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OBJECTIVE: To evaluate a series of prospective life course models testing whether the timing of pubertal development is a pathway through which prepubertal risk factors may influence adulthood cardiometabolic health. METHODS: Subjects were 655 female participants in the NICHD Study of Early Child Care and Youth Development (SECCYD) and recent SECCYD 30-year follow-up, the Study of Health in Early and Adult Life (SHINE). Prepubertal risk factors included maternal menarcheal age, child race/ethnicity, child health status indicators, and child adversity indicators. Pubertal timing was indexed by breast development onset (Tanner stage [TS] II), pubic hair onset (TS II) and menarcheal age. Adulthood cardiometabolic risk (CMR) was indexed by a composite of waist circumference, systolic blood pressure, diastolic blood pressure, hemoglobin A1c, C-reactive protein, and high-density lipoprotein. RESULTS: Inspection of paths between the prepubertal risk factors, pubertal timing indicators, and adulthood CMR composite showed later breast development onset (-0.173, p < .01), later pubic hair onset (-0.182, p < .01), and later menarche (-0.145, p < .01) each predicted lower adulthood CMR, and each pubertal timing indicator mediated effects of prepubertal risk factors on adulthood CMR. Specifically, the timing of breast development onset and menarche mediated effects of maternal menarcheal age, Black (vs. White), Asian/PI (vs. White), child BMI percentile, and child SES on adulthood CMR (all ps < .05), and the timing of pubic hair onset mediated effects of maternal menarcheal age, Black (vs. White), and child BMI percentile on adulthood CMR (all ps < .10). CONCLUSION: Findings in the current study contribute to the broader literature by identifying pubertal development and its timing as a potentially important pathway through which early life exposures may shape adulthood cardiometabolic health and disease. These findings have important implications for novel opportunities for increased surveillance and potential intervention focusing on pubertal development as a target to improve health more broadly.

An individual participant data meta-analysis was conducted to test pre-registered hypotheses about how the configuration of attachment relationships to mothers and fathers predicts children's language competence. Data from seven studies (published between 1985 and 2014) including 719 children (M[subscript age]: 19.84 months; 51% female; 87% White) were included in the linear mixed effects analyses. Mean language competence scores exceeded the population average across children with different attachment configurations. Children with two secure attachment relationships had higher language competence scores compared to those with one or no secure attachment relationships (d = 0.26). Children with two organized attachment relationships had higher language competence scores compared to those with one organized attachment relationship (d = 0.23), and this difference was observed in older versus younger children in exploratory analyses. Mother-child and father-child attachment quality did not differentially predict language competence, supporting the comparable importance of attachment to both parents in predicting developmental outcomes. [This article was written by the Collaboration on Attachment to Multiple Parents and Outcomes Synthesis.]

Abstract Background Age-related macular degeneration (AMD) is a leading cause of vision loss. Photobiomodulation (PBM) offers a controversial approach for managing dry AMD, aiming to halt or reverse progression through mitochondrial activity modulation. However, the efficacy and clinical relevance of PBM as a potential approach for managing dry AMD remain debated. Methods We systematically searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) comparing PBM versus a sham in patients with dry AMD. We performed trial sequential analysis (TSA) and minimal clinically important difference (MCID) calculations to assess statistical and clinical significance applying a random-effects model with 95% confidence intervals (CI). Results We included three RCTs comprising 247 eyes. The pooled analysis showed that PBM significant improved BCVA (MD 1.76 letters; 95% CI: 0.04 to 3.48) and drusen volume (MD -0.12 mm³; 95% CI: -0.22 to -0.02) as compared with a sham control. However, the TSA indicated that the current sample sizes were insufficient for reliable conclusions. No significant differences were observed in GA area. The MCID analysis suggested that the statistically significant results did not translate into clinically significant benefits. In the quality assessment, all studies were deemed to have a high risk of bias. Conclusion This meta-analysis points limitations in the current evidence base for PBM in dry AMD treatment, with issues around small sample sizes. Statistically significant improvements do not translate into clinical benefits. The research underscores need for larger RCTs to validate PBM’s therapeutic potential for dry AMD.

Abstract Background Past research describes robust associations between education and health, yet findings have generally been limited to the examination of education as the number of years of education or educational attainment. Little is known about the specific features or processes underpinning education that are health protective. The objective of the current study was to address this gap by examining specific aspects of early education pertaining to student characteristics and experiences, as well as features of the classroom environment, in predicting cardiometabolic health in adulthood. Methods Subjects were 1364 participants in the NICHD Study of Early Child Care and Youth Development (SECCYD, 1991–2009) and recent SECCYD 30-year follow-up, the Study of Health in Early and Adult Life (SHINE, 2018–2022). Models examined individual education indicators (student social skills, student-teacher relationship quality, and classroom emotional and instructional quality in the period of elementary school and student academic performance between ages 54 months and 15 years) in relation to a composite of cardiometabolic risk in adulthood (ages 26–31), reflecting central adiposity, blood pressure, insulin resistance, inflammation, and dyslipidemia. Models were adjusted for key explanatory factors including socio-demographics, infant characteristics, parental socioeconomic status (SES), and child health status. Follow-up analyses were performed to test potential mediators of early education effects on adult health, including adult SES (educational attainment, household income) and health behaviors (diet quality, activity level, sleep duration, smoking). Results In adjusted models, results showed greater student social skills, indexed by a mean of annual teacher ratings between kindergarten and 6th grade, predicted lower cardiometabolic risk in adulthood (β=-0.009, p 0.05). Conclusions Findings point to the potential significance of early student social competence as a link to long-term health, possibly via the acquisition of resources needed for the maintenance of health, as well as through engagement in health behaviors supporting healthy eating. However, more research is needed to replicate these findings and to elaborate on the role of early student social competence and the pathways explaining its effects on cardiometabolic health in adulthood.

Introduction: Adverse epidermal growth factor receptor (EGFR) dermatological events affect many patients and can impair the patient’s quality of life (QoL), leading to dose reduction or discontinuation of therapy. Objective: To carry out the translation, cross-cultural adaptation, reliability and validity of the Functional Evaluation of Cancer Therapy - Epidermal Growth Factor Receptor Inhibitor 18 (FACT-EGFRI-18) to be utilized in Portuguese. Method: Study to evaluate the cross-cultural adaptation, reliability and construct validation of the FACT-EGFRI-18 translated into Portuguese. To evaluate cross-cultural adaptation, semantic analysis was performed by ten patients and content analysis by experts. Reliability was assessed by internal consistency analysis using Cronbach’s alpha coefficient. Construct validity was determined by the correlation between the translated FACT-EGFRI-18 and the Dermatology Life Quality Index (DLQI) answered by 30 participants with cancer undergoing treatment with EGFR. A descriptive analysis of the study population was performed and Cronbach’s alpha coefficient was calculated to determine the internal consistency of the Portuguese version of the FACTEGFRI- 18 and Pearson’s demonstration coefficient was applied to determine the transparency between the questionnaires. ANOVA test was performed to compare the mean FACT-EGFRI-18 score according to demographic variables. Results: The semantic evaluation showed that all the participants understood the items of the translated questionnaire, which revealed strong internal consistency (Cronbach’s alpha = 0.89) and validity (Pearson's correlation = 0.66). Conclusion: The FACT-EGFRI-18 was easily understood by the patients and the results support its reliability and validity.

PurposeThe purpose of the current study, The National Institute of Child Health and Human Development (NICHD) Study of Health in Early and Adult Life (SHINE), was to build on the landmark Study of Early Child Care and Youth Development (SECCYD), a longitudinal birth cohort initiated in 1991, by conducting a health-focused follow-up of the now adult participants. This effort has produced an invaluable resource for the pursuit of life course research examining links between early life risk and resilience factors and adulthood health and disease risk.ParticipantsOf the 927 NICHD SECCYD participants available for recruitment in the current study, 705 (76.1%) participated in the study. Participants were between 26 and 31 years and living in diverse geographic locations throughout the USA.Findings to dateIn descriptive analyses, the sample exhibited risk on health status indicators, especially related to obesity, hypertension and diabetes. Of particular concern, the prevalence of hypertension (29.4%) and diabetes (25.8%) exceeded national estimates in similar-age individuals. Health behaviour indicators generally tracked with the parameters of poor health status, showing a pattern of poor diet, low activity and disrupted sleep. The juxtaposition of the sample's relatively young age (mean=28.6 years) and high educational status (55.6% college educated or greater) with its poor health status is noteworthy, suggesting a dissociation between health and factors that are typically health protective. This is consistent with observed population health trends, which show a worsening of cardiometabolic health status in younger generations of Americans.Future plansThe current study, SHINE, lays the groundwork for future analyses in which the uniquely robust measures collected as a part of the original NICHD SECCYD will be leveraged to pinpoint specific early life risk and resilience factors as well as the correlates and potential mechanisms accounting for variability in health and disease risk indicators in young adulthood.

Individual differences in the quality of early experiences with primary caregivers have been reliably implicated in the development of socioemotional adjustment and, more recently, physical health. However, few studies have examined the development of such associations with physical health into the adult years. To that end, the current study used prospective, longitudinal data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (N = 1,306, 52% male, 77% White/non-Hispanic) to investigate whether associations between direct observations of maternal sensitivity in the first 3 years of life and repeated assessments of two commonly used, objective indicators of physical health (i.e., body mass and mean arterial blood pressure) remained stable or diminished in magnitude over time. Associations between early maternal sensitivity and lower body mass remained relatively stable from age 54 months to 26 years and were robust to the modeling of autoregressive and second-order stability processes as well as the inclusion of potential demographic confounders. In contrast, although associations between early caregiving and lower mean arterial pressure remained relatively stable from Grade 4 to age 15 years (the oldest age for which mean arterial pressure was assessed thus far), these associations were not robust to the inclusion of covariates and the modeling of second-order stability processes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Prior research has demonstrated that teacher-student relationships characterized by high levels of closeness and low levels of conflict are associated with higher levels of academic achievement among children. At the same time: (a) some research suggests that the quality of teacher-student relationships in part reflects the quality of early caregiving, and (b) the observed quality of early care by primary caregivers robustly predicts subsequent academic achievement. Given the potential for associations between teacher-student relationship quality and academic achievement to thus be confounded by the quality of early parenting experiences, the present study examined to what extent children's experiences in early life with primary caregivers (i.e., ages 3 to 42 months) and relationships with teachers during grade school (i.e., Kindergarten to Grade 6) were uniquely associated with an objective assessment of academic achievement at age 16 years in a sample born into poverty (N = 267; 45% female; 65% White/non-Hispanic; 41% of mothers did not complete high school). Early maternal sensitivity, though a strong predictor of later academic achievement, was not reliably associated with either teacher-reports or interview-based assessments of teacher-student relationship quality in grade school. Nonetheless, early maternal sensitivity and teacher-student relationship quality were each uniquely associated with later academic achievement, above and beyond key demographic variables. Taken together, the present results highlight that the quality of children's relationships with adults at home and at school independently, but not interactively, predicted later academic achievement in a high-risk sample.

Abstract Mast cells (MCs) are immune cells that play roles in both normal and abnormal processes. They have been linked to tumor progression in several types of cancer, including non-small cell lung cancer (NSCLC). However, the exact role of MCs in NSCLC is still unclear. Some studies have shown that the presence of a large number of MCs is associated with poor prognosis, while others have suggested that MCs have protective effects. To better understand the role of MCs in NSCLC, we aimed to identify the initial mechanisms underlying the communication between MCs and lung cancer cells. Here, we recapitulated cell-to-cell contact by exposing MCs to membranes derived from lung cancer cells and confirming their activation, as evidenced by increased phosphorylation of the ERK and AKT kinases. Profiling of the microRNAs that were selectively enriched in the extracellular vesicles (EVs) released by the lung cancer-activated MCs revealed that they contained significantly increased amounts of miR-100-5p and miR-125b, two protumorigenic miRNAs. We explored the pathways regulated by these miRNAs via enrichment analysis using the KEGG database, demonstrating that these two miRNAs regulate p53 signaling, cancer pathways, and pathways associated with apoptosis and the cell cycle.

Abstract Personalized medicine has revolutionized approaches to treatment in the field of lung cancer by enabling therapies to be specific to each patient. However, physicians encounter an immense number of challenges in providing the optimal treatment regimen for the individual given the sheer complexity of clinical aspects such as tumor molecular profile, tumor microenvironment, expected adverse events, acquired or inherent resistance mechanisms, the development of brain metastases, the limited availability of biomarkers and the choice of combination therapy. The integration of innovative next-generation technologies such as deep learning—a subset of machine learning—and radiomics has the potential to transform the field by supporting clinical decision making in cancer treatment and the delivery of precision therapies while integrating numerous clinical considerations. In this review, we present a brief explanation of the available technologies, the benefits of using these technologies in predicting immunotherapy response in lung cancer, and the expected future challenges in the context of precision medicine.

LIM homeobox 4 (LHX4) is a transcription factor crucial for anterior pituitary (AP) development. Patients with LHX4 mutation suffer from combined pituitary hormone deficiency (CPHD), short statures, reproductive and metabolic disorders and lethality in some cases. Lhx4-knockout (KO) mice fail to develop a normal AP and die shortly after birth. Here, we characterize a zebrafish lhx4-KO model to further investigate the importance of LHX4 in pituitary gland development and regulation. At the embryonic and larval stages, these fish express lower levels of tshb mRNA compared with their wildtype siblings. In adult lhx4-KO fish, the expressions of pituitary hormone-encoding transcripts, including growth hormone (gh), thyroid stimulating hormone (tshb), proopiomelanocortin (pomca) and follicle stimulating hormone (fshb), are reduced, the pomca promoter-driven expression in corticotrophs is dampened and luteinizing hormone (lhb)-producing gonadotrophs are severely depleted. In contrast to Lhx4-KO mice, Lhx4-deficient fish survive to adulthood, but with a reduced body size. Importantly, lhx4-KO males reach sexual maturity and are reproductively competent, whereas the females remain infertile with undeveloped ovaries. These phenotypes, which are reminiscent of those observed in CPHD patients, along with the advantages of the zebrafish for developmental genetics research, make this lhx4-KO fish an ideal vertebrate model to study the outcomes of LHX4 mutation.

Individual differences in the quality of early experiences with primary caregivers have been reliably implicated in the development of socioemotional adjustment and, more recently, physical health. However, few studies have examined the development of such associations with physical health into the adult years. To that end, the current study used prospective, longitudinal data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (N = 1,306, 52% male, 77% White/non-Hispanic) to investigate whether associations between direct observations of maternal sensitivity in the first 3 years of life and repeated assessments of two commonly used, objective indicators of physical health (i.e., body mass and mean arterial blood pressure) remained stable or diminished in magnitude over time. Associations between early maternal sensitivity and lower body mass remained relatively stable from age 54 months to 26 years and were robust to the modeling of autoregressive and second-order stability processes as well as the inclusion of potential demographic confounders. In contrast, although associations between early caregiving and lower mean arterial pressure remained relatively stable from Grade 4 to age 15 years (the oldest age for which mean arterial pressure was assessed thus far), these associations were not robust to the inclusion of covariates and the modeling of second-order stability processes.

Gravure printing is a type of printing method that uses metal cylinders with engraved cells that hold ink. The ink is transferred directly to the paper or other material by pressing it against the cylinder. The flow associated with gravure printing includes a flow in a liquid bridge formed in the contact region of the cylinders and a thin-film coating flow of the ink. The flow is governed by viscous and capillary forces. In many cases, the flow is unstable, which leads to the formation of instability patterns on the printed surfaces. The analysis of these instabilities is a very challenging problem, especially since industrial inks are usually rheologically complex. In this experimental and theoretical study, the flow of inks on a rotating cylinder is analysed, accounting for the shear-rate-dependent liquid viscosity. A theoretical solution for the film flow allows us to predict the width of the liquid bridge between two cylinders. Moreover, it is shown that the measured characteristic size of the printed pattern is of the same order as the predicted liquid bridge width. We observe a nearly linear dependence of pattern size and liquid bridge width.

ContextPrepubertal obesity is a well-established predictor of earlier pubertal onset, which is itself a risk factor for poor health and well-being. Identifying specific patterns of weight gain in early life may help explain differential risk for earlier pubertal onset.ObjectiveThe objective of the study was to examine patterns of weight gain across infancy and early childhood in relation to pubertal onset outcomes.Design setting and participantsParticipants were 426 girls in the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development, a longitudinal birth cohort of children and their families followed between birth and adolescence.Main outcome measuresThree pubertal onset outcomes were examined, including age at menarche and ages at Tanner stage II for dimensions of breast and pubic hair development.ResultsIn infancy (birth to 15 months), greater percent weight gain and higher birthweight predicted earlier pubertal onset for all outcomes (Ps < 0.05). In early childhood (24 months to grade 1), body mass index (BMI) trajectories reflecting BMI values that were persistently high or changed from low to high over time (vs BMI values that were stable at median or low levels), predicted younger ages at menarche and the onset of breast (Ps < 0.05), but not pubic hair (Ps > 0.05), development. All associations were independent of breastfeeding, maternal menarcheal age, and race/ethnicity.ConclusionsDistinct patterns of early life weight gain predict differential risk for earlier onset puberty. Focusing on these patterns for earlier and more targeted intervention may help lessen life course linkages between prepubertal obesity, accelerated pubertal development, and negative postpubertal outcomes.

Increasingly, attachment representations are being assessed via secure base script knowledge - the degree to which individuals show awareness of the temporal-causal schema that summarizes the basic features of seeking and receiving effective support from caregivers during times of need. Limited research has assessed the links between secure base script knowledge and aspects of adult functioning and the role that secure base script knowledge may play in accounting for associations between early caregiving quality and adulthood functioning. We used follow-up assessments of the NICHD Study of Early Child Care and Youth Development cohort (N = 585) to examine whether secure base script knowledge at age 18 years: (a) is associated with later romantic relationship quality, depressive symptoms, and body mass index (BMI) at age 26 years, and (b) mediates expected associations between the quality of maternal and paternal sensitivity across the first 15 years of life and age-26 outcomes. More access to, and elaborated knowledge of the secure base script predicted less extreme hostility with romantic partners, and better emotional and physical health. Moreover, secure base script knowledge mediated the links between early maternal and paternal sensitivity and both later romantic partner hostility and depressive symptoms, but not BMI.

Retrospective self-report assessments of adults' childhood experiences with their parents are widely employed in psychological science, but such assessments are rarely validated against actual parenting experiences measured during childhood. Here, we leveraged prospectively acquired data characterizing mother-child and father-child relationship quality using observations, parent reports, and child reports covering infancy through adolescence. At age 26 years, approximately 800 participants completed a retrospective measure of maternal and paternal emotional availability during childhood. Retrospective reports of childhood emotional availability demonstrated weak convergence with composites reflecting prospectively acquired observations (R2s = .01-.05) and parent reports (R2s = .02-.05) of parenting quality. Retrospective parental availability was more strongly associated with prospective assessments of child-reported parenting quality (R2s = .24-.25). However, potential sources of bias (i.e., depressive symptoms and family closeness and cohesiveness at age 26 years) accounted for more variance in retrospective reports (39%-40%) than did prospective measures (26%), suggesting caution when using retrospective reports of childhood caregiving quality as a proxy for prospective data.