Feasibility and Acceptability of an Online Family Literacy Program in an Under-Resourced Community During the COVID-19 Pandemic.

OBJECTIVE: The objective of this study was to examine the feasibility and acceptability of an online family literacy program (FLP) among low-income Latino families during the COVID-19 pandemic. METHODS: We conducted a mixed methods pilot study. Latino parent-child dyads participated in an 8-week online FLP conducted on video conferencing software, developed through a cross-sector health care-education partnership. We conducted surveys and structured observation to assess feasibility and acceptability and in-depth interviews to gain insight into the context of participants' experiences during the pandemic. RESULTS: The 35 participating parent-child dyads all identified as Latino, 83% reported limited English proficiency, and 60% of parents did not achieve a high school diploma. Nearly two-thirds of families participated in at least half of the sessions. On average, parents welcomed, liked, approved, and found the program appealing. While 86% experienced a technology problem at least once during sessions, all were resolved with minimal assistance. During qualitative interviews, we identified 3 themes that provide insight into their experiences with the FLP within the broader context of the pandemic: (1) disruption in family routine and financial strain caused by COVID-19 intensified family stress, (2) the forced transition to remote learning highlighted the inequities experienced by Latino preschool children, and (3) the FLP empowered parents and enhanced health and education experiences. CONCLUSION: Latino families had high participation levels in an online FLP and found it acceptable. Additional work is needed to understand how similar primary care programs can be leveraged to promote optimal development during a time of heightened need.

Divergent roles for kidney proximal tubule and granulocyte PAD4 in ischemic AKI.

We previously demonstrated that kidney peptidylarginine deiminase-4 (PAD4) plays a critical role in ischemic acute kidney injury (AKI) in mice by promoting renal tubular inflammation and neutrophil infiltration (Ham A, Rabadi M, Kim M, Brown KM, Ma Z, D'Agati V, Lee HT. Am J Physiol Renal Physiol 307: F1052-F1062, 2014). Although the role of PAD4 in granulocytes including neutrophils is well known, we surprisingly observed profound renal proximal tubular PAD4 induction after renal ischemia-reperfusion (I/R) injury. Here we tested the hypothesis that renal proximal tubular PAD4 rather than myeloid-cell lineage PAD4 plays a critical role in exacerbating ischemic AKI by utilizing mice lacking PAD4 in renal proximal tubules (PAD4ff PEPCK Cre mice) or in granulocytes (PAD4ff LysM Cre mice). Mice lacking renal proximal tubular PAD4 were significantly protected against ischemic AKI compared with wild-type (PAD4ff) mice. Surprisingly, mice lacking PAD4 in myeloid cells were also protected against renal I/R injury although this protection was less compared with renal proximal tubular PAD4-deficient mice. Renal proximal tubular PAD4-deficient mice had profoundly reduced renal tubular apoptosis, whereas myeloid-cell PAD4-deficient mice showed markedly reduced renal neutrophil infiltration. Taken together, our studies suggest that both renal proximal tubular PAD4 as well as myeloid-cell lineage PAD4 play a critical role in exacerbating ischemic AKI. Renal proximal tubular PAD4 appears to contribute to ischemic AKI by promoting renal tubular apoptosis, whereas myeloid-cell PAD4 is preferentially involved in promoting neutrophil infiltration to the kidney and inflammation after renal I/R.

ATP induces PAD4 in renal proximal tubule cells via P2X7 receptor activation to exacerbate ischemic AKI.

We previously demonstrated that renal tubular peptidylarginine deiminase-4 (PAD4) is induced after ischemia-reperfusion (IR) injury and this induction of PAD4 exacerbates ischemic acute kidney injury (AKI) by promoting renal tubular inflammation and neutrophil infiltration. However, the mechanisms of renal tubular PAD4 induction after IR remain unknown. Here, we tested the hypothesis that ATP, a proinflammatory danger-associated molecular pattern (DAMP) ligand released from necrotic cells after IR injury, induces renal tubular PAD4 and exacerbates ischemic AKI via P2 purinergic receptor activation. ATP as well as ATPγS (a nonmetabolizable ATP analog) induced PAD4 mRNA, protein, and activity in human and mouse renal proximal tubule cells. Supporting the hypothesis that ATP induces renal tubular PAD4 via P2X7 receptor activation, A804598 (a selective P2X7 receptor antagonist) blocked the ATP-mediated induction of renal tubular PAD4 whereas BzATP (a selective P2X7 receptor agonist) mimicked the effects of ATP by inducing renal tubular PAD4 expression and activity. Moreover, ATP-mediated calcium influx in renal proximal tubule cells was blocked by A804598 and was mimicked by BzATP. P2X7 activation by BzATP also induced PAD4 expression and activity in mouse kidney in vivo. Finally, supporting a critical role for PAD4 in P2X7-mediated exacerbation of renal injury, BzATP exacerbated ischemic AKI in PAD4 wild-type mice but not in PAD4-deficient mice. Taken together, our studies show that ATP induces renal tubular PAD4 via P2X7 receptor activation to exacerbate renal tubular inflammation and injury after IR.