Abnormal ECG Findings in Athletes: Clinical Evaluation and Considerations.

PURPOSE OF REVIEW: Pre-participation cardiovascular evaluation with electrocardiography is normal practice for most sporting bodies. Awareness about sudden cardiac death in athletes and recognizing how screening can help identify vulnerable athletes have empowered different sporting disciplines to invest in the wellbeing of their athletes. RECENT FINDINGS: Discerning physiological electrical alterations due to athletic training from those representing cardiac pathology may be challenging. The mode of investigation of affected athletes is dependent on the electrical anomaly and the disease(s) in question. This review will highlight specific pathological ECG patterns that warrant assessment and surveillance, together with an in-depth review of the recommended algorithm for evaluation

The Function of Heterodimeric AP-1 Comprised of c-Jun and c-Fos in Activin Mediated Spemann Organizer Gene Expression

BACKGROUND:Activator protein-1 (AP-1) is a mediator of BMP or FGF signaling during Xenopus embryogenesis. However, specific role of AP-1 in activin signaling has not been elucidated during vertebrate development. METHODOLOGY/PRINCIPAL FINDINGS:We provide new evidence showing that overexpression of heterodimeric AP-1 comprised of c-jun and c-fos (AP-1(c-Jun/c-Fos)) induces the expression of BMP-antagonizing organizer genes (noggin, chordin and goosecoid) that were normally expressed by high dose of activin. AP-1(c-Jun/c-Fos) enhanced the promoter activities of organizer genes but reduced that of PV.1, a BMP4-response gene. A loss of function study clearly demonstrated that AP-1(c-Jun/c-Fos) is required for the activin-induced organizer and neural gene expression. Moreover, physical interaction of AP-1(c-Jun/c-Fos) and Smad3 cooperatively enhanced the transcriptional activity of goosecoid via direct binding on this promoter. Interestingly, Smad3 mutants at c-Jun binding site failed in regulation of organizer genes, indicating that these physical interactions are specifically necessary for the expression of organizer genes. CONCLUSIONS/SIGNIFICANCE:AP-1(c-Jun/c-Fos) plays a specific role in organizer gene expression in downstream of activin signal during early Xenopus embryogenesis

Omi/Htra2 Protease Is Associated With Tubular Cell Apoptosis And Fibrosis Induced By Unilateral Ureteral Obstruction

Kidney fibrosis, a typical characteristic of chronic renal disease, is associated with tubular epithelial cell apoptosis. The results of our recent studies have shown that Omi/HtrA2 (Omi), a proapoptotic mitochondrial serine protease, performs a crucial function in renal tubular epithelial apoptotic cell death in animal models of acute kidney injury, including cisplatin toxicity and ischemia-reperfusion insult. However, the role of Omi in tubulointerstitial disease-associated fibrosis in the kidney remains to be clearly defined. We evaluated the potential function and molecular mechanism of Omi in ureteral obstruction-induced kidney epithelial cell apoptosis and fibrosis. The mice were subjected to unilateral ureteral obstruction (UUO) via the ligation of the left ureter near the renal pelvis. UUO increased the protein level of Omi in the cytosolic fraction of the kidney, with a concomitant reduction in the mitochondrial fraction. UUO reduced the X-linked inhibitor of apoptosis protein (XIAP), a substrate of Omi, and pro-caspase-3, whereas it increased cleaved poly(ADP-ribose) polymerase (cleaved PARP) and the number of terminal deoxynucleotidyl transferase dUTP nickend labeling (TUNEL)-positive cells. When mice were treated with ucf-101, an inhibitor of the proteolytic activity of Omi (6.19 μg/day ip), on a daily basis beginning 2 days before UUO and continuing until the end of the experiment, the Omi inhibitor protected XIAP cleavage after UUO and reduced the increment of PARP cleavage and the numbers of TUNEL-positive cells. Furthermore, the Omi inhibitor significantly attenuated UUO-induced increases in fibrotic characteristics in the kidney, including the atrophy and dilation of tubules, expansion of the interstitium, and increases in the expression of collagens, α-smooth muscle actin, and fibronectin. In conclusion, Omi/HtrA2 is associated with apoptotic signaling pathways in tubular epithelial cells activated by unilateral ureteral obstruction, thereby resulting in kidney fibrosis. Copyright © 2010 the American Physiological Society

Direct response elements of BMP within the PV.1A promoter are essential for its transcriptional regulation during early Xenopus development.

Xvent homeobox genes encode transcription factors that repress organizer genes and are essential for dorsoventral specification during early embryogenesis in Xenopus. In contrast to the Xvent-2 gene subfamily, Xvent-1 subfamily members, including PV.1A, have been proposed as indirect targets of Bone Morphogenetic Protein-4 (BMP-4) signaling. Because PV.1A is a critical downstream mediator of, and tightly regulated by, BMP-4 signaling, we hypothesized that its promoter contains a direct BMP-4 response element to effect this transcriptional regulation. We demonstrate that direct regulation by BMP-4 is necessary for transcription of PV.1A: its proximal promoter contains cis-acting binding elements for Smads and Oaz crucial to induction in response to BMP-4 signaling. In addition to these direct cis-acting BMP-4 responsive elements, an indirect Xvent-2 response element and several repressive elements exist in the PV.1A promoter to regulate its transcription. In summary, PV.1A undergoes combinatorial regulation during early Xenopus development as both the direct target of BMP-4 signaling and as the direct and indirect target of positive and negative regulatory factors

Thinking in clinical nursing practice: A study of critical care nurses\u27 thinking applying the think-aloud, protocol analysis method

Purpose: The purpose of the paper is to discover the patterns and processes of decision-making in clinical nursing practice. Methods: A set of think-aloud data from five critical care nurses during 40 to 50 minutes of caregiving in intensive care units were obtained and analyzed by applying the procedures recommended by Ericsson and Simon for protocol analysis. Results: Four thinking processes before acting were identified to constitute various sorts of thoughts in which the nurses were engaged during patient care: reviewing, validation, consideration, rationalization, and action. In addition, three patterns of sequential streaming of thinking (short, intermediate, long) were identified to reveal various ways the nurses dealt with clinical situations involving nursing tasks and responsibilities. Conclusion: This study specifies the initial categories of thoughts for each of the processes and various patterns with which these processes are sequentially combined, providing insights into the ways nurses think about problems and address their concerns. The findings suggest that the thinking in clinical practice involves more than focused decision-making and reasoning, and needs to be examined from a broader perspective. © 2007 Korean Society of Nursing Science

Omi/HtrA2 protease is associated with tubular cell apoptosis and fibrosis induced by unilateral ureteral obstruction

Kidney fibrosis, a typical characteristic of chronic renal disease, is associated with tubular epithelial cell apoptosis. The results of our recent studies have shown that Omi/HtrA2 (Omi), a proapoptotic mitochondrial serine protease, performs a crucial function in renal tubular epithelial apoptotic cell death in animal models of acute kidney injury, including cisplatin toxicity and ischemia-reperfusion insult. However, the role of Omi in tubulointerstitial disease-associated fibrosis in the kidney remains to be clearly defined. We evaluated the potential function and molecular mechanism of Omi in ureteral obstruction-induced kidney epithelial cell apoptosis and fibrosis. The mice were subjected to unilateral ureteral obstruction (UUO) via the ligation of the left ureter near the renal pelvis. UUO increased the protein level of Omi in the cytosolic fraction of the kidney, with a concomitant reduction in the mitochondrial fraction. UUO reduced the X-linked inhibitor of apoptosis protein (XIAP), a substrate of Omi, and pro-caspase-3, whereas it increased cleaved poly(ADP-ribose) polymerase (cleaved PARP) and the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells. When mice were treated with ucf-101, an inhibitor of the proteolytic activity of Omi (6.19 μg/day ip), on a daily basis beginning 2 days before UUO and continuing until the end of the experiment, the Omi inhibitor protected XIAP cleavage after UUO and reduced the increment of PARP cleavage and the numbers of TUNEL-positive cells. Furthermore, the Omi inhibitor significantly attenuated UUO-induced increases in fibrotic characteristics in the kidney, including the atrophy and dilation of tubules, expansion of the interstitium, and increases in the expression of collagens, α-smooth muscle actin, and fibronectin. In conclusion, Omi/HtrA2 is associated with apoptotic signaling pathways in tubular epithelial cells activated by unilateral ureteral obstruction, thereby resulting in kidney fibrosis

IFT46 plays crucial roles in craniofacial and cilia development

The intraflagellar transport (IFT) system is essential for bidirectional movement of ciliary components from the basal body to the tip beneath the ciliary sheath and is conserved for cilia and flagella formation in most vertebrates. IFT complex A is involved in anterograde trafficking, whereas complex B is involved in retrograde trafficking. IFT46 is well known as a crucial component of IFT complex B, however, its developmental functions are poorly understood. In this study, we investigated the novel functions of IFT46 during vertebrate development, especially, ciliogenesis and neurogenesis, because IFT46 is strongly expressed in both multiciliated cells of epithelial and neural tissues. Knockdown of IFT46 using morpholino microinjections caused shortening of the body axis as well as the formation of fewer and shorter cilia. Furthermore, loss of IFT46 down-regulated the expression of the neural plate and neural tube markers, thus may influence Wnt/planar cell polarity and the sonic hedgehog signaling pathway during neurogenesis. In addition, loss of IFT46 caused craniofacial defects by interfering with cartilage formation. In conclusion, our results depict that IFT46 plays important roles in cilia as well as in neural and craniofacial development.clos

Transcriptional regulation of Xbr-1a/Xvent-2 homeobox gene: Analysis of its promoter region

Xvent homeobox proteins are induced by BMP-4 signaling and have been known to mediate many BMP-4 activities as key downstream transcriptional factors. In order to investigate the regulatory mode of Xvent transcription, we isolated genomic DNA of the Xbr-1a/Xvent-2 containing the promoter region responsive to BMP-4 signaling. The cis-acting elements located within the Xbr-1a/Xvent-2 promoter and the regulation modes by BMP-4 signaling were analyzed by serial deletion and site-directed mutagenesis experiments. The upstream -235 bp of the promoter retained the full transcriptional activity and BMP-4-response when compared with the longest promoter construct. Further analysis indicated that two separated 15 bp regions contained a strong positive element and BMP-4-response element. Site-directed mutagenesis of those regions suggests that those two regions cooperate for the promoter activity and BMP-4-response. Moreover, we found that the transcription factors, Oaz and PEBP2αA, were able to elicit additive effects with BMP-4 signaling on Xbr-1a/Xvent-2 reporter activities. These results indicate that transcriptional regulation of the Xbr-1a/Xvent-2 gene occurs in a complex mode through the cooperation of various transcription factors. © 2002 Elsevier Science (USA). All rights reserved.FALS