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Abstract Background Research in the neurosciences has highlighted the importance of intersubjective relationships in promoting neuromental development of the child. Children’s learning in early childhood occurs mainly in a dyadic context of an interaction with their parents: from this perspective, good dialogic parent–child communication is required to be promoted also through good educational practices. Dialogic Book-Sharing (DBS), a dialogic form of parent–child communication through the use of wordless picture books, provides a privileged ‘intersubjective’ space and is highly effective in promoting communication, language, attention, behavioural development and the parent–child relationship. DBS programme, successfully previously trialled in South Africa and the UK, will be applied for the first time in Italy for research purposes in Italian health, educational and maternal-child centres. Methods A multicentre randomised controlled trial is being conducted to evaluate DBS parenting intervention for children aged between 14 and 20 months. Parent–child dyads are randomly allocated to a book-sharing intervention group or to a wait-list control group. In the intervention, parents are trained in supportive book-sharing with their children by local staff of the centres. DBS intervention is carried out in small groups over a period of 4 weeks. Data are collected at baseline, post-intervention and at 6 months post-intervention with a questionnaire and video recording of parent–child interaction. Discussion DBS programme in early childhood could enhance the educational resources offered by Italian health, educational and maternal-child centres, in support of child’s development and parenting. DBS represents a strategic opportunity for bringing about positive effects, also in terms of prevention of socio-emotional and cognitive difficulties. As such it represents a promising response to the new social, health and educational needs of the post-COVID-19 pandemic era caused by the social isolation measures. Furthermore, the application of the DBS methodology is a way to promote the use of books, and thereby counteract the excessive use of technological devices already present in early childhood. Trial registration The trial is registered on the International Standard Randomised Controlled Trial Number database, registration number ISRCTN11755019 Registered on 2 November 2023. This is version 1 of the protocol for the trial.

Abstract Background The immune mechanisms associated with infection-induced disease exacerbations in asthma and COPD are not fully understood. Toll-like receptor (TLR) 3 has an important role in recognition of double-stranded viral RNA, which leads to the production of various inflammatory mediators. Thus, an understanding of TLR3 activation should provide insight into the mechanisms underlying virus-induced exacerbations of pulmonary diseases. Methods TLR3 knock-out (KO) mice and C57B6 (WT) mice were intranasally administered repeated doses of the synthetic double stranded RNA analog poly(I:C). Results There was a significant increase in total cells, especially neutrophils, in BALF samples from poly(I:C)-treated mice. In addition, IL-6, CXCL10, JE, KC, mGCSF, CCL3, CCL5, and TNFα were up regulated. Histological analyses of the lungs revealed a cellular infiltrate in the interstitium and epithelial cell hypertrophy in small bronchioles. Associated with the pro-inflammatory effects of poly(I:C), the mice exhibited significant impairment of lung function both at baseline and in response to methacholine challenge as measured by whole body plethysmography and an invasive measure of airway resistance. Importantly, TLR3 KO mice were protected from poly(I:C)-induced changes in lung function at baseline, which correlated with milder inflammation in the lung, and significantly reduced epithelial cell hypertrophy. Conclusion These findings demonstrate that TLR3 activation by poly(I:C) modulates the local inflammatory response in the lung and suggest a critical role of TLR3 activation in driving lung function impairment. Thus, TLR3 activation may be one mechanism through which viral infections contribute toward exacerbation of respiratory disease.

Background: Investigating the effects of breaking up sedentary behavior with short bouts of Yoga and Tai-Chi on glycemic control, concentration, and well-being in healthy individuals. Methods: In this randomized balanced incomplete block study, 15 adults (age = 26 [2.50] y, 8 females) completed 2 of 3 protocols: uninterrupted sitting (Control), sitting interrupted with 3 minutes of Yoga every 30 minutes, or with 3 minutes of Tai-Chi every 30 minutes. Protocols lasted 7.5 hours and included a standardized diet. Glucose was measured every 30 minutes with a glucometer (Abbott FreeStyle Libre). Concentration and well-being were recorded with self-reported ecological momentary assessment. Area under the curve was calculated for glucose data. Statistical analyses were performed as a hierarchical repeated-measures model. Results: Glucose area under the curve for the Yoga intervention (34.55 [3.12] mmol/L) was significantly lower than the Control (38.14 [3.18] mmol/L; P <.05). There was a trend toward lower glucose in the Tai-Chi group compared with the Control, but no significant differences were found (AUCTai-Chi = 36.64 [3.11] mmol/L; P =.57). Mean concentration in all groups decreased throughout the day, with the largest decrease in the Control. Well-being for the Yoga and Control groups decreased but increased with Tai-Chi. Concentration and well-being responses were not statistically significant between intervention groups. Conclusions: Breaking up sedentary behavior using 3-minute bouts of Yoga significantly lowers blood glucose in healthy individuals without compromising concentration or well-being. Tai-Chi did not provide the same significant effect on glucose levels but allowed better maintenance of concentration and well-being. These interventions provide effective ways to combat the deleterious effects of prolonged sedentary time while maintaining concentration and well-being. [ABSTRACT FROM AUTHOR]

This study evaluated the impact of a parenting intervention on children's cognitive and socioemotional development in a group of caregivers and their 21-to-28-month-old children in a low-income South African township. A randomized controlled trial compared an experimental group (n = 70) receiving training in dialogic book-sharing (8 weekly group sessions) with a wait-list control group (n = 70). They were assessed before the intervention, immediately following it, and at a six month follow-up. The intervention had positive effects on child language and attention, but not behavior problems, prosocial behavior, or theory of mind. Intervention caregivers were less verbally and psychologically harsh, showed more sensitivity and reciprocity and more complex cognitive talk. This program benefitted parenting and child development and holds promise for low-income contexts.

Interventions that train parents to share picture books with children are seen as a strategy for supporting child language development. We conducted meta-analyses using robust variance estimation modeling on results from 19 RCTs (N[subscript total] = 2,594; M[subscript child age] = 1-6 years). Overall, book-sharing interventions had a small sized effect on both expressive language (d = 0.41) and receptive language (d = 0.26). They had a large effect on caregiver book-sharing competence (d = 1.01). The impact of the intervention on child language was moderated by intervention dosage, with lower dosage associated with a minimal impact. Child age and caregiver education level were unrelated to child outcome. This review and meta-analysis confirms the promise of book-sharing interventions for enhancing and accelerating child language development.

Small airway chronic inflammation is a major pathologic feature of chronic obstructive pulmonary disease (COPD) and is refractory to current treatments. Dendritic cells (DCs) accumulate around small airways in COPD. DCs are critical mediators of Ag surveillance and Ag presentation and amplify adaptive immune responses. How DCs accumulate around airways remains largely unknown. We use 2-photon DC imaging of living murine lung sections to directly visualize the dynamic movement of living DCs around airways in response to either soluble mediators (IL-1β) or environmental stimuli (cigarette smoke or TLR3 ligands) implicated in COPD pathogenesis. We find that DCs accumulate around murine airways primarily by increasing velocity (chemokinesis) rather than directional migration (chemotaxis) in response to all three stimuli. DC accumulation maximally occurs in a specific zone located 26-50 μm from small airways, which overlaps with zones of maximal DC velocity. Our data suggest that increased accumulation of DCs around airways results from increased numbers of highly chemokinetic DCs entering the lung from the circulation with balanced rates of immigration and emigration. Increases in DC accumulation and chemokinesis are partially dependent on ccr6, a crucial DC chemokine receptor, and fibroblast expression of the integrin αvβ8, a critical activator of TGF-β. αvβ8-Mediated TGF-β activation is known to enhance IL-1β-dependent fibroblast expression of the only known endogenous ccr6 chemokine ligand, ccl20. Taken together, these data suggest a mechanism by which αvβ8, ccl20, and ccr6 interact to lead to DC accumulation around airways in response to COPD-relevant stimuli.

The meaning, mechanism, and function of imitation in early infancy have been actively discussed since Meltzoff and Moore's (1977) report of facial and manual imitation by human neonates. Oostenbroek et al. (2016) claim to challenge the existence of early imitation and to counter all interpretations so far offered. Such claims, if true, would have implications for theories of social-cognitive development. Here we identify 11 flaws in Oostenbroek et al.'s experimental design that biased the results toward null effects. We requested and obtained the authors' raw data. Contrary to the authors' conclusions, new analyses reveal significant tongue-protrusion imitation at all four ages tested (1, 3, 6, and 9 weeks old). We explain how the authors missed this pattern and offer five recommendations for designing future experiments. Infant imitation raises fundamental issues about action representation, social learning, and brain--behavior relations. The debate about the origins and development of imitation reflects its importance to theories of developmental science.

Hepatic myofibroblasts are activated in response to chronic liver injury of any etiology to produce a fibrous scar. Despite extensive studies, the origin of myofibroblasts in different types of fibrotic liver diseases is unresolved. To identify distinct populations of myofibroblasts and quantify their contribution to hepatic fibrosis of two different etiologies, collagen-α1(I)-GFP mice were subjected to hepatotoxic (carbon tetrachloride; CCl4) or cholestatic (bile duct ligation; BDL) liver injury. All myofibroblasts were purified by flow cytometry of GFP(+) cells and then different subsets identified by phenotyping. Liver resident activated hepatic stellate cells (aHSCs) and activated portal fibroblasts (aPFs) are the major source (>95%) of fibrogenic myofibroblasts in these models of liver fibrosis in mice. As previously reported using other methodologies, hepatic stellate cells (HSCs) are the major source of myofibroblasts (>87%) in CCl4 liver injury. However, aPFs are a major source of myofibroblasts in cholestatic liver injury, contributing >70% of myofibroblasts at the onset of injury (5 d BDL). The relative contribution of aPFs decreases with progressive injury, as HSCs become activated and contribute to the myofibroblast population (14 and 20 d BDL). Unlike aHSCs, aPFs respond to stimulation with taurocholic acid and IL-25 by induction of collagen-α1(I) and IL-13, respectively. Furthermore, BDL-activated PFs express high levels of collagen type I and provide stimulatory signals to HSCs. Gene expression analysis identified several novel markers of aPFs, including a mesothelial-specific marker mesothelin. PFs may play a critical role in the pathogenesis of cholestatic liver fibrosis and, therefore, serve as an attractive target for antifibrotic therapy.

Airway remodeling, caused by inflammation and fibrosis, is a major component of chronic obstructive pulmonary disease (COPD) and currently has no effective treatment. Transforming growth factor-β (TGF-β) has been widely implicated in the pathogenesis of airway remodeling in COPD. TGF-β is expressed in a latent form that requires activation. The integrin αvβ8 (encoded by the itgb8 gene) is a receptor for latent TGF-β and is essential for its activation. Expression of integrin αvβ8 is increased in airway fibroblasts in COPD and thus is an attractive therapeutic target for the treatment of airway remodeling in COPD. We demonstrate that an engineered optimized antibody to human αvβ8 (B5) inhibited TGF-β activation in transgenic mice expressing only human and not mouse ITGB8. The B5 engineered antibody blocked fibroinflammatory responses induced by tobacco smoke, cytokines, and allergens by inhibiting TGF-β activation. To clarify the mechanism of action of B5, we used hydrodynamic, mutational, and electron microscopic methods to demonstrate that αvβ8 predominantly adopts a constitutively active, extended-closed headpiece conformation. Epitope mapping and functional characterization of B5 revealed an allosteric mechanism of action due to locking-in of a low-affinity αvβ8 conformation. Collectively, these data demonstrate a new model for integrin function and present a strategy to selectively target the TGF-β pathway to treat fibroinflammatory airway diseases.

Postnatal maternal depression is associated with poorer child emotional and behavioral functioning, but it is unclear whether this occurs following brief episodes or only with persistent depression. Little research has examined the relation between postnatal anxiety and child outcomes. The present study examined the role of postnatal major depressive disorder (MDD) and generalized anxiety disorder (GAD) symptom chronicity on children's emotional and behavioral functioning at 24 months. Following postnatal screening mothers (n = 296) were identified as having MDD, GAD, MDD and GAD, or no disorder at 3 months postnatal; the average age was 32.3 (SD = 5.0), 91.9% self-identified as Caucasian, and 62.2% were married. Maternal disorder symptom severity was assessed by questionnaires and structured interview at 3, 6, 10, 14, and 24 months postpartum. At 24 months, child emotional negativity and behavior were assessed using questionnaires and by direct observation. Latent trait-state-occasion modeling was used to represent maternal disorder symptom chronicity; both stable trait and time-specific occasion portions of maternal symptomatology were examined in relation to child outcomes. Only the stable trait portion of maternal MDD and GAD symptom severity were related to maternal report of child behavior problems and higher levels of emotional negativity. Persistent maternal MDD, but not GAD, symptom severity was related to higher levels of child emotional negativity as measured observationally. These data suggest that children's behavior problems and emotional negativity are adversely affected by persistent maternal depression, and possibly anxiety. This has implications for interventions to prevent negative effects of postnatal psychopathology on children.

Background: Consistent with evidence from high-income countries (HICs), we previously showed that, in an informal peri-urban settlement in a low-middle income country, training parents in book sharing with their infants benefitted infant language and attention (Vally, Murray, Tomlinson, & Cooper, [Vally, Z., 2015]). Here, we investigated whether these benefits were explained by improvements in carer-infant interactions in both book-sharing and non-book-sharing contexts. We also explored whether infant socioemotional development benefitted from book sharing. Methods: We conducted a randomized controlled trial in Khayelitsha, South Africa. Carers of 14-16-month-old infants were randomized to 8 weeks' training in book sharing (n = 49) or a wait-list control group (n = 42). In addition to the cognitive measures reported previously, independent assessments were made at base line and follow-up of carer-infant interactions during book sharing and toy play. Assessments were also made, at follow-up only, of infant prosocial behaviour in a "help task", and of infant imitation of doll characters' nonsocial actions and an interpersonal interaction. Eighty-two carer-infant pairs (90%) were assessed at follow-up. (Trial registration ISRCTN39953901). Results: Carers who received the training showed significant improvements in book-sharing interactions (sensitivity, elaborations, reciprocity), and, to a smaller extent, in toy-play interactions (sensitivity). Infants in the intervention group showed a significantly higher rate of prosocial behaviour, and tended to show more frequent imitation of the interpersonal interaction. Improvements in carer behaviour during book sharing, but not during toy play, mediated intervention effects on all infant cognitive outcomes, and tended to mediate intervention effects on infant interpersonal imitation. Conclusions: Training in book sharing, a simple, inexpensive intervention that has been shown to benefit infant cognitive development in a low-middle income country, also shows promise for improving infant socioemotional outcomes in this context. Benefits are mediated by improvements in carer-infant interactions, particularly in book-sharing contexts.

Background: Dialogic book-sharing is an interactive form of shared reading. It has been shown in high income countries (HICs) to be of significant benefit to child cognitive development. Evidence for such benefit in low and middle income countries (LMICs) is scarce, although a feasibility study of our own produced encouraging findings. Accordingly, we aimed to establish the impact on child language and attention of providing training in dialogic booksharing to carers of infants in an impoverished South African community. Methods: We conducted a randomized controlled trial in Khayelitsha, an informal settlement in South Africa. Mothers of infants aged between 14 and 16 months were recruited and randomized to either 8 weeks of manualized training in dialogic book-sharing or a no-intervention control group. Independent assessments were made of infant language and attention at baseline and following training. The trial was registered (ISRCTN39953901). Results: Ninety one carer-infant dyads were recruited and randomized to the intervention group (n = 49) or the control group (n = 42), 82 (90%) of whom were available for follow-up assessments. On a standardized carer report of infant vocabulary, compared to those in the control group, carers who received the intervention reported a significantly greater increase in the number of words understood by their infants as well as a larger increase in the number of words that their infant understood and could vocalize. Intervention group children also showed substantially greater gains on a measure of sustained attention. Conclusions: In line with evidence from HICs, a dialogic book-sharing programme delivered to an impoverished South African sample was shown to be of considerable benefit to the development of child language and focussed attention. The training programme, which is simple and inexpensive to deliver, has the potential to benefit child cognitive development in LMIC contexts where such development is commonly compromised.