Association between maternal prenatal depressive symptoms and offspring epigenetic aging at 3-5 weeks.

Epigenetic clocks are emerging as tools for assessing acceleration and deceleration of biological age during childhood. Maternal depression during pregnancy may affect the biological aging of offspring and related development. In a low-income cohort of mother-child dyads, we investigated the relationship between prenatal maternal depressive symptoms and infant epigenetic age residuals, which represent the deviation (acceleration or deceleration) that exists between predicted biological age and chronological age. The epigenetic age residuals were derived from a pediatric-specific buccal epithelial clock. We hypothesized that maternal depressive symptoms, both sub-clinical and elevated (clinical level), would be associated with estimated biological age deceleration in offspring during early infancy. We analyzed data from 94 mother-child dyads using the Edinburgh Postnatal Depression Scale (EPDS) and DNA methylation derived from offspring buccal cells collected at 3-5 weeks of age. There was a significant non-linear association between the EPDS score and epigenetic age residual (ß = -0.017, 95% confidence interval: -0.03,-0.01, P = <0.01). The results indicated that infants of mothers with sub-clinical depressive symptoms had the lowest infant epigenetic age residuals while infants of mothers with no-to-low depressive symptoms had the highest and experienced biological age acceleration. Maternal depressive symptoms may influence the biological aging of offspring living in poverty.

Current Recommended Estrogen Dosing for Pubertal Induction in Turner Syndrome Results in Normal Uterine Growth.

CONTEXT: Most individuals with Turner syndrome (TS) require estrogen for pubertal induction. Current estrogen dosing guidelines are based on expert consensus opinion. OBJECTIVE: Evaluate whether current international guidelines for estrogen dosing during pubertal induction of individuals with TS result in normal uterine growth. We hypothesized that uterine size in individuals with TS who reached adult estrogen dosing is smaller than in mature females without TS. METHODS: Cross-sectional study of patients with TS at the Cincinnati Center for Pediatric and Adult Turner Syndrome Care. Twenty-nine individuals (age 15-26 years) with primary ovarian insufficiency who reached adult estrogen dosing (100 µg of transdermal or 2 mg of oral 17ß-estradiol) were included. Comparison of uterine measurements with a published sample of 292 age-appropriate (age 15-20 years) controls without TS. Uterine length, volume, and fundal-cervical ratio (FCR) were measured. Clinical information (karyotype, Tanner staging for breast development, laboratory data) was extracted from an existing institutional patient registry. RESULTS: There was no evidence of compromise of the uterine size/configuration in the TS cohort compared with the controls; in fact, uterine length, mean 7.7 cm (±1.3) vs 7.2 cm (±1.0) (P = .03), and volume, mean 60.6 cm3 (±26.6) vs 50.5 cm3 (±20.5) (P = .02), were both larger in individuals with TS. CONCLUSION: Current international guidelines for hormone replacement using 17ß-estradiol in individuals with TS appear adequate to allow for normal uterine growth by the end of pubertal induction.

Neonatal AVPR1a Methylation and In-Utero Exposure to Maternal Smoking.

(1) Introduction: Epigenetic changes have been proposed as a biologic link between in-utero exposure to maternal smoking and health outcomes. Therefore, we examined if in-utero exposure to maternal smoking was associated with infant DNA methylation (DNAm) of cytosine-phosphate-guanine dinucleotides (CpG sites) in the arginine vasopressin receptor 1A AVPR1a gene. The AVPR1a gene encodes a receptor that interacts with the arginine vasopressin hormone and may influence physiological stress regulation, blood pressure, and child development. (2) Methods: Fifty-two infants were included in this cohort study. Multivariable linear models were used to examine the effect of in-utero exposure to maternal smoking on the mean DNAm of CpG sites located at AVPR1a. (3) Results: After adjusting the model for substance use, infants with in-utero exposure to maternal smoking had a reduction in DNAm at AVPR1a CpG sites by -0.02 (95% CI -0.03, -0.01) at one month of age. In conclusion, in-utero exposure to tobacco smoke can lead to differential patterns of DNAm of AVPR1a among infants. Conclusions: Future studies are needed to identify how gene expression in response to early environmental exposures contributes to health outcomes.

Epigenome-wide association of neonatal methylation and trimester-specific prenatal PM2.5 exposure.

Exposure to particulate matter with an aerodynamic diameter smaller than 2.5 microns (PM2.5) can affect birth outcomes through physiological pathways such as inflammation. One potential way PM2.5 affects physiology could be through altering DNA methylation (DNAm). Considering that exposures during specific windows of gestation may have unique effects on DNAm, we hypothesized a timing-specific association between PM2.5 exposure during pregnancy and DNAm in the neonatal epithelial-cell epigenome. Methods: After collecting salivary samples from a cohort of 91 neonates, DNAm was assessed at over 850,000 cytosine-guanine dinucleotide (CpG) methylation sites on the epigenome using the MethylationEPIC array. Daily ambient PM2.5 concentrations were estimated based on the mother's address of primary residence during pregnancy. PM2.5 was averaged over the first two trimesters, separately and combined, and tested for association with DNAm through an epigenome-wide association (EWA) analysis. For each EWA, false discovery rate (FDR)-corrected P < 0.05 constituted a significant finding and every CpG site with uncorrected P < 0.0001 was selected to undergo pathway and network analysis to identify molecular functions enriched by them. Results: Our analysis showed that cg18705808 was associated with the combined average of PM2.5. Pathway and network analysis revealed little similarity between the first two trimesters. Previous studies reported that TMEM184A, the gene regulated by cg18705808, has a putative role in inflammatory pathways. Conclusions: The differences in pathway and network analyses could potentially indicate trimester-specific effects of PM2.5 on DNAm. Further analysis with greater temporal resolution would be valuable to fully characterize the effect of PM2.5 on DNAm and child development.

Resilience in relation to older adults with multimorbidity: A scoping review.

The purpose of this scoping review is to identify conceptual and theoretical resilience models, types of resilience measures, and outcomes regarding resilience in relation to older adults with multimorbidity. PubMed, Embase, CINAHL, and PsycINFO were searched, and we identified 14 studies to July 2021. Most models operationalize resilience as dependent on the social and environmental context of older adults. Three of the five resilience measures in the included studies are used to evaluate general resilience. They are primarily psychological or psychosocial in nature, and measuring physical resilience therefore may help to better understand individuals' ability to cope with the physical challenges associated with various chronic diseases. Quality of life and physical activity were common outcomes in studies of resilience. Findings highlight the need for studies that incorporate physiological measures or physical properties of resilience and longitudinal studies that capture the dynamic process of resilience in older adults with multimorbidity.

Substance Use and Utilization of Prenatal and Postpartum Care.

OBJECTIVES: Prenatal and postpartum care for women with substance use is important due to increased risk of poor health outcomes. The influence of substance use on perinatal care utilization is not well characterized, especially postpartum care. The objective of this study was to examine the effect of substance use during pregnancy on prenatal and postpartum care utilization in a nationally representative sample and to identify maternal characteristics associated with inadequate prenatal and postpartum care among women with substance use. METHODS: Pregnancy Risk Assessment Monitoring System data (2016-2018) from 8 states were used for this study. Logistic regression models adjusted for complex survey weights and confounder variables were used to estimate the odds of not receiving adequate prenatal care and postpartum care. Weighted Rao-Scott chi-square tests were used to examine maternal characteristics associated with care utilization among women who reported substance use during pregnancy. RESULTS: The study included 15,131 women, with 5.3% who reported illicit substance use during pregnancy. In multivariable models, substance use was associated with an increase in the odds of not receiving adequate prenatal care (OR 1.69, CI 1.32, 2.17) and not receiving postpartum care (OR: 1.47, CI 1.10, 1.95). Among women who reported substance use, depression and smoking status were associated with not receiving adequate prenatal or postpartum care. CONCLUSIONS: Substance use during pregnancy is independently associated with disparities in prenatal and postpartum care access. Future studies are needed to identify how barriers lead to care inequalities and importantly, to identify strategies to improve care utilization.

Caregivers of individuals with Rubinstein-Taybi syndrome: Perspectives, experiences, and relationships with medical professionals.

Rubinstein-Taybi syndrome (RTS) is a rare genetic disorder. Family-centered care (FCC) is a healthcare delivery approach that aims to create an equal partnership between caregivers and providers. FCC has been shown to improve parental wellbeing, their knowledge of the condition and care, and improve their feelings of self-efficacy and personal control. The purpose of this study was to explore the healthcare experiences of family caregivers of children and adults with RTS to understand the issues they encounter when working with medical professionals and to examine their perspectives on how to improve FCC. Primary family caregivers of individuals with RTS took an online mixed-method survey that contained three primary components: a demographic survey, the Measures of Processes of Care-20 (MPOC-20) [a measure of the FCC an individual feels they receive], and a qualitative assessment of negative and positive interactions with medical professionals and priority areas for improvement. Qualitative data were analyzed using thematic analysis. Quantitative data were analyzed with descriptive statistics. An analysis of variance test was used to determine whether values statistically differed between different-age groups of individuals with RTS being cared for. Sixty-three caregivers completed the survey. The average score of the Providing General Information subscale of the MPOC-20 was 3.18, lower than that seen in other studies. The average scores of the other subscales of the MPOC-20 ranged from 4.60 to 5.02, comparable to other studies of caregivers of children with other medical conditions. All aspects of FCC were ranked as important by caregivers. There were no differences in MPOC-20 values between those caring for the individuals with RTS in different-age groups reviewed. In the qualitative responses, parents noted that experiences with medical professionals would be improved if healthcare providers actively provided FCC, collaborated with parents and other providers, respected caregivers' time and breadth of knowledge and lived experience, gave a more balanced description of the condition, showed greater respect toward their loved ones and included them in the conversation, and made an effort to learn about RTS. The changes that parents would like to see in their child's care were not specific to one discipline and could be implemented by all healthcare specialists. While caregivers report that they receive moderate levels of FCC, they indicated that areas of FCC could be improved.

Association Between Maternal Adverse Childhood Experiences and Neonatal SCG5 DNA Methylation-Effect Modification by Prenatal Home Visiting.

Maternal childhood adversity and trauma may elicit biological changes that impact the next generation through epigenetic responses measured in DNA methylation (DNAm). These epigenetic associations could be modified by the early postnatal environment through protective factors, such as early childhood home visiting (HV) programs that aim to mitigate deleterious intergenerational effects of adversity. In a cohort of 53 mother-child pairs recruited in 2015-2016 for the Pregnancy and Infant Development Study (Cincinnati, Ohio), we examined the association between maternal adverse childhood experiences (ACEs) and neonatal DNAm in the secretogranin V gene (SCG5), which is important in neuroendocrine function. We examined prenatal HV as an effect modifier. Mothers completed a questionnaire on ACEs during pregnancy, and infant buccal samples were collected 1 month postpartum. Multivariable linear regression was used to examine the association between maternal ACEs and neonatal DNAm expressed as M-values averaged across 4 cytosine-phosphate-guanine dinucleotide sites. A higher number of maternal ACEs (>3) was associated with a 5.79-percentage-point lower offspring DNAm (95% confidence interval: -10.44, -1.14), and the association was modified by the number of home visits received during pregnancy. In a population of at-risk mother-child dyads, preliminary evidence suggests that maternal ACEs have a relationship with offspring SCG5 DNAm that differs by the amount of prenatal HV.

Elevated Anthropometric and Metabolic Indicators among Young Adult Offspring of Mothers with Pregestational Diabetes: Early Results from the Transgenerational Effect on Adult Morbidity Study (the TEAM Study).

Exposure to maternal diabetes in utero increases the risk in the offspring for a range of metabolic disturbances. However, the timing and variability of in utero hyperglycemic exposure necessary to cause impairment have not been elucidated. The TEAM Study was initiated to evaluate young adult offspring of mothers with pregestational diabetes mellitus. This paper outlines the unique enrollment challenges of the TEAM Study and preliminary analysis of the association between exposure to diabetes in pregnancy and adverse metabolic outcomes. The TEAM Study enrolls offspring of women who participated in a Diabetes in Pregnancy (DiP) Program Project Grant between 1978 and 1995. The DiP Study collected medical and obstetric data across pregnancy. The first 96 eligible offspring of women with pregestational diabetes were age-, sex-, and race-matched to adults from the National Health and Nutrition Examination Survey (NHANES) 2015-2016 with an OGTT. Descriptive and regression analyses were employed to compare TEAM participants to NHANES participants. Among a subset of TEAM participants, we compared the metabolic outcomes across maternal glucose profiles using a longitudinal data clustering technique that characterizes level and variability, in maternal glucose across pregnancy. By comparing categories of BMI, TEAM Study participants had over 2.0 times the odds of being obese compared to matched NHANES participants (for class III obesity, OR = 2.81; 95% confidence interval (CI): 1.15, 6.87). Increasing levels of two-hour glucose were also associated with in utero exposure to pregestational diabetes in matched analyses. Exposure to pregestational diabetes in utero may be associated with an increased risk of metabolic impairment in the offspring with clinical implications.

Pregnancy and Infant Development (PRIDE)-a preliminary observational study of maternal adversity and infant development.

BACKGROUND: Children from socioeconomically disadvantaged families have a markedly elevated risk for impaired cognitive and social-emotional development. Children in poverty experience have a high risk for developmental delays. Poverty engenders disproportionate exposure to psychological adversity which may contribute to impaired offspring development; however the effect may be mitigated by social support and other aspects of resilience. Our objective was to determine the association between maternal stress, adversity and social support and early infant neurobehavior and child behavior at two and three years. METHODS: We conducted a longitudinal mother-infant cohort study nested within a regional home visiting program in Cincinnati, Ohio. Four home study visits were completed to collect measures of maternal stress, adversity and social support and infant and child behavior. A measure of infant neurobehavior ('high-arousal' infant) was derived from the NICU Network Neurobehavioral Scale (NNNS) at 1 month and externalizing and internalizing symptoms were measured by the Child Behavior Checklist (CBCL) at 24 and 36 months. Linear and logistic regression identified associations between maternal risk/protective factors and infant and child behavioral measures. We used stratification and multiplicative interaction terms to examine potential interactions. RESULTS: We enrolled n = 55 pregnant mothers and follow 53 mother-offspring dyads at 1 month, 40 dyads at 24 months and 27 dyads at 36 months. Maternal adversity and protective factors were not associated with neurobehavior at one month. However, maternal depression and measures of distress in pregnancy were significantly associated with internalizing and externalizing symptoms at 24 and 36 months. CONCLUSIONS: This pilot study established the feasibility of conducting longitudinal research within a community intervention program. In addition, although there were no statistically significant associations between maternal psychosocial factors in pregnancy and infant neurobehavior, there were several associations at 24 months, primarily internalizing symptoms, which persisted through 36 months. Future work will replicate findings within a larger study as well as explore mediators and modifiers of these associations.

Effectiveness of Interdisciplinary Leadership Training for Early Career Professionals in the Field of Developmental Disabilities.

INTRODUCTION: The purpose of this paper is to describe the curriculum and self-reported outcomes on measures of interdisciplinary leadership skills for work within the field of developmental disabilities from trainees in one interprofessional training program. METHODS: The paper highlights one program's curriculum and strategy for capturing self-report survey measures from trainees in cohorts from 2014-2018 (n = 86) on two surveys (Interdisciplinary Attitudes and Skills and Leadership Self-Evaluation Form) and three time points across the training year: before training (T1), mid-year (T2), and after training (T3). RESULTS: Data from 86 trainees are reported including demographics (nearly 80% white, 92% female), non-descriptive statistics due to non-normative samples, and tertiles demonstrating changes between time points. Significant differences between medians are reported between T1-T3 specifically related to utilizing interdisciplinary skills and gains in leadership competencies. Specific utilization of skills was reported to be 'Greatly' attributable to the LEND program related to sharing ideas and asking for help across disciplines. DISCUSSION: Trainees' self-report from before training to after training indicates an increase in competence and utilization of interdisciplinary skills to be expected from participation in the curriculum. Self-report measures are.

Opioid Requirement following Arthroscopic Knee Surgery: Are There Predictive Factors Associated with Long-Term Use.

The purpose of this study is to identify patterns of postoperative narcotic use and determine the impact of psychosocial and perioperative factors on postoperative opioid consumption following arthroscopic knee surgery. Fifty consecutive patients undergoing arthroscopic knee surgery were prospectively enrolled. Patients were contacted via telephone at 1 week postoperatively to report their pain level and opioid consumption. The patient was contacted again at 2 weeks, 4 weeks, and 90 days as necessary until opioid cessation, at which time the patient's plan for unused pills was inquired. Opioid consumption was compared using t-tests and one-way analysis of variance for demographic and surgical factors. Linear regression was used to determine whether the Pain Catastrophizing Scale (PCS), Resilience Scale (RS-11), International Knee Documentation Committee questionnaire, or patient-reported pain at 1 week predicted higher opioid consumption. The average morphine equivalent dose of opioid consumption was 142 mg. Sixty-four percent consumed less than 100 mg, and 68% discontinued opioid use by 1 week postoperatively. Seventy-four percent reported surplus pills, and 49% of those patients plans for pill disposal. Factors associated with higher consumption included undergoing a major procedure, having a regional anesthesia block, and higher area deprivation index score (p < 0.05). Higher PCS scores and reported average pain level at 1 week were predictive of higher opioid consumption (p < 0.05). In conclusion, a majority of patients undergoing outpatient knee surgery did not require the entirety of their narcotic prescription. The majority of patients consumed less than 100 mg of morphine equivalents and discontinued opioid use by 1 week postoperatively. Ligament reconstruction, living in an area with a higher index of deprivation, and higher score on the PCS were associated with greater opioid consumption. Overall, patient knowledge regarding opioid disposal was poor, and patients would likely benefit from additional education prior to surgery.

Long-Term Neurocognitive and Psychosocial Outcomes After Acute Myeloid Leukemia: A Childhood Cancer Survivor Study Report.

BACKGROUND: Survivors of childhood acute myeloid leukemia (AML) are vulnerable to medical late effects of treatment; however, less is known about their psychosocial outcomes. This study evaluated neurocognitive and psychosocial outcomes in long-term AML survivors treated with bone marrow transplantation (BMT) or intensive chemotherapy (IC) without BMT. METHODS: AML survivors (N = 482; median age at diagnosis = 8 [range = 0-20] years; median age at evaluation = 30 [range = 18-49] years) treated with BMT (n = 183) or IC (n = 299) and sibling controls (N = 3190; median age at evaluation = 32 [range = 18-58] years) from the Childhood Cancer Survivor Study were compared on emotional distress (Brief Symptom Inventory-18), neurocognitive problems (Childhood Cancer Survivor Study Neurocognitive Questionnaire), health-related quality of life (SF-36), and social attainment. Outcomes were dichotomized (impaired vs nonimpaired) using established criteria, and relative risks (RRs) were estimated with multivariable Poisson regression, adjusted for age at evaluation and sex. RESULTS: AML survivors were more likely than siblings to report impairment in overall emotional (RR = 2.19, 95% confidence interval [CI] = 1.51 to 3.18), neurocognitive (RR = 2.03, 95% CI = 1.47 to 2.79), and physical quality of life (RR = 2.71, 95% CI = 1.61 to 4.56) outcomes. Survivors were at increased risk for lower education (RR = 1.15, 95% CI = 1.03 to 1.30), unemployment (RR = 1.41, 95% CI = 1.16 to 1.71), lower income (RR = 1.39, 95% CI = 1.17 to 1.65), and not being married or having a partner (RR = 1.33, 95% CI = 1.17 to 1.51). BMT-treated survivors did not differ statistically significantly from IC-treated on any outcome measure. CONCLUSIONS: AML survivors are at increased risk for psychosocial impairment compared with siblings; however, BMT does not confer additional risk for psychosocial late effects compared with treatment without BMT.

Associations Between Maternal Community Deprivation and Infant DNA Methylation of the SLC6A4 Gene.

Introduction: Poverty is negatively associated with health and developmental outcomes. DNA methylation (DNAm) has been proposed as a mechanism that underlies the association between adversity experienced by mothers in poverty and health and developmental outcomes in their offspring. Previous studies have identified associations between individual-level measures of stress and adversity experienced by a mother during pregnancy and infant DNAm. We hypothesized that independent of individual stresses, a mother's community-level deprivation while she is pregnant may also be associated with DNAm among the genes of her offspring that are related to stress response and/or development. Methods: Pregnant mothers (N = 53) completed assessments that measured stress, adversity, and mental health. To evaluate community-level deprivation, mothers' addresses were linked to census-level socioeconomic measures including a composite index of deprivation that combines multiple community-level indicators such as income and highest level of education received. Infant buccal cells were collected at about age 4 weeks to measure DNAm of candidate genes including NR3C1, SCG5, and SLC6A4, which are associated with the stress response and or social and emotional development. Multivariable models were employed to evaluate the association between maternal community deprivation and infant DNAm of candidate genes. Results: No significant associations were identified between maternal community-level deprivation and the methylation of NR3C1 or SCG5, however, maternal community-level deprivation was significantly associated with higher mean methylation across 8 CpG sites in SLC6A4. Conclusion: This study identified an association between community-level measures of deprivation experienced by a mother during pregnancy and DNAm in their offspring. These findings may have implications for understanding how the community context can impact early biology and potential function in the next generation.

Combinations of adverse childhood events and risk of postpartum depression among mothers enrolled in a home visiting program.

PURPOSE: The purpose of this study was to examine how combinations of adverse childhood events (ACEs) contribute to the risk of postpartum depression and the mediating role of prenatal social support. METHODS: The Adverse Childhood Experiences Scale Questionnaire and the Edinburgh Postnatal Depression Scale Questionnaire were used to measure the study's exposure and outcome. Among a cohort of 419 mothers enrolled in a home visiting (HV) program, latent class analyses were used to identify classes of ACEs exposure. General linear models assessed the risk of postpartum depression, and prenatal social support was examined as a mediator. RESULTS: Four distinct classes of ACE exposure were identified. On the Edinburgh Postnatal Depression scale, mothers who were classified in Classes 1-3 scored higher by 2.6-4.4 points compared with women in Class 0. ACE class was found to be indirectly associated with postpartum depression scores through prenatal social support. CONCLUSIONS: Identifying combinations of ACEs in an HV program has the potential to improve the characterization of ACEs among low-income perinatal women in the United States. Elucidating how these combinations contribute to the risk of postpartum depression has the potential to identify women at increased risk, which can help HV programs prioritize prevention efforts.

A Nomogram for Predicting 30-day Mortality in Elderly Patients Undergoing Hemiarthroplasty for Femoral Neck Fractures.

INTRODUCTION: Femoral neck fractures in the elderly are increasingly common as a result of a growing geriatric population with 1-year mortality rates approaching 35%. While preoperative medical optimization and early time to surgery have reduced morbidity and mortality, patients with numerous medical comorbidities remain high risk for death in the perioperative period. Identifying those with greatest risk with a scoring system or nomogram may assist multidisciplinary teams in reducing mortality following hemiarthroplasty. PURPOSE: Identify predictors of 30-day mortality in elderly patients who underwent hemiarthroplasty for a femoral neck fracture to generate a predictive nomogram to determine the probability of post-operative mortality. METHODS: Retrospective evaluation using data from the ACS-NSQIP database from 2005 to 2014 with CPT code 27125 for hip hemiarthroplasty. Multiple factors including demographics and comorbidities were compared in patients who experienced 30-day mortality and those who did not. T-test and chi-square tests were used to analyze data and a multivariate model was generated using logistic regression. RESULTS: Advanced age (odds ratio (OR) 1.04), underweight BMI (OR 1.55), male sex (OR 1.80), reduced functional status (OR 2.04), heart failure within 30 days prior to surgery (OR 2.22), American Society of Anesthesiologists grade > 2 (OR > 2.50), disseminated cancer (OR 3.43) were all found to have statistically significant odds ratios for 30-day mortality following hemiarthroplasty. CONCLUSION: A tool based on easily identifiable risk factors, demographics, and comorbidities was developed that can help predict elderly patients who will experience mortality within 30 days of following hemiarthroplasty. In addition to identifying high risk patients, the nomogram can serve as a counseling tool for physicians to use with patients and their families to assist with better understanding of perioperative mortality risk.

Disparities Affect Developmental Risk for Head Start Preschoolers.

PURPOSE: This paper presents an analysis of Head Start (HStart) preschooler data by severity of developmental concern, while considering socio-demographic and other factors that highlight racial and ethnic disparities in the early identification of developmental delay or disability (DD). DESIGN AND METHODS: We conducted an analysis of 2014-2015 academic year data for preschool-aged children in HStart in both urban and suburban centers in a large Midwestern city. Descriptive statistics were used to determine the prevalence of developmental concerns and compare characteristics of children with mild-to-moderate versus severe developmental concerns; differences between groups were compared using t-tests and chi-square tests. Multivariate logistic regression was used to determine the independent effect of each predictor of concern severity. RESULTS: Nearly one-third of HStart preschoolers were identified with developmental concern; 70% were mild-to-moderate risk for DD and the remaining severe risk. Neither group was routinely referred to healthcare for evaluation or treatment, and most of the severe risk group did not qualify nor receive treatment for DD with an Individualized Education Plan. Suburban and urban preschoolers with severe concern were less likely to be African American or Latinx, suggesting that racially and ethnically diverse preschoolers in HStart may be under-identified and under-treated. CONCLUSIONS: Lags in the educational diagnosis of DD may mirror the disparities in diagnosis and treatment of DD among minority groups. Primary care is the first line for detection and treatment of DD, and offers a unique opportunity to act for racially and ethnically diverse HStart preschoolers disproportionately at-risk for DD.

Functional data analysis and prediction tools for continuous glucose-monitoring studies.

INTRODUCTION: To identify phenotypes of type 1 diabetes based on glucose curves from continuous glucose-monitoring (CGM) using functional data (FD) analysis to account for longitudinal glucose patterns. We present a reliable prediction model that can accurately predict glycemic levels based on past data collected from the CGM sensor and real-time risk of hypo-/hyperglycemic for individuals with type 1 diabetes. METHODS: A longitudinal cohort study of 443 type 1 diabetes patients with CGM data from a completed trial. The FD analysis approach, sparse functional principal components (FPCs) analysis was used to identify phenotypes of type 1 diabetes glycemic variation. We employed a nonstationary stochastic linear mixed-effects model (LME) that accommodates between-patient and within-patient heterogeneity to predict glycemic levels and real-time risk of hypo-/hyperglycemic by creating specific target functions for these excursions. RESULTS: The majority of the variation (73%) in glucose trajectories was explained by the first two FPCs. Higher order variation in the CGM profiles occurred during weeknights, although variation was higher on weekends. The model has low prediction errors and yields accurate predictions for both glucose levels and real-time risk of glycemic excursions. CONCLUSIONS: By identifying these distinct longitudinal patterns as phenotypes, interventions can be targeted to optimize type 1 diabetes management for subgroups at the highest risk for compromised long-term outcomes such as cardiac disease or stroke. Further, the estimated change/variability in an individual's glucose trajectory can be used to establish clinically meaningful and patient-specific thresholds that, when coupled with probabilistic predictive inference, provide a useful medical-monitoring tool.

RNA Interference-Mediated Inhibition of ESCRT in Mammalian Cells.

Specific depletion of proteins from cultured cells using RNA interference (RNAi) has been a useful technique in assessing protein function for many years. RNAi allows the degradation of specific, targeted mRNA, allowing the effects of protein depletion on cellular processes to be examined. Here, I present a protocol for the depletion of proteins from cultured HeLa cells and list specific reagents and considerations for targeting the endosomal sorting complexes required for transport (ESCRT).

Birth Planning in Uncertain or Life-Limiting Fetal Diagnoses: Perspectives of Physicians and Parents.

Background: Providers often use birth plans to document parents' wishes for their fetus with a life-limiting condition. Objective: The objective of the study was to (1) discover important components of a birth plan for parents and providers who carry them out, and (2) understand the experience of parents and providers with birth plans. Methods: The study design involves mixed-methods, descriptive, exploratory survey. This involves parents (n = 20) of a pregnancy complicated by a life-limiting diagnosis and providers who care for them (n = 116). The approach involves descriptive and univariate analyses for quantitative data and thematic analysis for qualitative data. Results: Consistent components for families and physicians were diagnosis and medical management of the infant. Families gave greater emphasis on memory-making preferences. Parents feel birth plans give them a sense of control. Themes emerged from parents' experience of creating a birth plan are as follows: sense of control, therapeutic, memory making, effective communication, feeling prepared, and unexpected events. Most physicians feel comfortable discussing goals of care with families but report insufficient time. The importance of components of birth plans and perception of the parents' understanding of the prognosis varied by specialty. Discussion: Birth plans are beneficial and provide a greater sense of control for parents. Most physicians feel comfortable utilizing them. More than one-third of the physicians do not feel that they have time to complete a birth plan with parents. Communication between physicians and families about limitations of the plan and the potential trajectories could be improved. Communication between maternal and neonatal care providers regarding parent expectations and understanding could also be improved.