Electrophysiological evaluation of phrenic nerve injury during cardiac surgery – a prospective, controlled, clinical study

BACKGROUND: According to some reports, left hemidiaphragmatic paralysis due to phrenic nerve injury may occur following cardiac surgery. The purpose of this study was to document the effects on phrenic nerve injury of whole body hypothermia, use of ice-slush around the heart and mammary artery harvesting. METHODS: Electrophysiology of phrenic nerves was studied bilaterally in 78 subjects before and three weeks after cardiac or peripheral vascular surgery. In 49 patients, coronary artery bypass grafting (CABG) and heart valve replacement with moderate hypothermic (mean 28°C) cardiopulmonary bypass (CPB) were performed. In the other 29, CABG with beating heart was performed, or, in several cases, peripheral vascular surgery with normothermia. RESULTS: In all patients, measurements of bilateral phrenic nerve function were within normal limits before surgery. Three weeks after surgery, left phrenic nerve function was absent in five patients in the CPB and hypothermia group (3 in CABG and 2 in valve replacement). No phrenic nerve dysfunction was observed after surgery in the CABG with beating heart (no CPB) or the peripheral vascular groups. Except in the five patients with left phrenic nerve paralysis, mean phrenic nerve conduction latency time (ms) and amplitude (mV) did not differ statistically before and after surgery in either group (p > 0.05). CONCLUSIONS: Our results indicate that CPB with hypothermia and local ice-slush application around the heart play a role in phrenic nerve injury following cardiac surgery. Furthermore, phrenic nerve injury during cardiac surgery occurred in 10.2 % of our patients (CABG with CPB plus valve surgery)

Competitive Performance Effects of Psychological Skill Training for Youth Swimmers

This study assessed the effect of two different psychological methods of skills training-self-talk and goal setting-on the swimming performance of youth swimmers. We allocated a convenience sample of club and county level youth swimmers ( N  = 49; M age  = 10.8, SD  = 1.25) to one of the three groups: self-talk, goal setting, or a control group engaged in no systematic psychological method of skills training. The groups were balanced in terms of competitive performance ability, age, and gender. Participants in the experimental conditions (self-talk and goal setting) completed a 5-week psychological skills intervention program and were measured on pre- and post-200-m swimming time in competition. After controlling for level of engagement in the program, analysis of covariance revealed a significant omnibus effect ( p  = .006, η p 2  = .20) with post hoc pairwise comparisons using magnitude-based statistics demonstrating that goal setting had a small positive effect compared with self-talk ( η 2 = .40; ± 0.45). Both self-talk ( η 2 = .50; ±0.48) and goal setting ( η 2 = .71; ±0.4) showed a small and moderate positive effect, respectively, relative to the control group. A social validation check confirmed that the swimmers found the intervention to be relevant, beneficial, and meaningful for improving performance. Psychological skills training may be effective in improving youth swimming performance; specific mechanisms underlying these benefits need further exploration

The Internal Sequence of the Peptide-Substrate Determines Its N-Terminus Trimming by ERAP1

Background: Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims N-terminally extended antigenic peptide precursors down to mature antigenic peptides for presentation by major histocompatibility complex (MHC) class I molecules. ERAP1 has unique properties for an aminopeptidase being able to trim peptides in vitro based on their length and the nature of their C-termini. Methodology/Principal Findings: In an effort to better understand the molecular mechanism that ERAP1 uses to trim peptides, we systematically analyzed the enzyme's substrate preferences using collections of peptide substrates. We discovered strong internal sequence preferences of peptide N-terminus trimming by ERAP1. Preferences were only found for positively charged or hydrophobic residues resulting to trimming rate changes by up to 100 fold for single residue substitutions and more than 40,000 fold for multiple residue substitutions for peptides with identical N-termini. Molecular modelling of ERAP1 revealed a large internal cavity that carries a strong negative electrostatic potential and is large enough to accommodate peptides adjacent to the enzyme's active site. This model can readily account for the strong preference for positively charged side chains. Conclusions/Significance: To our knowledge no other aminopeptidase has been described to have such strong preferences for internal residues so distal to the N-terminus. Overall, our findings indicate that the internal sequence of the peptide can affect its trimming by ERAP1 as much as the peptide's length and C-terminus. We therefore propose that ERAP1 recognizes the full length of its peptide-substrate and not just the N- and C- termini. It is possible that ERAP1 trimming preferences influence the rate of generation and the composition of antigenic peptides in vivo

Identification of Retinoic Acid in a High Content Screen for Agents that Overcome the Anti-Myogenic Effect of TGF-Beta-1

Transforming growth factor beta 1 (TGF-β1) is an inhibitor of muscle cell differentiation that is associated with fibrosis, poor regeneration and poor function in some diseases of muscle. When neutralizing antibodies to TGF-β1 or the angiotensin II inhibitor losartan were used to reduce TGF-β1 signaling, muscle morphology and function were restored in mouse models of Marfan Syndrome and muscular dystrophy. The goal of our studies was to identify additional agents that overcome the anti-myogenic effect of TGF-β1.A high-content cell-based assay was developed in a 96-well plate format that detects the expression of myosin heavy chain (MHC) in C2C12 cells. The assay was used to quantify the dose-dependent responses of C2C12 cell differentiation to TGF-β1 and to the TGF-β1 Type 1 receptor kinase inhibitor, SB431542. Thirteen agents previously described as promoting C2C12 differentiation in the absence of TGF-β1 were screened in the presence of TGF-β1. Only all-trans retinoic acid and 9-cis retinoic acid allowed a maximal level of C2C12 cell differentiation in the presence of TGF-β1; the angiotensin-converting enzyme inhibitor captopril and 10 nM estrogen provided partial rescue. Vitamin D was a potent inhibitor of retinoic acid-induced myogenesis in the presence of TGF-β1. TGF-β1 inhibits myoblast differentiation through activation of Smad3; however, retinoic acid did not inhibit TGF-β1-induced activation of a Smad3-dependent reporter gene in C2C12 cells.Retinoic acid alleviated the anti-myogenic effect of TGF-β1 by a Smad3-independent mechanism. With regard to the goal of improving muscle regeneration and function in individuals with muscle disease, the identification of retinoic acid is intriguing in that some retinoids are already approved for human therapy. However, retinoids also have well-described adverse effects. The quantitative, high-content assay will be useful to screen for less-toxic retinoids or combinations of agents that promote myoblast differentiation in the presence of TGF-β1

Exploring stressors and coping among volunteer, part-time and full-time sports coaches

© 2018 Informa UK Limited, trading as Taylor & Francis Group The stressor and coping experiences of full-time and paid coaches have been reported in the literature, yet researchers have largely overlooked the experiences of part-time and voluntary coaches who make a substantial contribution to the coaching workforce. This study aimed to begin addressing these voids by exploring volunteer, part-time and full-time coaches’ stressors and coping strategies. In addition, this study aimed to explore both men and women coaches’ experiences of stressors and coping because most published literature has focused on the experiences of male coaches. Guided by our interpretive paradigm and blended constructionist and critical realist perspective, theoretically informed semi-structured interviews were conducted with 19 men and women coaches who represented a range of team and individual sports. Data were thematically analysed using an abductive approach. We constructed 141 codes that were represented by three themes of stressors (coach-related, athlete-related and organisational) and 131 codes relating to coping, which we grouped into seven themes (problem-solving, information seeking, escape, negotiation, self-reliance, dyadic coping and support seeking). Based on these findings, we propose several impactful recommendations for researchers and practitioners. For example, we recommend that researchers continue to generate rich understanding of stressors and coping among coaches who are working on different employment bases to work towards the development of effective stress management interventions. Further, we encourage national governing bodies work with practitioners to incorporate specific foci on stress and stress management during coach education programmes to contribute to more effective performance under pressure

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]