The kinetics of lactate production and removal during whole-body exercise

<p>Abstract</p> <p>Background</p> <p>Based on a literature review, the current study aimed to construct mathematical models of lactate production and removal in both muscles and blood during steady state and at varying intensities during whole-body exercise. In order to experimentally test the models in dynamic situations, a cross-country skier performed laboratory tests while treadmill roller skiing, from where work rate, aerobic power and blood lactate concentration were measured. A two-compartment simulation model for blood lactate production and removal was constructed.</p> <p>Results</p> <p>The simulated and experimental data differed less than 0.5 mmol/L both during steady state and varying sub-maximal intensities. However, the simulation model for lactate removal after high exercise intensities seems to require further examination.</p> <p>Conclusions</p> <p>Overall, the simulation models of lactate production and removal provide useful insight into the parameters that affect blood lactate response, and specifically how blood lactate concentration during practical training and testing in dynamical situations should be interpreted.</p

An individually-tailored multifactorial intervention program for older fallers in a middle-income developing country: Malaysian Falls Assessment and Intevention Trial (MyFAIT)

Background: In line with a rapidly ageing global population, the rise in the frequency of falls will lead to increased healthcare and social care costs. This study will be one of the few randomized controlled trials evaluating a multifaceted falls intervention in a low-middle income, culturally-diverse older Asian community. The primary objective of our paper is to evaluate whether individually tailored multifactorial interventions will successfully reduce the number of falls among older adults. Methods: Three hundred community-dwelling older Malaysian adults with a history of (i) two or more falls, or (ii) one injurious fall in the past 12 months will be recruited. Baseline assessment will include cardiovascular, frailty, fracture risk, psychological factors, gait and balance, activities of daily living and visual assessments. Fallers will be randomized into 2 groups: to receive tailored multifactorial interventions (intervention group); or given lifestyle advice with continued conventional care (control group). Multifactorial interventions will target 6 specific risk factors. All participants will be re-assessed after 12 months. The primary outcome measure will be fall recurrence, measured with monthly falls diaries. Secondary outcomes include falls risk factors; and psychological measures including fear of falling, and quality of life.Previous studies evaluating multifactorial interventions in falls have reported variable outcomes. Given likely cultural, personal, lifestyle and health service differences in Asian countries, it is vital that individually-tailored multifaceted interventions are evaluated in an Asian population to determine applicability of these interventions in our setting. If successful, these approaches have the potential for widespread application in geriatric healthcare services, will reduce the projected escalation of falls and fall-related injuries, and improve the quality of life of our older community

Factors associated with spontaneous stone passage in a contemporary cohort of patients presenting with acute ureteric colic. Results from the MIMIC Study (A Multi-centre cohort study evaluating the role of Inflammatory Markers in patients presenting with acute ureteric Colic)

Objectives There is conflicting data on the role of white blood cell count (WBC) and other inflammatory markers in spontaneous stone passage in patients with acute ureteric colic. The aim of the study was to assess the relationship of WBC and other routinely collected inflammatory and clinical markers including stone size, stone position and Medically Expulsive Therapy use (MET) with spontaneous stone passage (SSP) in a large contemporary cohort of patients with acute ureteric colic. Subjects and Methods Multi‐centre retrospective cohort study coordinated by the British Urology Researchers in Surgical Training (BURST) Research Collaborative at 71 secondary care hospitals across 4 countries (United Kingdom, Republic of Ireland, Australia and New Zealand). 4170 patients presented with acute ureteric colic and a computer tomography confirmed single ureteric stone. Our primary outcome measure was SSP as defined by the absence of need for intervention to assist stone passage. Multivariable mixed effects logistic regression was used to explore the relationship between key patient factors and SSP. Results 2518 patients were discharged with conservative management and had further follow up with a SSP rate of 74% (n = 1874/2518). Sepsis after discharge with conservative management was reported in 0.6% (n = 16/2518). On multivariable analysis neither WBC, Neutrophils or CRP were seen to predict SSP, with an adjusted OR of 0.97 [95% CI 0.91 to 1.04, p = 0.38], 1.06 [95% CI 0.99 to 1.13, p = 0.1] and 1.00 [95% CI 0.99 to 1.00, p = 0.17], respectively. Medical expulsive therapy (MET) also did not predict SSP [adjusted OR 1.11 [95% CI 0.76 to 1.61]). However, stone size and stone position were significant predictors. SSP for stones 7mm. For stones in the upper ureter the SSP rate was 52% [95% CI 48 to 56], middle ureter was 70% [95% CI 64 to 76], and lower ureter was 83% [95% CI 81 to 85]. Conclusion In contrast to the previously published literature, we found that in patients with acute ureteric colic who are discharged with initial conservative management, neither WBC, Neutrophil count or CRP help determine the likelihood of spontaneous stone passage. We also found no overall benefit from the use of MET. Stone size and position are important predictors and our findings represent the most comprehensive stone passage rates for each mm increase in stone size from a large contemporary cohort adjusting for key potential confounders. We anticipate that these data will aid clinicians managing patients with acute ureteric colic and help guide management decisions and the need for intervention

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Anaerobiosis revisited: growth of Saccharomyces cerevisiae under extremely low oxygen availability

The budding yeast Saccharomyces cerevisiae plays an important role in biotechnological applications, ranging from fuel ethanol to recombinant protein production. It is also a model organism for studies on cell physiology and genetic regulation. Its ability to grow under anaerobic conditions is of interest in many industrial applications. Unlike industrial bioreactors with their low surface area relative to volume, ensuring a complete anaerobic atmosphere during microbial cultivations in the laboratory is rather difficult. Tiny amounts of O2 that enter the system can vastly influence product yields and microbial physiology. A common procedure in the laboratory is to sparge the culture vessel with ultrapure N2 gas; together with the use of butyl rubber stoppers and norprene tubing, O2 diffusion into the system can be strongly minimized. With insights from some studies conducted in our laboratory, we explore the question ‘how anaerobic is anaerobiosis?’. We briefly discuss the role of O2 in non-respiratory pathways in S. cerevisiae and provide a systematic survey of the attempts made thus far to cultivate yeast under anaerobic conditions. We conclude that very few data exist on the physiology of S. cerevisiae under anaerobiosis in the absence of the anaerobic growth factors ergosterol and unsaturated fatty acids. Anaerobicity should be treated as a relative condition since complete anaerobiosis is hardly achievable in the laboratory. Ideally, researchers should provide all the details of their anaerobic set-up, to ensure reproducibility of results among different laboratories. A correction to this article is available online at http://eprints.whiterose.ac.uk/131930/ https://doi.org/10.1007/s00253-018-9036-

Testing for NBUL using goodness of fit approach with applications

Life distribution, NBUL aging class, U-statistic, Efficiency, Reliability, Life testing, Exponential distribution, Hypothesis testing, Monte Carlo method, Power and censored data,