Cytokines and persistent viral infections

Intracellular pathogens such as the human immunodeficiency virus, hepatitis C and B or Epstein–Barr virus often cause chronic viral infections in humans. Persistence of these viruses in the host is associated with a dramatic loss of T-cell immune response due to functional T-cell exhaustion. Developing efficient immunotherapeutic approaches to prevent viral persistence and/or to restore a highly functional T-cell mediated immunity remains a major challenge. During the last two decades, numerous studies aimed to identify relevant host-derived factors that could be modulated to achieve this goal. In this review, we focus on recent advances in our understanding of the role of cytokines in preventing or facilitating viral persistence. We concentrate on the impact of multiple relevant cytokines in T-cell dependent immune response to chronic viral infection and the potential for using cytokines as therapeutic agents in mice and humans.     

Modelling human power and endurance

A generalised three component hydraulic model has been proposed to represent the human bioenergetic processes relating internal energy stores to performance during exercise, and into recovery. Further development of the model allows testable predictions to be made. In particular in this paper I examine certain hypotheses of chemical fuel shortage as a subgroup of the potential causes of fatigue, and their implications for maximal power and for endurance. The assumption that the limitation to sustainable power is direct proportionality to the glycogen store remaining, appears the most feasible. Based on this assumption, equations for the decline in maximum attainable power over time, the endurance at fixed workrates and the endurance at incremental tests (as a function of the increment slope) are obtained. Using published data for fit males, the maximum exertable power declines after about 6 s at 972 W to very low levels after about 2 min. For constant powers selected between 208 and 927 W, endurance declines from ad infinitum to only 6 s. Endurance at VO2max is predicted to be about 9 min. For incremental exercise tests of slope ranging from 30 W/min to 60 W/min, endurance lessens from 14 to 9 min. In these tests the anaerobic threshold is reached in times between 6 and 3 min. Although the power at termination of a test increases with incremental slope, terminal oxygen consumption is effectively constant. Almost all these model predictions are observed to correspond well with published experimental findings. These results suggest that the model can be used to represent an adequate overview of the operation of the human bioenergetic system.     

高校心理咨询工作者枯竭的原因及预防

枯竭会影响高校心理咨询工作者的工作绩效和身心健康,本文针对高校心理咨询工作的现状,从个人特征、当事人特征、工作特征三个方面分析了高校心理咨询工作者枯竭的原因,并提出了一些预防措施。     

Measuring Frailty in HIV-infected Individuals. Identification of Frail Patients is the First Step to Amelioration and Reversal of Frailty

A simple, validated protocol consisting of a battery of tests is available to identify elderly patients with frailty syndrome. This syndrome of decreased reserve and resistance to stressors increases in incidence with increasing age. In the elderly, frailty may pursue a step-wise loss of function from non-frail to pre-frail to frail. We studied frailty in HIV-infected patients and found that ~20% are frail using the Fried phenotype using stringent criteria developed for the elderly^1,2. In HIV infection the syndrome occurs at a younger age.HIV patients were checked for 1) unintentional weight loss; 2) slowness as determined by walking speed; 3) weakness as measured by a grip dynamometer; 4) exhaustion by responses to a depression scale; and 5) low physical activity was determined by assessing kilocalories expended in a week''s time. Pre-frailty was present with any two of five criteria and frailty was present if any three of the five criteria were abnormal.The tests take approximately 10-15 min to complete and they can be performed by medical assistants during routine clinic visits. Test results are scored by referring to standard tables. Understanding which of the five components contribute to frailty in an individual patient can allow the clinician to address relevant underlying problems, many of which are not evident in routine HIV clinic visits.     

uHIIT显著改善男性减脂效果

本研究旨在探讨以心率控制方式进行12周的上坡高强度间歇训练(uphill high-intensityinterval training,uHIIT)和中等水平强度持续训练(moderate-intensity continuous training, MCT)对于中年过重肥胖男性的身体组成(体脂肪百分比和净体重)、代谢症候指标(安静血压,血糖,高低密度脂蛋白胆固醇,总胆固醇和甘油三脂)及心肺耐力指标(最大摄氧量,无氧阈值和力竭时间)的影响。本研究通过对25位中年过重肥胖男性(BMI>24)训练前后的身体组成与代谢症候指标进行检测,并进行渐增强度测验,以评估心肺耐力指标。前测后,受试者随机分配至uHIIT组(心率控制强度为90%HRmax,运动2 min休息1 min共7次进行约20 min)、MCT组(心率控制强度为65%～70%HR_max,运动约40 min)与控制组。进行每周3次为期12周的训练后,再接受相同的测试1次。研究显示,相较于控制组,uHIIT组与MCT组的最大摄氧量(V4O_2max)、无氧阈值、力竭时间、臀部脂肪皆显著改善,且uHIIT组在V4O_2max增加量上显著高于MCT组,仅有uHIIT组的血压、体脂肪百分比和腿部脂肪显著改善。本研究表明,uHIIT与MCT皆可改善中年肥胖男性心肺耐力,同时uHIIT对于减脂与血压的改善较为显著,但其余代谢指标受到运动的影响较小,减脂效果上uHIIT的运动效益优于MCT,建议运动时应重视运动强度。     

Individual Differences in the Diurnal Cortisol Response to Stress

The objectives of this study were to explore individual differences associated with diverse reactions in cortisol secretion under different stress levels. This study was part of a larger project concerning working hours and health. Thirty-four white-collar workers participated under two different conditions; one work week with a high stress level (H) and one with a lower stress level (L) as measured through self-rated stress during workdays. Based on the morning cortisol concentration during a workday subjects were divided into two groups. One group consisted of subjects whose morning level of cortisol increased in response to the high-stress week, compared to their morning levels in the low-stress condition (Group 1). The other group consisted of subjects whose morning cortisol response was the opposite, with a lower level under the high stress condition (Group 2). Subjects wore actiwatches, completed a sleep diary, and rated their sleepiness and stress for one work week in each condition, i.e., high and low stress. Saliva samples for measures of cortisol were collected on a Wednesday. Group 2 reported higher workload, fatigue, and exhaustion during both weeks. Since there were no differences in perceived stress, neither within nor between groups, the data indicate that there are other factors influencing morning cortisol. The results suggest that one component modulating the cortisol response might be the level of exhaustion, probably related to work overload. Higher levels of stress in exhausted individuals might suppress morning cortisol levels.     

T cell exhaustion and Interleukin 2 downregulation

T cells reactive to tumor antigens and viral antigens lose their reactivity when exposed to the antigen-rich environment of a larger tumor bed or viral load. Such non-responsive T cells are termed exhausted. T cell exhaustion affects both CD8+ and CD4+ T cells. T cell exhaustion is attributed to the functional impairment of T cells to produce cytokines, of which the most important may be Interleukin 2 (IL2). IL2 performs functions critical for the elimination of cancer cells and virus infected cells. In one such function, IL2 promotes CD8+ T cell and natural killer (NK) cell cytolytic activities. Other functions include regulating naïve T cell differentiation into Th1 and Th2 subsets upon exposure to antigens. Thus, the signaling pathways contributing to T cell exhaustion could be linked to the signaling pathways contributing to IL2 loss. This review will discuss the process of T cell exhaustion and the signaling pathways that could be contributing to T cell exhaustion.     

Physiological responses of young and elderly men to prolonged exercise at critical power

The critical power (CP) of a muscle group or individual may represent the highest rate of work which can be performed for an extended period. We investigated this concept in young (n = 13, 24.5 years) and elderly (n = 12, 70.7 years) active men by first determining CP and then comparing responses elicited by 24 min of cycle exercise at power outputs (omega) corresponding to CP. Values from the final 2 min of the 24-min ride were expressed relative to maximal values established in a ramp test. CP for the elderly was only 65% that for the young, but on a relative basis, it was significantly higher both in terms of omega (67 vs 62% of omega max) and oxygen consumption (VO2) (91.5 vs 85.2% of maximum oxygen consumption). There were no group differences in relative values for ventilation (VE), heart rate or respiratory exchange ratio (R). During the 24-min ride, VO2 and R achieved a plateau in both groups, while VE, blood lactate and arterial PCO2 continued to change in the young. It was concluded that CP can be determined in active elderly men, but that CP may not represent a true non-fatiguing work rate in either young or elderly men.     

Plasma Hsp72 (HSPA1A) and Hsp27 (HSPB1) expression under heat stress: influence of exercise intensity

Extracellular heat-shock protein 72 (eHsp72) expression during exercise-heat stress is suggested to increase with the level of hyperthermia attained, independent of the rate of heat storage. This study examined the influence of exercise at various intensities to elucidate this relationship, and investigated the association between eHsp72 and eHsp27. Sixteen male subjects cycled to exhaustion at 60% and 75% of maximal oxygen uptake in hot conditions (40°C, 50% RH). Core temperature, heart rate, oxidative stress, and blood lactate and glucose levels were measured to determine the predictor variables associated with eHsp expression. At exhaustion, heart rate exceeded 96% of maximum in both conditions. Core temperature reached 39.7°C in the 60% trial (58.9 min) and 39.0°C in the 75% trial (27.2 min) (P < 0.001). The rate of rise in core temperature was 2.1°C h⁻¹ greater in the 75% trial than in the 60% trial (P < 0.001). A significant increase and correlation was observed between eHsp72 and eHsp27 concentrations at exhaustion (P < 0.005). eHsp72 was highly correlated with the core temperature attained (60% trial) and the rate of increase in core temperature (75% trial; P < 0.05). However, no common predictor variable was associated with the expression of both eHsps. The similarity in expression of eHsp72 and eHsp27 during moderate- and high-intensity exercise may relate to the duration (i.e., core temperature attained) and intensity (i.e., rate of increase in core temperature) of exercise. Thus, the immuno-inflammatory release of eHsp72 and eHsp27 in response to exercise in the heat may be duration and intensity dependent.