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; CCl ₄) 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 CCl ₄ 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.
The aim of this study was to determine the developmental risk pathway to depression by 16 years in offspring of postnatally depressed mothers.
This was a prospective longitudinal study of offspring ...of postnatally depressed and nondepressed mothers; child and family assessments were made from infancy to 16 years. A total of 702 mothers were screened, and probable cases interviewed. In all, 58 depressed mothers (95% of identified cases) and 42 nondepressed controls were recruited. A total of 93% were assessed through to 16-year follow-up. The main study outcome was offspring lifetime clinical depression (major depression episode and dysthymia) by 16 years, assessed via interview at 8, 13, and 16 years. It was analysed in relation to postnatal depression, repeated measures of child vulnerability (insecure infant attachment and lower childhood resilience), and family adversity.
Children of index mothers were more likely than controls to experience depression by 16 years (41.5% versus 12.5%; odds ratio = 4.99; 95% confidence interval = 1.68-14.70). Lower childhood resilience predicted adolescent depression, and insecure infant attachment influenced adolescent depression via lower resilience (model R(2) = 31%). Family adversity added further to offspring risk (expanded model R(2) = 43%).
Offspring of postnatally depressed mothers are at increased risk for depression by 16 years of age. This may be partially explained by within child vulnerability established in infancy and the early years, and by exposure to family adversity. Routine screening for postnatal depression, and parenting support for postnatally depressed mothers, might reduce offspring developmental risks for clinical depression in childhood and adolescence.
Macrophages promote tissue remodeling but few mechanisms exist to modulate their activity during tissue fibrosis. Serum amyloid P (SAP), a member of the pentraxin family of proteins, signals through ...Fcgamma receptors which are known to affect macrophage activation. We determined that IPF/UIP patients have increased protein levels of several alternatively activated pro-fibrotic (M2) macrophage-associated proteins in the lung and monocytes from these patients show skewing towards an M2 macrophage phenotype. SAP therapeutically inhibits established bleomycin-induced pulmonary fibrosis, when administered systemically or locally to the lungs. The reduction in aberrant collagen deposition was associated with a reduction in M2 macrophages in the lung and increased IP10/CXCL10. These data highlight the role of macrophages in fibrotic lung disease, and demonstrate a therapeutic action of SAP on macrophages which may extend to many fibrotic indications caused by over-exuberant pro-fibrotic macrophage responses.
Purpose
To use the World Health Organisation’s International Classification of Functioning to measure disability following critical illness using patient-reported outcomes.
Methods
A prospective, ...multicentre cohort study conducted in five metropolitan intensive care units (ICU). Participants were adults who had been admitted to the ICU, received more than 24 h of mechanical ventilation and survived to hospital discharge. The primary outcome was measurement of disability using the World Health Organisation’s Disability Assessment Schedule 2.0. The secondary outcomes included the limitation of activities and changes to health-related quality of life comparing survivors with and without disability at 6 months after ICU.
Results
We followed 262 patients to 6 months, with a mean age of 59 ± 16 years, and of whom 175 (67%) were men. Moderate or severe disability was reported in 65 of 262 (25%). Predictors of disability included a history of anxiety/depression odds ratio (OR) 1.65 (95% confidence interval (CI) 1.22, 2.23),
P
= 0.001; being separated or divorced OR 2.87 (CI 1.35, 6.08),
P
= 0.006; increased duration of mechanical ventilation OR 1.04 (CI 1.01, 1.08),
P
= 0.03 per day; and not being discharged to home from the acute hospital OR 1.96 (CI 1.01, 3.70)
P
= 0.04. Moderate or severe disability at 6 months was associated with limitation in activities, e.g. not returning to work or studies due to health (
P
< 0.002), and reduced health-related quality of life (
P
< 0.001).
Conclusion
Disability measured using patient-reported outcomes was prevalent at 6 months after critical illness in survivors and was associated with reduced health-related quality of life. Predictors of moderate or severe disability included a prior history of anxiety or depression, separation or divorce and a longer duration of mechanical ventilation.
Trial registration: NCT02225938.
There is strong evidence that neonates imitate previously unseen behaviours. These behaviours are predominantly used in social interactions, demonstrating neonates' ability and motivation to engage ...with others. Research on neonatal imitation can provide a wealth of information about the early mirror neuron system (MNS), namely its functional characteristics, its plasticity from birth and its relation to skills later in development. Although numerous studies document the existence of neonatal imitation in the laboratory, little is known about its natural occurrence during parent–infant interactions and its plasticity as a consequence of experience. We review these critical aspects of imitation, which we argue are necessary for understanding the early action–perception system. We address common criticisms and misunderstandings about neonatal imitation and discuss methodological differences among studies. Recent work reveals that individual differences in neonatal imitation positively correlate with later social, cognitive and motor development. We propose that such variation in neonatal imitation could reflect important individual differences of the MNS. Although postnatal experience is not necessary for imitation, we present evidence that neonatal imitation is influenced by experience in the first week of life.
Postnatal depression in women is associated with adverse effects on both maternal health and children's development. It is unclear whether depression in men at this time poses comparable risks. The ...present study set out to assess the association between depression in men in the postnatal period and later psychiatric disorders in their children and to investigate predisposing factors for depression in men following childbirth.
A population-based cohort of 10,975 fathers and their children from the Avon Longitudinal Study of Parents and Children (ALSPAC) was recruited in the prenatal period and followed for 7 years. Paternal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale and later child psychiatric disorder (DSM-IV) with the Development and Well-Being Assessment.
Depression in fathers in the postnatal period was significantly associated with psychiatric disorder in their children 7 years later (adjusted OR 1.72, 95% CI 1.07-2.77), most notably oppositional defiant/conduct disorders (adjusted OR 1.94, 95% CI 1.04-3.61), after adjusting for maternal depression and paternal educational level. A history of severe depression and high prenatal symptom scores for depression and anxiety were the strongest predictors of paternal depression in the postnatal period.
Depression in fathers in the postnatal period is associated with later psychiatric disorders in their children, independently of maternal postnatal depression. Further research into the risks associated with paternal psychopathology is required because this could represent an important opportunity for public health intervention.
By two-three months, infants show active social expressions during face-to-face interactions. These interactions are important, as they provide the foundation for later emotional regulation and ...cognition, but little is known about how infant social expressiveness develops. We considered two different accounts. One emphasizes the contingency of parental responsiveness, regardless of its form; the other, the functional architecture account, emphasizes the preparedness of both infants and parents to respond in specific ways to particular forms of behaviour in their partner. We videotaped mother-infant interactions from one to nine weeks, and analysed them with a micro-analytic coding scheme. Infant social expressiveness increased through the nine-week period, particularly after 3 weeks. This development was unrelated to the extent of maternal contingent responsiveness, even to infant social expressions. By contrast, specific forms of response that mothers used preferentially for infant social expressions-mirroring, marking with a smile- predicted the increase in these infant behaviours over time. These results support a functional architecture account of the perceptual and behavioural predispositions of infants and parents that allow young infants to capitalize on relatively limited exposure to specific parental behaviours, in order to develop important social capacities.
Background: Maternal depression is known to be associated with impairments in child cognitive development, although the effect of timing of exposure to maternal depression is unclear.
Methods: Data ...collected for the Avon Longitudinal Study of Parents and Children, a longitudinal study beginning in pregnancy, included self‐report measures of maternal depression the Edinburgh Postnatal Depression Scale, completed on 6 occasions up to 3 years of age, and IQ of the index child (WISC) measured at aged 8 years. We used these data to assign women to 8 groups according to whether depression occurred in the antenatal, postnatal, preschool period, any combination of these times, or not at all. We compared a model comprising all patterns of depression (saturated model) with models nested within this to test whether there is a relationship between depression and child cognitive development and, if so, whether there is a sensitive period. We then investigated the relationship with child IQ for each model, following adjustment for confounders.
Results: Six thousand seven hundred and thirty‐five of 13,615 children from singleton births (49.5%, of eligible core sample) attended a research clinic at 8 years and completed a WISC with a score ≥ 70. A total of 5,029 mothers of these children had completed mood assessments over the 3 time periods. In unadjusted analyses, all three sensitive period models were as good as the saturated model, as was an accumulation model. Of the sensitive period models, only that for antenatal exposure was a consistently better fit than the accumulation model. After multiple imputation for missing data (to n = 6,735), there was no effect of postnatal depression on child IQ independent of depression at other times −0.19 IQ points, 95% confidence interval (CI) −1.5 to 1.1 points. There was an effect of antenatal depression (−3.19 IQ points, 95% CI: −4.33 to −2.06) which attenuated following adjustment (−0.64 IQ points, 95% CI: −1.68 to 0.40).
Conclusions: The postnatal period is not a sensitive one for the effect of maternal depression on child cognitive development.
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