An Equity-Focused Assessment of Evidence-Based Parenting Intervention Research.

Evidence-based parenting interventions (EBPI) support children and families to promote resilience, address emotional and behavioral concerns, and prevent or address issues related to child maltreatment. Critiques of EBPIs include concerns about their relevance and effectiveness for diverse populations when they are implemented at population scale. Research methods that center racial equity and include community-based participatory approaches have the potential to address some of these concerns. The purpose of the present review was to document the extent to which methods associated with promoting racial equity in research have been used in studies that contribute to the evidence base for programs that meet evidentiary standards for a clearinghouse that was developed to support the Family First Prevention Services Act in the United States. We developed a coding system largely based on the Culturally Responsive Evaluation model. A sample of 47 papers that are part of the evidence base for ten in-home parent skill-based programs were reviewed and coded. Only three of 28 possible codes were observed to occur in over half of the studies (including race/ethnicity demographic characteristics, conducting measure reliability for the study sample, and including information on socioeconomic status). Although the overall presence of equity-informed methods was low, a positive trend was observed over time. This review highlights ways in which rigorous research can incorporate racial equity into the planning, design, execution, and interpretation and dissemination of programs of study. We posit that doing so improves the external validity of studies while maintaining high-quality research that can contribute to an evidence base.

Tofacitinib Inhibits STAT Phosphorylation and Matrix Metalloproteinase-3, -9 and -13 Production by C28/I2 Human Juvenile Chondrocytes.

Purpose: This in vitro study was designed to determine the effect of the pan-Janus kinase inhibitor, Tofacitinib, on basal and interleukin-6 (IL-6)-induced signal transducers and activators of transcription (STAT) phosphorylation and matrix metalloproteinase (MMP) gene expression and MMP production by C28/I2 human chondrocytes. Methods: C28/I2 chondrocytes were grown to a confluent high-density and treated either with recombinant human IL-6 (rhIL-6; 10-20ng/mL) or maintained in the basal state for up to 60 min. MMP gene expression was determined using RT-PCR and MMP production by semi-quantitative immunohistochemistry. The effect of IL-6 with or without Tofacitinib on activation of STAT proteins was determined from quantitative Western blots. Results: C28/I2 chondrocytes produced STAT1, STAT3 and STAT5AB which were phosphorylated (p) following treatment with rhIL-6 for 30 min. Tofacitinib (2.5nM-100nM) decreased rhIL-6-induced activation of STAT1, STAT3, and STAT5AB as well as decreasing the expression of MMP3 and MMP13 but not MMP9, MMP1 or MMP2. In addition, Tofacitinib (50nM) reduced the number of rhIL-6-induced MMP3-, and MMP13- antibody-positive C28/I2 chondrocytes. However, Tofacitinib did decrease the number of MMP9-antibody-positive C28/I2 chondrocytes. Conclusion: Taken together, these data showed that Tofacitinib, a pan-JAK small molecule inhibitor employed for the medical therapy of rheumatoid arthritis was a potent inhibitor of rhIL-6-induced STAT phosphorylation that appeared to be coupled to the inhibition of MMP-3, -9 and -13 production by C28/I2 chondrocytes.

Progestin therapy to prevent preterm birth: History and effectiveness of current strategies and development of novel approaches.

In the 1930s the "progestin" hormone produced by the corpus luteum was isolated and found to be a Δ4-keto-steroid. It was aptly named progesterone (P4) and in the following 30 years the capacity of P4 and derivatives to prevent preterm birth (PTB) was examined. Outcomes of multiple small studies suggested that progestin prophylaxis beginning at mid-gestation decreases the risk for PTB. Subsequent larger trials found that prophylaxis with weekly intramuscular injections of 17α-hydroxyprogesterone caproate (17HPC) beginning at mid-gestation decreased PTB risk in women with a history of PTB. Other trials found that daily vaginal P4 prophylaxis, also beginning at mid-gestation decreased PTB risk in women with a short cervix. Currently, prophylaxis with 17HPC (in women with a history of PTB) or vaginal P4 (in women with a short cervix) are used to prevent PTB. Recent advances in understanding the molecular biology of P4 signaling in uterine cells is revealing novel progestin-based targets for PTB prevention. One possibility is to use selective P4 receptor (PR) modulators (SPRMs) to boost PR anti-inflammatory activity that blocks labor, while simultaneously preventing PR phosphorylation that causes loss of P4/PR anti-inflammatory activity. This may be achieved by SPRMs that induce a specific PR conformation that prevents site-specific serine phosphorylation that inhibits anti-inflammatory activity. Further advances in understanding how P4 promotes uterine quiescence and how its labor blocking actions are withdrawn to trigger parturition will reveal novel therapeutic targets to more effectively prevent PTB.