Little time, lasting impact: Bereaved caregiver perceptions of legacy in perinatal and infant loss.

BACKGROUND: Legacy interventions are standard in most children's hospitals, but little is known about how bereaved parents understand and describe the concept of legacy that these interventions are designed to Address. The aim of this qualitative study was to understand the legacy experiences and perceptions of parents who have experienced perinatal or early infant (less than three months of age) loss. METHODS: Grounded in constructionist epistemology and phenomenological qualitative traditions, ten bereaved parents completed an in-depth phenomenological interview regarding their perceptions of and experiences with the legacy of their deceased child. Interviews were transcribed verbatim and analyzed using an open, inductive coding process to illuminate the essence of participants' experiences. RESULTS: Three themes were identified: 1) legacies are composed of memories and experiences that have a lasting effect on others; 2) healthcare experiences both generate and participate in infants' legacies; and 3) parents' legacy perceptions are shaped by cultural conceptions, spiritual beliefs, and grief experiences. Parents described experiences and interactions with community members and healthcare providers that honored or challenged their perceptions of their child's unique legacy. CONCLUSIONS: In the context of perinatal or early infant loss, bereaved parents describe legacy as enduring, unique to each child and family, and heavily influenced by healthcare experiences and staff relationships. Parent-led, legacy-oriented interventions are needed in maternal/fetal, labor/delivery, and neonatal intensive care settings to support parent coping with loss.

Transfer of hepatocellular microRNA regulates cytochrome P450 2E1 in renal tubular cells.

BACKGROUND: Extracellular microRNAs enter kidney cells and modify gene expression. We used a Dicer-hepatocyte-specific microRNA conditional-knock-out (Dicer-CKO) mouse to investigate microRNA transfer from liver to kidney. METHODS: Dicerflox/flox mice were treated with a Cre recombinase-expressing adenovirus (AAV8) to selectively inhibit hepatocyte microRNA production (Dicer-CKO). Organ microRNA expression was measured in health and following paracetamol toxicity. The functional consequence of hepatic microRNA transfer was determined by measuring the expression and activity of cytochrome P450 2E1 (target of the hepatocellular miR-122), and by measuring the effect of serum extracellular vesicles (ECVs) on proximal tubular cell injury. In humans with liver injury we measured microRNA expression in urinary ECVs. A murine model of myocardial infarction was used as a non-hepatic model of microRNA release. FINDINGS: Dicer-CKO mice demonstrated a decrease in kidney miR-122 in the absence of other microRNA changes. During hepatotoxicity, miR-122 increased in kidney tubular cells; this was abolished in Dicer-CKO mice. Depletion of hepatocyte microRNA increased kidney cytochrome P450 2E1 expression and activity. Serum ECVs from mice with hepatotoxicity increased proximal tubular cell miR-122 and prevented cisplatin toxicity. miR-122 increased in urinary ECVs during human hepatotoxicity. Transfer of microRNA was not restricted to liver injury -miR-499 was released following cardiac injury and correlated with an increase in the kidney. INTERPRETATION: Physiological transfer of functional microRNA to the kidney is increased by liver injury and this signalling represents a new paradigm for understanding the relationship between liver injury and renal function. FUNDING: Kidney Research UK, Medical Research Scotland, Medical Research Council.