Cardiac Troponin I-Interacting Kinase Affects Cardiomyocyte S-Phase Activity but Not Cardiomyocyte Proliferation.

BACKGROUND: Identifying genetic variants that affect the level of cell cycle reentry and establishing the degree of cell cycle progression in those variants could help guide development of therapeutic interventions aimed at effecting cardiac regeneration. We observed that C57Bl6/NCR (B6N) mice have a marked increase in cardiomyocyte S-phase activity after permanent coronary artery ligation compared with infarcted DBA/2J (D2J) mice. METHODS: Cardiomyocyte cell cycle activity after infarction was monitored in D2J, (D2J×B6N)-F1, and (D2J×B6N)-F1×D2J backcross mice by means of bromodeoxyuridine or 5-ethynyl-2'-deoxyuridine incorporation using a nuclear-localized transgenic reporter to identify cardiomyocyte nuclei. Genome-wide quantitative trait locus analysis, fine scale genetic mapping, whole exome sequencing, and RNA sequencing analyses of the backcross mice were performed to identify the gene responsible for the elevated cardiomyocyte S-phase phenotype. RESULTS: (D2J×B6N)-F1 mice exhibited a 14-fold increase in cardiomyocyte S-phase activity in ventricular regions remote from infarct scar compared with D2J mice (0.798±0.09% versus 0.056±0.004%; P<0.001). Quantitative trait locus analysis of (D2J×B6N)-F1×D2J backcross mice revealed that the gene responsible for differential S-phase activity was located on the distal arm of chromosome 3 (logarithm of the odds score=6.38; P<0.001). Additional genetic and molecular analyses identified 3 potential candidates. Of these, Tnni3k (troponin I-interacting kinase) is expressed in B6N hearts but not in D2J hearts. Transgenic expression of TNNI3K in a D2J genetic background results in elevated cardiomyocyte S-phase activity after injury. Cardiomyocyte S-phase activity in both Tnni3k-expressing and Tnni3k-nonexpressing mice results in the formation of polyploid nuclei. CONCLUSIONS: These data indicate that Tnni3k expression increases the level of cardiomyocyte S-phase activity after injury.

Myocardial Polyploidization Creates a Barrier to Heart Regeneration in Zebrafish.

Correlative evidence suggests that polyploidization of heart muscle, which occurs naturally in post-natal mammals, creates a barrier to heart regeneration. Here, we move beyond a correlation by demonstrating that experimental polyploidization of zebrafish cardiomyocytes is sufficient to suppress their proliferative potential during regeneration. Initially, we determined that zebrafish myocardium becomes susceptible to polyploidization upon transient cytokinesis inhibition mediated by dominant-negative Ect2. Using a transgenic strategy, we generated adult animals containing mosaic hearts composed of differentially labeled diploid and polyploid-enriched cardiomyocyte populations. Diploid cardiomyocytes outcompeted their polyploid neighbors in producing regenerated heart muscle. Moreover, hearts composed of equivalent proportions of diploid and polyploid cardiomyocytes failed to regenerate altogether, demonstrating that a critical percentage of diploid cardiomyocytes is required to achieve heart regeneration. Our data identify cardiomyocyte polyploidization as a barrier to heart regeneration and suggest that mobilizing rare diploid cardiomyocytes in the human heart will improve its regenerative capacity.

Postoperative endophthalmitis: caution is the watchword.

Postoperative endophthalmitis is the most feared complication following cataract surgery. It can be caused by infection entering the eye during surgery or by inadequately cleaned instruments. Sterile phaco handpieces might retain remnants of soft lens matter or visco-elastic which might later contaminate other patients, causing inflammation in their eyes. The costs of an endophthalmitis outbreak are heavy, including poor patient outcomes, temporary theatre closure, rising waiting lists and damage to a hospital's reputation. This article raises awareness of endophthalmitis and provides useful recommendations for ophthalmic theatre personnel.

Moving from novice to expert - the value of learning in clinical practice: a literature review.

The Fitness for Practice Report (UKCC 1999) acknowledged the importance of competent nursing practice and shared the responsibility for achieving this by making United Kingdom National Health Service employees jointly responsible for this with higher education teachers. This article presents a wide review of educational literature, to discover how both the constructivist and the sociocultural approach to learning will promote nursing expertise. Consideration of both these approaches to learning is germane to pre and post registration nursing courses, given that learning is both culturally situated and individually constructed from a variety of different sources, and the review demonstrates the pivotal position of the mentor and other practice teachers.