The inability of the adult mammalian heart to regenerate represents a fundamental barrier in heart failure management. In contrast, the neonatal heart retains a transient regenerative capacity, but the underlying mechanisms for the developmental loss of cardiac regenerative capacity in mammals are not fully understood. Wnt/β-catenin signaling has been proposed as a key cardio-regenerative pathway driving cardiomyocyte proliferation. Here, we show that Wnt/β-catenin signaling potentiates neonatal mouse cardiomyocyte proliferation in vivo and immature human pluripotent stem cell-derived cardiomyocyte (hPSC-CM) proliferation in vitro. In contrast, Wnt/β-catenin signaling in adult mice is cardioprotective but fails to induce cardiomyocyte proliferation. Transcriptional profiling and chromatin immunoprecipitation sequencing of neonatal mouse and hPSC-CM revealed a core Wnt/β-catenin-dependent transcriptional network governing cardiomyocyte proliferation. In contrast, β-catenin failed to re-engage this neonatal proliferative gene network in the adult heart despite partial transcriptional re-activation of a neonatal glycolytic gene program. These findings suggest that β-catenin may be repurposed from regenerative to protective functions in the adult heart in a developmental process dependent on the metabolic status of cardiomyocytes.

Informal caregivers include family, friends, and significant others who provide important support for people who have attempted suicide or experienced suicidal ideation. Despite the prevalence of suicidal behaviour worldwide, they remain an understudied population. This review aimed to synthesise the literature on the experiences and support needs of informal caregivers of people who have attempted suicide or experienced suicidal ideation. We conducted a systematic review according to PRISMA guidelines. Searches of peer-reviewed literature in Medline, Emcare, Embase, EBM Reviews, and PsycINFO identified 21 studies (4 quantitative and 17 qualitative), published between 1986 and 2021. Informal carers commonly reported symptoms of depression and anxiety, for which they receive little assistance. They also expressed a desire for more involvement and education in the professional care of suicidality. Together, the studies indicated a need to improve the way informal caregiving is managed in professional healthcare settings. This review identified potential avenues for future research, as well as broad areas which require attention in seeking to improve the care of suicidal people and their caregivers.

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