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The cognitive and socioemotional development of 733 children was examined longitudinally from ages 4 to 8 years as a function of the quality of their preschool experiences in community child-care centers, after adjusting for family selection factors related to child-care quality and development. These results provide evidence that child-care quality has a modest long-term effect on children's patterns of cognitive and socioemotional development at least through kindergarten, and in some cases, through second grade. Differential effects on children's development were found for two aspects of child-care quality. Observed classroom practices were related to children's language and academic skills, whereas the closeness of the teacher-child relationship was related to both cognitive and social skills, with the strongest effects for the latter. Moderating influences of family characteristics were observed for some outcomes, indicating stronger positive effects of child-care quality for children from more at-risk backgrounds. These findings contribute further evidence of the long-term influences of the quality of child-care environments on children's cognitive and social skills through the elementary school years and are consistent with a bioecological model of development that considers the multiple environmental contexts that the child experiences. [ABSTRACT FROM AUTHOR]

Background: Researchers have increasingly recognized the importance of structural and social determinants of health (SSDOH) as key drivers of a multitude of diseases and health outcomes. The Multi-Ethnic Study of Atherosclerosis (MESA) is an ongoing, longitudinal cohort study of subclinical cardiovascular disease (CVD) that has followed geographically and racially/ethnically diverse participants starting in 2000. Since its inception, MESA has incorporated numerous SSDOH assessments and instruments to study in relation to CVD and aging outcomes. In this paper, we describe the SSDOH data available in MESA, systematically review published papers using MESA that were focused on SSDOH and provide a roadmap for future SSDOH-related studies., Methods and Findings: The study team reviewed all published papers using MESA data (n = 2,125) through January 23, 2023. Two individuals systematically reviewed titles, abstracts, and full text to determine the final number of papers (n = 431) that focused on at least one SSDOH variable as an exposure, outcome, or stratifying/effect modifier variable of main interest (discrepancies resolved by a third individual). Fifty-seven percent of the papers focused on racialized/ethnic groups or other macrosocial/structural factors (e.g., segregation), 16% focused on individual-level inequalities (e.g. income), 14% focused on the built environment (e.g., walking destinations), 10% focused on social context (e.g., neighborhood socioeconomic status), 34% focused on stressors (e.g., discrimination, air pollution), and 4% focused on social support/integration (e.g., social participation). Forty-seven (11%) of the papers combined MESA with other cohorts for cross-cohort comparisons and replication/validation (e.g., validating algorithms)., Conclusions: Overall, MESA has made significant contributions to the field and the published literature, with 20% of its published papers focused on SSDOH. Future SSDOH studies using MESA would benefit by using recently added instruments/data (e.g., early life educational quality), linking SSDOH to biomarkers to determine underlying causal mechanisms linking SSDOH to CVD and aging outcomes, and by focusing on intersectionality, understudied SSDOH (i.e., social support, social context), and understudied outcomes in relation to SSDOH (i.e., sleep, respiratory health, cognition/dementia)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Besser et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Emerging evidence suggests that a number of factors can influence blood-based biomarker levels for Alzheimer's disease (AD) and Alzheimer's related dementias (ADRD). We examined the associations that demographic and clinical characteristics have with AD/ADRD blood-based biomarker levels in an observational continuation of a clinical trial cohort of older individuals with type 2 diabetes and overweight or obesity., Methods: Participants aged 45-76 years were randomized to a 10-year Intensive Lifestyle Intervention (ILI) or a diabetes support and education (DSE) condition. Stored baseline and end of intervention (8-13 years later) plasma samples were analyzed with the Quanterix Simoa HD-X Analyzer. Changes in Aβ42, Aβ40, Aβ42/Aβ40, ptau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were evaluated in relation to randomization status, demographic, and clinical characteristics., Results: In a sample of 779 participants from the Look AHEAD cohort, we found significant associations between blood-based biomarkers for AD/ADRD and 15 of 18 demographic (age, gender, race and ethnicity, education) and clinical characteristics (APOE, depression, alcohol use, smoking, body mass index, HbA1c, diabetes duration, diabetes treatment, estimated glomerular filtration rate, hypertension, and history of cardiovascular disease) ., Conclusions: Blood-based biomarkers of AD/ADRD are influenced by common demographic and clinical characteristics. These factors should be considered carefully when interpreting these AD/ADRD blood biomarker values for clinical or research purposes., Competing Interests: The authors report no conflicts of interest., (© The Author(s) 2024.)

Background: Daytime sleepiness is common in older adults and may result from poor nighttime sleep due to sleep disordered breathing, fragmented sleep, or other sleep disorders. Daytime sleepiness may be associated with cognition in older adults., Objectives: We investigated the association between self-reported daytime sleepiness and cognitive function in the Look AHEAD clinical trial., Design: Observational follow-up of a randomized clinical trial of an intensive lifestyle intervention., Setting: Clinic., Participants: Participants (n=1,778) aged 45-76 years at baseline with type 2 diabetes and overweight or obesity., Interventions: Participants were randomized to an intensive lifestyle intervention for weight loss or a control condition of diabetes support and education., Measurements: Participants provided self-reported levels of daytime sleepiness at baseline and years 12-13. Cognitive function was assessed with a neurocognitive battery at years 12-13 and 18-20., Results: Participants who reported having frequent daytime sleepiness (often or always) performed significantly worse than others on the cognitive composite (-0.35; p-value=0.014) after controlling for covariates. When stratified by intervention arm, participants assigned to the intensive lifestyle intervention who reported often/always having daytime sleepiness performed worse on Digit Symbol Coding (-0.63; p-value=0.05) and Trail Making Part-B (-0.56; p-value=0.02) after controlling for covariates. Statistical interactions revealed associations between daytime sleepiness and the following covariates: race and ethnicity, APOE ε4 carrier status, baseline history of cardiovascular disease, and depression., Conclusions: Daytime sleepiness over ~13 years predicted poorer cognitive performance in older individuals who, by virtue of having diabetes and overweight/obesity, are at high risk for sleep disorders and cognitive impairment., Competing Interests: Adam Spira received honoraria for serving as a consultant to Merck and from Springer Nature Switzerland AG for guest editing special issues of Current Sleep Medicine Reports. The other authors report no conflicts of interest., (© The Authors 2023.)

Calcitonin (CT) and neurotensin (NT) secreting cell lines (6-23,44-2) were established from a transplantable rat medullary thyroid carcinoma (rMTC). The 44-2 line was used to obtain two colony clones 44-2 B and C secreting 20-30-fold greater NT than CT. These cells were used to study the regulation of Ca2+-modulated NT secretion and to ascertain the role of K+ and NE in the rapid release of NT. Medium NT was measured by a specific RIA with the antiserum N-1-11. Secretion experiments were in replicate 35 mm dishes in Krebs-Ringer-bicarbonate buffer supplemented with 90 mg% glucose (KRBG). Ca2+ (0.5-4.0 mM) stimulated NT release in a dose-dependent manner with an ED50 of 2.0 mM. Ca2+ was required for NT release induced by the Ca2+ ionophore, ionomycin, also K+ (50 mM) and norepinephrine (NE). To determine the mode of NT release in the presence of control (1.0 mM Ca2+) or experimental conditions (Ca2+ 1.0 mM plus 10(-6) NE and/or 50 mM K+), 44-2 cells were incubated in KRBG using an experimental paradigm wherein medium was changed at 10-min intervals, and NT release was quantitated. NE stimulated release of NT by these cells and the amount of NT released with each repetitive pulse of NE remained constant throughout the experiment. K+ (50 mM) elicited a rapid release of NT in the first 0-10 min incubation and the amount of NT released into the buffer was greater than that measured with NE; however, in these experiments, the response to K+ declined progressively and reached basal values at 20-30 min. Our results show neither pulse stimulation nor continuous incubation of cells with NE affected the response of the cells to a subsequent challenge with K+. These results suggest the presence of differentially stimulated, releasable pools of NT in these cells. We conclude that these newly established 44-2 B and C cells provide a useful model to study the regulation of NT release.