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Importance: The 2021 Child Tax Credit (CTC) expansion, as part of the American Rescue Plan Act, offered financial relief through generous monthly tax benefits to families with children amid the COVID-19 pandemic. In light of heightened concerns about mental health during the pandemic, the expanded CTC may have alleviated parental mental health challenges, especially within families with low income. Objective: To investigate the association between the 2021 CTC expansion and mental health among parents with low income as measured by depression and anxiety symptoms. Design, Setting, and Participants: This repeated cross-sectional study used data from the Household Pulse Survey covering April 14, 2021, to January 10, 2022, in the US. A difference-in-difference-in-differences estimator combined with propensity score matching was used to estimate the association of the expanded CTC with mental health symptoms among households with income less than $35 000. Exposure: The monthly payment of expanded CTC from July 15 to December 15, 2021. Main Outcomes and Measures: Parental mental health was measured by analyzing depression and anxiety symptoms using logistic regression. Results: The weighted sample comprised 546 366 adults (mean [SD] age, 43.02 [14.54] years; 52.9% female). The most common education level was high school or less (36.0%), the highest frequency of household income distribution was $50 000 to $74 999 (16.1%), and the majority of the sample was employed (67.3%). The weighted mean (SD) number of children in the household was 0.92 (1.18). For the full sample, receiving expanded CTC benefits was associated with lower odds of experiencing anxiety symptoms (odds ratio, 0.730; 95% CI, 0.598-0.890). Subgroup analyses indicated that the positive associations of the policy with anxiety symptoms were particularly pronounced among the female, working-age (17-60 years), non-Hispanic White, and higher education groups. However, the policy expansion had no association with depression. Conclusions and Relevance: These findings may provide valuable evidence for policy makers to consider when deliberating on the possibility of making the CTC expansion permanent or transforming it into a universal program.

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Childhood trauma and interpersonal sensitivity impact the development of mood disorders. In this study, we investigate the association between childhood trauma and interpersonal sensitivity in patients with mood disorders. A total 775 patients (major depressive disorder [MDD, n = 241], bipolar I disorder [BD I, n = 119], and bipolar II disorder [BD II, n = 415]) and 734 controls. For evaluation, we used the Childhood Trauma Questionnaire-Short Form (CTQ) and Interpersonal Sensitivity Measure (IPSM). We examined between-group differences for each subscale in the CTQ and IPSM. Patients with BD II had significantly higher IPSM total scores than patients with MDD, BD I, or controls. The CTQ total score was related to the IPSM total score in all participants and subgroups. Among the CTQ subscales, emotional abuse showed the highest correlation with the IPSM total score, while separation anxiety and fragile inner self showed higher positive correlations with CTQ than the other subscales of IPSM in all patient groups and the control group, respectively. The findings reveal that childhood trauma and interpersonal sensitivity are positively correlated among patients with MDD, BD I, and BD II, and that interpersonal sensitivity is higher in patients with BD II than those with BD I or MDD. Childhood trauma is associated with interpersonal sensitivity, and each trauma type has a different impact on mood disorders. We expect that this study will encourage future research on interpersonal sensitivity and childhood trauma in mood disorders to improve treatment approaches.

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This paper provides new evidence on inequalities in resources for children age 3-4 by parental education using harmonized data from six advanced industrialized countries-United States, United Kingdom, France, Germany, Netherlands, and Japan-that represent different social welfare regime types. We analyze inequalities in two types of resources for young children-family income, and center-based child care-applying two alternative measures of parental education-highest parental education, and maternal education. We hypothesize that inequalities in resources by parental education will be less pronounced in countries where social policies are designed to be more equalizing. The results provide partial support for this hypothesis: the influence of parental education on resources for children does vary by the social policy context, although not in all cases. We also find that the measurement of parental education matters: income disparities are smaller under a maternal-only definition whereas child care disparities are larger. Moreover, the degree of divergence between the two sets of estimates differs across countries. We provide some of the first systematic evidence about how resources for young children vary depending on parents' education and the extent to which such inequalities are buffered by social policies. We find that while early inequalities are a fact of life in all six countries, the extent of those inequalities varies considerably. Moreover, the results suggest that social policy plays a role in moderating the influence of parental education on resources for children.

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We examined whether inaccurate teacher judgements of primary school student achievement correlate with students' gender and whether such bias contributes to gender achievement gaps in language and mathematics. Our study used ex-post harmonised longitudinal data from England, Germany, and the US. We observed domain-specific teacher judgement bias with a positive bias for girls in the language domain and for boys in mathematics. Furthermore, biased teacher judgements partly mediated the effect of gender on later achievement. Despite these common findings, cross-country differences emerged in the extent of teacher judgement bias as well as its mediation of gender achievement gaps. We conclude that this is a topic of relevance across national contexts and where the institutional and societal setting needs more attention in future research.

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BACKGROUND: There are significant cross-country differences in socio-economic gradients in later childhood and adulthood overweight/obesity; few studies assess whether this cross-national variation is evident from early childhood. Furthermore, the role of childcare in explaining overweight/obesity gradients might vary across countries, given differences in access, quality and heterogeneity within. Additionally, childcare is linked to parental characteristics such as maternal employment. The interplay between childcare and employment in producing early overweight/obesity gradients has received little attention, and might vary cross-nationally. METHODS: Using harmonized data from six high-quality, large datasets, we explore the variation in gradients in early overweight/obesity (at age 3-4 years old) by parental education across several high-income countries (USA, UK, France, the Netherlands, Germany and Japan). We then assess whether differential formal group care use attenuates some of these gradients, and whether this varies across maternal employment. RESULTS: Gradients in early childhood overweight/obesity by parental education are evident across several developed countries. Countries with higher overall prevalence of early overweight/obesity did not have the largest inequalities across education groups. The contribution of formal group care to producing these gradients varied across countries and across maternal employment status. CONCLUSION: Early childhood inequalities in overweight/obesity are pervasive across developed countries, as noted for older children and adults. However, mechanisms producing these gradients vary across national contexts. Our study shows that, given the right context, quality childcare and maternal employment can successfully support healthy weight trajectories and not contribute (or even reduce) social inequalities in early overweight/obesity.

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Socioeconomic inequalities in childhood Body Mass Index (BMI) are becoming increasingly more pronounced across the world. Although countries differ in the direction and strength of these inequalities, cross-national comparative research on this topic is rare. This paper draws on harmonized longitudinal cohort data from four wealthy countries-Germany, the Netherlands, the United Kingdom (UK), and the United States (US)-to 1) map cross-country differences in the magnitude of socioeconomic inequalities in childhood BMI, and 2) to examine cross-country differences in the role of three energy-balance-related behaviors-physical activity, screen time, and breakfast consumption-in explaining these inequalities. Children were aged 5-7 at our first timepoint and were followed up at age 8-11. We used data from the German National Educational Panel Study, the Dutch Generation R study, the UK Millennium Cohort Study and the US Early Childhood Longitudinal-Kindergarten Study. All countries revealed significant inequalities in childhood BMI. The US stood out in having the largest inequalities. Overall, inequalities between children with low versus medium educated parents were smaller than those between children with high versus medium educated parents. The role of energy-balance-related behaviors in explaining inequalities in BMI was surprisingly consistent. Across countries, physical activity did not, while screen time and breakfast consumption did play a role. The only exception was that breakfast consumption did not play a role in the US. Cross-country differences emerged in the relative contribution of each behavior in explaining inequalities in BMI: Breakfast consumption was most important in the UK, screen time explained most in Germany and the US, and breakfast consumption and screen time were equally important in the Netherlands. Our findings suggest that what constitutes the most effective policy intervention differs across countries and that these should target both children from medium as well as low educated families.

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OBJECTIVE: Mood disorder and borderline personality pathology (BPP) are frequently comorbid and relate to childhood trauma. We investigated the relationship between childhood trauma and BPP features in mood disorder patients versus controls. METHODS: A total of 488 mood disorder patients, particularly major depressive disorder (MDD), bipolar I disorder (BD I), and bipolar II disorder (BD II), and 734 controls were included. We examined between-group BPP-related differences and correlated between BPP and childhood trauma using the Childhood Trauma Questionnaire-Short Form (CTQ) and the Personality Assessment Inventory-Borderline Features Scale. RESULTS: BD II patients showed significantly higher BPP. Emotional abuse and neglect were prominently associated with BPP, while affective instability and negative relationships exhibited a stronger association with childhood trauma. We also found a positive relationship between childhood trauma and BPP in MDD, BD I, and BD II patients. CONCLUSION: The findings of the present study imply that BPP features are more likely to be found in patients with BD II than BD I or MDD. Mood disorder patients with severe childhood trauma may have higher BPP features. Thus, further study of the relationship between childhood trauma and BPP features could improve the therapeutic approaches and help understand patients with mood disorders.

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BACKGROUND: Child allowance (CA) in South Korea was first introduced in September 2018. CA provides a monthly allowance to children from birth to age 5. To date, existing studies on the effects of CA in Korea have focused mainly on household economic outcomes. The current study is the first to examine the effect of CA on maternal physical and mental health, measured by self-reported health status, depression, and life satisfaction. METHODS: We use nationally representative data from the Korea Welfare Panel Study (KOWEPS) from 2017 to 2018. The analytic sample consists of 772 Korean mothers whose youngest child is between age 2 and age 7. Taking advantage of an exogenous policy change and the age eligibility of the policy, we employ a difference-in-regression-discontinuities (DRD) strategy to identify the effects of CA on self-reported health status, depression, and life satisfaction. RESULTS: Overall, we find suggestive evidence that the introduction of CA contributed to reducing depression while improving self-reported health and life satisfaction. In particular, the policy reform had a significant effect on life satisfaction, showing that CA improves life satisfaction by 0.497 points. CONCLUSIONS: Results suggest that CA can improve both physical and mental health for eligible mothers. Such findings are indicative of a causal link between income and health. There has been a recent political movement to raise the age threshold of CA to up to age 18 to cover older children and increase benefit levels. Our findings provide important policy implications for the political discussion on CA expansion.

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The University of North Dakota's comprehensive approach aims to boost American Indian representation in medicine and public health.

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Human pluripotent stem cells (hPSCs) are an essential cell source in tissue engineering, studies of development, and disease modeling. Efficient, broadly amenable protocols for rapid lineage induction of hPSCs are of great interest in the stem cell biology field. We describe a simple, robust method for differentiation of hPSCs into mesendoderm in defined conditions utilizing single-cell seeding (SCS) and BMP4 and Activin A (BA) treatment. BA treatment was readily incorporated into existing protocols for chondrogenic and endothelial progenitor cell differentiation, while fine-tuning of BA conditions facilitated definitive endoderm commitment. After prolonged differentiation in vitro or in vivo, BA pretreatment resulted in higher mesoderm and endoderm levels at the expense of ectoderm formation. These data demonstrate that SCS with BA treatment is a powerful method for induction of mesendoderm that can be adapted for use in mesoderm and endoderm differentiation.

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Dysfunction of gamma-aminobutyric acid (GABA) and/or glutamate neurotransmitter systems have increasingly been implicated in the aetiology of Major Depressive Disorder (MDD). It has been proposed that alterations in GABA and/or glutamate result in an imbalance of inhibition and excitation. In a review of the current literature, we identified studies using Magnetic Resonance Spectroscopy (MRS) to examine the neurotransmitters GABA, glutamate, and the composite glutamate/glutamine measure Glx in patients diagnosed with MDD and healthy controls. Results showed patients with MDD had significantly lower GABA levels compared to controls (-0.35 [-0.61,-0.10], p = 0.007). No significant difference was found between levels of glutamate. Sub-analyses were performed, including only studies where the Anterior Cingulate Cortex (ACC) was the region of interest. GABA and Glx levels were lower in the ACC of MDD patients (-0.56 [-0.93,-0.18] p = 0.004, and 0.40 [-0.81,0.01] p = 0.05). This review indicates widespread cortical reduction of GABA in MDD, with a trend towards a localised reduction of Glx in the ACC. However, given both GABA and glutamate appear decreased a simple interpretation in terms of an imbalance of overall excitation-inhibition is not feasible.

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The stakes are particularly high when interpretations differ on evidence for treating diabetes, a condition affecting 30 million Americans and costing $245 billion annually. New guidelines from the American College of Physicians recommend less stringent blood sugar targets for most people with diabetes. Other professional groups think that's a terrible idea.

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Varying drug prices by indication could be an important value-based strategy in oncology, where multiple indications are becoming the rule. But will administrative costs offset any benefit? And legal and regulatory obstacles could get in the way.

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Building on a similar effort in California, Catalyst for Payment Reform is proposing a standardized set of 50 ACO measures. A timely development. In the first quarter of last year, an estimated 19.1 million lives were covered by 715 commercial ACOs, compared with 17.2 million lives a year earlier.

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Community health workers liaise between underserved populations and clinicians, help patients and resources to manage disease, and provide health education, informal counseling, and social support. Interest in community health workers is shifting away from narrowly focused intervention on a single disease toward care coordination of multiple chronic conditions.

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To take just one example: A 2017 meta-analysis published in the Cochrane Database of Systematic Reviews found that interventions with financial incentives-typically small vouchers ($50 monthly or less) for retail items like groceries-increased smoking cessation rates during pregnancy.

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Ideally, disease modeling using patient-derived induced pluripotent stem cells (iPSCs) enables analysis of disease initiation and progression. This requires any pathological features of the patient cells used for reprogramming to be eliminated during iPSC generation. Hutchinson-Gilford progeria syndrome (HGPS) is a segmental premature aging disorder caused by the accumulation of the truncated form of Lamin A known as Progerin within the nuclear lamina. Cellular hallmarks of HGPS include nuclear blebbing, loss of peripheral heterochromatin, defective epigenetic inheritance, altered gene expression, and senescence. To model HGPS using iPSCs, detailed genome-wide and structural analysis of the epigenetic landscape is required to assess the initiation and progression of the disease. We generated a library of iPSC lines from fibroblasts of patients with HGPS and controls, including one family trio. HGPS patient-derived iPSCs are nearly indistinguishable from controls in terms of pluripotency, nuclear membrane integrity, as well as transcriptional and epigenetic profiles, and can differentiate into affected cell lineages recapitulating disease progression, despite the nuclear aberrations, altered gene expression, and epigenetic landscape inherent to the donor fibroblasts. These analyses demonstrate the power of iPSC reprogramming to reset the epigenetic landscape to a revitalized pluripotent state in the face of widespread epigenetic defects, validating their use to model the initiation and progression of disease in affected cell lineages.

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STUDY OBJECTIVE: Patients with obstructive sleep apnea (OSA) frequently exhibit higher rates of dyslipidemia, a risk factor for cardiovascular and cerebrovascular disorders. Treatment for OSA by CPAP may improve cholesterol metabolism. This meta-regression analysis (MA) estimates the effect of CPAP treatment on dyslipidemia. METHODS: PubMed and Cochrane libraries were searched by utilizing different combinations of keywords: CPAP, obstructive sleep apnea, serum lipids, dyslipidemia, cholesterol, total cholesterol (TC), low density lipoprotein, LDL, high density lipoprotein, HDL, triglyceride, and TG. Inclusion criteria were: (1) English articles and (2) studies with an adult population with the diagnosis of OSA who were treated with CPAP. The OSA group must have cholesterol profile including TC, LDLc, HDLc, and TG, without and with CPAP treatment. Fifty-four studies were reviewed, while 29 studies pooled for MA. RESULTS: Thirty-four datasets from 29 studies with 1,958 subjects pooled. Treatment duration range was from 2 days to 1 year. TC standardized mean differences (SMD) ranged from -41.5 to -0.077, pooled mean difference (PMD) was -5.660 (LL -6.715 to UL -4.606, p < 0.001). SMD in LDL ranged from -3.7 to 0; PMD was -0.488 (LL -0.715 to UL -0.261, p < 0.001). HDL SMD ranged from -0.498 to 1.94. The PMD was 0.207 (LL 0.05 to UL 0.364, p < 0.01). TG SMD ranged from -9.327 to 1.98; PMD was -0.054 (LL -0.124 to UL 0.016, p < 0.129). CONCLUSIONS: CPAP treatment for OSA seems to improve dyslipidemia (decrease in total cholesterol and LDL, and increase in HDL). It does not appear to affect TG levels.

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Induced-pluripotent stem cells (iPSCs) are a potential alternative cell source in regenerative medicine, which includes the use of differentiated iPSCs for cell therapies to treat coronary artery and/or peripheral arterial diseases. Late-outgrowth endothelial progenitor cells (late-EPCs) are a unique primary cell present in peripheral blood that exhibit high proliferative capacity, are being used in a wide variety of clinical trials, and have the ability to differentiate into mature endothelial cells. The objective of this study was to reprogram peripheral blood-derived late-EPCs to a pluripotent state under feeder-free and defined culture conditions. Late-EPCs that were retrovirally transduced with OCT4, SOX2, KLF4, c-MYC, and iPSC colonies were derived in feeder-free and defined media conditions. EPC-iPSCs expressed pluripotent markers, were capable of differentiating to cells from all three germ-layers, and retained a normal karyotype. Transcriptome analyses demonstrated that EPC-iPSCs exhibit a global gene expression profile similar to human embryonic stem cells (hESCs). We have generated iPSCs from late-EPCs under feeder-free conditions. Thus, peripheral blood-derived late-outgrowth EPCs represent an alternative cell source for generating iPSCs.

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Functional nucleic acids are DNA and RNA aptamers that bind targets, or they are deoxyribozymes and ribozymes that have catalytic activity. These functional DNA and RNA sequences can be identified from random-sequence pools by in vitro selection, which requires choosing the length of the random region. Shorter random regions allow more complete coverage of sequence space but may not permit the structural complexity necessary for binding or catalysis. In contrast, longer random regions are sampled incompletely but may allow adoption of more complicated structures that enable function. In this study, we systematically examined random region length (N(20) through N(60)) for two particular deoxyribozyme catalytic activities, DNA cleavage and tyrosine-RNA nucleopeptide linkage formation. For both activities, we previously identified deoxyribozymes using only N(40) regions. In the case of DNA cleavage, here we found that shorter N(20) and N(30) regions allowed robust catalytic function, either by DNA hydrolysis or by DNA deglycosylation and strand scission via ß-elimination, whereas longer N(50) and N(60) regions did not lead to catalytically active DNA sequences. Follow-up selections with N(20), N(30), and N(40) regions revealed an interesting interplay of metal ion cofactors and random region length. Separately, for Tyr-RNA linkage formation, N(30) and N(60) regions provided catalytically active sequences, whereas N(20) was unsuccessful, and the N(40) deoxyribozymes were functionally superior (in terms of rate and yield) to N(30) and N(60). Collectively, the results indicate that with future in vitro selection experiments for DNA and RNA catalysts, and by extension for aptamers, random region length should be an important experimental variable.

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