An Evaluation of Ischaemic Preconditioning as a Method of Reducing Ischaemia Reperfusion Injury in Liver Surgery and Transplantation

Liver Ischaemia Reperfusion (IR) injury is a major cause of post-operative liver dysfunction, morbidity and mortality following liver resection surgery and transplantation. There are no proven therapies for IR injury in clinical practice and new approaches are required. Ischaemic Preconditioning (IPC) can be applied in both a direct and remote fashion and has been shown to ameliorate IR injury in small animal models. Its translation into clinical practice has been difficult, primarily by a lack of knowledge regarding the dominant protective mechanisms that it employs. A review of all current studies would suggest that IPC/RIPC relies on creating a small tissue injury resulting in the release of adenosine and l-arginine which act through the Adenosine receptors and the haem-oxygenase and endothelial nitric oxide synthase systems to reduce hepatocyte necrosis and improve the hepatic microcirculation post reperfusion. The next key step is to determine how long the stimulus requires to precondition humans to allow sufficient injury to occur to release the potential mediators. This would open the door to a new therapeutic chapter in this field

Neutrophil Gelatinase-Associated Lipocalin (NGAL) in predicting acute kidney injury following orthotopic liver transplantation: A systematic review

Background: Acute kidney injury (AKI) is common after orthotopic liver transplantation (OLT) usually occurring early post-transplant. Multiple causes include graft preservation injury, blood loss, hypotension but also severity of recipient liver disease. Early intervention in AKI has both short and long term patient benefits. Unfortunately there are no current clinical biomarkers of early AKI. Aim: To assess the value of NGAL in predicting AKI following OLT. Methods: Ovid MEDLINE and EMBASE were searched between the years of 2000 and 2017 for studies using keywords: Neutrophil Gelatinase Associated Lipocalin or NGAL variants combined with synonyms for liver transplantation. Results: 96 studies were identified. 11 studies including 563 patients were considered suitable for analysis. Both urinary (uNGAL) and plasma NGAL (pNGAL) measurement were found to predict AKI after liver transplantation. Optimal reported area under the receiver-operator characteristics curve (AUROC) values of 0.5–0.83 and 0.54–0.86 respectively. Conclusions: NGAL is a good predictor of early AKI post OLT although there is considerable variation in the published results. Further studies with prospectively defined cut-off values, standardized definitions of AKI and rigorous data reporting should be conducted to establish its clinical usefulness and limitations

Effects of treatment dosage of whole-body cryotherapy upon post-match recovery of endocrine and biochemical markers in elite rugby league players: An experimental study

Background and Aims: The use of whole-body cryotherapy (WBC) for athletic recovery is becoming increasingly popular despite the lack of evidence supporting the dosage parameters in its implementation. The aim of the current study was to investigate the dose–response effects of WBC following match-play in elite rugby league players. Methods: We observed endocrine (salivary cortisol and testosterone) and biochemical (creatine kinase) responses following three separate post-match recovery periods in elite rugby league players. Comparisons were made between a single exposure (3 min at −120°C to -−135°C) of WBC to two consecutive exposures (2 × 3 min), to a control (no exposure) during the recovery trials. Recovery characteristics were measured 36 h prematch, immediately postmatch, and 60 h postmatch. Results: Cortisol concentrations remained unchanged in its pattern of response during the postmatch recovery periods across all WBC doses. Testosterone concentrations increased significantly (p < 0.0005) at 60 h, in the WBC2 trial. The Testosterone:Cortisol ratio increased significantly (p < 0.0005) at 60 h in the WBC2 trial, while during the WBC0 trial it did not recover to baseline levels. No significant effect on creatine kinase concentration was observed, although a statistical trend was shown in WBC2 for improved reduction of this marker at 60 h. Conclusions: These findings suggest that two, consecutive exposures to WBC immediately following fatiguing rugby league competition appear to stimulate an increase to the anabolic endocrine profile of participants by 60 h post-match, and may reduce the CK concentration. Coaches and athletes should consider the treatment dosage of WBC when used to optimize the desired response following a high-stress environment

Anaemia in patients with chronic liver disease and its association with morbidity and mortality following liver transplantation

Pre-operative anaemia and the need for intra-operative transfusion have been associated with increased morbidity and mortality following cardiac and major non-cardiac surgery. Anaemia is highly prevalent in patients with severe chronic liver disease. Whether this correlates with an altered morbidity and mortality following liver transplant has not been established. METHODS: Prospectively collected data was analysed for the period 1998-2012. Donor and recipient characteristics, blood profiles and complications were recorded. Graft and patient survival was calculated. All patients were followed up for 1 year or until death. Pre-operative haemoglobin levels were correlated with patient demographics and outcome using a binary logistic regression analysis. RESULTS: Pre-operative anaemia, according to WHO criteria, occurred in 73% of patients. Anaemia was more common with advanced liver disease (higher MELD score). As MELD score increased, Haemoglobin levels dropped. Anaemic patients were more commonly transfused (p < 0.001), spent longer ventilated (7 day vs 5 days, p = 0.005) and required longer ITU stays (8 days vs 6 days, p = 0.015). Pre-operative anaemia did not correlate with patient morbidity or mortality. CONCLUSIONS: Reduced haemoglobin levels reflect the severity of chronic liver disease but are not an independent risk factor for a poor outcome following liver transplantation

Physicochemical property distributions for accurate and rapid pairwise protein homology detection

<p>Abstract</p> <p>Background</p> <p>The challenge of remote homology detection is that many evolutionarily related sequences have very little similarity at the amino acid level. Kernel-based discriminative methods, such as support vector machines (SVMs), that use vector representations of sequences derived from sequence properties have been shown to have superior accuracy when compared to traditional approaches for the task of remote homology detection.</p> <p>Results</p> <p>We introduce a new method for feature vector representation based on the physicochemical properties of the primary protein sequence. A distribution of physicochemical property scores are assembled from 4-mers of the sequence and normalized based on the null distribution of the property over all possible 4-mers. With this approach there is little computational cost associated with the transformation of the protein into feature space, and overall performance in terms of remote homology detection is comparable with current state-of-the-art methods. We demonstrate that the features can be used for the task of pairwise remote homology detection with improved accuracy versus sequence-based methods such as BLAST and other feature-based methods of similar computational cost.</p> <p>Conclusions</p> <p>A protein feature method based on physicochemical properties is a viable approach for extracting features in a computationally inexpensive manner while retaining the sensitivity of SVM protein homology detection. Furthermore, identifying features that can be used for generic pairwise homology detection in lieu of family-based homology detection is important for applications such as large database searches and comparative genomics.</p

Time-of-day variation on performance measures in repeated-sprint tests: A systematic review.

The lack of standardization of methods and procedures have hindered agreement in the literature related to time-of-day effects on repeated sprint performance and needs clarification. Therefore, the aim of the present study was to investigate and systematically review the evidence relating to time-of-day based on performance measures in repeated-sprints. The entire content of PubMed (MEDLINE), Scopus, SPORTDiscus® (via EBSCOhost) and Web of Science was searched. Only experimental research studies conducted in male adult participants aged ≥18yrs, published in English before June 2019 were included. Studies assessing repeated-sprints between a minimum of two time-points during the day (morning versus evening) were deemed eligible. The primary search revealed that a total of 10 out of 112 articles were considered eligible and subsequently included. Seven articles were deemed strong and three moderate quality. Eight studies found repeated-sprint performance across the first, first few, or all sprints, to increase in favor of the evening. The magnitude of difference is dependent on the modality and the exercise protocol used. The non-motorized treadmill established an average 3.5–8.5% difference in distance covered, average and peak velocity, and average power, across all sprints in three studies and in peak power in two studies. In cycling, power output differed across all sprints by 6.0% in one study and 8.0% for the first sprint only in five studies. All four studies measuring power decrement values (i.e. rate of fatigue) established differences up to 4.0% and two out of five studies established total work to be significantly higher by 8.0%. Repeated-sprint performance is affected by time-of-day with greater performance in the late/early afternoon. The magnitude is dependent on the variable assessed and the mode of exercise. There is a clear demand for more rigorous investigations which control factors that specifically relate to investigations of time-of-day and are specific to the sport of individuals

Ultrafast Ge-Te bond dynamics in a phase-change superlattice

A long-standing question for avant-garde data storage technology concerns the nature of the ultrafast photoinduced phase transformations in the wide class of chalcogenide phase-change materials (PCMs). Overall, a comprehensive understanding of the microstructural evolution and the relevant kinetics mechanisms accompanying the out-of-equilibrium phases is still missing. Here, after overheating a phase-change chalcogenide superlattice by an ultrafast laser pulse, we indirectly track the lattice relaxation by time resolved x-ray absorption spectroscopy (tr-XAS) with a sub-ns time resolution. The approach to the tr-XAS experimental results reported in this work provides an atomistic insight of the mechanism that takes place during the cooling process; meanwhile a first-principles model mimicking the microscopic distortions accounts for a straightforward representation of the observed dynamics. Finally, we envisage that our approach can be applied in future studies addressing the role of dynamical structural strain in PCMs.M.M. acknowledges the support of the BACH beamline staff during the synchrotron experiments and Roberta Ciprian for insightful discussions. This work was supported by EU within FP7 project PASTRY [GA 317764]

Football-induced fatigue in hypoxia impairs repeated sprint ability and perceptual-cognitive skills

The present study investigated the effects of football-induced fatigue during hypoxia on RS and perceptual-cognitive skills. Ten male semi-professional football players underwent four sessions; a control session (0-m) to quantify RS in a non-fatigued state; and three further sessions at hypoxia (0-m;1500-m;3000-m) examining RS and perceptual-cognitive skill responses for a given physical workload. Anticipation and decision-making accuracy were obtained at the 30-min mark of each half. The mean number of trials (%) in which the player made the correct response was used for analysis. HR, TC, RPE and % saturation of O2 were measured during the warm-up, football-induced fatigue and RS test. It was found that HR, RPE and % saturation of O2 were different between conditions (P<0.05; ES=0.44-6.13). Further, RS were affected by football-induced fatigue for DC (4.8%; P=0.019; ES=0.68) and AV (5.5%; P=0.006; ES=0.79). In hypoxia, it was observed that football-induced fatigue decreased by 6.5% in DC, 6.3% in AV and 3.1% in PV at 1500-m compared to 0-m (P<0.05). Further significant changes were found at 3000-m compared to 0-m decreasing 12.8% in DC, 12.8% in AV and 6.2% in PV (P<0.0005). More pronounced declines in perceptual-cognitive skills were found as altitude increased (5.0-12.5 %; P<0.05; ES=1.17-2.41) and between both halves (5.3-6.7 %; P<0.05). The data demonstrates that the RS test was highly sensitive to fatigue and hypoxia for a given physical load. Simulated matches in hypoxia revealed larger decreases, when compared to normoxia in RS and perceptual-cognitive skills, highlighting the need for optimal acclimatisation strategies, including physical and technical preparation, prior to playing a

The simple, conventional markers of fatigue - variations in neuromuscular performance, creatine kinase and hydration status in elite soccer players over a season.

Background and Purpose: Fixture congestion, game-intensities and limited recovery negatively influence physical/ physiological responses during a competitive soccer season. Therefore, the aim of the investigation was to examine weekly alterations in neuromuscular performance markers, creatine kinase and hydration in elite soccer players throughout a season. Study Design: Longitudinal Observational Study. Methods: Sixteen male professional soccer players competing in the English Football League Championship were assessed over the course of a season. All players provided a urine sample, a blood sample to assess creatine-kinase concentration and performed a countermovement jump test at the start of the season, in-season, pre-and post-match over 38 weeks. Results: Jump height was the most common marker of performance to be significantly reduced in season compared to baseline (-5.4 to -11.3%, P <0.05) with 45.2% of the time-points affected. Measures of FT:CT (-7.5 to -12.4%) and AP (-9.4 to -11.5%), also showed significant deteriorations throughout the season compared to baseline (P<0.05) at several time-points. Max force (MF) significantly increased in-season (+5.1 to 7.0%) in 20% of the observed time-points compared to baseline. CK concentration significantly increased during 19% of the time-points (P<0.05; 62 to 159%). Urine osmolality demonstrated significant differences in-season compared to baseline, but none to levels of dehydration. Conclusion: Monitoring elite soccer players over the course of a competitive season shows alterations in neuromuscular performance and hydration status. These data suggest that assessing counter-movement jump performance may be a useful marker for monitoring responses to training/competition, while creatine-kinase and hydration status may be limited