Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise

Background: Consensus for an operational definition of post-exertion malaise (PEM) and which symptoms best characterize PEM has not been established and may be due to variability within and between studies. Purpose: Determine the magnitude of the effect of maximal and submaximal physical exertion on multiple myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) symptoms that are associated with PEM and explore variability among two studies in which mood, fatigue, and pain symptoms were measured before and after exercise. Methods: Symptoms were measured before, and 48 and 72 hours after exercise in study 1 (ME/CFS = 13; Controls = 11) and before and 24 hours after exercise in study 2 (ME/CFS = 15, Controls = 15). Between-study variability was examined by comparing Hedges d effect sizes (95% CI) from studies 1 and 2. Within-patient group variability was examined via inspection of dot density plots. Results: In study 1, large increases in general fatigue (Δ = 1.05), reduced motivation (Δ = 0.93), feelings of fatigue (Δ = 0.90), feelings of confusion (Δ = 0.93), and total mood disturbance (Δ = 0.90) were found at 72 hours. In study 2, a large increase in affective/sensory pain (Δ = 0.79) was found at 24 hours. Dot density plots in both studies revealed substantial variability among people with ME/CFS relative to healthy control participants. Conclusions: PEM symptoms are variable among people with ME/CFS and several gaps in the literature need to be addressed before guidelines for measuring PEM in the clinical or research setting can be established

Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Post exertion malaise is one of the most debilitating aspects of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, yet the neurobiological consequences are largely unexplored. The objective of the study was to determine the neural consequences of acute exercise using functional brain imaging. Fifteen female Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients and 15 healthy female controls completed 30 min of submaximal exercise (70% of peak heart rate) on a cycle ergometer. Symptom assessments (e.g. fatigue, pain, mood) and brain imaging data were collected one week prior to and 24 h following exercise. Functional brain images were obtained during performance of: 1) a fatiguing cognitive task – the Paced Auditory Serial Addition Task, 2) a non-fatiguing cognitive task – simple number recognition, and 3) a non-fatiguing motor task – finger tapping. Symptom and exercise data were analyzed using independent samples t-tests. Cognitive performance data were analyzed using mixed-model analysis of variance with repeated measures. Brain responses to fatiguing and non-fatiguing tasks were analyzed using linear mixed effects with cluster-wise (101-voxels) alpha of 0.05. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients reported large symptom changes compared to controls (effect size ≥0.8, p \u3c 0.05). Patients and controls had similar physiological responses to exercise (p \u3e 0.05). However, patients exercised at significantly lower Watts and reported greater exertion and leg muscle pain (p \u3c 0.05). For cognitive performance, a significant Group by Time interaction (p \u3c 0.05), demonstrated pre- to post-exercise improvements for controls and worsening for patients. Brain responses to finger tapping did not differ between groups at either time point. During number recognition, controls exhibited greater brain activity (p \u3c 0.05) in the posterior cingulate cortex, but only for the pre-exercise scan. For the Paced Serial Auditory Addition Task, there was a significant Group by Time interaction (p \u3c 0.05) with patients exhibiting increased brain activity from pre- to post-exercise compared to controls bilaterally for inferior and superior parietal and cingulate cortices. Changes in brain activity were significantly related to symptoms for patients (p \u3c 0.05). Acute exercise exacerbated symptoms, impaired cognitive performance and affected brain function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients. These converging results, linking symptom exacerbation with brain function, provide objective evidence of the detrimental neurophysiological effects of post-exertion malaise

Relationships between cardiorespiratory fitness, hippocampal volume, and episodic memory in a population at risk for Alzheimer’s disease

Introduction: Cardiorespiratory fitness (CRF) has been shown to be related to brain health in older adults. In individuals at risk for developing Alzheimer\u27s disease (AD), CRF may be a modifiable risk factor that could attenuate anticipated declines in brain volume and episodic memory. The objective of this study was to determine the association between CRF and both hippocampal volume and episodic memory in a cohort of cognitively healthy older adults with familial and/or genetic risk for Alzheimer\u27s disease (AD). Methods: Eighty‐six enrollees from the Wisconsin Registry for Alzheimer\u27s Prevention participated in this study. Participants performed a graded maximal exercise test, underwent a T‐1 anatomical magnetic resonance imaging scan, and completed the Rey Auditory Verbal Learning Test (RAVLT). Results: There were no significant relationships between CRF and HV or RAVLT memory scores for the entire sample. When the sample was explored on the basis of gender, CRF was significantly associated with hippocampal volume for women. For men, significant positive associations were observed between CRF and RAVLT memory scores. Summary: These results suggest that CRF may be protective against both hippocampal volume and episodic memory decline in older adults at risk for AD, but that the relationships may be gender specific

Efficacy and cost-effectiveness of a web-based and mobile stress-management intervention for employees: design of a randomized controlled trial

Background: Work-related stress is associated with a variety of mental and emotional problems and can lead to substantial economic costs due to lost productivity, absenteeism or the inability to work. There is a considerable amount of evidence on the effectiveness of traditional face-to-face stress-management interventions for employees; however, they are often costly, time-consuming, and characterized by a high access threshold. Web-based interventions may overcome some of these problems yet the evidence in this field is scarce. This paper describes the protocol for a study that will examine the efficacy and cost-effectiveness of a web-based guided stress-management training which is based on problem solving and emotion regulation and aimed at reducing stress in adult employees. Methods. The study will target stressed employees aged 18 and older. A randomized controlled trial (RCT) design will be applied. Based on a power calculation of d=.35 (1-β of 80%, α =.05), 264 participants will be recruited and randomly assigned to either the intervention group or a six-month waitlist control group. Inclusion criteria include an elevated stress level (Cohen's Perceived Stress Scale-10 ≥ 22) and current employment. Exclusion criteria include risk of suicide or previously diagnosed psychosis or dissociative symptoms. The primary outcome will be perceived stress, and secondary outcomes include depression and anxiety. Data will be collected at baseline and seven weeks and six months after randomization. An extended follow up at 12 months is planned for the intervention group. Moreover, a cost-effectiveness analysis will be conducted from a societal perspective and will include both direct and indirect health care costs. Data will be analyzed on an intention-to-treat basis and per protocol. Discussion. The substantial negative consequences of work-related stress emphasize the necessity for effective stress-management trainings. If the proposed internet intervention proves to be (cost-) effective, a preventative, economical stress-management tool will be conceivable. The strengths and limitations of the present study are discussed. Trial registration. German Register of Clinical Studies (DRKS): DRKS00004749. © 2013 Heber et al.; licensee BioMed Central Ltd

Mutualism and Adaptive Divergence: Co-Invasion of a Heterogeneous Grassland by an Exotic Legume-Rhizobium Symbiosis

Species interactions play a critical role in biological invasions. For example, exotic plant and microbe mutualists can facilitate each other's spread as they co-invade novel ranges. Environmental context may influence the effect of mutualisms on invasions in heterogeneous environments, however these effects are poorly understood. We examined the mutualism between the legume, Medicago polymorpha, and the rhizobium, Ensifer medicae, which have both invaded California grasslands. Many of these invaded grasslands are composed of a patchwork of harsh serpentine and relatively benign non-serpentine soils. We grew legume genotypes collected from serpentine or non-serpentine soil in both types of soil in combination with rhizobium genotypes from serpentine or non-serpentine soils and in the absence of rhizobia. Legumes invested more strongly in the mutualism in the home soil type and trends in fitness suggested that this ecotypic divergence was adaptive. Serpentine legumes had greater allocation to symbiotic root nodules in serpentine soil than did non-serpentine legumes and non-serpentine legumes had greater allocation to nodules in non-serpentine soil than did serpentine legumes. Therefore, this invasive legume has undergone the rapid evolution of divergence for soil-specific investment in the mutualism. Contrary to theoretical expectations, the mutualism was less beneficial for legumes grown on the stressful serpentine soil than on the non-serpentine soil, possibly due to the inhibitory effects of serpentine on the benefits derived from the interaction. The soil-specific ability to allocate to a robust microbial mutualism may be a critical, and previously overlooked, adaptation for plants adapting to heterogeneous environments during invasion

Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Post exertion malaise is one of the most debilitating aspects of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, yet the neurobiological consequences are largely unexplored. The objective of the study was to determine the neural consequences of acute exercise using functional brain imaging. Fifteen female Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients and 15 healthy female controls completed 30 min of submaximal exercise (70% of peak heart rate) on a cycle ergometer. Symptom assessments (e.g. fatigue, pain, mood) and brain imaging data were collected one week prior to and 24 h following exercise. Functional brain images were obtained during performance of: 1) a fatiguing cognitive task – the Paced Auditory Serial Addition Task, 2) a non-fatiguing cognitive task – simple number recognition, and 3) a non-fatiguing motor task – finger tapping. Symptom and exercise data were analyzed using independent samples t-tests. Cognitive performance data were analyzed using mixed-model analysis of variance with repeated measures. Brain responses to fatiguing and non-fatiguing tasks were analyzed using linear mixed effects with cluster-wise (101-voxels) alpha of 0.05. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients reported large symptom changes compared to controls (effect size ≥0.8, p 0.05). However, patients exercised at significantly lower Watts and reported greater exertion and leg muscle pain (p This accepted article is published as Cook D, Light A, Light K, Broderick G, Shields M, Dougherty R, Meyer J, VanRiper S, Stegner A, Ellingson L, Vernon S (2017). Neural Consequences of Post-Exertion Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Brain, Behavior & Immunity, 62; 87-99. doi: 10.1016/j.bbi.2017.02.009. </p

Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise

Background: Consensus for an operational definition of post-exertion malaise (PEM) and which symptoms best characterize PEM has not been established and may be due to variability within and between studies. Purpose: Determine the magnitude of the effect of maximal and submaximal physical exertion on multiple myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) symptoms that are associated with PEM and explore variability among two studies in which mood, fatigue, and pain symptoms were measured before and after exercise. Methods: Symptoms were measured before, and 48 and 72 hours after exercise in study 1 (ME/CFS = 13; Controls = 11) and before and 24 hours after exercise in study 2 (ME/CFS = 15, Controls = 15). Between-study variability was examined by comparing Hedges d effect sizes (95% CI) from studies 1 and 2. Within-patient group variability was examined via inspection of dot density plots. Results: In study 1, large increases in general fatigue (Δ = 1.05), reduced motivation (Δ = 0.93), feelings of fatigue (Δ = 0.90), feelings of confusion (Δ = 0.93), and total mood disturbance (Δ = 0.90) were found at 72 hours. In study 2, a large increase in affective/sensory pain (Δ = 0.79) was found at 24 hours. Dot density plots in both studies revealed substantial variability among people with ME/CFS relative to healthy control participants. Conclusions: PEM symptoms are variable among people with ME/CFS and several gaps in the literature need to be addressed before guidelines for measuring PEM in the clinical or research setting can be established.This article is published as Lindheimer J, Meyer J, Stegner A, Rougherty R, Van Riper S, Shields M, Reisner A, Shukla S, Light A, Yale S, Cook D (2017). Symptom variability following acute exercise in ME/CFS: A perspective on measuring post-exertion malaise. Fatigue: Biomedicine, Health & Behavior, 5(2); 69-88. doi: 10.1080/21641846.2017.1321166.</p

Cost effectiveness of guided Internet-based interventions for depression in comparison with control conditions: An individual–participant data meta-analysis

Background: There is limited evidence on the cost effectiveness of Internet-based treatments for depression. The aim was to evaluate the cost effectiveness of guided Internet-based interventions for depression compared to controls. Methods: Individual–participant data from five randomized controlled trials (RCT), including 1,426 participants, were combined. Cost-effectiveness analyses were conducted at 8 weeks, 6 months, and 12 months follow-up. Results: The guided Internet-based interventions were more costly than the controls, but not statistically significant (12 months mean difference = €406, 95% CI: − 611 to 1,444). The mean differences in clinical effects were not statistically significant (12 months mean difference = 1.75, 95% CI: −.09 to 3.60 in Center for Epidemiologic Studies Depression Scale [CES-D] score,.06, 95% CI: −.02 to.13 in response rate, and.00, 95% CI: −.03 to.03 in quality-adjusted life-years [QALYs]). Cost-effectiveness acceptability curves indicated that high investments are needed to reach an acceptable probability that the intervention is cost effective compared to control for CES-D and response to treatment (e.g., at 12-month follow-up the probability of being cost effective was.95 at a ceiling ratio of 2,000 €/point of improvement in CES-D score). For QALYs, the intervention's probability of being cost effective compared to control was low at the commonly accepted willingness-to-pay threshold (e.g., at 12-month follow-up the probability was.29 and. 31 at a ceiling ratio of 24,000 and 35,000 €/QALY, respectively). Conclusions: Based on the present findings, guided Internet-based interventions for depression are not considered cost effective compared to controls. However, only a minority of RCTs investigating the clinical effectiveness of guided Internet-based interventions also assessed cost effectiveness and were included in this individual–participant data meta-analysis

Meeting physical activity recommendations may be protective against temporal lobe atrophy in older adults at risk for Alzheimer's disease.

INTRODUCTION: Physical activity (PA) is associated with brain health in older adults. However, it is unknown whether the current physical activity recommendations (PAR) impart substantive benefit. The objective of this study was to compare temporal lobe volumes between older adults who met PAR and those who did not. METHODS: Ninety-one enrollees from the Wisconsin Registry for Alzheimer's Prevention wore an accelerometer for seven consecutive days to quantify their PA behaviors and underwent a T-1 anatomic magnetic resonance imaging scan. Participants were categorized as either having met PAR or not based on the US Department of Health and Human Services recommendations of 150 minutes of moderate-to-vigorous physical activity per week. RESULTS: Participants who met PAR possessed significantly greater inferior (η(2) P = .050) and anterior (η(2) P = .055) temporal lobe volumes compared with those who did not (P DISCUSSION: Individuals at-risk for AD experience accelerated rates of brain atrophy. These results suggest that regular engagement in PA at or above PAR could attenuate this decline.This article is published as Dougherty R, Ellingson L, Schultz S, Boots E, Meyer J, Lindheimer J, Van Riper S, Stegner A, Edwards D, Oh J, Koscik R, Dowling M, Gallagher C, Carlsson C, Rowley H, Bendlin B, Asthana S, Hermann B, Sager M, Johnson S, Okonkwo O, Cook D (2016). Meeting physical activity recommendations may be protective against temporal lobe atrophy in older adults at risk for Alzheimer's disease. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 4; 14-17. doi:10.1016/j.dadm.2016.03.005. </p