Reproducibility of creatine kinase: how useful is this measurement tool?

Establishing the reproducibility of a measurement is essential for repeated testing to ensure that any systematic change is a result of an external influence (i.e. intervention), as oppossed to normal random variation. Although some degree of error is inherent in any measure, a measurement tool should yield consistent results that do not fluctuate to an unacceptable degree from one test to another. Creatine kinase (CK) is consistently measured in the blood as a marker of exercise induced muscle damage (EIMD). However, its usefulness as a predictive tool to examine the temporal pattern, and magnitude of muscle damage has been questioned. PURPOSE:The main aim of the present study was to employ a variety of reproducibility statistics in order to examine the typical level of measurement error for CK. METHODS: Fifty (36 male, 14 female), apparently healthy participants completed three trials on three separate occasions with each trial separated by 48 - 72 h. The initial trial served as a familiarisation. During trials 2 and 3 (48 h), CK measures were obtained using standard fingerprick technique, and analysed in duplicate immediatley using a colorimetric assay procedure. Each participant completed their trials at the same time of day, following identical pre-test procedures. RESULTS: The intra-test coefficient of variation (CV) within our laboratory was 9%. Dependent t-tests indicated there was no systematic bias between trials (p = 0.82). The interdian CV displayed low reproducibility (20%). Furthermore, the 95% limits of agreement (LoA) were -69.7 to 63.5 iµ/L. However, the intraclass correlation coefficient (ICC) was 0.90, which can be clasified as displaying ‘high’ reproducibility. CONCLUSION: The interdian CV demonstrates that under identical resting conditions (48 h apart), CK displays inherent low absoulte reproducibility, which may obscure a true experimental effect. However, interpretation of the ICC, suggests that CK has high relative reproducibility. The high range of observed CK values is thought to have increased the size of the correlation. Subsequently, an indivdual change in CK following EIMD may not be indicative of the magnitude of damage, and may simply be a result of the inherent variation (e.g. biological). Therefore, it is advised that caution should be taken when using CK within experimental research, and as an indication of when an athlete has recovered, and is able to recommence training

The cytokine response to a 30 min downhill run

ISEI Abstract – 7 The cytokine response to a 30 min downhill run L TAYLOR1, CHRISMAS BCR1, CARROLL S2, SMITH A3, PEMBERTON P3, SIEGLER JC4 and MIDGLEY AW5. 1 Applied Sport and Exercise Physiology (ASEP) & Muscle Cellular and Molecular Physiology (MCMP) research groups, Institute of Sport and Physical Activity Research (ISPAR), Department of Sport & Exercise Sciences, University of Bedfordshire, Bedford, UK. 2Department of Sport, Health & Exercise Science, The University of Hull, Hull, UK. 3Department of Clinical Biochemistry, Central Manchester Foundation Trust, Manchester, UK. 4School of Science & Health, University of Western Sydney, Sydney, Australia. 5Department of Sport & Physical Activity, Edge Hill University, Ormskirk, UK. ABSTRACT Eccentric exercise has been ubiquitously shown to result in exericse induced muscle damage (EIMD), accompanied with delayed onset muscle soreness (DOMS). Although eccentric exercise may induce greater neuromuscular adaptation, functional performance may be impaired, and soreness may persist for several days following this type of exercise. This is primarily thought to be due to structural damage to the muscle fibres. In addition to the mechanical theory of EIMD, it has been suggested that an increased inflammatory response may be associated with DOMS. Furthermore, it is possible that the inflammatory response may play a role in mediating recovery, and adaptation following EIMD. However, the effects of EIMD on markers of inflammation have produced inconsistent results. PURPOSE: The main aim of the present study was to investigate the cytokine response to a 30 min downhill run. METHODS: Fifty (36 male, 14 female), apparently healthy participants performed a 30 min downhill run (-12.5%, 70% Vmax). Interleukin 6 (IL-6), high sensitivity C reactive protein (hs-CRP), and tumor necrosis factor alpha (TNF-α) were measured at 1 h, 24 h and 48 h post downhill run. Additionally, isometric maximum voluntary contraction (MVC), and perceived muscle soreness were measured at 24 h and 48 h post downhill run. RESULTS: Detectable levles of TNF-α were only present in three participants, and therefore, these data were excluded from the analysis. There was no significant difference in IL-6 or hs-CRP at any time point (p \u3e 0.10). However, there was a significant decrease in MVC (p ≤ 0.001). On average MVC decreased by 11% and 8% in the dominant and non-dominant leg at 24 h and 48 h respectively. Furthermore, there was a significant increase in muscle soreness (p \u3c 0.001). On average soreness increased by 49 mm and 51 mm 24 h and 48 h post downhill run. CONCLUSION: The significant increase in muscle soreness in the present study is indicative of EIMD. Furthermore, the significant decrement in MVC at 24 h and 48 h post downhill run, demonstrates that neuromuscular function was impaired. The lack of any significant increase in the cytokine response, supports the theory that mechanical damage is the primary mechanism associated with the EIMD and DOMS phenomenon. Nevertheless, when interpreting these results it is important to consider that due to the sampling times employed in the present study, an inflammatory response may have been missed

Complementarity Endures: No Firewall for an Infalling Observer

We argue that the complementarity picture, as interpreted as a reference frame change represented in quantum gravitational Hilbert space, does not suffer from the "firewall paradox" recently discussed by Almheiri, Marolf, Polchinski, and Sully. A quantum state described by a distant observer evolves unitarily, with the evolution law well approximated by semi-classical field equations in the region away from the (stretched) horizon. And yet, a classical infalling observer does not see a violation of the equivalence principle, and thus a firewall, at the horizon. The resolution of the paradox lies in careful considerations on how a (semi-)classical world arises in unitary quantum mechanics describing the whole universe/multiverse.Comment: 11 pages, 1 figure; clarifications and minor revisions; v3: a small calculation added for clarification; v4: some corrections, conclusion unchange

Stem-cell competition

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62534/1/418025a.pd

Proctitis following stereotactic body radiation therapy for prostate cancer

Background Proctitis after radiation therapy for prostate cancer remains an ongoing clinical challenge and critical quality of life issue. SBRT could minimize rectal toxicity by reducing the volume of rectum receiving high radiation doses and offers the potential radiobiologic benefits of hypofractionation. This study sought to evaluate the incidence and severity of proctitis following SBRT for prostate cancer. Methods Between February 2008 and July 2011, 269 men with clinically localized prostate cancer were treated definitively with SBRT monotherapy at Georgetown University Hospital. All patients were treated to 35-36.25Gy in 5 fractions delivered with the CyberKnife Radiosurgical System (Accuray). Rectal bleeding was recorded and scored using the CTCAE v.4. Telangiectasias were graded using the Vienna Rectoscopy Score (VRS). Proctitis was assessed via the Bowel domain of the Expanded Prostate Index Composite (EPIC)-26 at baseline and at 1, 3, 6, 9, 12, 18 and 24 months post-SBRT. Results The median age was 69 years with a median prostate volume of 39 cc. The median follow-up was 3.9 years with a minimum follow-up of two years. The 2-year actuarial incidence of late rectal bleeding ≥ grade 2 was 1.5%. Endoscopy revealed VRS Grade 2 rectal telangiectasias in 11% of patients. All proctitis symptoms increased at one month post-SBRT but returned to near-baseline with longer follow-up. The most bothersome symptoms were bowel urgency and frequency. At one month post-SBRT, 11.2% and 8.5% of patients reported a moderate to big problem with bowel urgency and frequency, respectively. The EPIC bowel summary scores declined transiently at 1 month and experienced a second, more protracted decline between 6 months and 18 months before returning to near-baseline at two years post-SBRT. Prior to treatment, 4.1% of men felt their bowel function was a moderate to big problem which increased to 11.5% one month post-SBRT but returned to near-baseline at two years post-SBRT. Conclusions In this single institution cohort, the rate and severity of proctitis observed following SBRT is low. QOL decreased on follow-up; however, our results compare favorably to those reported for patients treated with alternative radiation modalities. Future prospective randomized studies are needed to confirm these observations

Evidence of the Trade-Off between Starvation and Predation Risks in Ducks

The theory of trade-off between starvation and predation risks predicts a decrease in body mass in order to improve flight performance when facing high predation risk. To date, this trade-off has mainly been validated in passerines, birds that store limited body reserves for short-term use. In the largest avian species in which the trade-off has been investigated (the mallard, Anas platyrhynchos), the slope of the relationship between mass and flight performance was steeper in proportion to lean body mass than in passerines. In order to verify whether the same case can be applied to other birds with large body reserves, we analyzed the response to this trade-off in two other duck species, the common teal (Anas crecca) and the tufted duck (Aythya fuligula). Predation risk was simulated by disturbing birds. Ducks within disturbed groups were compared to non-disturbed control birds. In disturbed groups, both species showed a much greater decrease in food intake and body mass during the period of simulated high risk than those observed in the control group. This loss of body mass allows reaching a more favourable wing loading and increases power for flight, hence enhancing flight performances and reducing predation risk. Moreover, body mass loss and power margin gain in both species were higher than in passerines, as observed in mallards. Our results suggest that the starvation-predation risk trade-off is one of the major life history traits underlying body mass adjustments, and these findings can be generalized to all birds facing predation. Additionally, the response magnitude seems to be influenced by the strategy of body reserve management

Lethal Influenza Virus Infection in Macaques Is Associated with Early Dysregulation of Inflammatory Related Genes

The enormous toll on human life during the 1918–1919 Spanish influenza pandemic is a constant reminder of the potential lethality of influenza viruses. With the declaration by the World Health Organization of a new H1N1 influenza virus pandemic, and with continued human cases of highly pathogenic H5N1 avian influenza virus infection, a better understanding of the host response to highly pathogenic influenza viruses is essential. To this end, we compared pathology and global gene expression profiles in bronchial tissue from macaques infected with either the reconstructed 1918 pandemic virus or the highly pathogenic avian H5N1 virus A/Vietnam/1203/04. Severe pathology was observed in respiratory tissues from 1918 virus-infected animals as early as 12 hours after infection, and pathology steadily increased at later time points. Although tissues from animals infected with A/Vietnam/1203/04 also showed clear signs of pathology early on, less pathology was observed at later time points, and there was evidence of tissue repair. Global transcriptional profiles revealed that specific groups of genes associated with inflammation and cell death were up-regulated in bronchial tissues from animals infected with the 1918 virus but down-regulated in animals infected with A/Vietnam/1203/04. Importantly, the 1918 virus up-regulated key components of the inflammasome, NLRP3 and IL-1β, whereas these genes were down-regulated by A/Vietnam/1203/04 early after infection. TUNEL assays revealed that both viruses elicited an apoptotic response in lungs and bronchi, although the response occurred earlier during 1918 virus infection. Our findings suggest that the severity of disease in 1918 virus-infected macaques is a consequence of the early up-regulation of cell death and inflammatory related genes, in which additive or synergistic effects likely dictate the severity of tissue damage

Type and extent of trans-disciplinary co-operation to improve food security, health and household environment in low and middle income countries: systematic review

Acknowledgements: We are grateful to Dr Steve Turner and Dr Adam Price for their insightful comments that improved the manuscript. We would like to thank Heather Clark and Bimbola Kalejaiye for their help in data extraction. We are also grateful to Melanie Bickerton and Dr Amudha Poobalan for their systematic review advice.Peer reviewedPublisher PD

Genomic Characterization of Methanomicrobiales Reveals Three Classes of Methanogens

BACKGROUND:Methanomicrobiales is the least studied order of methanogens. While these organisms appear to be more closely related to the Methanosarcinales in ribosomal-based phylogenetic analyses, they are metabolically more similar to Class I methanogens. METHODOLOGY/PRINCIPAL FINDINGS:In order to improve our understanding of this lineage, we have completely sequenced the genomes of two members of this order, Methanocorpusculum labreanum Z and Methanoculleus marisnigri JR1, and compared them with the genome of a third, Methanospirillum hungatei JF-1. Similar to Class I methanogens, Methanomicrobiales use a partial reductive citric acid cycle for 2-oxoglutarate biosynthesis, and they have the Eha energy-converting hydrogenase. In common with Methanosarcinales, Methanomicrobiales possess the Ech hydrogenase and at least some of them may couple formylmethanofuran formation and heterodisulfide reduction to transmembrane ion gradients. Uniquely, M. labreanum and M. hungatei contain hydrogenases similar to the Pyrococcus furiosus Mbh hydrogenase, and all three Methanomicrobiales have anti-sigma factor and anti-anti-sigma factor regulatory proteins not found in other methanogens. Phylogenetic analysis based on seven core proteins of methanogenesis and cofactor biosynthesis places the Methanomicrobiales equidistant from Class I methanogens and Methanosarcinales. CONCLUSIONS/SIGNIFICANCE:Our results indicate that Methanomicrobiales, rather than being similar to Class I methanogens or Methanomicrobiales, share some features of both and have some unique properties. We find that there are three distinct classes of methanogens: the Class I methanogens, the Methanomicrobiales (Class II), and the Methanosarcinales (Class III)

Effects of Dopamine on Sensitivity to Social Bias in Parkinson's Disease

Patients with Parkinson's disease (PD) sometimes develop impulsive compulsive behaviours (ICBs) due to their dopaminergic medication. We compared 26 impulsive and 27 non-impulsive patients with PD, both on and off medication, on a task that examined emotion bias in decision making. No group differences were detected, but patients on medication were less biased by emotions than patients off medication and the strongest effects were seen in patients with ICBs. PD patients with ICBs on medication also showed more learning from negative feedback and less from positive feedback, whereas off medication they showed the opposite effect