Reptilian Heart Development And The Molecular Basis Of Cardiac Chamber Evolution

The emergence of terrestrial life witnessed the need for more sophisticated circulatory systems. This has evolved in birds, mammals and crocodilians into complete septation of the heart into left and right sides, allowing separate pulmonary and systemic circulatory systems, a key requirement for the evolution of endothermy(1-3). However, the evolution of the amniote heart is poorly understood. Reptilian hearts have been the subject of debate in the context of the evolution of cardiac septation: do they possess a single ventricular chamber or two incompletely septated ventricles(4-7)? Here we examine heart development in the red-eared slider turtle, Trachemys scripta elegans (a chelonian), and the green anole, Anolis carolinensis (a squamate), focusing on gene expression in the developing ventricles. Both reptiles initially form a ventricular chamber that homogenously expresses the T-box transcription factor gene Tbx5. In contrast, in birds and mammals, Tbx5 is restricted to left ventricle precursors(8,9). In later stages, Tbx5 expression in the turtle (but not anole) heart is gradually restricted to a distinct left ventricle, forming a left-right gradient. This suggests that Tbx5 expression was refined during evolution to pattern the ventricles. In support of this hypothesis, we show that loss of Tbx5 in the mouse ventricle results in a single chamber lacking distinct identity, indicating a requirement for Tbx5 in septation. Importantly, misexpression of Tbx5 throughout the developing myocardium to mimic the reptilian expression pattern also results in a single mispatterned ventricular chamber lacking septation. Thus ventricular septation is established by a steep and correctly positioned Tbx5 gradient. Our findings provide a molecular mechanism for the evolution of the amniote ventricle, and support the concept that altered expression of developmental regulators is a key mechanism of vertebrate evolution

Audit of enuresis referrals on the waiting list for a tertiary hospital outpatient clinic.

AIM: Enuresis, defined as intermittent incontinence occurring exclusively during sleep, affects 4-19% of children, but can be effectively treated using education and alarm-bell therapies. However, delays in treatment are likely to impact upon the quality of life of the child, parents and carers. Poor quality and incomplete referrals are thought to be a major driver of inefficiencies. The aim of this study was to explore characteristics of enuresis referrals on the waiting list for a general medicine clinic at a tertiary paediatric hospital. METHODS: An audit was conducted to examine all enuresis referrals on the general medicine outpatient clinic waiting list in February 2019 at The Royal Children's Hospital, Melbourne. Enuresis referrals with an organic cause and those for children less than 5 years of age were excluded. RESULTS: Of the 2613 referrals on the general medicine waiting list, 486 of 2613 (19%) were related to enuresis. The median age of patients on the waiting list was 8 years and 65% (315/486) were male. Sufficient detail was provided to determine temporal and disease stratification in 45% (218/486) of referrals; primary versus secondary enuresis, and monosymptomatic versus non-monosymptomatic enuresis. The mean number of days on the waiting list calculated at the time of data extraction (13 February 2019) was 226 (±179) days. CONCLUSIONS: The findings from this study suggest that there are long waiting times for enuresis services and referrals often do not contain complete information