Synaptic injury in the inner plexiform layer of the retina is associated with progression in multiple sclerosis.

While neurodegeneration underlies the pathological basis for permanent disability in multiple sclerosis (MS), predictive biomarkers for progression are lacking. Using an animal model of chronic MS, we find that synaptic injury precedes neuronal loss and identify thinning of the inner plexiform layer (IPL) as an early feature of inflammatory demyelination-prior to symptom onset. As neuronal domains are anatomically segregated in the retina and can be monitored longitudinally, we hypothesize that thinning of the IPL could represent a biomarker for progression in MS. Leveraging our dataset with over 800 participants enrolled for more than 12 years, we find that IPL atrophy directly precedes progression and propose that synaptic loss is predictive of functional decline. Using a blood proteome-wide analysis, we demonstrate a strong correlation between demyelination, glial activation, and synapse loss independent of neuroaxonal injury. In summary, monitoring synaptic injury is a biologically relevant approach that reflects a potential driver of progression.

Effects of homicide timing on test scores: Quasi-experimental evidence from two cities in Colombia.

This study examines the effect of homicides around schools on the standardized test scores of fifth and ninth graders (N = 4729; Mage = 12.71 years, SDage = 2.13) using a quasi-experimental design in two Colombian cities. Exposure to homicides occurring within 7 days of the test and within 500 m of the school decreases test scores by 0.10 SD. Effects show a greater sensitivity to timing than distance, becoming null as the time to the testing date increases but remaining consistent across larger radii. Since students in the study are on average exposed to 12.1 homicides per year, even short-lived learning losses can accumulate to impair learning for substantial portions of the school year. Findings are discussed, considering previous empirical work.

Remyelination protects neurons from DLK-mediated neurodegeneration.

Chronic demyelination is theorized to contribute to neurodegeneration and drive progressive disability in demyelinating diseases like multiple sclerosis. Here, we describe two genetic mouse models of inducible demyelination, one distinguished by effective remyelination, and the other by remyelination failure and persistent demyelination. By comparing these two models, we find that remyelination protects neurons from apoptosis, improves conduction, and promotes functional recovery. Chronic demyelination of neurons leads to activation of the mitogen-associated protein kinase (MAPK) stress pathway downstream of dual leucine zipper kinase (DLK), which ultimately induces the phosphorylation of c-Jun in the nucleus. Both pharmacological inhibition and CRISPR/Cas9-mediated disruption of DLK block c-Jun phosphorylation and the apoptosis of demyelinated neurons. These findings provide direct experimental evidence that remyelination is neuroprotective and identify DLK inhibition as a potential therapeutic strategy to protect chronically demyelinated neurons.

Unconditional Cash Transfers and Maternal Assessments of Children's Health, Nutrition, and Sleep: A Randomized Clinical Trial.

Importance: Children experiencing poverty are more likely to experience worse health outcomes, including injury, chronic illness, worse nutrition, and poorer sleep. The extent to which poverty reduction improves these outcomes is unknown. Objective: To evaluate the effect of a 3-year, monthly unconditional cash transfer on health, nutrition, sleep, and health care utilization among children experiencing poverty who were healthy at birth. Design, Setting, and Participants: This longitudinal randomized clinical trial recruited 1000 mother-infant dyads between May 2018 and June 2019. Dyads were recruited from postpartum wards in 12 hospitals in 4 US cities: New York, New York; Omaha, Nebraska; New Orleans, Louisiana; and Minneapolis/St Paul, Minnesota. Eligibility criteria included an annual income less than the federal poverty line, legal age for consent, English or Spanish speaking, residing in the state of recruitment, and an infant admitted to the well-baby nursery who will be discharged to the mother's custody. Data analysis was conducted from July 2022 to August 2023. Intervention: Mothers were randomly assigned to receive either a high-cash gift ($333/mo, or $3996/y) or a low-cash gift ($20/mo, or $240/y) for the first several years of their child's life. Main Outcomes and Measures: Primary preregistered outcomes reported here include an index of child health and medical care and child sleep disturbances. Secondary preregistered outcomes reported include children's consumption of healthy and unhealthy foods. Results: A total of 1000 mother-infant dyads were enrolled, with 400 randomized to the high-cash gift group and 600 to the low-cash gift group. Participants were majority Black (42%) and Hispanic (41%); 857 mothers participated in all 3 waves of data collection. We found no statistically detectable differences between the high-cash and low-cash gift groups in maternal assessments of children's health (effect size [ES] range, 0.01-0.08; SE range, 0.02-0.07), sleep (ES range, 0.01-0.10; SE, 0.07), or health care utilization (ES range, 0.01-0.11; SE range, 0.03-0.07). However, mothers in the high-cash gift group reported higher child consumption of fresh produce at child age 2 years, the only time point it was measured (ES, 0.17; SE, 0.07; P = .03). Conclusions and Relevance: In this study, unconditional cash transfers to mothers experiencing poverty did not improve reports of their child's health, sleep, or health care utilization. However, stable income support of this magnitude improved toddlers' consumption of fresh produce. Healthy newborns tend to grow into healthy toddlers, and the impacts of poverty reduction on children's health and sleep may not be fully borne out until later in life. Trial Registration: ClinicalTrials.gov Identifier: NCT03593356.

Predicting adolescent and young adult outcomes from emotional support and cognitive stimulation offered by preschool-age home and early care and education settings.

Children's early environmental experiences are often considered highly influential for later life development. Yet, environmental contexts, such as the home and early care and education (ECE) setting, and multiple aspects of each setting, are not typically examined concurrently. In this study, we examined associations between cognitive stimulation and emotional support in the home and ECE setting during the preschool years (36-54 months) with adolescent (age 15; n = 708; 52% female) and adult (age 26; n = 584; 54% female) outcomes using data from the Study of Early Child Care and Youth Development, a study conducted at 10 sites across the United States. Cognitive stimulation in the home was significantly related to increased academic achievement at age 15 and educational attainment at age 26. Home emotional support was related to decreased behavior problems and increased social skills at age 15. No significant associations were found between either emotional support or cognitive stimulation in ECE and children's later development. These findings provide further support that the child's home environment during early childhood plays a substantial role in development. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Effect of a U.S. Poverty Reduction Intervention on Maternal Assessments of Young Children's Health, Nutrition, and Sleep: A Randomized Control Trial.

Importance: Children experiencing poverty are more likely to experience worse health outcomes during the first few years of life, including injury, chronic illness, worse nutrition, and poorer sleep. The extent to which a poverty reduction intervention improves children's health, nutrition, sleep, and healthcare utilization is unknown. Objective: To determine the effect of a 3-year, monthly unconditional cash transfer on health, nutrition, sleep, and healthcare utilization of children experiencing poverty who are healthy at birth. Design: Longitudinal randomized control trial. Setting: Mother-infant dyads were recruited from postpartum wards in 12 hospitals in four cities across the U.S. Participants: 1,000 mothers were enrolled in the study. Eligibility criteria included: an annual income below the federal poverty line, being of legal age for consent, speaking English or Spanish, residing in the state of recruitment, and having an infant admitted to the well-baby nursery with plans to be discharged to the custody of the mother. Intervention: Mothers were randomly assigned to receive either a high-cash gift ($333 per month, or $3,996 per year; n=400) or a low-cash gift ($20 per month, or $240 per year; n=600) for the first several years of their child's life. Main Outcomes and Measures: Pre-registered maternal assessments of the focal child's health, nutrition, sleep, and healthcare utilization were collected at children's ages 1, 2, and 3. Results: Enrolled participants were majority Black (42%) and Hispanic (41%). 857 mothers participated in all three waves of data collection. We found no statistically detectable differences between the high-cash and low-cash gift groups in maternal assessments of children's overall health, sleep, or healthcare utilization. However, mothers in the high-cash gift group reported higher child consumption of fresh produce compared with mothers in the low-cash gift group at age 2, the only time point it was measured (ß=0.17, SE=0.07, p=0.03). Conclusions and Relevance: In this RCT, unconditional cash transfers to mothers experiencing poverty did not improve their reports of their child's health, sleep, or healthcare utilization. However, stable income support of this magnitude improved toddler's consumption of fresh produce. Healthy newborns tend to grow into healthy toddlers, and the impacts of poverty reduction on children's health and sleep may not be fully borne out until later in life. Trial Registration: Baby's First Years (BFY; ID NCT03593356) https://clinicaltrials.gov/ct2/show/NCT03593356?term=NCT03593356&draw=2&rank=1.

Attention and behavior problems in childhood predict adult financial status, health, and criminal activity: A conceptual replication and extension of Moffitt et al. (2011) using cohorts from the United States and the United Kingdom.

This study is a conceptual replication of a widely cited study by Moffitt et al. (2011) which found that attention and behavior problems in childhood (a composite of impulsive hyperactive, inattentive, and impulsive-aggressive behaviors labeled "self-control") predicted adult financial status, health, and criminal activity. Using data from longitudinal cohort studies in the United States (n = 1,168) and the United Kingdom (n = 16,506), we largely reproduced their pattern of findings that attention and behavior problems measured across the course of childhood predicted a range of adult outcomes including educational attainment (ßU.S. = -0.22, ßU.K. = -0.13) and spending time in jail (ORU.S. = 1.74, ORU.K. = 1.48). We found that associations with outcomes in education, work, and finances diminished in the presence of additional covariates for children's home environment and achievement but associations for other outcomes were more robust. We also found that attention and behavior problems across distinct periods of childhood were associated with adult outcomes. Specific attention and behavior problems showed some differences in predicting outcomes in the U.S. cohort, with attention problems predicting lower educational attainment and hyperactivity/impulsivity predicting ever spending time in jail. Together with the findings from Moffitt et al., our study makes clear that childhood attention and behavior problems are associated with a range of outcomes in adulthood for cohorts born in the 1950s, 1970s, and 1990s across three countries. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

EVALUATING CONTRADICTORY EXPERIMENTAL AND NON-EXPERIMENTAL ESTIMATES OF NEIGHBORHOOD EFFECTS ON ECONOMIC OUTCOMES FOR ADULTS.

Although non-experimental studies find robust neighborhood effects on adults, such findings have been challenged by results from the Moving to Opportunity (MTO) residential mobility experiment. Using a within-study comparison design, this paper compares experimental and non-experimental estimates from MTO and a parallel analysis of the Panel Study of Income Dynamics (PSID). Striking similarities were found between non-experimental estimates based on MTO and PSID. No clear evidence was found that different estimates are related to duration of adult exposure to disadvantaged neighborhoods, non-linear effects of neighborhood conditions, magnitude of the change in neighborhood context, frequency of moves, treatment effect heterogeneity, or measurement, although uncertainty bands around our estimates were sometimes large. One other possibility is that MTO-induced moves might have been unusually disruptive, but results are inconsistent for that hypothesis. Taken together, the findings suggest that selection bias might account for evidence of neighborhood effects on adult economic outcomes in non-experimental studies.

End of the road: Astrocyte endfeet regulate OPC migration and myelination.

Oligodendrocyte precursor cells (OPCs) use the vasculature as a scaffold for their migration. In this issue of Neuron, Su et al. determine that astrocytic ensheathment of the vasculature mediates OPC detachment from blood vessels via the secretion of semaphorins, regulating the timing of oligodendrocyte differentiation.

Thanksgiving and Christmas gatherings before the 2020-21 winter surge of COVID-19 in the United States.

Objective: COVID-19 in the US disproportionately affected, and continues to affect, racial/ethnic minorities. Although risky social gatherings for Thanksgiving and Christmas in 2020 contributed substantially to the "winter surge" in cases and deaths, no research examines potential racial/ethnic differences in behaviors related to holiday gatherings. Design: We used the Understanding America Survey (UAS) - Coronavirus Tracking, a nationally representative study of US adults, to examine associations between race/ethnicity and risky holiday gathering behavior (i.e., gathering with non-household members and with little to no social distancing or mask-wearing). We applied logistic regression models to examine racial/ethnic and socioeconomic differences in risky holiday gatherings while accounting for a person's pre-holiday perception of COVID-19 risk as well as related behaviors. Results: Non-Hispanic Black adults showed a lower prevalence of attending a risky Thanksgiving gathering than did non-Hispanic White adults (15 % vs 43 %, p <.001). The magnitude of this racial/ethnic difference was also found for risky Christmas gatherings. Hispanic and "Other" race/ethnicity adults also appeared less likely than non-Hispanic whites to attend a risky holiday gathering. Higher-income households attended a risky holiday gathering more frequently, when compared with lower income households (p <.001). Logistic regression results, which controlled for other COVID-19 related behaviors, support these main findings. Conclusions: Racial/ethnic minorities, and non-Hispanic Black adults in particular, appeared least likely to have engaged in risky holiday gatherings in late 2020. If replicated, our findings appear consistent with the notion that behavioral modification among racial/ethnic minorities may have reduced the intensity of the 2020/21 "winter surge" in COVID-19.

Unconditional cash transfers and maternal substance use: findings from a randomized control trial of low-income mothers with infants in the U.S.

BACKGROUND: Policy debates over anti-poverty programs are often marked by pernicious stereotypes suggesting that direct cash transfers to people residing in poverty encourage health-risking behaviors such as smoking, drinking, and other substance use. Causal evidence on this issue is limited in the U.S. Given the prominent role of child allowances and other forms of cash assistance in the 2021 American Rescue Plan and proposed Build Back Better legislation, evidence on the extent to which a monthly unconditional cash gift changes substance use patterns among low-income mothers with infants warrants attention, particularly in the context of economic supports that can help improve early environments of children. METHOD: We employ a multi-site, parallel-group, randomized control trial in which 1,000 low-income mothers in the U.S. with newborns were recruited from hospitals shortly after the infant's birth and randomly assigned to receive either a substantial ($333) or a nominal ($20) monthly cash gift during the early years of the infant's life. We estimate the effect of the unconditional cash transfer on self-report measures of maternal substance use (i.e., alcohol, cigarette, or opioid use) and household expenditures on alcohol and cigarettes after one year of cash gifts. RESULTS: The cash gift difference of $313 per month had small and statistically nonsignificant impacts on group differences in maternal reports of substance use and household expenditures on alcohol or cigarettes. Effect sizes ranged between - 0.067 standard deviations and + 0.072 standard deviations. The estimated share of the $313 group difference spent on alcohol and tobacco was less than 1%. CONCLUSIONS: Our randomized control trial of monthly cash gifts to mothers with newborn infants finds that a cash gift difference of $313 per month did not significantly change maternal use of alcohol, cigarettes, or opioids or household expenditures on alcohol or cigarettes. Although the structure of our cash gifts differs somewhat from that of a government-provided child allowance, our null effect findings suggest that unconditional cash transfers aimed at families living in poverty are unlikely to induce large changes in substance use and expenditures by recipients. TRIAL REGISTRATION: Registered on Clinical Trials.gov NCT03593356 in July of 2018.

The impact of a poverty reduction intervention on infant brain activity.

Early childhood poverty is a risk factor for lower school achievement, reduced earnings, and poorer health, and has been associated with differences in brain structure and function. Whether poverty causes differences in neurodevelopment, or is merely associated with factors that cause such differences, remains unclear. Here, we report estimates of the causal impact of a poverty reduction intervention on brain activity in the first year of life. We draw data from a subsample of the Baby's First Years study, which recruited 1,000 diverse low-income mother-infant dyads. Shortly after giving birth, mothers were randomized to receive either a large or nominal monthly unconditional cash gift. Infant brain activity was assessed at approximately 1 y of age in the child's home, using resting electroencephalography (EEG; n = 435). We hypothesized that infants in the high-cash gift group would have greater EEG power in the mid- to high-frequency bands and reduced power in a low-frequency band compared with infants in the low-cash gift group. Indeed, infants in the high-cash gift group showed more power in high-frequency bands. Effect sizes were similar in magnitude to many scalable education interventions, although the significance of estimates varied with the analytic specification. In sum, using a rigorous randomized design, we provide evidence that giving monthly unconditional cash transfers to mothers experiencing poverty in the first year of their children's lives may change infant brain activity. Such changes reflect neuroplasticity and environmental adaptation and display a pattern that has been associated with the development of subsequent cognitive skills.

A Roadmap to Reducing Child Poverty.

Can the United States dramatically reduce the number of its children living in poverty? This article summarizes key conclusions of the report issued by National Academies of Sciences, Engineering and Medicine's Committee on Building an Agenda to Reduce the Number of Children in Poverty by Half in 10 Years. These conclusions focus on the causal evidence linking poverty reduction and child well-being as well as a host of policy and program ideas directed toward poverty reduction. The Committee found that packages of work-oriented and income support program are able to simultaneously reduce child poverty and increase the number of adult workers in low-income families. Costs of these policies are also considered.

Baby's First Years: Design of a Randomized Controlled Trial of Poverty Reduction in the United States.

Childhood economic disadvantage is associated with lower cognitive and social-emotional skills, reduced educational attainment, and lower earnings in adulthood. Despite these robust correlations, it is unclear whether family income is the cause of differences observed between children growing up in poverty and their more fortunate peers or whether these differences are merely due to the many other aspects of family life that co-occur with poverty. Baby's First Years is the first randomized controlled trial in the United States designed to identify the causal impact of poverty reduction on children's early development. A total of 1000 low-income mothers of newborns were enrolled in the study and began receiving a monthly unconditional cash gift for the first several years of their children's lives. Mothers were randomly assigned to receive either a large monthly cash gift or a nominal monthly cash gift. All monthly gifts are administered via debit card and can be freely spent with no restrictions. Baby's First Years aims to answer whether poverty reduction in early childhood (1) improves children's developmental outcomes and promotes healthier brain functioning, and (2) improves family functioning and better enables parents to support child development. Here we present the rationale and design of the study as well as potential implications for science and policy.

Chronic Demyelination and Axonal Degeneration in Multiple Sclerosis: Pathogenesis and Therapeutic Implications.

PURPOSE OF REVIEW: Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system (CNS). Inflammatory attacks in MS lead to both demyelination and axonal damage. However, due to incomplete remyelination most MS lesions remain chronically demyelinated. In parallel, there is axonal degeneration in the CNS of MS patients, contributing to progressive disability. There are currently no approved therapies that adequately restore myelin or protect axons from degeneration. In this review, we will discuss the pathophysiology of axonal loss and chronic demyelination in MS and how understanding this pathophysiology is leading to the development of new MS therapeutics. RECENT FINDINGS: Ongoing research into the function of oligodendrocytes and myelin has revealed the importance of their relationship with neuronal health. Demyelination in MS leads to a number of pathophysiologic changes contributing to axonal generation. Among these are mitochondrial dysfunction, persistent neuroinflammation, and the effects of reactive oxygen and nitrogen species. With this information, we review currently approved and investigational therapies designed to restore lost or damaged myelin and protect against neuronal degeneration. The development of therapies to restore lost myelin and protect neurons is a promising avenue of investigation for the benefit of patients with MS.

Neuron-Oligodendrocyte Interactions in the Structure and Integrity of Axons.

The myelination of axons by oligodendrocytes is a highly complex cell-to-cell interaction. Oligodendrocytes and axons have a reciprocal signaling relationship in which oligodendrocytes receive cues from axons that direct their myelination, and oligodendrocytes subsequently shape axonal structure and conduction. Oligodendrocytes are necessary for the maturation of excitatory domains on the axon including nodes of Ranvier, help buffer potassium, and support neuronal energy metabolism. Disruption of the oligodendrocyte-axon unit in traumatic injuries, Alzheimer's disease and demyelinating diseases such as multiple sclerosis results in axonal dysfunction and can culminate in neurodegeneration. In this review, we discuss the mechanisms by which demyelination and loss of oligodendrocytes compromise axons. We highlight the intra-axonal cascades initiated by demyelination that can result in irreversible axonal damage. Both the restoration of oligodendrocyte myelination or neuroprotective therapies targeting these intra-axonal cascades are likely to have therapeutic potential in disorders in which oligodendrocyte support of axons is disrupted.

The Kindergarten Early Development Instrument Predicts Third Grade Academic Proficiency.

School readiness skills predict later educational achievement, health, and social-emotional outcomes. Measures of school readiness can provide valuable information to assess both the impact of strategies and policies that prepare children for school as well as informing strategies for improving children's educational trajectories across their school years. The Early Development Instrument (EDI) is a measure of school readiness skills based on teacher-reported observational recall. It has been used extensively in Canada and Australia and is in the early stages of adoption in a number of U.S. cities. The current study uses data from roughly 3,000 children followed longitudinally from kindergarten through third grade from 7 school districts in Orange County, California. The study assesses whether EDI ratings in kindergarten predict third grade proficiency in mathematics and English Language Arts on state assessments. Ratings on the EDI were strongly associated with proficiency in both academic areas, even in the presence of controls for child-level factors and neighborhood fixed effects. Among its components, ratings on the language and cognitive development, communication skills and general knowledge, and social competence domains strongly differentiated children's likelihood of later proficiency in both academic areas. Implications for improving comprehensive early childhood education and schooling policies based on indicators of school readiness are discussed.