GRPso and Resopso. A computerized questionnaire was completed by the practitioners. We performed descriptive statistics and studied the profile of the practitioners, their level of confidence with continuation of biological agents during pregnancy, and their reported practices on the use of biological agents in pregnancy. Statistical analyses were performed using XLSTAT. A p-value of less than 0.05 was considered significant. RESULTS: A total of 63 dermatologists (women: 71%; mean age 43.8 years) participated in this study, the majority of whom were hospital-based (87%). Recommendations were followed by 36.5% of practitioners, while 44% reported discontinuing biologic agents on diagnosis of pregnancy, and 20.5% reported using these agents during pregnancy. Among dermatologists with more than ten years of experience, 19% reported following the SmPC. Among dermatologists with a patient base >200 (patients treated with biologic agents for psoriasis), 19% reported following the SmPC compared to 54% of practitioners with less than 50 patients. The mean age of dermatologists following the SmPC was 41 years vs. 47 years for those not following the SmPC. DISCUSSION: The majority of practitioners do not follow recommendations on discontinuation of biologic agents before the planning of pregnancy by patients.

Birth outcomes in relation to neighborhood food access and individual food insecurity during pregnancy in the Environmental Influences on Child Health Outcomes (ECHO)-wide cohort study.

BACKGROUND: Limited access to healthy foods, resulting from residence in neighborhoods with low-food access or from household food insecurity, is a public health concern. Contributions of these measures during pregnancy to birth outcomes remain understudied. OBJECTIVES: We examined associations between neighborhood food access and individual food insecurity during pregnancy with birth outcomes. METHODS: We used data from 53 cohorts participating in the nationwide Environmental Influences on Child Health Outcomes-Wide Cohort Study. Participant inclusion required a geocoded residential address or response to a food insecurity question during pregnancy and information on birth outcomes. Exposures include low-income-low-food-access (LILA, where the nearest supermarket is >0.5 miles for urban or >10 miles for rural areas) or low-income-low-vehicle-access (LILV, where few households have a vehicle and >0.5 miles from the nearest supermarket) neighborhoods and individual food insecurity. Mixed-effects models estimated associations with birth outcomes, adjusting for socioeconomic and pregnancy characteristics. RESULTS: Among 22,206 pregnant participants (mean age 30.4 y) with neighborhood food access data, 24.1% resided in LILA neighborhoods and 13.6% in LILV neighborhoods. Of 1630 pregnant participants with individual-level food insecurity data (mean age 29.7 y), 8.0% experienced food insecurity. Residence in LILA (compared with non-LILA) neighborhoods was associated with lower birth weight [ß -44.3 g; 95% confidence interval (CI): -62.9, -25.6], lower birth weight-for-gestational-age z-score (-0.09 SD units; -0.12, -0.05), higher odds of small-for-gestational-age [odds ratio (OR) 1.15; 95% CI: 1.00, 1.33], and lower odds of large-for-gestational-age (0.85; 95% CI: 0.77, 0.94). Similar findings were observed for residence in LILV neighborhoods. No associations of individual food insecurity with birth outcomes were observed. CONCLUSIONS: Residence in LILA or LILV neighborhoods during pregnancy is associated with adverse birth outcomes. These findings highlight the need for future studies examining whether investing in neighborhood resources to improve food access during pregnancy would promote equitable birth outcomes.

A policy approach to identifying food and beverage products that are ultra-processed and high in added salt, sugar and saturated fat in the United States: a cross-sectional analysis of packaged foods.

Background: Governments globally aim to reduce the intake of unhealthy foods. Many policies exist that aim to address foods high in saturated fat, salt and sugar (HFSS) but the identification of ultra-processed foods (UPF) have presented a greater challenge due to the lack of an appropriate policy definition. To support policymakers, we provide approaches that can support governments to identify both HFSS foods and UPFs. Methods: Four approaches combining elements of UPF definitions (i.e., presence of additives) and HFSS definitions were compared attempting to simplify and standardize the identification of less healthy products. Nationally representative food purchase data from NielsenIQ linked with nutrition facts label data were used to examine the mean proportion of product volume purchased by US households to be targeted. Differences between approaches were examined using Student t test; Bonferroni adjusted P value < 0.0001 was considered significant. Findings: In 2020, 50% of 33,054,687 products purchased by US households were considered UPFs (65% of foods and 38% of beverages) and 43% HFSS (65% of foods and 26% of beverages), however there was not 100% agreement between the two definitions (P < 0.0001). By starting with HFSS criteria and adding elements of UPF (colors and flavors), we were able to provide a method with 100% agreement between the identification of UPFs and HFSS products. Interpretation: Results demonstrated how combining HFSS criteria with UPF criteria can be used to identify less healthy foods and ensure policymakers have both a simple and accurate method to target products for policy intervention. Funding: Bloomberg Philanthropies and the Global Food Research Program of UNC-Chapel Hill provided funds.

Wheel Replacing Pyramid: Better Paradigm Representing Totality of Evidence-Based Medicine.

Background: Evidence-based medicine (EBM), as originally conceived, used all types of peer-reviewed evidence to guide medical practice and decision-making. During the SARS-CoV-2 Coronavirus disease (COVID-19) pandemic, the standard usage of EBM, modeled by the Evidence-Based Medicine Pyramid, undermined EBM by incorrectly using pyramid levels to assign relative quality. The resulting pyramid-based thinking is biased against reports both in levels beneath randomized control trials (RCTs) and those omitted from the pyramid entirely. Thus, much of the evidence was ignored. Our desire for a more encompassing and effective medical decision-making process to apply to repurposed drugs led us to develop an alternative to the EBM Pyramid for EBM. Herein, we propose the totality of evidence (T-EBM) wheel. Objectives: To create an easily understood graphic that models EBM by incorporating all peer-reviewed evidence that applies to both new and repurposed medicines, and to demonstrate its potential utility using ivermectin as a case study. Methods: The graphics were produced using Microsoft Office Visio Professional 2003 except for part of the T-EBM wheel sunburst chart, which was produced using Microsoft 365 Excel. For the case study, PubMed® was used by searching for peer-reviewed reports containing "ivermectin" and either "covid" or "sars" in the title. Reports were filtered for those using ivermectin-based protocols in the treatment of COVID-19. The resulting 265 reports were evaluated for their study design types and treatment outcomes. The three-ringed graphical T-EBM wheel was composed of two inner rings showing all types of reports and an outer ring showing outcomes for each type. Findings-Conclusions: The T-EBM wheel avoids the biases of the EBM Pyramid and includes all types of reports in the pyramid along with reports such as population and mechanistic studies. In both early and late stages of medical emergencies, pyramid-based thinking may overlook indications of efficacy in regions of the T-EBM wheel beyond RCTs. This is especially true when searching for ways to prevent and treat a novel disease with repurposed therapeutics before RCTs, safety assessments, and mechanisms of action of novel therapeutics are established. As such, T-EBM Wheels should replace the EBM Pyramids in medical decision-making and education. T-EBM Wheels can be expanded upon by implementing multiple outer rings, one for each different kind of outcome (efficacy, safety, etc.). A T-EBM Wheel can be created for any proprietary or generic medicine. The ivermectin (IVM) T-EBM Wheel displays the efficacy of IVM-based treatments of COVID-19 in a color-coded graphic, visualizing each type of evidence and the proportions of each of their outcomes (positive, inconclusive, negative).

Brain Mechanisms Explaining Postural Imbalance in Traumatic Brain Injury: A Systematic Review.

Introduction: Persisting imbalance and falls in community-dwelling traumatic brain injury (TBI) survivors are linked to reduced long-term survival. However, a detailed understanding of the impact of TBI upon the brain mechanisms mediating imbalance is lacking. To understand the state of the art concerning the brain mechanisms mediating imbalance in TBI, we performed a systematic review of the literature. Methods: PubMed, Web of Science, and Scopus were searched and peer-reviewed research articles in humans, with any severity of TBI (mild, moderate, severe, or concussion), which linked a postural balance assessment (objective or subjective) with brain imaging (through computed tomography, T1-weighted imaging, functional magnetic resonance imaging [fMRI], resting-state fMRI, diffusion tensor imaging, magnetic resonance spectroscopy, single-photon emission computed tomography, electroencephalography, magnetoencephalography, near-infrared spectroscopy, and evoked potentials) were included. Out of 1940 articles, 60 were retrieved and screened, and 25 articles fulfilling inclusion criteria were included. Results: The most consistent finding was the link between imbalance and the cerebellum; however, the regions within the cerebellum were inconsistent. Discussion: The lack of consistent findings could reflect that imbalance in TBI is due to a widespread brain network dysfunction, as opposed to focal cortical damage. The inconsistency in the reported findings may also be attributed to heterogeneity of methodology, including data analytical techniques, small sample sizes, and choice of control groups. Future studies should include a detailed clinical phenotyping of vestibular function in TBI patients to account for the confounding effect of peripheral vestibular disorders on imbalance and brain imaging.

Epigenome-wide association study identifies neonatal DNA methylation associated with two-year attention problems in children born very preterm.

Prior research has identified epigenetic predictors of attention problems in school-aged children but has not yet investigated these in young children, or children at elevated risk of attention problems due to preterm birth. The current study evaluated epigenome-wide associations between neonatal DNA methylation and attention problems at age 2 years in children born very preterm. Participants included 441 children from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study, a multi-site study of infants born < 30 weeks gestational age. DNA methylation was measured from buccal swabs collected at NICU discharge using the Illumina MethylationEPIC Bead Array. Attention problems were assessed at 2 years of adjusted age using the attention problems subscale of the Child Behavior Checklist (CBCL). After adjustment for multiple testing, DNA methylation at 33 CpG sites was associated with child attention problems. Differentially methylated CpG sites were located in genes previously linked to physical and mental health, including several genes associated with ADHD in prior epigenome-wide and genome-wide association studies. Several CpG sites were located in genes previously linked to exposure to prenatal risk factors in the NOVI sample. Neonatal epigenetics measured at NICU discharge could be useful in identifying preterm children at risk for long-term attention problems and related psychiatric disorders, who could benefit from early prevention and intervention efforts.

Approaches to protocol standardization and data harmonization in the ECHO-wide cohort study.

The United States (U.S.) National Institutes of Health-funded Environmental influences on Child Health Outcomes (ECHO)-wide Cohort was established to conduct high impact, transdisciplinary science to improve child health and development. The cohort is a collaborative research design in which both extant and new data are contributed by over 57,000 children across 69 cohorts. In this review article, we focus on two key challenging issues in the ECHO-wide Cohort: data collection standardization and data harmonization. Data standardization using a Common Data Model and derived analytical variables based on a team science approach should facilitate timely analyses and reduce errors due to data misuse. However, given the complexity of collaborative research designs, such as the ECHO-wide Cohort, dedicated time is needed for harmonization and derivation of analytic variables. These activities need to be done methodically and with transparency to enhance research reproducibility. IMPACT: Many collaborative research studies require data harmonization either prior to analyses or in the analyses of compiled data. The Environmental influences on Child Health Outcomes (ECHO) Cohort pools extant data with new data collection from over 57,000 children in 69 cohorts to conduct high-impact, transdisciplinary science to improve child health and development, and to provide a national database and biorepository for use by the scientific community at-large. We describe the tools, systems, and approaches we employed to facilitate harmonized data for impactful analyses of child health outcomes.

Contributions of prenatal risk factors and neonatal epigenetics to cognitive outcome in children born very preterm.

Children born less than 30 weeks gestational age (GA) are at high risk for neurodevelopmental delay compared to term peers. Prenatal risk factors and neonatal epigenetics could help identify preterm children at highest risk for poor cognitive outcomes. We aimed to understand the associations among cumulative prenatal risk, neonatal DNA methylation, and child cognitive ability at age 3 years, including whether DNA methylation mediates the association between prenatal risk and cognitive ability. We studied 379 neonates (54% male) born less than 30 weeks GA who had DNA methylation measured at neonatal intensive care unit discharge along with 3-year follow-up data. Cumulative prenatal risk was calculated from 24 risk factors obtained from maternal report and medical record and epigenome-wide neonatal DNA methylation was assayed from buccal swabs. At 3-year follow-up, child cognitive ability was assessed using the Bayley Scales of Infant and Toddler Development (third edition). Cumulative prenatal risk and DNA methylation at two cytosine-phosphate-guanines (CpGs) were uniquely associated with child cognitive ability. Using high-dimensional mediation analysis, we also identified differential methylation of 309 CpGs that mediated the association between cumulative prenatal risk and child cognitive ability. Many of the associated CpGs were located in genes (TNS3, TRAPPC4, MAD1L1, APBB2, DIP2C, TRAPPC9, DRD2) that have previously been associated with prenatal exposures and/or neurodevelopmental phenotypes. Our findings suggest a role for both prenatal risk factors and DNA methylation in explaining outcomes for children born preterm and suggest we should further study DNA methylation as a potential mechanism underlying the association between prenatal risk and child neurodevelopment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The viable bioengineered allogeneic cellularized construct StrataGraft® synthesizes, deposits, and organizes human extracellular matrix proteins into tissue type-specific structures and secretes soluble factors associated with wound healing.

BACKGROUND: StrataGraft® (allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen-dsat) is an FDA-approved viable bioengineered allogeneic cellularized construct for adult patients with deep partial-thickness burns requiring surgery. We characterized the structural and functional properties of StrataGraft to improve product understanding by evaluating extracellular matrix (ECM) molecule distribution and secreted protein factor expression in vitro. METHODS: ECM protein expression was determined using indirect immunofluorescence on construct cross sections using commercial antibodies against collagen III, IV, VI, laminin-332, and decorin. Human collagen I expression was verified by enzyme-linked immunosorbent assay (ELISA) for collagen I C-terminal propeptide. Soluble protein factor secretion was quantified by multiplex biomarker assays and singleplex ELISA in conditioned media from meshed constructs. RESULTS: StrataGraft cellular components produced collagen I, collagen III, collagen VI, and decorin in patterns indicating an organized ECM. Distributions of collagen IV and laminin-332 indicated formation of basement membranes and dermal-epidermal junctions. Soluble protein factors were observed in the pg/cm2/h range from 1 h to the experiment end at 168 h. CONCLUSIONS: The organization of the ECM proteins was like human skin and the viable cellular components provided sustained secretion of soluble wound healing factors, making StrataGraft an attractive option for treating severe burns.