CCL24 regulates biliary inflammation and fibrosis in primary sclerosing cholangitis.

ˆCCL24 is a pro-fibrotic, pro-inflammatory chemokine expressed in several chronic fibrotic diseases. In the liver, CCL24 plays a role in fibrosis and inflammation, and blocking CCL24 led to reduced liver injury in experimental models. We studied the role of CCL24 in primary sclerosing cholangitis (PSC) and evaluated the potential therapeutic effect of blocking CCL24 in this disease. Multidrug resistance gene 2-knockout (Mdr2-/-) mice demonstrated CCL24 expression in liver macrophages and were used as a relevant experimental PSC model. CCL24-neutralizing monoclonal antibody, CM-101, significantly improved inflammation, fibrosis, and cholestasis-related markers in the biliary area. Moreover, using spatial transcriptomics, we observed reduced proliferation and senescence of cholangiocytes following CCL24 neutralization. Next, we demonstrated that CCL24 expression was elevated under pro-fibrotic conditions in primary human cholangiocytes and macrophages, and it induced proliferation of primary human hepatic stellate cells and cholangiocytes, which was attenuated following CCL24 inhibition. Correspondingly, CCL24 was found to be highly expressed in liver biopsies of patients with PSC. CCL24 serum levels correlated with Enhanced Liver Fibrosis score, most notably in patients with high alkaline phosphatase levels. These results suggest that blocking CCL24 may have a therapeutic effect in patients with PSC by reducing liver inflammation, fibrosis, and cholestasis.

Change the Things You Can: Modifiable Parent Characteristics Predict High-Quality Early Language Interaction Within Socioeconomic Status.

Purpose Understanding variability sources in early language interaction is critical to identifying children whose development is at risk and designing interventions. Variability across socioeconomic status (SES) groups has been extensively explored. However, SES is a limited individual clinical indicator. For example, it is not generally directly modifiable. The purpose of this study was to examine if child language ability, input quantity and quality, and dyadic interaction were associated with modifiable caregiver characteristics-self-efficacy and developmental knowledge. Method We conducted secondary analyses using the baseline data (n = 41 dyads enrolled, n = 30 analyzed) from a longitudinal study. Mothers and children (1;0-2;3 [years;months]) in low-income households completed demographic questionnaires, self-efficacy and developmental knowledge measures, child language assessments, and interaction samples. We used linear regression models to examine the relationship between self-efficacy, developmental knowledge, and outcomes. Results Child receptive and expressive language scores were significantly associated with mothers' self-efficacy, knowledge, and Efficacy × Knowledge interaction. Specifically, maternal self-efficacy was positively associated with child language only in the context of high developmental knowledge. Neither self-efficacy nor developmental knowledge was significantly associated with the number of total or different words mothers produced. However, self-efficacy was significantly and positively associated with the rate of child-initiated conversational turns per minute, controlling for the number of child utterances. Mothers with higher self-efficacy responded more readily to their children than those with lower self-efficacy. Conclusions Child language ability and interaction quality vary based on modifiable parent characteristics. Modifiable individual characteristics should be considered in early language interaction within and across SES groups.

Parents' Evaluations of Their Children's Dysphonia: The Mamas and the Papas.

OBJECTIVES: This study aimed to evaluate the validity and reliability of a Hebrew translation of the Pediatric Voice Handicap Index (pVHI). It also examined differences between mothers and fathers in evaluating their child's dysphonia. STUDY DESIGN: Observational design. METHODS: The pVHI was first translated and adapted to Hebrew. The translated version was, then, administered to a group of 141 parents of children aged younger than 14 years. Fifty-eight parents had a dysphonic child, and 83 had a nondysphonic child. Based on the parents' responses to the pVHI, statistical analyses were performed, evaluating validity and reliability, as well as group differences. Following, a subset of the participants, in which only cases where the responses of both parents were available, was examined for evaluating differences between the responses of mothers (n = 46) and fathers (n = 46). RESULTS: Statistical analyses revealed high reliability of the Hebrew version of the pVHI (Cronbach alpha = .97). Parents of the dysphonic children rated their children significantly higher than parents of the nondysphonic group (P < 0.001). Mothers of the dysphonic children rated their children significantly higher than the fathers, on all subscales of the questionnaire (≥0.001 P < 0.047). In contrast, no significant differences were found between mothers and fathers of the nondysphonic children (P > 0.05). CONCLUSIONS: The Hebrew version of the pVHI is a reliable tool for quantifying parents' perception of their child's voice handicap. Mothers of dysphonic children evaluate their children's voice handicap more severely than fathers, whereas both parents of nondysphonic children perform this evaluation similarly.