Parent–child similarity on autism and ADHD traits and children's social functioning and psychological well-being at 3 years

BackgroundThere is a pressing need for research on neurodevelopmental conditions to focus on predictors of resilient or positive outcomes, rather than core symptoms and impairment. One promising avenue is to consider whether child–parent similarity contributes to a protective family environment. For instance, investigations of the similarity–fit hypothesis have shown that parent–child attention-deficit/hyperactivity disorder (ADHD) trait similarity is associated with more favourable parent or child ratings of parenting and parent–child interaction. However, very little similarity–fit research has focused on autism, and none to date has investigated whether parent–child trait similarity is more broadly predictive of children's outcomes beyond parent–child interaction. We assessed whether parent–child autism and ADHD trait similarity predicted children's social functioning and psychological well-being in early childhood in a family history cohort. MethodsOur analytic sample comprised 222 children (45.5% female) and their parents from a longitudinal family history (autism and/or ADHD) cohort. A novel parent–child trait similarity measure was computed for autism and ADHD traits in each parent–child pair, and robust hierarchical regression was used to assess whether mother–child and father–child autism and ADHD similarity predicted children's social functioning and psychological well-being at age 3 years, after accounting for the main effects of parent and child traits. ResultsMother–child autism trait similarity positively predicted both social functioning and psychological well-being in children, while mother–child ADHD trait similarity positively predicted children's social functioning (but not well-being). Furthermore, father–child autism trait similarity positively predicted children's social functioning, though it fell just short of statistical significance in outlier-robust regression. ConclusionsOur findings suggest that parent–child neurodevelopmental trait similarity may act as a protective or promotive factor for children's early social functioning and psychological well-being. Further work is warranted to determine whether there are similar effects in later childhood and to investigate the potential mechanisms underlying similarity–fit effects on children's outcomes.</p

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Branching morphogenesis

ABSTRACT Over the past 5 years, several studies have begun to uncover the links between the classical signal transduction pathways and the physical mechanisms that are used to sculpt branched tissues. These advances have been made, in part, thanks to innovations in live imaging and reporter animals. With modern research tools, our conceptual models of branching morphogenesis are rapidly evolving, and the differences in branching mechanisms between each organ are becoming increasingly apparent. Here, we highlight four branched epithelia that develop at different spatial scales, within different surrounding tissues and via divergent physical mechanisms. Each of these organs has evolved to employ unique branching strategies to achieve a specialized final architecture.</jats:p

Plasticity in airway smooth muscle differentiation during mouse lung development

SummarySmooth muscle differentiation has been proposed to sculpt airway epithelial branches in mammalian lungs. Serum response factor (SRF) acts with its cofactor myocardin to promote the expression of contractile smooth muscle markers. However, smooth muscle cells exhibit a variety of phenotypes beyond contractile that are independent of SRF/myocardin-induced transcription. To determine whether airway smooth muscle exhibits phenotypic plasticity during embryonic development, we deleted Srf from the pulmonary mesenchyme. Srf-mutant lungs branch normally, and the mesenchyme exhibits normal cytoskeletal features and patterning. scRNA-seq revealed an Srf-null smooth muscle cluster wrapping the airways of mutant lungs that lacks contractile smooth muscle markers but retains many features of control smooth muscle. Srf-null airway smooth muscle exhibits a synthetic phenotype, compared to the contractile phenotype of mature wildtype airway smooth muscle. Our findings reveal plasticity in airway smooth muscle differentiation and demonstrate that a synthetic smooth muscle layer is sufficient for airway branching morphogenesis.</jats:p

Origins of smooth muscle and evolutionary specializations of the pulmonary mesenchyme in the vertebrate lung

SummaryEvolution has generated a beautiful diversity of epithelial architectures in the lungs of terrestrial vertebrates, from the tree-like lungs of mammals, to the sac-like lungs of reptiles, to the looped airways of birds. The physical mechanisms that generate pulmonary epithelia of such different shapes are just beginning to be uncovered. Pulmonary smooth muscle plays stage-dependent roles in shaping the epithelium during lung development in the mouse, anole, and chicken. We hypothesized that differences in the timing and spatial patterns of smooth muscle differentiation correspond to distinct patterns of gene expression in the pulmonary mesenchyme. To test this hypothesis and investigate differences in pulmonary smooth muscle patterning across terrestrial vertebrates, we generated scRNA-seq datasets from lungs of mouse, anole, and chicken embryos. These data revealed that smooth muscle regulators are expressed in similar patterns in mouse and anole lungs, in which epithelial branches are sculpted by smooth muscle, but diverge in chicken lungs, in which the epithelium branches in the absence of smooth muscle. Pulmonary smooth muscle differentiates from the lung mesenchyme in mouse and anole. Surprisingly, however, bioinformatic and experimental evidence suggest that pulmonary smooth muscle is derived from vascular smooth muscle in chicken. Furthermore, our data revealed differences in the timing and extent of smooth muscle innervation across species. These findings highlight how terrestrial vertebrates have evolutionarily repurposed similar morphogenetic motifs to build lungs that suit their energetic needs.</jats:p