Perinatal stress, fatigue, depressive symptoms, and immune modulation in late pregnancy and one month postpartum.

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Cheng, C Y; Pickler, R H

2014-01-01

Stress and fatigue are common complaints of pregnant and postpartum women as is depression. These symptoms may be related to immunomodulation. However, few studies have examined these relationships. The aim of this study was to examine the relationships among stress, fatigue, depression, and cytokines as markers of immune modulation in prenatal and postpartum women. Women completed questionnaires and gave blood samples during late pregnancy and again at 4-6 weeks postpartum. Blood was analyzed for cytokines as measures of immune modulation. Stress, fatigue, and depression were experienced at moderately high levels, with higher levels of fatigue and depression in the postpartum but higher stress in the prenatal period. Levels of several cytokines were increased in the postpartum over the prenatal period. Stress and depression were related in the prenatal period and stress, depression, and fatigue were related in the postpartum. While various cytokines were related to each other in both periods, only stress was related to MIP-1β, a cytokine that may be important for childbirth processes. More studies, especially longitudinal and interventional studies, are needed to increase our knowledge about etiology, patterns, symptoms, factors, and management of maternal distress. The search for reliable biomarkers for at-risk mothers remains a priority.

Evidence of inflammatory immune signaling in chronic fatigue syndrome: A pilot study of gene expression in peripheral blood

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Vernon Suzanne D

2008-09-01

Full Text Available Abstract Background Genomic profiling of peripheral blood reveals altered immunity in chronic fatigue syndrome (CFS however interpretation remains challenging without immune demographic context. The object of this work is to identify modulation of specific immune functional components and restructuring of co-expression networks characteristic of CFS using the quantitative genomics of peripheral blood. Methods Gene sets were constructed a priori for CD4+ T cells, CD8+ T cells, CD19+ B cells, CD14+ monocytes and CD16+ neutrophils from published data. A group of 111 women were classified using empiric case definition (U.S. Centers for Disease Control and Prevention and unsupervised latent cluster analysis (LCA. Microarray profiles of peripheral blood were analyzed for expression of leukocyte-specific gene sets and characteristic changes in co-expression identified from topological evaluation of linear correlation networks. Results Median expression for a set of 6 genes preferentially up-regulated in CD19+ B cells was significantly lower in CFS (p = 0.01 due mainly to PTPRK and TSPAN3 expression. Although no other gene set was differentially expressed at p Conclusion Dissection of blood microarray profiles points to B cell dysfunction with coordinated immune activation supporting persistent inflammation and antibody-mediated NK cell modulation of T cell activity. This has clinical implications as the CD19+ genes identified could provide robust and biologically meaningful basis for the early detection and unambiguous phenotyping of CFS.

Astrocyte atrophy and immune dysfunction in self-harming macaques.

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Lee, Kim M; Chiu, Kevin B; Sansing, Hope A; Inglis, Fiona M; Baker, Kate C; MacLean, Andrew G

2013-01-01

Self-injurious behavior (SIB) is a complex condition that exhibits a spectrum of abnormal neuropsychological and locomotor behaviors. Mechanisms for neuropathogenesis could include irregular immune activation, host soluble factors, and astrocyte dysfunction. We examined the role of astrocytes as modulators of immune function in macaques with SIB. We measured changes in astrocyte morphology and function. Paraffin sections of frontal cortices from rhesus macaques identified with SIB were stained for glial fibrillary acidic protein (GFAP) and Toll-like receptor 2 (TLR2). Morphologic features of astrocytes were determined using computer-assisted camera lucida. There was atrophy of white matter astrocyte cell bodies, decreased arbor length in both white and gray matter astrocytes, and decreased bifurcations and tips on astrocytes in animals with SIB. This was combined with a five-fold increase in the proportion of astrocytes immunopositive for TLR2. These results provide direct evidence that SIB induces immune activation of astrocytes concomitant with quantifiably different morphology.

Astrocyte atrophy and immune dysfunction in self-harming macaques.

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Kim M Lee

Full Text Available BACKGROUND: Self-injurious behavior (SIB is a complex condition that exhibits a spectrum of abnormal neuropsychological and locomotor behaviors. Mechanisms for neuropathogenesis could include irregular immune activation, host soluble factors, and astrocyte dysfunction. METHODS: We examined the role of astrocytes as modulators of immune function in macaques with SIB. We measured changes in astrocyte morphology and function. Paraffin sections of frontal cortices from rhesus macaques identified with SIB were stained for glial fibrillary acidic protein (GFAP and Toll-like receptor 2 (TLR2. Morphologic features of astrocytes were determined using computer-assisted camera lucida. RESULTS: There was atrophy of white matter astrocyte cell bodies, decreased arbor length in both white and gray matter astrocytes, and decreased bifurcations and tips on astrocytes in animals with SIB. This was combined with a five-fold increase in the proportion of astrocytes immunopositive for TLR2. CONCLUSIONS: These results provide direct evidence that SIB induces immune activation of astrocytes concomitant with quantifiably different morphology.

Chronic fatigue in Ehlers-Danlos syndrome-Hypermobile type.

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Hakim, Alan; De Wandele, Inge; O'Callaghan, Chris; Pocinki, Alan; Rowe, Peter

2017-03-01

Chronic fatigue is an important contributor to impaired health-related quality of life in Ehlers-Danlos syndrome. There is overlap in the symptoms and findings of EDS and chronic fatigue syndrome. A proportion of those with CFS likely have EDS that has not been identified. The evaluation of chronic fatigue in EDS needs to include a careful clinical examination and laboratory testing to exclude common causes of fatigue including anemia, hypothyroidisim, and chronic infection, as well as dysfunction of major physiological or organ systems. Other problems that commonly contribute to fatigue in EDS include sleep disorders, chronic pain, deconditioning, cardiovascular autonomic dysfunction, bowel and bladder dysfunction, psychological issues, and nutritional deficiencies. While there is no specific pharmacological treatment for fatigue, many medications are effective for specific symptoms (such as headache, menstrual dysfunction, or myalgia) and for co-morbid conditions that result in fatigue, including orthostatic intolerance and insomnia. Comprehensive treatment of fatigue needs to also evaluate for biomechanical problems that are common in EDS, and usually involves skilled physical therapy and attention to methods to prevent deconditioning. In addition to managing specific symptoms, treatment of fatigue in EDS also needs to focus on maintaining function and providing social, physical, and nutritional support, as well as providing on-going medical evaluation of new problems and review of new evidence about proposed treatments. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

[Effects of self-foot reflexology on stress, fatigue, skin temperature and immune response in female undergraduate students].

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Lee, Young-Mee

2011-02-01

The purpose of this study was to evaluate the effects of self-foot reflexology on stress (perceived stress, urine cortisol level, and serum cortisol level), fatigue, skin temperature and immune response in female undergraduate students. The research design was a nonequivalent control group pretest-post test design. Participants were 60 university students: 30 in the experiment group and 30 in the control group. The period of this study was from April to June 2010. The program was performed for 1 hr a session, three times a week for 6 weeks. The data were analyzed using the SPSS/WIN 17.0 program. The results showed that self-foot reflexology was effective in reducing perceived stress and fatigue, and raised skin temperature in female undergraduate students. But cortisol levels and immune response were not statistically significant different. The results of this study indicate that self-foot reflexology is an effective nursing intervention in reducing perceived stress and fatigue and, in improving skin temperature. Therefore, it is recommended that this be used in clinical practice as an effective nursing intervention for in female undergraduate students.

Is chronic fatigue syndrome an autoimmune disorder of endogenous neuropeptides, exogenous infection and molecular mimicry?

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Staines, Donald R

2004-01-01

documented symptoms of CFS are explained by vasoactive neuropeptide compromise, namely fatigue and nervous system dysfunction through impaired acetylcholine activity, myalgia through nitric oxide and endogenous opioid dysfunction, chemical sensitivity through peroxynitrite and adenosine dysfunction, and immunological disturbance through changes in immune modulation. Perverse immunological memory established against these substances or their receptors may be the reason for the protracted nature of this condition. The novel status of these substances together with their extremely small concentrations in blood and tissues means that clinical research into them is still in its infancy. A biologically plausible theory of CFS causation associated with vasoactive neuropeptide dysfunction would promote a coherent and systematic approach to research into this and other possibly associated disabling conditions.

Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome.

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Lattie, Emily G; Antoni, Michael H; Fletcher, Mary Ann; Penedo, Frank; Czaja, Sara; Lopez, Corina; Perdomo, Dolores; Sala, Andreina; Nair, Sankaran; Fu, Shih Hua; Klimas, Nancy

2012-08-01

Stressors and emotional distress responses impact chronic fatigue syndrome (CFS) symptoms, including fatigue. Having better stress management skills might mitigate fatigue by decreasing emotional distress. Because CFS patients comprise a heterogeneous population, we hypothesized that the role of stress management skills in decreasing fatigue may be most pronounced in the subgroup manifesting the greatest neuroimmune dysfunction. In total, 117 individuals with CFS provided blood and saliva samples, and self-report measures of emotional distress, perceived stress management skills (PSMS), and fatigue. Plasma interleukin-1-beta (IL-1β, IL-2, IL-6, IL-10, and tumor necrosis factor-alpha (TNF-α), and diurnal salivary cortisol were analyzed. We examined relations among PSMS, emotional distress, and fatigue in CFS patients who did and did not evidence neuroimmune abnormalities. Having greater PSMS related to less fatigue (p=.019) and emotional distress (pfatigue levels most strongly in CFS patients in the top tercile of IL-6, and emotional distress mediated the relationship between PSMS and fatigue most strongly in patients with the greatest circulating levels of IL-6 and a greater inflammatory (IL-6):anti-inflammatory (IL-10) cytokine ratio. CFS patients having greater PSMS show less emotional distress and fatigue, and the influence of stress management skills on distress and fatigue appear greatest among patients who have elevated IL-6 levels. These findings support the need for research examining the impact of stress management interventions in subgroups of CFS patients showing neuroimmune dysfunction. Copyright © 2012 Elsevier Inc. All rights reserved.

Implications of immune dysfunction on endometriosis associated infertility.

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Miller, Jessica E; Ahn, Soo Hyun; Monsanto, Stephany P; Khalaj, Kasra; Koti, Madhuri; Tayade, Chandrakant

2017-01-24

Endometriosis is a complex, inflammatory disease that affects 6-10% of reproductive-aged women. Almost half of the women with endometriosis experience infertility. Despite the excessive prevalence, the pathogenesis of endometriosis and its associated infertility is unknown and a cure is not available. While many theories have been suggested to link endometriosis and infertility, a consensus among investigators has not emerged. In this extensive review of the literature as well as research from our laboratory, we provide potential insights into the role of immune dysfunction in endometriosis associated infertility. We discuss the implication of the peritoneal inflammatory microenvironment on various factors that contribute to infertility such as hormonal imbalance, oxidative stress and how these could further lead to poor oocyte, sperm and embryo quality, impaired receptivity of the endometrium and implantation failure.

Unstimulated cortisol secretory activity in everyday life and its relationship with fatigue and chronic fatigue syndrome: a systematic review and subset meta-analysis.

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Powell, Daniel J H; Liossi, Christina; Moss-Morris, Rona; Schlotz, Wolff

2013-11-01

The hypothalamic-pituitary-adrenal (HPA) axis is a psychoneuroendocrine regulator of the stress response and immune system, and dysfunctions have been associated with outcomes in several physical health conditions. Its end product, cortisol, is relevant to fatigue due to its role in energy metabolism. The systematic review examined the relationship between different markers of unstimulated salivary cortisol activity in everyday life in chronic fatigue syndrome (CFS) and fatigue assessed in other clinical and general populations. Search terms for the review related to salivary cortisol assessments, everyday life contexts, and fatigue. All eligible studies (n=19) were reviewed narratively in terms of associations between fatigue and assessed cortisol markers, including the cortisol awakening response (CAR), circadian profile (CP) output, and diurnal cortisol slope (DCS). Subset meta-analyses were conducted of case-control CFS studies examining group differences in three cortisol outcomes: CAR output; CAR increase; and CP output. Meta-analyses revealed an attenuation of the CAR increase within CFS compared to controls (d=-.34) but no statistically significant differences between groups for other markers. In the narrative review, total cortisol output (CAR or CP) was rarely associated with fatigue in any population; CAR increase and DCS were most relevant. Outcomes reflecting within-day change in cortisol levels (CAR increase; DCS) may be the most relevant to fatigue experience, and future research in this area should report at least one such marker. Results should be considered with caution due to heterogeneity in one meta-analysis and the small number of studies. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Effects of aroma self-foot reflexology massage on stress and immune responses and fatigue in middle-aged women in rural areas].

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Kim, Ja Ok; Kim, In Sook

2012-10-01

This study was done to examine the effects of aroma self-foot reflexology massage on stress and immune responses and fatigue in middle-aged women in rural areas. The study was a nonequivalent control group pre-post test design. The participants were 52 middle-aged women from rural areas of which 26 were assigned to the experimental group and 26 to the control group. Data were collected from July to September, 2011 and analyzed using SPSS Win 17.0 version program. The intervention was conducted 3 times a week for six weeks. There were significant differences in reported perceived stress, systolic blood pressure, diastolic blood pressure and fatigue between the two groups. However, the issue of salivary cortisol and immune response were not significant. Aroma self-foot reflexology massage can be utilized as an effective intervention for perceived stress, systolic blood pressure, diastolic blood pressure and fatigue in middle-aged woman in rural areas.

Converging Pathways in Autism Spectrum Disorders: Interplay Between Synaptic Dysfunction and Immune Responses

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Irina eVoineagu

2013-11-01

Full Text Available Autism spectrum disorders (ASD are highly heritable, yet genetically heterogeneous neurodevelopmental conditions. Recent genome-wide association and gene expression studies have provided evidence supporting the notion that the large number of genetic variants associated with ASD converge toward a core set of dysregulated biological processes. Here we review recent data demonstrating the involvement of synaptic dysfunction and abnormal immune responses in ASD, and discuss the functional interplay between the two phenomena.

Efficacy of kinesiology tape versus postural correction exercises on neck disability and axioscapular muscles fatigue in mechanical neck dysfunction: A randomized blinded clinical trial.

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El-Abd, Aliaa M; Ibrahim, Abeer R; El-Hafez, Haytham M

2017-04-01

Mechanical neck dysfunction (MND), with axioscapular muscles fatigue, is highly prevalent worldwide. While postural correction is commonly used for its treatment, efficacy of kinesiology tape (KT) has received considerable attention. To determine the effectiveness of KT versus correction exercises on neck disability, and axioscapular muscles fatigue in MND patients. 46 MND patients were randomly assigned into 1 of 2 groups receiving 4 weeks treatment of either KT or correction exercises. Neck disability and axioscapular muscles fatigue as median frequency of electromyography (EMG-MF) were measured pre and post treatment. Group-by-time interaction was not significant in the multivariable test. Post hoc tests revealed that KT produced more disability reduction than the postural exercises. However, there was no significant interaction for EMG-MF. KT has been found to be more effective than postural exercises to reduce neck disability. However, both modalities have similar effects to reduce axioscapular muscles fatigue. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immune System Dysfunction in the Elderly.

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Fuentes, Eduardo; Fuentes, Manuel; Alarcón, Marcelo; Palomo, Iván

2017-01-01

Human aging is characterized by both physical and physiological frailty that profoundly affects the immune system. In this context aging is associated with declines in adaptive and innate immunity established as immunosenescence. Immunosenescence is a new concept that reflects the age-associated restructuring changes of innate and adaptive immune functions. Thus elderly individuals usually present chronic low-level inflammation, higher infection rates and chronic diseases. A study of alterations in the immune system during aging could provide a potentially useful biomarker for the evaluation of immune senescence treatment. The immune system is the result of the interplay between innate and adaptive immunity, yet the impact of aging on this function is unclear. In this article the function of the immune system during aging is explored.

Atopic dermatitis: immune deviation, barrier dysfunction, IgE autoreactivity and new therapies

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Masutaka Furue

2017-07-01

Full Text Available Atopic dermatitis (AD is a chronic or chronically relapsing, eczematous, severely pruritic skin disorder mostly associated with IgE elevation and skin barrier dysfunction due to decreased filaggrin expression. The lesional skin of AD exhibits Th2- and Th22-deviated immune reactions that are progressive during disease chronicity. Th2 and Th22 cytokines further deteriorate the skin barrier by inhibiting filaggrin expression. Some IgEs are reactive to self-antigens. The IgE autoreactivity may precipitate the chronicity of AD. Upon activation of the ORAI1 calcium channel, atopic epidermis releases large amounts of thymic stromal lymphopoietin (TSLP, which initiates the Th2 and Th22 immune response. Th2-derived interleukin-31 and TSLP induce an itch sensation. Taken together, TSLP/Th2/Th22 pathway is a promising target for developing new therapeutics for AD. Enhancing filaggrin expression using ligands for the aryl hydrocarbon receptor may also be an adjunctive measure to restore the disrupted barrier function specifically for AD.

Attenuation of phosphamidon-induced oxidative stress and immune dysfunction in rats treated with N-acetylcysteine

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S.G. Suke

2008-09-01

Full Text Available The effect of N-acetylcysteine, a thiolic antioxidant, on attenuation of phosphamidon-induced oxidative stress and immune dysfunction was evaluated in adult male Wistar rats weighing 200-250 g. Rats were divided into four groups, 8 animals/group, and treated with phosphamidon, N-acetylcysteine or the combination of both for 28 days. Oral administration of phosphamidon (1.74 mg/kg, an organophosphate insecticide, increased serum malondialdehyde (3.83 ± 0.18 vs 2.91 ± 0.24 nmol/mL; P < 0.05 and decreased erythrocyte superoxide dismutase (567.8 ± 24.36 vs 749.16 ± 102.61 U/gHb; P < 0.05, catalase activity (1.86 ± 0.18 vs 2.43 ± 0.08 U/gHb; P < 0.05 and whole blood glutathione levels (1.25 ± 0.21 vs 2.28 ± 0.08 mg/gHb; P < 0.05 showing phosphamidon-induced oxidative stress. Phosphamidon exposure markedly suppressed humoral immune response as assessed by antibody titer to ovalbumin (4.71 ± 0.51 vs 8.00 ± 0.12 -log2; P < 0.05, and cell-mediated immune response as assessed by leukocyte migration inhibition (25.24 ± 1.04 vs 70.8 ± 1.09%; P < 0.05 and macrophage migration inhibition (20.38 ± 0.99 vs 67.16 ± 5.30%; P < 0.05 response. Phosphamidon exposure decreased IFN-у levels (40.7 ± 3.21 vs 55.84 ± 3.02 pg/mL; P < 0.05 suggesting a profound effect of phosphamidon on cell-mediated immune response. A phosphamidon-induced increase in TNF-α level (64.19 ± 6.0 vs 23.16 ± 4.0 pg/mL; P < 0.05 suggests a contributory role of immunocytes in oxidative stress. Co-administration of N-acetylcysteine (3.5 mmol/kg, orally with phosphamidon attenuated the adverse effects of phosphamidon. These findings suggest that oral N-acetylcysteine treatment exerts protective effect and attenuates free radical injury and immune dysfunction caused by subchronic phosphamidon exposure.

The association of fatigue, pain, depression and anxiety with work and activity impairment in immune mediated inflammatory diseases.

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Murray W Enns

Full Text Available Impairment in work function is a frequent outcome in patients with chronic conditions such as immune-mediated inflammatory diseases (IMID, depression and anxiety disorders. The personal and economic costs of work impairment in these disorders are immense. Symptoms of pain, fatigue, depression and anxiety are potentially remediable forms of distress that may contribute to work impairment in chronic health conditions such as IMID. The present study evaluated the association between pain [Medical Outcomes Study Pain Effects Scale], fatigue [Daily Fatigue Impact Scale], depression and anxiety [Hospital Anxiety and Depression Scale] and work impairment [Work Productivity and Activity Impairment Scale] in four patient populations: multiple sclerosis (n = 255, inflammatory bowel disease (n = 248, rheumatoid arthritis (n = 154 and a depression and anxiety group (n = 307, using quantile regression, controlling for the effects of sociodemographic factors, physical disability, and cognitive deficits. Each of pain, depression symptoms, anxiety symptoms, and fatigue individually showed significant associations with work absenteeism, presenteeism, and general activity impairment (quantile regression standardized estimates ranging from 0.3 to 1.0. When the distress variables were entered concurrently into the regression models, fatigue was a significant predictor of work and activity impairment in all models (quantile regression standardized estimates ranging from 0.2 to 0.5. These findings have important clinical implications for understanding the determinants of work impairment and for improving work-related outcomes in chronic disease.

Innate Immune Signalling Genetics of Pain, Cognitive Dysfunction and Sickness Symptoms in Cancer Pain Patients Treated with Transdermal Fentanyl.

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Daniel T Barratt

Full Text Available Common adverse symptoms of cancer and chemotherapy are a major health burden; chief among these is pain, with opioids including transdermal fentanyl the mainstay of treatment. Innate immune activation has been implicated generally in pain, opioid analgesia, cognitive dysfunction, and sickness type symptoms reported by cancer patients. We aimed to determine if genetic polymorphisms in neuroimmune activation pathways alter the serum fentanyl concentration-response relationships for pain control, cognitive dysfunction, and other adverse symptoms, in cancer pain patients. Cancer pain patients (468 receiving transdermal fentanyl were genotyped for 31 single nucleotide polymorphisms in 19 genes: CASP1, BDNF, CRP, LY96, IL6, IL1B, TGFB1, TNF, IL10, IL2, TLR2, TLR4, MYD88, IL6R, OPRM1, ARRB2, COMT, STAT6 and ABCB1. Lasso and backward stepwise generalised linear regression were used to identify non-genetic and genetic predictors, respectively, of pain control (average Brief Pain Inventory < 4, cognitive dysfunction (Mini-Mental State Examination ≤ 23, sickness response and opioid adverse event complaint. Serum fentanyl concentrations did not predict between-patient variability in these outcomes, nor did genetic factors predict pain control, sickness response or opioid adverse event complaint. Carriers of the MYD88 rs6853 variant were half as likely to have cognitive dysfunction (11/111 than wild-type patients (69/325, with a relative risk of 0.45 (95% CI: 0.27 to 0.76 when accounting for major non-genetic predictors (age, Karnofsky functional score. This supports the involvement of innate immune signalling in cognitive dysfunction, and identifies MyD88 signalling pathways as a potential focus for predicting and reducing the burden of cognitive dysfunction in cancer pain patients.

Post-traumatic hypopituitarism and fatigue.

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Masel, Brent E; Zgaljardic, Dennis J; Forman, Jack

2017-10-01

Post-traumatic hypopituitarism (PTH) associated with chronic cognitive, psychiatric, and/or behavioural sequelae is common following moderate to severe traumatic brain injury (TBI). More specifically, due to a cascade of hormonal deficiencies secondary to PTH, individuals with TBI may experience debilitating fatigue that can negatively impact functional recovery, as it can limit participation in brain injury rehabilitation services and lead to an increase in maladaptive lifestyle practices. While the mechanisms underlying fatigue and TBI are not entirely understood, the current review will address the specific anatomy and physiology of the pituitary gland, as well as the association between pituitary dysfunction and fatigue in individuals with TBI.

Innate Immune Signalling Genetics of Pain, Cognitive Dysfunction and Sickness Symptoms in Cancer Pain Patients Treated with Transdermal Fentanyl

Science.gov (United States)

Barratt, Daniel T.; Klepstad, Pål; Dale, Ola; Kaasa, Stein; Somogyi, Andrew A.

2015-01-01

Common adverse symptoms of cancer and chemotherapy are a major health burden; chief among these is pain, with opioids including transdermal fentanyl the mainstay of treatment. Innate immune activation has been implicated generally in pain, opioid analgesia, cognitive dysfunction, and sickness type symptoms reported by cancer patients. We aimed to determine if genetic polymorphisms in neuroimmune activation pathways alter the serum fentanyl concentration-response relationships for pain control, cognitive dysfunction, and other adverse symptoms, in cancer pain patients. Cancer pain patients (468) receiving transdermal fentanyl were genotyped for 31 single nucleotide polymorphisms in 19 genes: CASP1, BDNF, CRP, LY96, IL6, IL1B, TGFB1, TNF, IL10, IL2, TLR2, TLR4, MYD88, IL6R, OPRM1, ARRB2, COMT, STAT6 and ABCB1. Lasso and backward stepwise generalised linear regression were used to identify non-genetic and genetic predictors, respectively, of pain control (average Brief Pain Inventory fentanyl concentrations did not predict between-patient variability in these outcomes, nor did genetic factors predict pain control, sickness response or opioid adverse event complaint. Carriers of the MYD88 rs6853 variant were half as likely to have cognitive dysfunction (11/111) than wild-type patients (69/325), with a relative risk of 0.45 (95% CI: 0.27 to 0.76) when accounting for major non-genetic predictors (age, Karnofsky functional score). This supports the involvement of innate immune signalling in cognitive dysfunction, and identifies MyD88 signalling pathways as a potential focus for predicting and reducing the burden of cognitive dysfunction in cancer pain patients. PMID:26332828

Gut inflammation in chronic fatigue syndrome

OpenAIRE

Lakhan, Shaheen E; Kirchgessner, Annette

2010-01-01

Abstract Chronic fatigue syndrome (CFS) is a debilitating disease characterized by unexplained disabling fatigue and a combination of accompanying symptoms the pathology of which is incompletely understood. Many CFS patients complain of gut dysfunction. In fact, patients with CFS are more likely to report a previous diagnosis of irritable bowel syndrome (IBS), a common functional disorder of the gut, and experience IBS-related symptoms. Recently, evidence for interactions between the intestin...

Problems with balance and binocular visual dysfunction are associated with post-stroke fatigue

DEFF Research Database (Denmark)

Schow, Trine; Teasdale, Thomas William; Jensen Quas, Kirsten

2017-01-01

Background: Fatigue after stroke is hard to define and measure and how it is associated with other complications after stroke still needs to be explored. These issues are relevant in stroke rehabilitation and in the patient’s daily life. Objective: To investigate fatigue after stroke and its rela...... in studying fatigue. The correlation analysis shown at this component differs from cognitive and physical fatigue and describes another aspect of PSF, important in future treatment and research........ The associations between MFIS factors and physical measures were assessed using pairwise correlations. Results: Three components were extracted from the MFIS, explaining 71% of variance: Cognitive fatigue, Physical fatigue and Arousal. We found that women register higher MFIS scores than men. There was a strong...... association between the level of Cognitive and Physical Fatigue and BVD, between Arousal and balance and dizziness, and between Cognitive Fatigue and gait. Conclusion: The three extracted components of MFIS proved clinically informative. The arousal component revealed particularly interesting results...

Research progress of exercise-induced fatigue

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Peng-yi DAI

2016-12-01

Full Text Available Exercise-induced fatigue is a comprehensive response to a variety of physiological and biochemical changes in the body, and can affect people's quality of life to different extents. If no timely recovery after occurrence of fatigue, accumulated gradually, it can lead to "burnout", a "overtraining syndrome", "chronic fatigue syndrome", etc., which will cause endocrine disturbance, immune suppression, even physical illness. Exercise-induced fatigue becomes an important factor endangering human health. In recent years, many experts and scholars at home and abroad are committed to the research of exercise-induced fatigue, and have put forward a variety of hypothesis to explain the cause of exercise-induced fatigue. They expect to find out the methods for preventing and eliminating exercise-induced fatigue. This article discusses mainly the pathogenesis, model building, elimination/ relief, etc. of exercise-induced fatigue to point out the research achievements of exercise-induced fatigue and its existing problems. DOI: 10.11855/j.issn.0577-7402.2016.11.14

Differing leukocyte gene expression profiles associated with fatigue in patients with prostate cancer versus chronic fatigue syndrome.

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Light, Kathleen C; Agarwal, Neeraj; Iacob, Eli; White, Andrea T; Kinney, Anita Y; VanHaitsma, Timothy A; Aizad, Hannah; Hughen, Ronald W; Bateman, Lucinda; Light, Alan R

2013-12-01

Androgen deprivation therapy (ADT) often worsens fatigue in patients with prostate cancer, producing symptoms similar to chronic fatigue syndrome (CFS). Comparing expression (mRNA) of many fatigue-related genes in patients with ADT-treated prostate cancer versus with CFS versus healthy controls, and correlating mRNA with fatigue severity may clarify the differing pathways underlying fatigue in these conditions. Quantitative real-time PCR was performed on leukocytes from 30 fatigued, ADT-treated prostate cancer patients (PCF), 39 patients with CFS and 22 controls aged 40-79, together with ratings of fatigue and pain severity. 46 genes from these pathways were included: (1) adrenergic/monoamine/neuropeptides, (2) immune, (3) metabolite-detecting, (4) mitochondrial/energy, (5) transcription factors. PCF patients showed higher expression than controls or CFS of 2 immune transcription genes (NR3C1 and TLR4), chemokine CXCR4, and mitochondrial gene SOD2. They showed lower expression of 2 vasodilation-related genes (ADRB2 and VIPR2), 2 cytokines (TNF and LTA), and 2 metabolite-detecting receptors (ASIC3 and P2RX7). CFS patients showed higher P2RX7 and lower HSPA2 versus controls and PCF. Correlations with fatigue severity were similar in PCF and CFS for only DBI, the GABA-A receptor modulator (r=-0.50, pfatigue and pain severity (r=+0.43 and +0.59, p=0.025 and p=0.001). PCF patients differed from controls and CFS in mean expression of 10 genes from all 5 pathways. Correlations with fatigue severity implicated DBI for both patient groups and P2RY1 for PCF only. These pathways may provide new targets for interventions to reduce fatigue. Copyright © 2013 Elsevier Ltd. All rights reserved.

Human Cytotoxic T Lymphocytes Form Dysfunctional Immune Synapses with B Cells Characterized by Non-Polarized Lytic Granule Release

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Anna Kabanova

2016-04-01

Full Text Available Suppression of the cytotoxic T cell (CTL immune response has been proposed as one mechanism for immune evasion in cancer. In this study, we have explored the underlying basis for CTL suppression in the context of B cell malignancies. We document that human B cells have an intrinsic ability to resist killing by freshly isolated cytotoxic T cells (CTLs, but are susceptible to lysis by IL-2 activated CTL blasts and CTLs isolated from immunotherapy-treated patients with chronic lymphocytic leukemia (CLL. Impaired killing was associated with the formation of dysfunctional non-lytic immune synapses characterized by the presence of defective linker for activation of T cells (LAT signaling and non-polarized release of the lytic granules transported by ADP-ribosylation factor-like protein 8 (Arl8. We propose that non-lytic degranulation of CTLs are a key regulatory mechanism of evasion through which B cells may interfere with the formation of functional immune synapses by CTLs.

Activation of the NLRP3 inflammasome in lipopolysaccharide-induced mouse fatigue and its relevance to chronic fatigue syndrome.

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Zhang, Zi-Teng; Du, Xiu-Ming; Ma, Xiu-Juan; Zong, Ying; Chen, Ji-Kuai; Yu, Chen-Lin; Liu, Yan-Gang; Chen, Yong-Chun; Zhao, Li-Jun; Lu, Guo-Cai

2016-04-05

The NLRP3 inflammasome (NOD-like receptor family, pyrin domain containing 3) is an intracellular protein complex that plays an important role in innate immune sensing. Its activation leads to the maturation of caspase-1 and regulates the cleavage of interleukin (IL)-1β and IL-18. Various studies have shown that activation of the immune system plays a pivotal role in the development of fatigue. However, the mechanisms underlying the association between immune activation and fatigue remained elusive, and few reports have described the involvement of NLRP3 inflammasome activation in fatigue. We established a mouse fatigue model with lipopolysaccharide (LPS, 3 mg/kg) challenge combined with swim stress. Both behavioural and biochemical parameters were measured to illustrate the characteristics of this model. We also assessed NLRP3 inflammasome activation in the mouse diencephalon, which is the brain region that has been suggested to be responsible for fatigue sensation. To further identify the role of NLRP3 inflammasome activation in the pathogenesis of chronic fatigue syndrome (CFS), NLRP3 KO mice were also subjected to LPS treatment and swim stress, and the same parameters were evaluated. Mice challenged with LPS and subjected to the swim stress test showed decreased locomotor activity, decreased fall-off time in a rota-rod test and increased serum levels of IL-1β and IL-6 compared with untreated mice. Serum levels of lactic acid and malondialdehyde (MDA) were not significantly altered in the treated mice. We demonstrated increased NLRP3 expression, IL-1β production and caspase-1 activation in the diencephalons of the treated mice. In NLRP3 KO mice, we found remarkably increased locomotor activity with longer fall-off times and decreased serum IL-1β levels compared with those of wild-type (WT) mice after LPS challenge and the swim stress test. IL-1β levels in the diencephalon were also significantly decreased in the NLRP3 KO mice. By contrast, IL-6 levels were

Fatigue in Patients with Parkinson’s Disease

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Kazuo Abe

2000-01-01

Full Text Available Purpose: Fatigue is a complaint frequently encountered among patients with Parkinson’s disease (PD, however, the pathophysiological mechanism remains unclear. Methods: We evaluated fatigue in 26 patients clinically diagnosed to have PD (16 men, 10 women and age- and sex- matched 26 controls (16 men, 10 women without neurological deficits by using a fatigue scale. In addition to neurological and neuropsychological examinations, all patients underwent MRI and SPECT using 99mTc-HMPAO. Results: Patients with PD had normal cognitive function as judged by the MMSE, but showed significantly high scores with the fatigue and depression scales in comparison to controls (p. There was no significant correlation between the depression scale and the fatigue scale, or between the degree of disability and the fatigue scale in patients with PD, although a significant correlation existed between the depression scale and the fatigue scale in controls. With SPECT, a significant correlation was found between the fatigue scale and the reduction of perfusion in the frontal lobe (p in patients with PD. Conclusions: The present study suggested that sense of fatigue in patients with PD might be associated with frontal lobe dysfunction.

Increased risk of organic erectile dysfunction in patients with chronic fatigue syndrome: a nationwide population-based cohort study.

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Chao, C-H; Chen, H-J; Wang, H-Y; Li, T-C; Kao, C-H

2015-07-01

Chronic fatigue syndrome (CFS) is a complex disorder characterized by profound and persistent fatigue and several comorbidities. CFS was previously reported to be associated with female sexual dysfunction. We propose that CFS might also be associated with organic erectile dysfunction (organic ED). We conducted a retrospective cohort study by using data from the National Health Insurance (NHI) Research Database. We identified 2156 male patients who were newly diagnosed with CFS between January 1, 2003 and December 31, 2006. After excluding those younger than 20 years and prevalent cases, 1976 patients were subjected to analysis, and 7904 people served as healthy controls. All study subjects were followed up from the index date to the date of organic ED diagnosis, withdrawal from the NHI program, or the end of 2011. Compared with the non-CFS cohort, the incidence density rate of organic ED was 1.88-fold higher than that in the CFS cohort (3.23 vs. 1.73 per 1000 person-years) with an adjusted hazard ratio (HR) of 1.88 (95% CI = 1.26-2.81) when adjusting for sex and comorbidities. The combined impacts of patients with CFS and cardiovascular disease (CVD), diabetes mellitus (DM), chronic kidney disease (CKD), depression, and anxiety showed a significant by joint association with organic ED risk compared with patients with no CFS and no counterpart comorbidity. The greatest magnitude of adjusted HR of ED for CFS was observed in individuals without any comorbidity (3.87, 1.95-7.66). The incidence of organic ED is higher among males aged 40 years and over for both CFS and non-CFS cohorts. As the number of comorbidity increases, the incidence of organic ED increases in males without CFS. Higher incidence of organic ED was observed in males with CVD, DM, CKD, depression, or anxiety for both CFS and non-CFS cohorts. © 2015 American Society of Andrology and European Academy of Andrology.

A role for homeostatic drive in the perpetuation of complex chronic illness: Gulf War Illness and chronic fatigue syndrome.

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Travis J A Craddock

Full Text Available A key component in the body's stress response, the hypothalamic-pituitary-adrenal (HPA axis orchestrates changes across a broad range of major biological systems. Its dysfunction has been associated with numerous chronic diseases including Gulf War Illness (GWI and chronic fatigue syndrome (CFS. Though tightly coupled with other components of endocrine and immune function, few models of HPA function account for these interactions. Here we extend conventional models of HPA function by including feed-forward and feedback interaction with sex hormone regulation and immune response. We use this multi-axis model to explore the role of homeostatic regulation in perpetuating chronic conditions, specifically GWI and CFS. An important obstacle in building these models across regulatory systems remains the scarcity of detailed human in vivo kinetic data as its collection can present significant health risks to subjects. We circumvented this using a discrete logic representation based solely on literature of physiological and biochemical connectivity to provide a qualitative description of system behavior. This connectivity model linked molecular variables across the HPA axis, hypothalamic-pituitary-gonadal (HPG axis in men and women, as well as a simple immune network. Inclusion of these interactions produced multiple alternate homeostatic states and sexually dimorphic responses. Experimental data for endocrine-immune markers measured in male GWI subjects showed the greatest alignment with predictions of a naturally occurring alternate steady state presenting with hypercortisolism, low testosterone and a shift towards a Th1 immune response. In female CFS subjects, expression of these markers aligned with an alternate homeostatic state displaying hypocortisolism, high estradiol, and a shift towards an anti-inflammatory Th2 activation. These results support a role for homeostatic drive in perpetuating dysfunctional cortisol levels through persistent

Porcine placenta mitigates protein-energy malnutrition-induced fatigue.

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Han, Na-Ra; Kim, Kyu-Yeop; Kim, Myong-Jo; Kim, Min-Ho; Kim, Hyung-Min; Jeong, Hyun-Ja

2013-01-01

Fatigue can be caused by a deficiency of nutrition or immune function. The goal of this study was to identify the effects of porcine placenta extract (PPE) and its constituents, amino acids (glutamic acid, glycine, arginine, and proline), on protein-energy malnutrition (PEM)-induced fatigue. Mice were administered a PEM diet and came to immunodeficient status. Simultaneously, the mice were administered PPE or amino acids and a forced swimming test (FST) was performed. We analyzed the levels of fatigue-related factors in serum, splenocytes, and muscles. In the FST, PPE or amino acids significantly decreased immobility times compared with the PEM diet. PPE or amino acids also significantly decreased the serum levels of fatigue-related factors after the FST. Additionally, PPE significantly decreased the levels of fatigue-related muscle parameters after the FST. In this in vitro study, PPE increased the mRNA and protein expression of Ki-67 and promoted the proliferation of splenocytes. PPE or amino acids significantly increased the levels of intracellular calcium and the translocation into the nucleus of nuclear factor of activated T-cells cytoplasmic in stimulated splenocytes. PPE or amino acids significantly decreased the production of fatigue-related inflammatory cytokines in the stimulated splenocytes. Additionally, the translocated levels of nuclear factor-κB in the nucleus and the degradation of the inhibitory protein, IκBα, in the cytosol were inhibited by PPE or amino acids. These results demonstrate that PPE and its constituents regulate PEM-induced fatigue through improving levels of immunity and decreasing fatigue-related factors. PPE may be a potential agent for a recovery from fatigue. Copyright © 2013 Elsevier Inc. All rights reserved.

Is there a cognitive signature for MS-related fatigue?

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Hanken, Katrin; Eling, Paul; Hildebrandt, Helmut

2015-04-01

The compensatory approach of fatigue argues that it is a state caused by task load. The neuropsychiatric approach argues that fatigue is a trait (like depression), unrelated to environmental challenges. We propose that fatigue is an internal state that can be measured behaviorally only by applying specific cognitive tasks. PubMed was searched for articles concerning the relation between fatigue and cognitive performance or brain atrophy or functional MRI, distinguishing between the following cognitive domains: learning/memory, cognitive speed/selective attention, language, visuospatial processing, working memory, alerting/vigilance. Only tasks assessing alerting/vigilance are strongly related to fatigue. Areas with brain atrophy in fatigue patients overlap with brain regions activated in healthy controls performing alerting/vigilance tasks. Fatigue is not a compensatory state, nor a psychogenic trait. It is a feeling with behavioral effects that seems to be caused by brain atrophy or a neurochemical dysfunction of the alerting/vigilance system. © The Author(s), 2014.

Effect of aerobic interval training on serum IL-10, TNFα, and adipokines levels in women with multiple sclerosis: possible relations with fatigue and quality of life.

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Mokhtarzade, Motahare; Ranjbar, Rouholah; Majdinasab, Nastaran; Patel, Darpan; Molanouri Shamsi, Mehdieh

2017-08-01

Multiple sclerosis is associated with immune system dysfunction and chronic inflammation; however, possible relations between immunologic and metabolic factors and some psychological indexes such as fatigue and quality of life, especially in relation to exercise training, have not yet been investigated. The present study was designed to investigate the effect of aerobic interval training on interleukin-10/tumor necrosis factor ratio and adipokine (leptin and adiponectin) concentrations in women with multiple sclerosis. Furthermore, the relationship between these factors with fatigue and quality of life were assessed. Forty women with multiple sclerosis (Expanded Disability Status Scale ≤3) were randomized into either a non-exercising control or training group. The training group performed 8-weeks of upper and lower limb aerobic interval training. Serum concentrations of tumor necrosis factorα, interleukin-10, leptin, and adiponectin were measured before and after the 8-week intervention. Moreover, antropometric measures and measures for fatigue and quality of life were determined at the onset of and after exercise training. The results revealed that leptin and tumor necrosis factorα levels significantly decreased subsequent to the aerobic interval training. Although blood adiponectin levels considerably increased in the training group, interleukin-10 and interleukin-10/tumor necrosis factorα ratio underwent no substantial change after the exercise training. In addition, the aerobic interval training was associated with improvement in fatigue, quality of life, and maximal oxygen consumption. Our findings suggested that aerobic interval training can be an effective strategy for managing the immune system at least by its significant impact on inflammatory cytokines and adipokines levels in women with multiple sclerosis. Additionally, this positive impact improved fatigue and adipose tissue indicators.

Syndrome de fatigue chronique: Revue de la littérature

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Turgeon, Sue A.

1991-01-01

Chronic fatigue syndrome, previously known as chronic mononucleosis or post-infectious faligue, is a poorly understood illness characterized by chronic debilitating fatigue, recurrent flu-like symptoms, and few clinical or laboratory abnormalities. While a significant incidence of psychiatric illness has been demonstrated among patients with the chronic fatigue syndrome, there is also evidence of subtle immune system abnormalities, leading some researchers to postulate a multi-fatorial psycho...

Exercising Impacts on Fatigue, Depression, and Paresthesia in Female Patients with Multiple Sclerosis.

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Razazian, Nazanin; Yavari, Zeinab; Farnia, Vahid; Azizi, Akram; Kordavani, Laleh; Bahmani, Dena Sadeghi; Holsboer-Trachsler, Edith; Brand, Serge

2016-05-01

Multiple sclerosis (MS) is a chronic progressive autoimmune disease impacting both body and mind. Typically, patients with MS report fatigue, depression, and paresthesia. Standard treatment consists of immune modulatory medication, though there is growing evidence that exercising programs have a positive influence on fatigue and psychological symptoms such as depression. We tested the hypothesis that, in addition to the standard immune regulatory medication, either yoga or aquatic exercise can ameliorate both fatigue and depression, and we examined whether these interventions also influence paresthesia compared with a nonexercise control condition. Fifty-four women with MS (mean age: M = 33.94 yr, SD = 6.92) were randomly assigned to one of the following conditions: yoga, aquatic exercise, or nonexercise control. Their existing immune modulatory therapy remained unchanged. Participants completed questionnaires covering symptoms of fatigue, depression, and paresthesia, both at baseline and on completion of the study 8 wk later. Compared with the nonexercise control condition and over time, fatigue, depression, and paresthesia decreased significantly in the yoga and aquatic exercise groups. On study completion, the likelihood of reporting moderate to severe depression was 35-fold higher in the nonexercise control condition than in the intervention conditions (yoga and aquatic exercising values collapsed). The pattern of results suggests that for females with MS and treated with standard immune regulatory medication, exercise training programs such as yoga and aquatic exercising positively impact on core symptoms of MS, namely, fatigue, depression, and paresthesia. Exercise training programs should be considered in the future as possible complements to standard treatments.

Immune thrombocytopenia with multi-organ dysfunction syndrome as a rare presentation of scrub typhus: a case report.

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Ittyachen, Abraham M; Abraham, Saramma P; Krishnamoorthy, Smitha; Vijayan, Anuroopa; Kokkat, Jayamohan

2017-10-06

Scrub typhus is an acute infectious illness caused by Orientia tsutsugamushi. It is endemic to a part of the world known as the "tsutsugamushi triangle". Humans are accidental hosts in this zoonotic disease. About a third of patients admitted with scrub typhus have evidence of multi-organ dysfunction. Multi-organ dysfunction secondary to scrub typhus carries a high mortality rate. We report a 65-year old lady who was admitted in a Tertiary Care Center in the state of Kerala in India, with 7 day history of fever, myalgia and reduced urine output. Head to foot examination revealed the presence of an eschar on her chest. One week prior to the onset of her illness she had gone trekking through a hilly forest area. She was clinically suspected to have scrub typhus, which was later confirmed with laboratory tests. She developed multi-organ dysfunction syndrome secondary to this illness. Though there was an improvement in the multi-organ dysfunction, thrombocytopenia alone failed to improve. Bone marrow study was done which was suggestive of immune thrombocytopenia. Patient was given a course of steroids with which the thrombocytopenia improved. Failure of platelet count to normalize even after there has been a general improvement of other markers of multi-organ dysfunction in scrub typhus should prompt the clinician to consider other potential causes of thrombocytopenia. An unusual finding as this calls for further research to understand the molecular mechanisms behind such an event. Further, considering the close similarity in clinical presentation of several tropical illnesses, meticulous history taking and a detailed physical examination needs to be emphasized.

Measurement of fatigue in industries.

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Saito, K

1999-04-01

Fatigue of workers is a complex phenomenon resulting from various factors in technically innovated modern industries, and it appears as a feeling of exhaustion, lowering of physiological functions, breakdown of autonomic nervous balance, and decrease in work efficiency. On the other hand industrial fatigue is caused by excessive workload, remarkable alteration in working posture and diurnal and nocturnal rhythms in daily life. Working modes in modern industries have changed from work with the whole body into that with the hands, arms, legs and/or eyes which are parts of the body, and from physical work to mental work. Visual display terminal (VDT) work is one of the most characteristic jobs in the various kinds of workplaces. A large number of fatigue tests have already been adopted, but it is still hard to draw a generalized conclusion as to the method of selecting the most appropriate test battery for a given work load. As apparatus for fatigue measurement of VDT work we have developed VRT (Visual Reaction Test) and the Portable Fatigue Meter. Furthermore, we have presented immune parameters of peripheral blood and splenic T cells for physical fatigue.

[Chronic fatigue syndrome--exercise and physical activity].

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Greenberg, Shai; Frid, Mordechai

2006-04-01

One of the major symptoms of chronic fatigue syndrome (CFS) is reduced exercise and functional capacity and increased fatigue symptoms following physical effort. A review of the literature indicates that patients that suffer from CFS are characterized by: low aerobic capacity, higher heart rate during sub-maximal exercise, higher subjective effort prescription, reduced muscle strength, and prolonged recovery period. Although several symptoms are a result of lack of physical activity, several mechanisms were suggested to explain those symptoms: pathological heart rate control, reduced aerobic metabolic capacity, reduced blood supply to the working muscles and nerve system dysfunction. Participating in guided exercise programs was found to be the most effective treatment in improving exercise and functional capacity, reducing fatigue syndromes and improving patients' daily function.

Changes of serum endocrine hormone levels in patients with cancerrelated fatigue and their correlation with anti-tumor immune response and tumor load

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Lu Yang

2017-08-01

Full Text Available Objective: To study the changes of serum endocrine hormone levels in patients with cancerrelated fatigue (CRF and their correlation with anti-tumor immune response and tumor load. Methods: A total of 137 patients who were diagnosed with primary lung cancer in West China Hospital, Sichuan University between June 2014 and November 2016 were selected and then divided into CRF group and control group according to their self-reported symptoms, serum was collected to determine the levels of endocrine hormones and tumor markers, and peripheral blood was collected to detect the levels of immune cells. Results: Serum ACTH and TSH levels of CRF group were significantly higher than those of control group while Cor, FT3 and FT4 levels were significantly lower than those of control group; peripheral blood CD11b+ CD15 - CD33+ CD14+ M-MDSC, CD11b+ CD15-CD33+ CD14- G-MDSC, CD4+ CD25+ CD127lowTreg and CD19+ CD5+ CD1d+ Breg levels as well as serum CEA, Cyfra21-1, SCC-Ag, HE4, GDF- 15 and PCNA levels of CRF group were significantly higher than those of control group, positively correlated with serum ACTH and TSH levels, and negatively correlated with Cor, FT3 and FT4 levels. Conclusion: The changes of thyroid hormone and adrenal cortical hormone levels in patients with cancer-related fatigue are closely related to the inhibited antitumor immune response and increased tumor load.

Symptoms of fatigue and coping strategies in maritime pilotage.

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Chambers, Timothy P; Main, Luana C

2015-01-01

Little is known regarding the symptoms of fatigue that maritime pilots experience during shift work. Moreover, the strategies these individuals use to cope with the onset of fatigue are also unknown. The current study explored the symptoms of fatigue and coping strategies experienced by maritime pilots when on-shift. Fifty maritime pilots were recruited via an advertisement in the national association's quarterly newsletter (Mage = 51.42; SD = 9.81). Participants responded to a modified version of the questionnaire used with aviation pilots that assessed overall fatigue, and the symptoms pilots associated with fatigue on duty. Methods pilots used to cope with fatigue before shift and when on the bridge were also assessed. There were significant effects for pilot vitality on 4 categories of fatigue: cognitive dysfunction; emotional disturbance; mean physical effects; and sleepiness. There were no significant effects for vitality on any of the self-reported coping strategy factors. The findings indicated that maritime pilots experience a variety of physical, behavioural, and cognitive fatigue symptoms when on shift. Some of these symptoms are similar to those reported by aviation pilots. However, unlike aviation pilots, maritime pilots reported utilising self-sufficient coping strategies to deal with the experience of fatigue.

[Immune dysfunction and cognitive deficit in stress and physiological aging (Part I): Pathogenesis and risk factors].

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Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A

2014-01-01

The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets. The brain, immune and endocrine systems being the principal adaptive systems in the body permanently share information both in the form of neural impulses and soluble mediators. The CNS differs from other organs due to several peculiarities that affect local immune surveillance. The brain cells secluded from the blood flow by a specialized blood-brain-barrier (BBB) can endogenously express pro- and anti-inflammatory cytokines without the intervention of the immune system. In normal brain the cytokine signaling rather contributes to exclusive brain function (e.g. long-term potentiation, synaptic plasticity, adult neurogenesis) than serves as immune communicator. The stress of different origin increases the serum cytokine levels and disrupts BBB. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Mass intrusion of biologically active peptides having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. In addition owing to BBB disruption dendritic cells and T cells also penetrate into the brain where they take up a perivascular position. The changes observed in stressed subject may accumulate during repeated episodes of stress forming a picture typical of the aging brain. Moreover long-term stress as well as physiological aging result in hormonal and immunological disturbances including hypothalamic-pituitary-adrenal axis depletion, regulatory T-cell accumulation and dehydroepiandrosterone decrease.

Dysregulated stress signal sensitivity and inflammatory disinhibition as a pathophysiological mechanism of stress-related chronic fatigue.

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Strahler, Jana; Skoluda, Nadine; Rohleder, Nicolas; Nater, Urs M

2016-09-01

Chronic stress and its subsequent effects on biological stress systems have long been recognized as predisposing and perpetuating factors in chronic fatigue, although the exact mechanisms are far from being completely understood. In this review, we propose that sensitivity of immune cells to glucocorticoids (GCs) and catecholamines (CATs) may be the missing link in elucidating how stress turns into chronic fatigue. We searched for in vitro studies investigating the impact of GCs or CATs on mitogen-stimulated immune cells in chronically stressed or fatigued populations, with 34 original studies fulfilling our inclusion criteria. Besides mixed cross-sectional findings for stress- and fatigue-related changes of GC sensitivity under basal conditions or acute stress, longitudinal studies indicate a decrease with ongoing stress. Research on CATs is still scarce, but initial findings point towards a reduction of CAT sensitivity under chronic stress. In the long run, resistance of immune cells to stress signals under conditions of chronic stress might translate into self-maintaining inflammation and inflammatory disinhibition under acute stress, which in turn lead to fatigue. Copyright © 2016 Elsevier Ltd. All rights reserved.

Metabolic gene expression changes in astrocytes in Multiple Sclerosis cerebral cortex are indicative of immune-mediated signaling

KAUST Repository

Zeis, T.

2015-04-01

Emerging as an important correlate of neurological dysfunction in Multiple Sclerosis (MS), extended focal and diffuse gray matter abnormalities have been found and linked to clinical manifestations such as seizures, fatigue and cognitive dysfunction. To investigate possible underlying mechanisms we analyzed the molecular alterations in histopathological normal appearing cortical gray matter (NAGM) in MS. By performing a differential gene expression analysis of NAGM of control and MS cases we identified reduced transcription of astrocyte specific genes involved in the astrocyte–neuron lactate shuttle (ANLS) and the glutamate–glutamine cycle (GGC). Additional quantitative immunohistochemical analysis demonstrating a CX43 loss in MS NAGM confirmed a crucial involvement of astrocytes and emphasizes their importance in MS pathogenesis. Concurrently, a Toll-like/IL-1β signaling expression signature was detected in MS NAGM, indicating that immune-related signaling might be responsible for the downregulation of ANLS and GGC gene expression in MS NAGM. Indeed, challenging astrocytes with immune stimuli such as IL-1β and LPS reduced their ANLS and GGC gene expression in vitro. The detected upregulation of IL1B in MS NAGM suggests inflammasome priming. For this reason, astrocyte cultures were treated with ATP and ATP/LPS as for inflammasome activation. This treatment led to a reduction of ANLS and GGC gene expression in a comparable manner. To investigate potential sources for ANLS and GGC downregulation in MS NAGM, we first performed an adjuvant-driven stimulation of the peripheral immune system in C57Bl/6 mice in vivo. This led to similar gene expression changes in spinal cord demonstrating that peripheral immune signals might be one source for astrocytic gene expression changes in the brain. IL1B upregulation in MS NAGM itself points to a possible endogenous signaling process leading to ANLS and GGC downregulation. This is supported by our findings that, among others

Epigenetic modifications and glucocorticoid sensitivity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

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de Vega, Wilfred C; Herrera, Santiago; Vernon, Suzanne D; McGowan, Patrick O

2017-02-23

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating idiopathic disease characterized by unexplained fatigue that fails to resolve with sufficient rest. Diagnosis is based on a list of symptoms and exclusion of other fatigue-related health conditions. Despite a heterogeneous patient population, immune and hypothalamic-pituitary-adrenal (HPA) axis function differences, such as enhanced negative feedback to glucocorticoids, are recurring findings in ME/CFS studies. Epigenetic modifications, such as CpG methylation, are known to regulate long-term phenotypic differences and previous work by our group found DNA methylome differences in ME/CFS, however the relationship between DNA methylome modifications, clinical and functional characteristics associated with ME/CFS has not been examined. We examined the DNA methylome in peripheral blood mononuclear cells (PBMCs) of a larger cohort of female ME/CFS patients using the Illumina HumanMethylation450 BeadChip Array. In parallel to the DNA methylome analysis, we investigated in vitro glucocorticoid sensitivity differences by stimulating PBMCs with phytohaemagglutinin and suppressed growth with dexamethasone. We explored DNA methylation differences using bisulfite pyrosequencing and statistical permutation. Linear regression was implemented to discover epigenomic regions associated with self-reported quality of life and network analysis of gene ontology terms to biologically contextualize results. We detected 12,608 differentially methylated sites between ME/CFS patients and healthy controls predominantly localized to cellular metabolism genes, some of which were also related to self-reported quality of life health scores. Among ME/CFS patients, glucocorticoid sensitivity was associated with differential methylation at 13 loci. Our results indicate DNA methylation modifications in cellular metabolism in ME/CFS despite a heterogeneous patient population, implicating these processes in immune and HPA

NLRP3 inflammasome activation mediates fatigue-like behaviors in mice via neuroinflammation.

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Zhang, Ziteng; Ma, Xiujuan; Xia, Zhenna; Chen, Jikuai; Liu, Yangang; Chen, Yongchun; Zhu, Jiangbo; Li, Jinfeng; Yu, Huaiyu; Zong, Ying; Lu, Guocai

2017-09-01

Numerous experimental and clinical studies have suggested that the interaction between the immune system and the brain plays an important role in the pathophysiology of chronic fatigue syndrome (CFS). The NLRP3 inflammasome is an important part of the innate immune system. This complex regulates proinflammatory cytokine interleukin-1β (IL-1β) maturation, which triggers different kinds of immune-inflammatory reactions. We employed repeated forced swims to establish a model of CFS in mice. NLRP3 knockout (KO) mice were also used to explore NLRP3 inflammasome activation in the mechanisms of CFS, using the same treatment. After completing repeated swim tests, the mice displayed fatigue-like behaviors, including locomotor activity and reduced fall-off time on the rota-rod test, which was accompanied by significantly higher mature IL-1β level in the prefrontal cortex (PFC) and malondialdehyde (MDA) level in serum. We also found increased NLRP3 protein expression, NLRP3 inflammasome formation and increased mature IL-1β production in the PFC, relative to untreated mice. The NLRP3 KO mice displayed significantly moderated fatigue behaviors along with decreased PFC and serum IL-1β levels under the same treatment. These findings demonstrated the involvement of NLRP3 inflammasome activation in the mechanism of swimming-induced fatigue. Future therapies targeting the NLRP3/IL-1β pathway may have significant potential for fatigue prevention and treatment. Copyright © 2017. Published by Elsevier Ltd.

The association between daytime napping and cognitive functioning in chronic fatigue syndrome.

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Gotts, Zoe M; Ellis, Jason G; Deary, Vincent; Barclay, Nicola; Newton, Julia L

2015-01-01

The precise relationship between sleep and physical and mental functioning in chronic fatigue syndrome (CFS) has not been examined directly, nor has the impact of daytime napping. This study aimed to examine self-reported sleep in patients with CFS and explore whether sleep quality and daytime napping, specific patient characteristics (gender, illness length) and levels of anxiety and depression, predicted daytime fatigue severity, levels of daytime sleepiness and cognitive functioning, all key dimensions of the illness experience. 118 adults meeting the 1994 CDC case criteria for CFS completed a standardised sleep diary over 14 days. Momentary functional assessments of fatigue, sleepiness, cognition and mood were completed by patients as part of usual care. Levels of daytime functioning and disability were quantified using symptom assessment tools, measuring fatigue (Chalder Fatigue Scale), sleepiness (Epworth Sleepiness Scale), cognitive functioning (Trail Making Test, Cognitive Failures Questionnaire), and mood (Hospital Anxiety and Depression Scale). Hierarchical Regressions demonstrated that a shorter time since diagnosis, higher depression and longer wake time after sleep onset predicted 23.4% of the variance in fatigue severity (p naps predicted 25.6% of the variance in objective cognitive dysfunction (p napping predicted 32.2% of the variance in subjective cognitive dysfunction (p naps, those who mainly napped in the afternoon, and those with higher levels of anxiety, were more likely to be in the moderately sleepy group. Napping, particularly in the afternoon is associated with poorer cognitive functioning and more daytime sleepiness in CFS. These findings have clinical implications for symptom management strategies.

Gender differences in chronic fatigue syndrome.

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Faro, Mònica; Sàez-Francás, Naia; Castro-Marrero, Jesús; Aliste, Luisa; Fernández de Sevilla, Tomás; Alegre, José

2016-01-01

Chronic fatigue syndrome (CFS) is a chronic condition that predominantly affects women. To date, there are few epidemiologic studies on CFS in men. The objective of the study was to assess whether there are gender-related differences in CFS, and to define a clinical phenotype in men. A prospective, cross-sectional cohort study was conducted including CFS patients at the time of diagnosis. Sociodemographic data, clinical variables, comorbid phenomena, fatigue, pain, anxiety/depression, and health quality of life, were assessed in the CFS population. A comparative study was also conducted between genders. The study included 1309 CFS patients, of which 119 (9.1%) were men. The mean age and symptoms onset were lower in men than women. The subjects included 30% single men vs. 15% single women, and 32% of men had specialist work vs. 20% of women. The most common triggering factor was an infection. Widespread pain, muscle spasms, dizziness, sexual dysfunction, Raynaud's phenomenon, morning stiffness, migratory arthralgias, drug and metals allergy, and facial oedema were less frequent in men. Fibromyalgia was present in 29% of men vs. 58% in women. The scores on physical function, physical role, and overall physical health of the SF-36 were higher in men. The sensory and affective dimensions of pain were lower in men. The clinical phenotype of the men with CFS was young, single, skilled worker, and infection as the main triggering agent. Men had less pain and less muscle and immune symptoms, fewer comorbid phenomena, and a better quality of life. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Cognition, depression, fatigue, and quality of life in primary Sj?gren's syndrome: correlations

OpenAIRE

Ko?er, Belgin; Tezcan, Mehmet Engin; Batur, Hale Zeynep; Haznedaro?lu, ?eminur; G?ker, Berna; ?rke?, Ceyla; ?etinkaya, R?meysa

2016-01-01

Abstract Objective The aim of the present study was to investigate the prevalence and pattern of cognitive dysfunction observed in primary Sj?gren's syndrome (PSS) and to examine the relationships between cognitive abilities, depression, fatigue, and quality of life. Materials and Methods Thirty?two subjects with PSS were compared with 19 healthy controls on comprehensive neuropsychological, depression, fatigue, health state, and daily?life activities tests. Results There was low performance ...

Pathophysiology and Immune Dysfunction in Endometriosis

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Ahn, Soo Hyun; Monsanto, Stephany P.; Miller, Caragh; Singh, Sukhbir S.; Thomas, Richard; Tayade, Chandrakant

2015-01-01

Endometriosis is an estrogen-dependent, chronic, proinflammatory disease prevalent in 10% of women of reproductive age worldwide. Characterized by the growth of endometrium-like tissue in aberrant locations outside of the uterus, it is responsible for symptoms including chronic pelvic pain, dysmenorrhea, and subfertility that degrade quality of life of women significantly. In Canada, direct and indirect economic cost of endometriosis amounts to 1.8 billion dollars, and this is elevated to 20 billion dollars in the United States. Despite decades of research, the etiology and pathophysiology of endometriosis still remain to be elucidated. This review aims to bring together the current understanding regarding the pathogenesis of endometriosis with specific focus on mechanisms behind vascularization of the lesions and the contribution of immune factors in facilitating lesion establishment and development. The role of hormones, immune cells, and cytokine signaling is highlighted, in addition to discussing the current pharmaceutical options available for management of pain symptoms in women with endometriosis. PMID:26247027

Pathophysiology and Immune Dysfunction in Endometriosis

Directory of Open Access Journals (Sweden)

Soo Hyun Ahn

2015-01-01

Full Text Available Endometriosis is an estrogen-dependent, chronic, proinflammatory disease prevalent in 10% of women of reproductive age worldwide. Characterized by the growth of endometrium-like tissue in aberrant locations outside of the uterus, it is responsible for symptoms including chronic pelvic pain, dysmenorrhea, and subfertility that degrade quality of life of women significantly. In Canada, direct and indirect economic cost of endometriosis amounts to 1.8 billion dollars, and this is elevated to 20 billion dollars in the United States. Despite decades of research, the etiology and pathophysiology of endometriosis still remain to be elucidated. This review aims to bring together the current understanding regarding the pathogenesis of endometriosis with specific focus on mechanisms behind vascularization of the lesions and the contribution of immune factors in facilitating lesion establishment and development. The role of hormones, immune cells, and cytokine signaling is highlighted, in addition to discussing the current pharmaceutical options available for management of pain symptoms in women with endometriosis.

Using endogenous saccades to characterize fatigue in multiple sclerosis.

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Ferreira, Marisa; Pereira, Paulo A; Parreira, Marta; Sousa, Inês; Figueiredo, José; Cerqueira, João J; Macedo, Antonio F

2017-05-01

Multiple Sclerosis (MS) is likely to cause dysfunction of neural circuits between brain regions increasing brain working load or a subjective overestimation of such working load leading to fatigue symptoms. The aim of this study was to investigate if saccades can reveal the effect of fatigue in patients with MS. Patients diagnosed with MS (EDSSendogenous generated saccade paradigm (valid and invalid trials). The fatigue severity scale (FSS) was used to assess the severity of fatigue. FSS scores were used to define two subgroups, the MS fatigue group (score above normal range) and the MS non-fatigue. Differences between groups were tested using linear mixed models. Thirty-one MS patients and equal number of controls participated in this study. FSS scores were above the normal range in 11 patients. Differences in saccade latency were found according to group (p<0.001) and trial validity (p=0.023). Differences were 16.9ms, between MS fatigue and MS non-fatigue, 15.5ms between MS fatigue and control. The mean difference between valid and invalid trials was 7.5ms. Differences in saccade peak velocity were found according to group (p<0.001), the difference between MS fatigue and control was 22.3°/s and between MS fatigue and non-fatigue was 12.3°/s. Group was a statistically significant predictor for amplitude (p<0.001). FSS scores were correlated with peak velocity (p=0.028) and amplitude (p=0.019). Consistent with the initial hypothesis, our study revealed altered saccade latency, peak velocity and amplitude in patients with fatigue symptoms. Eye movement testing can complement the standard inventories when investigating fatigue because they do not share similar limitations. Our findings contribute to the understanding of functional changes induced by MS and might be useful for clinical trials and treatment decisions. Copyright © 2017 Elsevier B.V. All rights reserved.

Maintenance of systemic immune functions prevents accelerated presbycusis.

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Iwai, Hiroshi; Baba, Susumu; Omae, Mariko; Lee, Shinryu; Yamashita, Toshio; Ikehara, Susumu

2008-05-07

There is no effective therapy for progressive hearing loss such as presbycusis, the causes of which remain poorly understood because of the difficulty of separating genetic and environmental contributions. In the present study, we show that the age-related dysfunctions of the systemic immune system in an animal model of accelerated presbycusis (SAMP1, senescence-accelerated mouse P1) can be corrected by allogeneic bone marrow transplantation (BMT). We also demonstrate that this presbycusis can be prevented; BMT protects the recipients from age-related hearing impairment and the degeneration of spiral ganglion cells (SGCs) as well as the dysfunctions of T lymphocytes, which have a close relation to immune senescence. No donor cells are infiltrated to the spiral ganglia, confirming that this experimental system using BMT is connected to the systemic immune system and does not contribute to transdifferentiation or fusion by donor hematopoietic stem cells (HSCs), or to the direct maintenance of ganglion cells by locally infiltrated donor immunocompetent cells. Therefore, another procedure which attempts to prevent the age-related dysfunctions of the recipient immune system is the inoculation of syngeneic splenocytes from young donors. These mice show no development of hearing loss, compared with the recipient mice with inoculation of saline or splenocytes from old donors. Our studies on the relationship between age-related systemic immune dysfunctions and neurodegeneration mechanisms open up new avenues of treatment for presbycusis, for which there is no effective therapy.

Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue

Science.gov (United States)

2012-01-01

Background As Chronic Fatigue Syndrome (CFS) has been known to follow Epstein-Bar virus (EBV) and other systemic infections; our objective was to describe differences in immune activation in post-infective CFS (PI-CFS) patients and recovered controls. We studied 301 adolescents prospectively over 24 months following the diagnosis of monospot-positive infectious mononucleosis (IM). We found an incidence of CFS at 6, 12 and 24 months of 13%, 7% and 4% respectively. Methods Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70), 13, 15, 17 and 23, IFN-γ, TNF-α and TNF-β in duplicate plasma samples available in bio-bank from 9 PI-CFS subjects and 12 recovered controls at 24 months post-infection. Results Standard comparative analysis indicated significant differences in IL-8 and 23 across subject groups. In constructing a linear classification model IL-6, 8 and 23 were selected by two different statistical approaches as discriminating features, with IL-1a, IL-2 and IFN-γ also selected in one model or the other. This supported an assignment accuracy of better than 80% at a confidence level of 0.95 into PI-CFS versus recovered controls. Conclusion These results suggest that co-expression patterns in as few as 5 cytokines associated with Th17 function may hold promise as a tool for the diagnosis of post-infectious CFS. PMID:22973830

Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue

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Broderick Gordon

2012-09-01

Full Text Available Abstract Background As Chronic Fatigue Syndrome (CFS has been known to follow Epstein-Bar virus (EBV and other systemic infections; our objective was to describe differences in immune activation in post-infective CFS (PI-CFS patients and recovered controls. We studied 301 adolescents prospectively over 24 months following the diagnosis of monospot-positive infectious mononucleosis (IM. We found an incidence of CFS at 6, 12 and 24 months of 13%, 7% and 4% respectively. Methods Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70, 13, 15, 17 and 23, IFN-γ, TNF-α and TNF-β in duplicate plasma samples available in bio-bank from 9 PI-CFS subjects and 12 recovered controls at 24 months post-infection. Results Standard comparative analysis indicated significant differences in IL-8 and 23 across subject groups. In constructing a linear classification model IL-6, 8 and 23 were selected by two different statistical approaches as discriminating features, with IL-1a, IL-2 and IFN-γ also selected in one model or the other. This supported an assignment accuracy of better than 80% at a confidence level of 0.95 into PI-CFS versus recovered controls. Conclusion These results suggest that co-expression patterns in as few as 5 cytokines associated with Th17 function may hold promise as a tool for the diagnosis of post-infectious CFS.

Immunosuppressive Tryptophan Catabolism and Gut Mucosal Dysfunction Following Early HIV Infection

NARCIS (Netherlands)

Jenabian, Mohammad-Ali; El-Far, Mohamed; Vyboh, Kishanda; Kema, Ido; Costiniuk, Cecilia T.; Thomas, Rejean; Baril, Jean-Guy; LeBlanc, Roger; Kanagaratham, Cynthia; Radzioch, Danuta; Allam, Ossama; Ahmad, Ali; Lebouche, Bertrand; Tremblay, Cecile; Ancuta, Petronela; Routy, Jean-Pierre

2015-01-01

Background. Tryptophan (Trp) catabolism into kynurenine (Kyn) contributes to immune dysfunction in chronic human immunodeficiency virus (HIV) infection. To better define the relationship between Trp catabolism, inflammation, gut mucosal dysfunction, and the role of early antiretroviral therapy

Differential associations between white blood cell counts and fatigue in young and older adults

DEFF Research Database (Denmark)

Avlund, Kirsten; Hokland, Marianne; Mehlsen, Mimi Yung

2012-01-01

The aims of this exploratory study were to study whether fatigue might be related to the cellular immune system by 1) analysing if the number of white blood cell subsets are related to fatigue and 2) if possible relationships vary in younger and older community-dwelling individuals....

Metabolic gene expression changes in astrocytes in Multiple Sclerosis cerebral cortex are indicative of immune-mediated signaling

KAUST Repository

Zeis, T.; Allaman, I.; Gentner, M.; Schroder, K.; Tschopp, J.; Magistretti, Pierre J.; Schaeren-Wiemers, N.

2015-01-01

Emerging as an important correlate of neurological dysfunction in Multiple Sclerosis (MS), extended focal and diffuse gray matter abnormalities have been found and linked to clinical manifestations such as seizures, fatigue and cognitive dysfunction

Study of the neuroendocrine and immunologic mechanism of fatigue caused by military operations

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Xin LI

2012-01-01

Full Text Available Objective  To observe the regularity of the changes in neuroendocrine-immune system caused by fatigue due to military operations, and explore the mechanism by which fatigue occurs in military operations. Methods  The subjects were 240 soldiers belonging to a field artillery force. The medical history and physical examination were taken before military operations, and fatigue assessment scale was accomplished as well. The following variables were measured in all the subjects: pituitary-adrenal [adrenocorticotropic hormone (ACTH, cortical hormone (B, 24-h urinary free cortisol (UFC], pituitary-gonadal [luteinizing hormone (LH, testosterone (T, estradiol (E2], pituitary-thyroid functions [serum thyroid stimulating hormone (TSH, tetraiodothyronine (TT4, triiodothyronine (TT3, free thyroxine (FT4, and free triiodothyronine (FT3], and cellular immune parameters (CD3+, CD4+, CD8+, CD4+/CD8+, B, NK. After 7 d of large-scale and high-intensity field exercises, the above variables were again measured in all the subjects. Results  After high-intensity military operations, the unpleasant feelings were significantly increased, and the compulsive and psychotic scores significantly decreased in the soldiers. In addition, the pituitary-adrenal and pituitary-gonadal hormone levels also decreased (all PPPConclusion  The depressed psychological tolerance in soldiers is the psychological factor of fatigue after a high-intensity military operation. The hypocorticoidism and inhibition of hypothalamic-pituitary-gonadal axis are the pathophysiological basis of military operation fatigue. Suppression of immune function is an important reason for an increase of susceptibility to disease after high-intensity military operations.

Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome.

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Nagy-Szakal, Dorottya; Williams, Brent L; Mishra, Nischay; Che, Xiaoyu; Lee, Bohyun; Bateman, Lucinda; Klimas, Nancy G; Komaroff, Anthony L; Levine, Susan; Montoya, Jose G; Peterson, Daniel L; Ramanan, Devi; Jain, Komal; Eddy, Meredith L; Hornig, Mady; Lipkin, W Ian

2017-04-26

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling. Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the

The association between daytime napping and cognitive functioning in chronic fatigue syndrome.

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Zoe M Gotts

Full Text Available The precise relationship between sleep and physical and mental functioning in chronic fatigue syndrome (CFS has not been examined directly, nor has the impact of daytime napping. This study aimed to examine self-reported sleep in patients with CFS and explore whether sleep quality and daytime napping, specific patient characteristics (gender, illness length and levels of anxiety and depression, predicted daytime fatigue severity, levels of daytime sleepiness and cognitive functioning, all key dimensions of the illness experience.118 adults meeting the 1994 CDC case criteria for CFS completed a standardised sleep diary over 14 days. Momentary functional assessments of fatigue, sleepiness, cognition and mood were completed by patients as part of usual care. Levels of daytime functioning and disability were quantified using symptom assessment tools, measuring fatigue (Chalder Fatigue Scale, sleepiness (Epworth Sleepiness Scale, cognitive functioning (Trail Making Test, Cognitive Failures Questionnaire, and mood (Hospital Anxiety and Depression Scale.Hierarchical Regressions demonstrated that a shorter time since diagnosis, higher depression and longer wake time after sleep onset predicted 23.4% of the variance in fatigue severity (p <.001. Being male, higher depression and more afternoon naps predicted 25.6% of the variance in objective cognitive dysfunction (p <.001. Higher anxiety and depression and morning napping predicted 32.2% of the variance in subjective cognitive dysfunction (p <.001. When patients were classified into groups of mild and moderate sleepiness, those with longer daytime naps, those who mainly napped in the afternoon, and those with higher levels of anxiety, were more likely to be in the moderately sleepy group.Napping, particularly in the afternoon is associated with poorer cognitive functioning and more daytime sleepiness in CFS. These findings have clinical implications for symptom management strategies.

Study of the Neurophysiology of Central Fatigue

Science.gov (United States)

2014-11-05

AGENCY NAME(S) AND ADDRESS (ES) U.S. Army Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 cognitive, fatigue, fatigability...Fatigability in Parkinson Disease. Movement Disorders 2012;27:e6. 4. Wang C, Ding M, Kluger BM. High-density EEG study of cue-evoked preparatory...258. 3. Kluger B, Wang C, Proemsey J, Ding M. Neuronal Correlates of Executive Dysfunction and Fatigability in Parkinson Disease. Movement Disorders

BP180 dysfunction triggers spontaneous skin inflammation in mice.

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Zhang, Yang; Hwang, Bin-Jin; Liu, Zhen; Li, Ning; Lough, Kendall; Williams, Scott E; Chen, Jinbo; Burette, Susan W; Diaz, Luis A; Su, Maureen A; Xiao, Shengxiang; Liu, Zhi

2018-06-04

BP180, also known as collagen XVII, is a hemidesmosomal component and plays a key role in maintaining skin dermal/epidermal adhesion. Dysfunction of BP180, either through genetic mutations in junctional epidermolysis bullosa (JEB) or autoantibody insult in bullous pemphigoid (BP), leads to subepidermal blistering accompanied by skin inflammation. However, whether BP180 is involved in skin inflammation remains unknown. To address this question, we generated a BP180-dysfunctional mouse strain and found that mice lacking functional BP180 (termed Δ NC16A ) developed spontaneous skin inflammatory disease, characterized by severe itch, defective skin barrier, infiltrating immune cells, elevated serum IgE levels, and increased expression of thymic stromal lymphopoietin (TSLP). Severe itch is independent of adaptive immunity and histamine, but dependent on increased expression of TSLP by keratinocytes. In addition, a high TSLP expression is detected in BP patients. Our data provide direct evidence showing that BP180 regulates skin inflammation independently of adaptive immunity, and BP180 dysfunction leads to a TSLP-mediated itch. The newly developed mouse strain could be a model for elucidation of disease mechanisms and development of novel therapeutic strategies for skin inflammation and BP180-related skin conditions.

Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease.

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Underhill, R A

2015-12-01

The etiology of myalgic encephalomyelitis also known as chronic fatigue syndrome or ME/CFS has not been established. Controversies exist over whether it is an organic disease or a psychological disorder and even the existence of ME/CFS as a disease entity is sometimes denied. Suggested causal hypotheses have included psychosomatic disorders, infectious agents, immune dysfunctions, autoimmunity, metabolic disturbances, toxins and inherited genetic factors. Clinical, immunological and epidemiological evidence supports the hypothesis that: ME/CFS is an infectious disease; the causal pathogen persists in patients; the pathogen can be transmitted by casual contact; host factors determine susceptibility to the illness; and there is a population of healthy carriers, who may be able to shed the pathogen. ME/CFS is endemic globally as sporadic cases and occasional cluster outbreaks (epidemics). Cluster outbreaks imply an infectious agent. An abrupt flu-like onset resembling an infectious illness occurs in outbreak patients and many sporadic patients. Immune responses in sporadic patients resemble immune responses in other infectious diseases. Contagion is shown by finding secondary cases in outbreaks, and suggested by a higher prevalence of ME/CFS in sporadic patients' genetically unrelated close contacts (spouses/partners) than the community. Abortive cases, sub-clinical cases, and carrier state individuals were found in outbreaks. The chronic phase of ME/CFS does not appear to be particularly infective. Some healthy patient-contacts show immune responses similar to patients' immune responses, suggesting exposure to the same antigen (a pathogen). The chronicity of symptoms and of immune system changes and the occurrence of secondary cases suggest persistence of a causal pathogen. Risk factors which predispose to developing ME/CFS are: a close family member with ME/CFS; inherited genetic factors; female gender; age; rest/activity; previous exposure to stress or toxins

Heat shock proteins and chronic fatigue in primary Sjögren's syndrome.

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Bårdsen, Kjetil; Nilsen, Mari Mæland; Kvaløy, Jan Terje; Norheim, Katrine Brække; Jonsson, Grete; Omdal, Roald

2016-04-01

Fatigue occurs frequently in patients with cancer, neurological diseases and chronic inflammatory diseases, but the biological mechanisms that lead to and regulate fatigue are largely unknown. When the innate immune system is activated, heat shock proteins (HSPs) are produced to protect cells. Some extracellular HSPs appear to recognize cellular targets in the brain, and we hypothesize that fatigue may be generated by specific HSPs signalling through neuronal or glial cells in the central nervous system. From a cohort of patients with primary Sjögren's syndrome, 20 patients with high and 20 patients with low fatigue were selected. Fatigue was evaluated with a fatigue visual analogue scale. Plasma concentrations of HSP32, HSP60, HSP72 and HSP90α were measured and analysed to determine if there were associations with the level of fatigue. Plasma concentrations of HSP90α were significantly higher in patients with high fatigue compared with those with low fatigue, and there was a tendency to higher concentrations of HSP72 in patients with high fatigue compared with patients with low fatigue. There were no differences in concentrations of HSP32 and HSP60 between the high- and low-fatigue groups. Thus, extracellular HSPs, particularly HSP90α, may signal fatigue in chronic inflammation. This supports the hypothesis that fatigue is generated by cellular defence mechanisms. © The Author(s) 2016.

Hyperexcitability to electrical stimulation and accelerated muscle fatiguability of taut bands in rats.

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Wang, Yong-Hui; Yin, Ming-Jing; Fan, Zhen-Zhen; Arendt-Nielsen, Lars; Ge, Hong-You; Yue, Shou-Wei

2014-04-01

Myofascial trigger points contribute significantly to musculoskeletal pain and motor dysfunction and may be associated with accelerated muscle fatiguability. The aim of this study was to investigate the electrically induced force and fatigue characteristics of muscle taut bands in rats. Muscle taut bands were dissected out and subjected to trains of electrical stimulation. The electrical threshold intensity for muscle contraction and maximum contraction force (MCF), electrical intensity dependent fatigue and electrical frequency dependent fatigue characteristics were assessed in three different sessions (n=10 each) and compared with non-taut bands in the biceps femoris muscle. The threshold intensity for muscle contraction and MCF at the 10th, 15th and 20th intensity dependent fatigue stimuli of taut bands were significantly lower than those of non-taut bands (all pbands were significantly lower than those at the 1st and 5th stimuli (all pbands than for non-taut bands (both pband itself was more excitable to electrical stimulation and significantly less fatigue resistant than normal muscle fibres.

Determinants of fatigue after first-ever ischemic stroke during acute phase.

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Shan-Shan Wang

Full Text Available Fatigue after stroke is common and has a negative impact on rehabilitation and survival. However, its pathogenesis and contributing factors remain unclear. The purpose of this study was to identify factors influencing the occurrence of fatigue after first-ever ischemic stroke in acute phase.We examined 265 consecutive patients with first-ever ischemic stroke during acute phase (within 2 weeks in two tertiary stroke care hospitals in Henan, China. We documented patients' demographic and clinical characteristics through face-to-face interviews using structured questionnaires and reviews of medical records. Post-stroke fatigue was defined as a score of ≥4 using the Fatigue Severity Scale. Multivariate logistic regression was used to examine post-stroke fatigue in relation to socio-demographic, lifestyle, clinical characteristics and family function.About 40% first-ever ischemic stroke patients experienced post-stroke fatigue in acute phase. Post-stroke fatigue was associated with lack of exercise before stroke (adjusted odds ratio 4.01, 95% CI 1.95-8.24, family dysfunction (2.63, 1.20-5.80, depression (2.39, 1.02-5.58, the presence of pre-stroke fatigue (4.89, 2.13-11.21, use of sedative medications (4.14, 1.58-10.88, coronary heart disease (3.38, 1.46-7.79 and more severe Modified Rankin Scale (2.55, 1.65-3.95.The causes of post-stroke fatigue are multifaceted. More physical exercise, improving family function, reducing depression and appropriate use of sedative medications may be helpful in preventing post-stroke fatigue.

Cognition, depression, fatigue, and quality of life in primary Sjögren's syndrome: correlations.

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Koçer, Belgin; Tezcan, Mehmet Engin; Batur, Hale Zeynep; Haznedaroğlu, Şeminur; Göker, Berna; İrkeç, Ceyla; Çetinkaya, Rümeysa

2016-12-01

The aim of the present study was to investigate the prevalence and pattern of cognitive dysfunction observed in primary Sjögren's syndrome (PSS) and to examine the relationships between cognitive abilities, depression, fatigue, and quality of life. Thirty-two subjects with PSS were compared with 19 healthy controls on comprehensive neuropsychological, depression, fatigue, health state, and daily-life activities tests. There was low performance in Clock Drawing, COWAT, Paced Auditory Serial Addition Test (PASAT), Colorless Word Reading (Stroop1) and Recognizing Colors (Stroop2) Patterns of STROOP test, SDLT, Auditory-Verbal Learning Test (AVLT), immediate and long-term verbal memory, Benton Judgment of Line Orientation Test (BJLOT), and in all the patterns of RCFT in PSS patients compared to the healthy control group ( p  < .05). It was observed an increased depression frequency and fatigue severity, impairment in health condition, and a decreased quality of life in PSS cases compared to the healthy controls ( p  < .05). All the depression, fatigue severity, and quality of life tests showed a significant positive correlation with each other ( p  < .05). A significant negative correlation between Clock Drawing and SF-36-BP ( p  = .031, r  = -.382) and SF-36-GH ( p  = .027, r  = -.392) was observed. Clock Drawing, PASAT, and AVLT are very useful tests to determine the subclinical and clinical cognitive dysfunction to evaluate attention, information processing speed, executive functions, and short-term and long-term verbal memory in PSS patients. Depression and fatigue may not affect the neuropsychological tests performance.

Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology.

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Stringer, Elizabeth Ann; Baker, Katharine Susanne; Carroll, Ian R; Montoya, Jose G; Chu, Lily; Maecker, Holden T; Younger, Jarred W

2013-04-09

Chronic fatigue syndrome (CFS) is a debilitating disorder characterized by persistent fatigue that is not alleviated by rest. The lack of a clearly identified underlying mechanism has hindered the development of effective treatments. Studies have demonstrated elevated levels of inflammatory factors in patients with CFS, but findings are contradictory across studies and no biomarkers have been consistently supported. Single time-point approaches potentially overlook important features of CFS, such as fluctuations in fatigue severity. We have observed that individuals with CFS demonstrate significant day-to-day variability in their fatigue severity. Therefore, to complement previous studies, we implemented a novel longitudinal study design to investigate the role of cytokines in CFS pathophysiology. Ten women meeting the Fukuda diagnostic criteria for CFS and ten healthy age- and body mass index (BMI)-matched women underwent 25 consecutive days of blood draws and self-reporting of symptom severity. A 51-plex cytokine panel via Luminex was performed for each of the 500 serum samples collected. Our primary hypothesis was that daily fatigue severity would be significantly correlated with the inflammatory adipokine leptin, in the women with CFS and not in the healthy control women. As a post-hoc analysis, a machine learning algorithm using all 51 cytokines was implemented to determine whether immune factors could distinguish high from low fatigue days. Self-reported fatigue severity was significantly correlated with leptin levels in six of the participants with CFS and one healthy control, supporting our primary hypothesis. The machine learning algorithm distinguished high from low fatigue days in the CFS group with 78.3% accuracy. Our results support the role of cytokines in the pathophysiology of CFS.

Gene expression in response to exercise in patients with chronic fatigue syndrome: a pilot study.

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Andrew Keech

2016-09-01

Full Text Available Chronic fatigue syndrome (CFS is a debilitating disorder of unknown pathogenesis, characterised by fatigue, which is exacerbated after minimal exercise. We examined the effect of a single bout of aerobic exercise on leucocyte mRNA expression of genes putatively linked to exaggerated afferent signalling as an under-pinning of the fatigue state. A carefully-characterised sample of patients with CFS (N = 10 and healthy matched control participants (N = 12 were included. Participant ratings of fatigue and other symptoms, as well as blood samples, were obtained at baseline, and five other time-points up to 72 hours after 25 minutes of moderate-intensity cycling exercise. Leucocyte mRNA of 19 metabolite-sensing, adrenergic, immune and neurotransmission genes was examined using quantitative polymerase chain reaction. Patients with CFS reported substantial fatigue, functional impairment and poor sleep at baseline (all p < 0.02, and exercise immediately induced worsened patients’ fatigue (effect size, ES = 1.17. There were no significant changes in gene expression after exercise and patients did not differ from control participants at any time point. Higher levels of expression of ficolin (FCN1 and a purinergic receptor (P2RX4 in patients with CFS were found when all time points were combined. Patients with CFS did not show significant exercise-induced changes in leucocyte mRNA of 19 metabolite-sensing, adrenergic, immune and neurotransmission genes despite a prominent exacerbation of fatigue.

Orchestration of pulmonary T cell immunity during Mycobacterium tuberculosis infection: immunity interruptus

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Behar, Samuel M.; Carpenter, Stephen M.; Booty, Matthew G.; Barber, Daniel L.; Jayaraman, Pushpa

2014-01-01

Despite the introduction almost a century ago of Mycobacterium bovis BCG (BCG), an attenuated form of M. bovis that is used as a vaccine against Mycobacterium tuberculosis, tuberculosis remains a global health threat and kills more than 1.5 million people each year. This is mostly because BCG fails to prevent pulmonary disease – the contagious form of tuberculosis. Although there have been significant advances in understanding how the immune system responds to infection, the qualities that define protective immunity against M. tuberculosis remain poorly characterized. The ability to predict who will maintain control over the infection and who will succumb to clinical disease would revolutionize our approach to surveillance, control, and treatment. Here we review the current understanding of pulmonary T cell responses following M. tuberculosis infection. While infection elicits a strong immune response that contains infection, M. tuberculosis evades eradication. Traditionally, its intracellular lifestyle and alteration of macrophage function are viewed as the dominant mechanisms of evasion. Now we appreciate that chronic inflammation leads to T cell dysfunction. While this may arise as the host balances the goals of bacterial sterilization and avoidance of tissue damage, it is becoming clear that T cell dysfunction impairs host resistance. Defining the mechanisms that lead to T cell dysfunction is crucial as memory T cell responses are likely to be subject to the same subject to the same pressures. Thus, success of T cell based vaccines is predicated on memory T cells avoiding exhaustion while at the same time not promoting overt tissue damage. PMID:25311810

Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response.

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Zhong, Hong; Ma, Minjuan; Liang, Tingming; Guo, Li

2018-01-01

In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs) have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction.

Sexual dysfunctions in psoriatic patients

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Maria Isabela Sarbu

2015-04-01

Full Text Available Psoriasis is a chronic, immune-mediated disorder with a worldwide occurrence characterized by well-defined infiltrated erythematous papules and plaques, covered by silvery white or yellowish scales. It is a physically, socially and emotionally invalidating disorder that affects 1-2% of the population. Sexual health is an important part of general health and sexual dysfunctions can negatively affect self-esteem, confidence, interpersonal relationships and the quality of life. Dermatology Life Quality Index (DLQI, Psoriasis Disability Index (PDI and the Impact of Psoriasis on Quality of Life (IPSO questionnaire are all questionnaires used to assess the quality of life of patients with psoriasis and each has one question regarding sexual dysfunction. Several scales were also designed to particularly assess sexual satisfaction in men and women. The aim of this paper is to perform an overview of the existing studies on sexual dysfunction in psoriatic patients.

Altered resting brain connectivity in persistent cancer related fatigue

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Johnson P. Hampson

2015-01-01

Full Text Available There is an estimated 3 million women in the US living as breast cancer survivors and persistent cancer related fatigue (PCRF disrupts the lives of an estimated 30% of these women. PCRF is associated with decreased quality of life, decreased sleep quality, impaired cognition and depression. The mechanisms of cancer related fatigue are not well understood; however, preliminary findings indicate dysfunctional activity in the brain as a potential factor. Here we investigate the relationship between PCRF on intrinsic resting state connectivity in this population. Twenty-three age matched breast cancer survivors (15 fatigued and 8 non-fatigued who completed all cancer-related treatments at least 12 weeks prior to the study, were recruited to undergo functional connectivity magnetic resonance imaging (fcMRI. Intrinsic resting state networks were examined with both seed based and independent component analysis methods. Comparisons of brain connectivity patterns between groups as well as correlations with self-reported fatigue symptoms were performed. Fatigued patients displayed greater left inferior parietal lobule to superior frontal gyrus connectivity as compared to non-fatigued patients (P < 0.05 FDR corrected. This enhanced connectivity was associated with increased physical fatigue (P = 0.04, r = 0.52 and poor sleep quality (P = 0.04, r = 0.52 in the fatigued group. In contrast greater connectivity in the non-fatigued group was found between the right precuneus to the periaqueductal gray as well as the left IPL to subgenual cortex (P < 0.05 FDR corrected. Mental fatigue scores were associated with greater default mode network (DMN connectivity to the superior frontal gyrus (P = 0.05 FDR corrected among fatigued subjects (r = 0.82 and less connectivity in the non-fatigued group (r = −0.88. These findings indicate that there is enhanced intrinsic DMN connectivity to the frontal gyrus in breast cancer survivors with persistent

Safety behaviors and sleep effort predict sleep disturbance and fatigue in an outpatient sample with anxiety and depressive disorders.

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Fairholme, Christopher P; Manber, Rachel

2014-03-01

Theoretical and empirical support for the role of dysfunctional beliefs, safety behaviors, and increased sleep effort in the maintenance of insomnia has begun to accumulate. It is not yet known how these factors predict sleep disturbance and fatigue occurring in the context of anxiety and mood disorders. It was hypothesized that these three insomnia-specific cognitive-behavioral factors would be uniquely associated with insomnia and fatigue among patients with emotional disorders after adjusting for current symptoms of anxiety and depression and trait levels of neuroticism and extraversion. Outpatients with a current anxiety or mood disorder (N = 63) completed self-report measures including the Dysfunctional Beliefs About Sleep Scale (DBAS), Sleep-Related Safety Behaviors Questionnaire (SRBQ), Glasgow Sleep Effort Scale (GSES), Pittsburgh Sleep Quality Index (PSQI), NEO Five-Factor Inventory (FFI), and the 21-item Depression Anxiety and Stress Scale (DASS). Multivariate path analysis was used to evaluate study hypotheses. SRBQ (B = .60, p relationship between safety behaviors and fatigue was strongest among individuals with greater levels of dysfunctional beliefs. Findings are consistent with cognitive behavioral models of insomnia and suggest that sleep-specific factors might be important treatment targets among patients with anxiety and depressive disorders with disturbed sleep. Copyright © 2013 Elsevier Inc. All rights reserved.

Fatigue During Head-And-Neck Radiotherapy: Prospective Study on 117 Consecutive Patients

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Jereczek-Fossa, Barbara Alicja; Santoro, Luigi; Alterio, Daniela; Franchi, Benedetta; Fiore, Maria Rosaria; Fossati, Piero; Kowalczyk, Anna; Canino, Paola; Ansarin, Mohssen; Orecchia, Roberto

2007-01-01

Purpose: Fatigue is an underevaluated cancer-related and treatment-related symptom. We analyzed fatigue in head and neck cancer patients undergoing radiotherapy (RT). Methods and Materials: A total of 117 patients were enrolled (mean age, 58 years). Radiation therapy (median dose, 66 Gy) was given with either exclusive or postoperative intent in 52 and 65 patients, respectively. Chemotherapy (CT) was added before and/or during RT in 61 patients. The patients completed a 20-item questionnaire (Multidimensional Fatigue Inventory [MFI-20]) before, during (weekly), and after RT. The impact of patient-, tumor-, and treatment-related factors on fatigue was evaluated with unifactorial and multifactorial tests. Results: Fatigue level increased during RT reaching a maximum at Week 6 and then slowly decreased. In multivariate stepwise regression analysis age (inversely related, p < 0.05), psychologic disorders (p < 0.005), and previous head-and-neck surgery (inversely related, p < 0.005) were correlated with higher pre-RT fatigue level. Pre-RT fatigue score (p < 0.0001), induction and/or concomitant CT (p = 0.035), need of cortisone during RT (p = 0.005), and thyroid disorders (p = 0.032) were correlated with higher during-RT fatigue level. Pre-RT fatigue score (p < 0.0001), induction and/or concomitant CT (p < 0.001), and need of cortisone during RT (p < 0.005) were correlated with higher post-RT fatigue level. No impact of gender, performance status, comorbidities other than psychologic and thyroid, tumor stage/site, RT intent, dose, volume, duration, or toxicity was observed. Conclusion: Fatigue affects all patients undergoing RT for head-and-neck cancer, reaches maximum score at the 6th week of RT, and slowly decreases thereafter. Age, thyroid dysfunction, psychologic disorders, pre-RT fatigue score, CT, and cortisone use are correlated with RT-related fatigue levels

Illness progression in chronic fatigue syndrome: a shifting immune baseline.

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Russell, Lindsey; Broderick, Gordon; Taylor, Renee; Fernandes, Henrique; Harvey, Jeanna; Barnes, Zachary; Smylie, AnneLiese; Collado, Fanny; Balbin, Elizabeth G; Katz, Ben Z; Klimas, Nancy G; Fletcher, Mary Ann

2016-03-10

Validation of biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) across data sets has proven disappointing. As immune signature may be affected by many factors, our objective was to explore the shift in discriminatory cytokines across ME/CFS subjects separated by duration of illness. Cytokine expression collected at rest across multiple studies for female ME/CFS subjects (i) 18 years or younger, ill for 2 years or less (n = 18), (ii) 18-50 years of age, ill for 7 years (n = 22), and (iii) age 50 years or older (n = 28), ill for 11 years on average. Control subjects were matched for age and body mass index (BMI). Data describing the levels of 16 cytokines using a chemiluminescent assay was used to support the identification of separate linear classification models for each subgroup. In order to isolate the effects of duration of illness alone, cytokines that changed significantly with age in the healthy control subjects were excluded a priori. Optimal selection of cytokines in each group resulted in subsets of IL-1α, 6, 8, 15 and TNFα. Common to any 2 of 3 groups were IL-1α, 6 and 8. Setting these 3 markers as a triple screen and adjusting their contribution according to illness duration sub-groups produced ME/CFS classification accuracies of 75-88 %. The contribution of IL-1α, higher in recently ill adolescent ME/CFS subjects was progressively less important with duration. While high levels of IL-8 screened positive for ME/CFS in the recently afflicted, the opposite was true for subjects ill for more than 2 years. Similarly, while low levels of IL-6 suggested early ME/CFS, the reverse was true in subjects over 18 years of age ill for more than 2 years. These preliminary results suggest that IL-1α, 6 and 8 adjusted for illness duration may serve as robust biomarkers, independent of age, in screening for ME/CFS.

Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response

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Hong Zhong

2018-01-01

Full Text Available In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction.

Keeping the immune system in check: a role for mitophagy.

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Lazarou, Michael

2015-01-01

Mitochondria play a central role in many facets of cellular function including energy production, control of cell death and immune signaling. Breakdown of any of these pathways because of mitochondrial deficits or excessive reactive oxygen species production has detrimental consequences for immune system function and cell viability. Maintaining the functional integrity of mitochondria is therefore a critical challenge for the cell. Surveillance systems that monitor mitochondrial status enable the cell to identify and either repair or eliminate dysfunctional mitochondria. Mitophagy is a selective form of autophagy that eliminates dysfunctional mitochondria from the population to maintain overall mitochondrial health. This review covers the major players involved in mitophagy and explores the role mitophagy plays to support the immune system.

Epigallocatechin gallate ameliorates chronic fatigue syndrome in mice: behavioral and biochemical evidence.

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Sachdeva, Anand Kamal; Kuhad, Anurag; Tiwari, Vinod; Chopra, Kanwaljit

2009-12-28

Three decades after the coining of the term chronic fatigue syndrome, the diagnosis of this illness is still symptom based and the aetiology remains elusive. Chronic fatigue syndrome pathogenesis seems to be multifactorial and the possible involvement of immune system is supported. The present study was designed to evaluate the effects of the epigallocatechin gallate in a mouse model of immunologically induced chronic fatigue. On 19th day, after lipopolysaccharide/Brucella abortus administration, the mice showed significant increase in immobility period, post swim fatigue and thermal hyperalgesia. Behavioral deficits were coupled with enhanced oxidative-nitrosative stress as evident by increased lipid peroxidation, nitrite levels and decreased endogenous antioxidant enzymes (superoxide dismutase, reduced glutathione and catalase) and inflammation (increased levels of tumor necrosis factor-alpha and tissue growth factor-beta). Chronic treatment with epigallocatechin gallate restored these behavioral and biochemical alterations in mice. The present study points out towards the beneficial effect of epigallocatechin gallate in the amelioration of chronic fatigue syndrome and thus may provide a new, effective and powerful strategy to treat chronic fatigue syndrome.

The albumin-bilirubin grade uncovers the prognostic relationship between hepatic reserve and immune dysfunction in HIV-associated hepatocellular carcinoma.

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Pinato, D J; Sharma, R; Citti, C; Platt, H; Ventura-Cots, M; Allara, E; Chen, T-Y; Dalla Pria, A; Jain, M; Mínguez, B; Kikuchi, L; Kaufman West, E; Merli, M; Kaplan, D E; Hasson, H; Marks, K; Nelson, M; Núñez, M; Aytaman, A; Bower, M; Bräu, N

2018-01-01

Hepatocellular carcinoma (HCC) is a leading cause of liver-related mortality in people living with HIV, where co-infection with hepatotropic viruses accelerates the course of chronic liver disease. To evaluate whether the albumin-bilirubin (ALBI) grade, a more accurate marker of liver dysfunction in HCC, might identify patients with progressive liver dysfunction in the context of HIV/hepatitis co-infection. Using uni- and multi-variable analyses, we studied the albumin-bilirubin grade as a predictor of overall survival (OS) in a large, multi-center cohort of patients with HIV-associated HCC recruited from 44 centres in 9 countries within the Liver Cancer in HIV study group. Patients who underwent liver transplantation were excluded. A total of 387 patients, predominantly HCV co-infected (78%) with balanced representation of all Barcelona Clinic Liver Cancer (BCLC) stages (A = 33%, B = 18%, C = 37%, D = 12%) were recruited. At HCC diagnosis, 84% had been on anti-retrovirals for a median duration of 8.8 years. The albumin-bilirubin grade identified significant differences in median survival of 97 months for grade 1 (95% CI 13-180 months), 17 months for grade 2 (95% CI 11-22 months) and 6 months for grade 3 (95% CI 4-9 months, P bilirubin grade correlated with lower CD4 counts (464/373/288 cells/mm 3 for grades 1/2/3) and higher HIV viraemia (3.337/8.701/61.845 copies/mL for grades 1/2/3, P bilirubin grade highlights the interplay between liver reserve and immune dysfunction as prognostic determinants in HIV-associated HCC. © 2017 John Wiley & Sons Ltd.

New York City social workers after 9/11: their attachment, resiliency, and compassion fatigue.

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Tosone, Carol; Bettmann, Joanna E; Minami, Takuya; Jasperson, Rachael A

2010-01-01

This study examines the relationship between attachment classification, resiliency, and compassion fatigue in New York social workers following 9/11. We used single occasion, quasi-random sampling, surveying 481 social workers living in Manhattan. Hierarchical regression analyses revealed that secure attachment is predictive of the ability to cope with secondary traumatic stress as well as capacity for resilience, explaining approximately 7% of the variance in both compassion fatigue and resiliency. These findings suggest that secure attachment may serve as a source of resilience for social workers, immunizing them from significant compassion fatigue. Such findings have significant implications for clinicians working with traumatized populations.

Lower limb vascular dysfunction in cyclists

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Thiago Ayala Melo Di Alencar

2013-06-01

Full Text Available Sports-related vascular insufficiency affecting the lower limbs is uncommon, and early signs and symptoms can be confused with musculoskeletal injuries. This is also the case among professional cyclists, who are always at the threshold between endurance and excess training. The aim of this review was to analyze the occurrence of vascular disorders in the lower limbs of cyclists and to discuss possible etiologies. Eighty-five texts, including papers and books, published from 1950 to 2012, were used. According to the literature reviewed, some cyclists receive a late diagnosis of vascular dysfunction due to a lack of familiarity of the medical team with this type of dysfunction. Data revealed that a reduced blood flow in the external iliac artery, especially on the left, is much more common than in the femoral and popliteal arteries, and that vascular impairment is responsible for the occurrence of early fatigue and reduced performance in cycling.

Evaluation of anti-fatigue and immunomodulating effects of quercetin in strenuous exercise mice

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Zhang, Wei-qiang

2017-04-01

The purpose of the present study was to investigate the anti-fatigue and immunomodulating effects of quercetin in strenuous exercise mice. Mice were given orally either corn oil or quercetin (20, 40 and 60 mg/kg body weight suspended in corn oil) by gavage once a day for 28 day. All mice were sacrificed after rotarod test and the major biochemical parameters were analyzed in serum and liver. The results indicated that quercetin possessed anti-fatigue effects by prolonging retention times, decreasing levels of blood lactate and serum urea nitrogen, and increasing levels of blood glucose, tissue glycogen and serum glucagon. Furthermore, quercetin could improve the immune function of fatigue mice by decreasing tumor necrosis factor-α levels, and elevated interleukin-10 levels. Quercetin possessed anti-fatigue effects may be related to its immunomodulating effects.

[Immune dysfunction and cognitive deficit in stress and physiological aging. Part II: New approaches to cognitive disorder prevention and treatment ].

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Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A

2014-01-01

Long-term stress as well as physiological aging result in similar immunological and hormonal disturbances including hypothalamic-pituitary-adrenal) axis depletion, aberrant immune response (regulatory T-cells, Tregs, and T(h17)-lymphocyte accumulation) and decreased dehydroepian-drosterone synthesis both in the brain and in the adrenal glands. Since the main mechanisms of inflammation control, "prompt" (stress hormones) and "delayed" (Tregs), are broken, serum cytokine levels increase and become sufficient for blood-brain-barrier disruption. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Structural and functional alterations of blood-brain-barrier as well as stress- (or age-) induced neuroinflammation promote influx of bone marrow derived dendritic cells and lymphocyte effectors into the brain parenchyma. Thereafter, mass intrusion ofpro-inflammatory mediators and immune cells having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets: 1) reduction of excessive Treg accumulation; 2) supporting hypothalamic-pituitary-adrenal axis and inflammatory reaction attenuation; 3) recovery of dehydroepiandrosterone level; 4) improvement of blood-brain-barrier function.

Cognitive and Physical Fatigue Tasks Enhance Pain, Cognitive Fatigue and Physical Fatigue in People with Fibromyalgia

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Dailey, Dana L; Keffala, Valerie J; Sluka, Kathleen A

2014-01-01

Objective Fibromyalgia is a condition characterized by chronic widespread muscle pain and fatigue. The primary objective of this study was to determine if pain, perceived cognitive fatigue, and perceived physical fatigue were enhanced in participants with fibromyalgia compared to healthy controls during a cognitive fatigue task, a physical fatigue task and a dual fatigue task. Methods Twenty four people with fibromyalgia and 33 healthy controls completed pain, fatigue and function measures. A cognitive fatigue task (Controlled Oral Word Association Test) and physical fatigue task (Valpar peg test) were done individually and combined for a dual fatigue task. Resting pain, perceived cognitive fatigue and perceived physical fatigue were assessed during each task using visual analogue scales. Function was assessed with shoulder range of motion and grip. Results People with fibromyalgia had significantly higher increases in pain, cognitive fatigue and physical fatigue when compared to healthy controls after completion of a cognitive fatigue task, a physical fatigue task, or a dual fatigue task (pfatigue tasks, respectively. Conclusions These data show that people with fibromyalgia show larger increases in pain, perceived cognitive fatigue and perceived physical fatigue to both cognitive and physical fatigue tasks compared to healthy controls. The increases in pain and fatigue during cognitive and physical fatigue tasks could influence subject participation in daily activities and rehabilitation. PMID:25074583

Energy Dissipation-Based Method for Fatigue Life Prediction of Rock Salt

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He, Mingming; Huang, Bingqian; Zhu, Caihui; Chen, Yunsheng; Li, Ning

2018-05-01

The fatigue test for rock salt is conducted under different stress amplitudes, loading frequencies, confining pressures and loading rates, from which the evaluation rule of the dissipated energy is revealed and analysed. The evolution of energy dissipation under fatigue loading is divided into three stages: the initial stage, the second stage and the acceleration stage. In the second stage, the energy dissipation per cycle remains stable and shows an exponential relation with the stress amplitude; the failure dissipated energy only depends on the mechanical behaviour of the rock salt and confining pressure, but it is immune to the loading conditions. The energy dissipation of fatigued rock salt is discussed, and a novel model for fatigue life prediction is proposed on the basis of energy dissipation. A simple model for evolution of the accumulative dissipated energy is established. Its prediction results are compared with the test results, and the proposed model is validated.

DNA methylation modifications associated with chronic fatigue syndrome.

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Wilfred C de Vega

Full Text Available Chronic Fatigue Syndrome (CFS, also known as myalgic encephalomyelitis, is a complex multifactorial disease that is characterized by the persistent presence of fatigue and other particular symptoms for a minimum of 6 months. Symptoms fail to dissipate after sufficient rest and have major effects on the daily functioning of CFS sufferers. CFS is a multi-system disease with a heterogeneous patient population showing a wide variety of functional disabilities and its biological basis remains poorly understood. Stable alterations in gene function in the immune system have been reported in several studies of CFS. Epigenetic modifications have been implicated in long-term effects on gene function, however, to our knowledge, genome-wide epigenetic modifications associated with CFS have not been explored. We examined the DNA methylome in peripheral blood mononuclear cells isolated from CFS patients and healthy controls using the Illumina HumanMethylation450 BeadChip array, controlling for invariant probes and probes overlapping polymorphic sequences. Gene ontology (GO and network analysis of differentially methylated genes was performed to determine potential biological pathways showing changes in DNA methylation in CFS. We found an increased abundance of differentially methylated genes related to the immune response, cellular metabolism, and kinase activity. Genes associated with immune cell regulation, the largest coordinated enrichment of differentially methylated pathways, showed hypomethylation within promoters and other gene regulatory elements in CFS. These data are consistent with evidence of multisystem dysregulation in CFS and implicate the involvement of DNA modifications in CFS pathology.

The impact of subjective cognitive fatigue and depression on cognitive function in patients with multiple sclerosis.

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Golan, Daniel; Doniger, Glen M; Wissemann, Karl; Zarif, Myassar; Bumstead, Barbara; Buhse, Marijean; Fafard, Lori; Lavi, Idit; Wilken, Jeffrey; Gudesblatt, Mark

2018-02-01

The association between subjective cognitive fatigue and objective cognitive dysfunction in patients with multiple sclerosis (PwMS) has been studied, with conflicting results. To explore the impact of fatigue on cognitive function, while controlling for the influence of depression, disability, comorbidities, and psychotropic medications. PwMS completed a computerized cognitive testing battery with age- and education-adjusted cognitive domain scores. Disability (Expanded Disability Status Scale (EDSS)), cognitive fatigue, and depression were concurrently evaluated. In all, 699 PwMS were included. Both cognitive fatigue and depression were significantly and negatively correlated with the same cognitive domains: information processing speed, executive function, attention, motor function, and memory (-0.15 ⩽ r ⩽ -0.14 for cognitive fatigue; -0.24 ⩽ r ⩽ -0.19 for depression). Multivariate analysis revealed significant but small independent correlations only between depression and neuropsychological test results, while cognitive fatigue had no independent correlation with objective cognitive function except for a trend toward impaired motor function in highly fatigued PwMS. Depression and cognitive fatigue accounted for no more than 6% of the variance in objective cognitive domain scores. Cognitive fatigue is not independently related to objective cognitive impairment. Depression may influence cognitive function of PwMS primarily when it is severe. Cognitive impairment in PwMS should not be ascribed to fatigue or mild depression.

Fatigue, psychosocial adaptation and quality of life one year after traumatic brain injury and suspected traumatic axonal injury; evaluations of patients and relatives: a pilot study.

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Esbjörnsson, Eva; Skoglund, Thomas; Sunnerhagen, Katharina S

2013-09-01

To describe fatigue and its relationship to cognition, psychosocial adjustment, quality of life (QoL), work status and relative's experiences 12 months after suspected traumatic axonal injury (TAI). Eighteen patients were assessed with the Daily Fatigue Impact Scale (D-FIS), the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS), the European Questionnaire 5 Dimensions health-related quality of life, the Glasgow Coma Outcome Scale Extended, and the European Brain Injury Questionnaire (EBIQ) (patient and relative). Return to work was registered. At 1 year, fatigue still caused great problems in daily life. Although fatigue and cognition (BNIS) did not correlate, the more fatigued patients subjectively experienced significantly more cognitive dysfunction. Although D-FIS and QoL did not correlate, most patients reported that feelings of tiredness and dullness related to having lower QoL. However, lower QoL was associated with cognitive and attention disability (BNIS), subjective perception of executive dysfunction, lack of motivation, and mood disturbances (EBIQ). Neither fatigue nor cognition associated with return to work. The general consequences of TAI showed good agreement between patients' and relatives' experiences. The patient's subjective experience of the impact of TAI seems to be most essential, as it is the objective reality that the patient responds to, and this should therefore be assessed and treated.

Immune mediated liver failure.

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Wang, Xiaojing; Ning, Qin

2014-01-01

Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capacity. Direct damage and immune-mediated liver injury are two major factors involved in this process. Increasing evidence has suggested the essential role of immune-mediated liver injury in the pathogenesis of liver failure. Here, we review the evolved concepts concerning the mechanisms of immune-mediated liver injury in liver failure from human and animal studies. Both innate and adaptive immunity, especially the interaction of various immune cells and molecules as well as death receptor signaling system are discussed. In addition, we highlight the concept of "immune coagulation", which has been shown to be related to the disease progression and liver injury exacerbation in HBV related acute-on-chronic liver failure.

The diagnostic value of endothelial function as a potential sensor of fatigue in health

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Yoshiko Ohno

2010-03-01

Full Text Available Yoshiko Ohno1,2, Teruto Hashiguchi1, Ryuichi Maenosono1, Hidetoshi Yamashita3, Yukio Taira3, Kazufumi Minowa3, Yoshihito Yamashita3, Yuko Kato3, Ko-ichi Kawahara1, Ikuro Maruyama11Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima City, Kagoshima Prefecture, Japan; 2Department of Community Health Nursing/Nursing Informatics, School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima City, Kagoshima Prefecture, Japan; 3Kagoshima Seikyo General Hospital, Kagoshima City, Kagoshima Prefecture, JapanPurpose: Many epidemiological research studies have shown that vital exhaustion and psychosocial factors are associated with the occurrence of cerebrocardiovascular disease (CCVD. Fatigue is thought to induce endothelial dysfunction and may be linked to the occurrence of CCVD; however, no studies have investigated this potential link. We studied to determine the effect of fatigue on endothelial function in healthy subjects with no traditional CCVD risk factors or potential confounding factors to be controlled.Subjects and methods: Peripheral arterial tonometry (PAT was used to evaluate endothelial function. The influence of the following parameters on endothelial function was analyzed in 74 office workers without traditional CCVD risk factors at health check-ups: endothelial function before and after work, subjective fatigue, lifestyle factors such as sleeping time, and psychosocial factors such as depression and social support.Results: Twenty-five subjects (33.8% had low endothelial function; reactive hyperemia (RH-PAT index <1.67, even though no abnormalities were reported in the health check-ups. There was no significant difference in endothelial function before versus after labor. Of note, endothelial function was associated with the individual’s level of subjective fatigue (t = 2.98, P = 0.008 and showed a daily fluctuation, sometimes to a pathological

Type 2 responses at the interface between immunity and fat metabolism.

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Odegaard, Justin I; Chawla, Ajay

2015-10-01

Adipose tissue resident leukocytes are often cast solely as the effectors of obesity and its attendant pathologies; however, recent observations have demonstrated that these cells support and effect 'healthy' physiologic function as well as pathologic dysfunction. Importantly, these two disparate outcomes are underpinned by similarly disparate immune programs; type 2 responses instruct and promote metabolic normalcy, while type 1 responses drive tissue dysfunction. In this Review, we summarize the literature regarding type 2 immunity's role in adipose tissue physiology and allude to its potential therapeutic implications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Oxidized lipoproteins are associated with markers of inflammation and immune activation in HIV-1 infection

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Kelesidis, T; Jackson, N; McComsey, GA; Wang, X; Elashoff, D; Dube, MP; Brown, TT; Yang, OO; Stein, JH; Currier, JS

2016-01-01

Objective The pathogenesis of immune dysfunction in chronic HIV-1 infection is unclear, and a potential role for oxidized lipids has been suggested. We hypothesize that both oxidized low- and high-density lipoproteins (HDLox, LDLox) contribute to HIV-1 related immune dysfunction. Study In the AIDS Clinical Trials Group (ACTG) A5260, 234 HIV-infected antiretroviral therapy (ART)-naïve participants were randomized to receive tenofovir-emtricitabine plus protease inhibitors or raltegravir and had HIV-1 RNA lipoproteins may contribute to persistent immune activation on ART. PMID:27603288

Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with Epstein Barr Virus

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Hickie Ian B

2006-01-01

Full Text Available Abstract Background Acute infectious diseases are typically accompanied by non-specific symptoms including fever, malaise, irritability and somnolence that usually resolve on recovery. However, in some individuals these symptoms persist in what is commonly termed post-infective fatigue. The objective of this pilot study was to determine the gene expression correlates of post-infective fatigue following acute Epstein Barr virus (EBV infection. Methods We followed 5 people with acute mononucleosis who developed post-infective fatigue of more than 6 months duration and 5 HLA-matched control subjects who recovered within 3 months. Subjects had peripheral blood mononuclear cell (PBMC samples collected at varying time points including at diagnosis, then every 2 weeks for 3 months, then every 3 months for a year. Total RNA was extracted from the PBMC samples and hybridized to microarrays spotted with 3,800 oligonucleotides. Results Those who developed post-infective fatigue had gene expression profiles indicative of an altered host response during acute mononucleosis compared to those who recovered uneventfully. Several genes including ISG20 (interferon stimulated gene, DNAJB2 (DnaJ [Hsp40] homolog and CD99, CDK8 (cyclin-dependent kinase 8, E2F2 (E2F transcription factor 2, CDK8 (cyclin-dependent kinase 8, and ACTN2 (actinin, alpha 2, known to be regulated during EBV infection, were differentially expressed in post-infective fatigue cases. Several of the differentially expressed genes affect mitochondrial functions including fatty acid metabolism and the cell cycle. Conclusion These preliminary data provide insights into alterations in gene transcripts associated with the varied clinical outcomes from acute infectious mononucleosis.

Areva fatigue concept. Fast fatigue evaluation, a new method for fatigue analysis

International Nuclear Information System (INIS)

Heinz, Benedikt; Bergholz, Steffen; Rudolph, Juergen

2011-01-01

Within the discussions on the long term operation (LTO) of nuclear power plants the ageing management is on the focus of that analysis. The knowledge of the operational thermal cyclic load data on components of the power plants and their evaluation in the fatigue analysis is a central concern. The changes in fatigue requirements (e.g. the consideration of environmentally assisted fatigue - EAF) recently discussed and LTO efforts are a strong motivation for the identification of margins in the existing fatigue analysis approaches. These margins should be considered within new approaches in order to obtain realistic (or more accurate) analysis results. Of course, these new analysis approaches have to be manageable and efficient. The Areva Fatigue Concept (AFC) offers the comprehensive conceptual basis for the consideration of fatigue on different levels and depths. The combination of data logging and automated fatigue evaluation are important modules of the AFC. Besides the established simplified stress based fatigue estimation Areva develops a further automated fatigue analysis method called Fast Fatigue Evaluation (FFE). This method comprises highly automated stress analyses at the fatigue relevant locations of the component. Hence, a component specific course of stress as a function of time is determined based on FAMOS or similar temperature measurement systems. The subsequent application of the rain flow cycle counting algorithm allows for the determination of the usage factor following the rules of the design code requirements. The new FFE approach constitutes a cycle counting method based on the real stresses in the component, and determined as result a rule-conformity cumulative usage factor. (orig.)

Mechanisms Explaining Muscle Fatigue and Muscle Pain in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a Review of Recent Findings.

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Gerwyn, Morris; Maes, Michael

2017-01-01

Here, we review potential causes of muscle dysfunction seen in many patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) such as the effects of oxidative and nitrosative stress (O&NS) and mitochondrial impairments together with reduced heat shock protein production and a range of metabolic abnormalities. Several studies published in the last few years have highlighted the existence of chronic O&NS, inflammation, impaired mitochondrial function and reduced heat shock protein production in many patients with ME/CFS. These studies have also highlighted the detrimental effects of chronically elevated O&NS on muscle functions such as reducing the time to muscle fatigue during exercise and impairing muscle contractility. Mechanisms have also been revealed by which chronic O&NS and or impaired heat shock production may impair muscle repair following exercise and indeed the adaptive responses in the striated muscle to acute and chronic increases in physical activity. The presence of chronic O&NS, low-grade inflammation and impaired heat shock protein production may well explain the objective findings of increased muscle fatigue, impaired contractility and multiple dimensions of exercise intolerance in many patients with ME/CFS.

Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints.

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Karachaliou, Niki; Cao, Maria Gonzalez; Teixidó, Cristina; Viteri, Santiago; Morales-Espinosa, Daniela; Santarpia, Mariacarmela; Rosell, Rafael

2015-06-01

Survival rates for metastatic lung cancer, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), are poor with 5-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system-with its capacity for memory, exquisite specificity and central and universal role in human biology-immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer.

Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints

International Nuclear Information System (INIS)

Karachaliou, Niki; Cao, Maria Gonzalez; Teixidó, Cristina; Viteri, Santiago; Morales-Espinosa, Daniela; Santarpia, Mariacarmela; Rosell, Rafael

2015-01-01

Survival rates for metastatic lung cancer, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), are poor with 5-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system—with its capacity for memory, exquisite specificity and central and universal role in human biology—immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer

Sleep, immunity and shift workers: A review

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Carlos Mauricio Oliveira de Almeida

2016-07-01

Full Text Available To date, shift workers represent between 15% and 25% of the modern day workforce. Work time poses a great challenge to workers as it requires that they balance productivity and sleep time between shifts. As a result, these workers experience chronic sleep deprivation with increased fatigue and drowsiness due to this sleep deprivation. The impact of this kind of work on the immune system is not yet known. We conducted a literature review with the aim of evaluating articles on this specific type of work's effects on sleep and immunity.

Tryptophan circuit in fatigue: From blood to brain and cognition.

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Yamashita, Masatoshi; Yamamoto, Takanobu

2017-11-15

Brain tryptophan and its neuroactive metabolites play key roles in central fatigue. However, previous brain function analysis targets may have included both glia and neurons together. Here, we clarified the fatigue-cognitive circuit of the central-peripheral linkage, including the role of glial-neuronal interaction in cognition. Using a rat model of central fatigue induced by chronic sleep disorder (CFSD), we isolated presynaptic terminals and oligodendrocytes. Results showed that compared to control group, presynaptic levels of tryptophan, kynurenine, and kynurenic acid, but not serotonin, in the CFSD group were higher in the hypothalamus and hippocampus. Moreover, CFSD group had higher oligodendrocytic levels of tryptophan, and impaired spatial cognitive memory accuracy and increased hyperactivity and impulsivity. These findings suggest that dynamic change in glial-neuronal interactions within the hypothalamus-hippocampal circuit causes central fatigue, and increased tryptophan-kynurenic acid pathway activity in this circuit causes reduced cognitive function. Additionally, CFSD group had 1.5 times higher plasma levels of tryptophan and kynurenine. Furthermore, in rats undergoing intraperitoneal administration of kynurenine (100mg/kg) versus vehicle, kynurenine-treated rats showed enhanced production of kynurenic acid in the hippocampus, with suppressed recall of retained spatial cognitive memory. The study revealed that uptake of periphery-derived kynurenine and tryptophan into the brain enhances kynurenic acid production in the brain, and the three factors produce amplification effect involved in the role of central-peripheral linkage in central fatigue, triggering cognitive dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

Cellular immune therapy for chronic lymphocytic leukemia

NARCIS (Netherlands)

Kater, Arnon P.; van Oers, Marinus H. J.; Kipps, Thomas J.

2007-01-01

Although chemotherapy can induce complete responses in patients with chronic lymphocytic leukemia (CLL), it is not considered curative. Treated patients generally develop recurrent disease requiring additional therapy, which can cause worsening immune dysfunction, myelosuppression, and selection for

Auto-immune hepatitis following delivery.

Science.gov (United States)

Saini, Vandana; Gupta, Mamta; Mishra, S K

2013-05-01

Auto-immune hepatitis first presenting in the early postpartum period is rare. Immunosuppressive effects of pregnancy result in delayed manifestation of auto-immune hepatitis, and in established cases, the spontaneous improvements are there. Auto-immune hepatitis should be considered in the differential diagnosis of liver dysfunction first presenting in the early postpartum period. A case of postpartum hepatitis of auto-immune aetiology is being presented here. It is disease of unknown aetiology, characterised by inflammation of liver (as evidenced by raised serum transaminases, presence of interface hepatitis on histological examination), hypergammaglobulinaemia (> 1.5 times normal), presence of auto-antibodies [(antinuclear antibodies (ANA)], smooth muscle antibody (SMA) and antibody to liver-kidney microsome type 1 (LKM1) in the absence of viral markers ie, hepatitis B (HBsAg) and C (AntiHCV) and excellent response to corticosteroid therapy.

Trauma: the role of the innate immune system

Directory of Open Access Journals (Sweden)

Rijkers GT

2006-05-01

Full Text Available Abstract Immune dysfunction can provoke (multiple organ failure in severely injured patients. This dysfunction manifests in two forms, which follow a biphasic pattern. During the first phase, in addition to the injury by trauma, organ damage is caused by the immune system during a systemic inflammatory response. During the second phase the patient is more susceptible for sepsis due to host defence failure (immune paralysis. The pathophysiological model outlined in this review encompasses etiological factors and the contribution of the innate immune system in the end organ damage. The etiological factors can be divided into intrinsic (genetic predisposition and physiological status and extrinsic components (type of injury or "traumaload" and surgery or "intervention load". Of all the factors, the intervention load is the only one which, can be altered by the attending emergency physician. Adjustment of the therapeutic approach and choice of the most appropriate treatment strategy can minimize the damage caused by the immune response and prevent the development of immunological paralysis. This review provides a pathophysiological basis for the damage control concept, in which a staged approach of surgery and post-traumatic immunomonitoring have become important aspects of the treatment protocol. The innate immune system is the main objective of immunomonitoring as it has the most prominent role in organ failure after trauma. Polymorphonuclear phagocytes and monocytes are the main effector-cells of the innate immune system in the processes that lead to organ failure. These cells are controlled by cytokines, chemokines, complement factors and specific tissue signals. The contribution of tissue barrier integrity and its interaction with the innate immune system is further evaluated.

Ebola VP40 in Exosomes Can Cause Immune Cell Dysfunction.

Science.gov (United States)

Pleet, Michelle L; Mathiesen, Allison; DeMarino, Catherine; Akpamagbo, Yao A; Barclay, Robert A; Schwab, Angela; Iordanskiy, Sergey; Sampey, Gavin C; Lepene, Benjamin; Nekhai, Sergei; Aman, M J; Kashanchi, Fatah

2016-01-01

Ebola virus (EBOV) is an enveloped, ssRNA virus from the family Filoviridae capable of causing severe hemorrhagic fever with up to 80-90% mortality rates. The most recent outbreak of EBOV in West Africa starting in 2014 resulted in over 11,300 deaths; however, long-lasting persistence and recurrence in survivors has been documented, potentially leading to further transmission of the virus. We have previously shown that exosomes from cells infected with HIV-1, HTLV-1 and Rift Valley Fever virus are able to transfer viral proteins and non-coding RNAs to naïve recipient cells, resulting in an altered cellular activity. In the current manuscript, we examined the effect of Ebola structural proteins VP40, GP, NP and VLPs on recipient immune cells, as well as the effect of exosomes containing these proteins on naïve immune cells. We found that VP40-transfected cells packaged VP40 into exosomes, and that these exosomes were capable of inducing apoptosis in recipient immune cells. Additionally, we show that presence of VP40 within parental cells or in exosomes delivered to naïve cells could result in the regulation of RNAi machinery including Dicer, Drosha, and Ago 1, which may play a role in the induction of cell death in recipient immune cells. Exosome biogenesis was regulated by VP40 in transfected cells by increasing levels of ESCRT-II proteins EAP20 and EAP45, and exosomal marker proteins CD63 and Alix. VP40 was phosphorylated by Cdk2/Cyclin complexes at Serine 233 which could be reversed with r-Roscovitine treatment. The level of VP40-containing exosomes could also be regulated by treated cells with FDA-approved Oxytetracycline. Additionally, we utilized novel nanoparticles to safely capture VP40 and other viral proteins from Ebola VLPs spiked into human samples using SDS/reducing agents, thus minimizing the need for BSL-4 conditions for most downstream assays. Collectively, our data indicates that VP40 packaged into exosomes may be responsible for the deregulation

Ebola VP40 in Exosomes Can Cause Immune Cell Dysfunction

Directory of Open Access Journals (Sweden)

Michelle L. Pleet

2016-11-01

Full Text Available Ebola virus (EBOV is an enveloped, ssRNA virus from the family Filoviridae capable of causing severe hemorrhagic fever with up to 80–90% mortality rates. The most recent outbreak of EBOV in West Africa starting in 2014 resulted in over 11,300 deaths; however, long-lasting persistence and recurrence in survivors has been documented, potentially leading to further transmission of the virus. We have previously shown that exosomes from cells infected with HIV-1, HTLV-1 and Rift Valley Fever virus are able to transfer viral proteins and non-coding RNAs to naïve recipient cells, resulting in an altered cellular activity. In the current manuscript, we examined the effect of Ebola structural proteins VP40, GP, NP and VLPs on recipient immune cells, as well as the effect of exosomes containing these proteins on naïve immune cells. We found that VP40-transfected cells packaged VP40 into exosomes, and that these exosomes were capable of inducing apoptosis in recipient immune cells. Additionally, we show that presence of VP40 within parental cells or in exosomes delivered to naïve cells could result in the regulation of RNAi machinery including Dicer, Drosha, and Ago 1, which may play a role in the induction of cell death in recipient immune cells. Exosome biogenesis was regulated by VP40 in transfected cells by increasing levels of ESCRT-II proteins EAP20 and EAP45, and exosomal marker proteins CD63 and Alix. VP40 was phosphorylated by Cdk2/Cyclin complexes at Serine 233 which could be reversed with r-Roscovitine treatment. The level of VP40-containing exosomes could also be regulated by treated cells with FDA-approved Oxytetracycline. Additionally, we utilized novel nanoparticles to safely capture VP40 and other viral proteins from Ebola VLPs spiked into human samples using SDS/reducing agents, thus minimizing the need for BSL-4 conditions for most downstream assays. Collectively, our data indicates that VP40 packaged into exosomes may be responsible

Fatigue

Science.gov (United States)

... to help you find out what's causing your fatigue and recommend ways to relieve it. Fatigue itself is not a disease. Medical problems, treatments, and personal habits can add to fatigue. These include Taking certain medicines, such as antidepressants, ...

T Follicular Helper Cells and B Cell Dysfunction in Aging and HIV-1 Infection.

Science.gov (United States)

Pallikkuth, Suresh; de Armas, Lesley; Rinaldi, Stefano; Pahwa, Savita

2017-01-01

T follicular helper (Tfh) cells are a subset of CD4 T cells that provide critical signals to antigen-primed B cells in germinal centers to undergo proliferation, isotype switching, and somatic hypermutation to generate long-lived plasma cells and memory B cells during an immune response. The quantity and quality of Tfh cells therefore must be tightly controlled to prevent immune dysfunction in the form of autoimmunity and, on the other hand, immune deficiency. Both Tfh and B cell perturbations appear during HIV infection resulting in impaired antibody responses to vaccines such as seasonal trivalent influenza vaccine, also seen in biologic aging. Although many of the HIV-associated defects improve with antiretroviral therapy (ART), excess immune activation and antigen-specific B and T cell responses including Tfh function are still impaired in virologically controlled HIV-infected persons on ART. Interestingly, HIV infected individuals experience increased risk of age-associated pathologies. This review will discuss Tfh and B cell dysfunction in HIV infection and highlight the impact of chronic HIV infection and aging on Tfh-B cell interactions.

A multi-ingredient containing carbohydrate, proteins L-glutamine and L-carnitine attenuates fatigue perception with no effect on performance, muscle damage or immunity in soccer players.

Directory of Open Access Journals (Sweden)

Fernando Naclerio

Full Text Available We investigated the effects of ingesting a multi-ingredient (53 g carbohydrate, 14.5 g whey protein, 5 g glutamine, 1.5 g L-carnitine-L-tartrate supplement, carbohydrate only, or placebo on intermittent performance, perception of fatigue, immunity, and functional and metabolic markers of recovery. Sixteen amateur soccer players ingested their respective treatments before, during and after performing a 90-min intermittent repeated sprint test. Primary outcomes included time for a 90-min intermittent repeated sprint test (IRS followed by eleven 15 m sprints. Measurements included creatine kinase, myoglobin, interleukine-6, Neutrophil; Lymphocytes and Monocyte before (pre, immediately after (post, 1 h and 24 h after exercise testing period. Overall, time for the IRS and 15 m sprints was not different between treatments. However, the perception of fatigue was attenuated (P<0.001 for the multi-ingredient (15.9±1.4 vs. placebo (17.8±1.4 but not for the carbohydrate (17.0±1.9 condition. Several changes in immune/inflammatory indices were noted as creatine kinase peaked at 24 h while Interleukin-6 and myoglobin increased both immediately after and at 1 h compared with baseline (P<0.05 for all three conditions. However, Myoglobin (P<0.05 was lower 1 h post-exercise for the multi-ingredient (241.8±142.6 ng·ml(-1 and CHO (265.4±187.8 ng·ml(-1 vs. placebo (518.6±255.2 ng·ml(-1. Carbohydrate also elicited lower neutrophil concentrations vs. multi-ingredient (3.9±1.5 10(9/L vs. 4.9±1.8 10(9/L, P = 0.016 and a reduced (P<0.05 monocytes count (0.36±0.09 10(9/L compared to both multi-ingredient (0.42±0.09 10(9/L and placebo (0.42±0.12 10(9/L. In conclusion, multi-ingredient and carbohydrate supplements did not improve intermittent performance, inflammatory or immune function. However, both treatments did attenuate serum myoglobin, while only carbohydrate blunted post-exercise leukocytosis.

Fatigue and thermal fatigue of Pb-Sn solder joints

International Nuclear Information System (INIS)

Frear, D.; Grivas, D.; McCormack, M.; Tribula, D.; Morris, J.W. Jr.

1987-01-01

This paper presents a fundamental investigation of the fatigue and thermal fatigue characteristics, with an emphasis on the microstructural development during fatigue, of Sn-Pb solder joints. Fatigue tests were performed in simple shear on both 60Sn-40Pb and 5Sn-95Pb solder joints. Isothermal fatigue tests show increasing fatigue life of 60Sn-40Pb solder joints with decreasing strain and temperature. In contrast, such behavior was not observed in the isothermal fatigue of 5Sn-95Pb solder joints. Thermal fatigue results on 60Sn-40Pb solder cycled between -55 0 C and 125 0 C show that a coarsened region develops in the center of the joint. Both Pb-rich and Sn-rich phases coarsen, and cracks form within these coarsened regions. The failure mode 60Sn-40Pb solder joints in thermal and isothermal fatigue is similar: cracks form intergranularly through the Sn-rich phase or along Sn/Pb interphase boundaries. Extensive cracking is found throughout the 5Sn-95Pb joint for both thermal and isothermal fatigue. In thermal fatigue the 5Sn-95Pb solder joints failed after fewer cycles than 60Sn-40Pb

Cancer cachexia decreases specific force and accelerates fatigue in limb muscle

Energy Technology Data Exchange (ETDEWEB)

Roberts, B. M. [1225 Center Drive, HPNP Building Room 1142, Department of Physical Therapy, University of Florida, Gainesville, FL 32610 (United States); Frye, G. S.; Ahn, B.; Ferreira, L. F. [1864 Stadium Road, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32610 (United States); Judge, A.R., E-mail: arjudge@phhp.ufl.edu [1225 Center Drive, HPNP Building Room 1142, Department of Physical Therapy, University of Florida, Gainesville, FL 32610 (United States)

2013-06-07

Highlights: •C-26 cancer cachexia causes a significant decrease in limb muscle absolute force. •C-26 cancer cachexia causes a significant decrease in limb muscle specific force. •C-26 cancer cachexia decreases fatigue resistance in the soleus muscle. •C-26 cancer cachexia prolongs time to peak twitch tension in limb muscle. •C-26 cancer cachexia prolongs one half twitch relaxation time in limb muscle. -- Abstract: Cancer cachexia is a complex metabolic syndrome that is characterized by the loss of skeletal muscle mass and weakness, which compromises physical function, reduces quality of life, and ultimately can lead to mortality. Experimental models of cancer cachexia have recapitulated this skeletal muscle atrophy and consequent decline in muscle force generating capacity. However, more recently, we provided evidence that during severe cancer cachexia muscle weakness in the diaphragm muscle cannot be entirely accounted for by the muscle atrophy. This indicates that muscle weakness is not just a consequence of muscle atrophy but that there is also significant contractile dysfunction. The current study aimed to determine whether contractile dysfunction is also present in limb muscles during severe Colon-26 (C26) carcinoma cachexia by studying the glycolytic extensor digitorum longus (EDL) muscle and the oxidative soleus muscle, which has an activity pattern that more closely resembles the diaphragm. Severe C-26 cancer cachexia caused significant muscle fiber atrophy and a reduction in maximum absolute force in both the EDL and soleus muscles. However, normalization to muscle cross sectional area further demonstrated a 13% decrease in maximum isometric specific force in the EDL and an even greater decrease (17%) in maximum isometric specific force in the soleus. Time to peak tension and half relaxation time were also significantly slowed in both the EDL and the solei from C-26 mice compared to controls. Since, in addition to postural control, the oxidative

Cancer cachexia decreases specific force and accelerates fatigue in limb muscle

International Nuclear Information System (INIS)

Roberts, B.M.; Frye, G.S.; Ahn, B.; Ferreira, L.F.; Judge, A.R.

2013-01-01

Highlights: •C-26 cancer cachexia causes a significant decrease in limb muscle absolute force. •C-26 cancer cachexia causes a significant decrease in limb muscle specific force. •C-26 cancer cachexia decreases fatigue resistance in the soleus muscle. •C-26 cancer cachexia prolongs time to peak twitch tension in limb muscle. •C-26 cancer cachexia prolongs one half twitch relaxation time in limb muscle. -- Abstract: Cancer cachexia is a complex metabolic syndrome that is characterized by the loss of skeletal muscle mass and weakness, which compromises physical function, reduces quality of life, and ultimately can lead to mortality. Experimental models of cancer cachexia have recapitulated this skeletal muscle atrophy and consequent decline in muscle force generating capacity. However, more recently, we provided evidence that during severe cancer cachexia muscle weakness in the diaphragm muscle cannot be entirely accounted for by the muscle atrophy. This indicates that muscle weakness is not just a consequence of muscle atrophy but that there is also significant contractile dysfunction. The current study aimed to determine whether contractile dysfunction is also present in limb muscles during severe Colon-26 (C26) carcinoma cachexia by studying the glycolytic extensor digitorum longus (EDL) muscle and the oxidative soleus muscle, which has an activity pattern that more closely resembles the diaphragm. Severe C-26 cancer cachexia caused significant muscle fiber atrophy and a reduction in maximum absolute force in both the EDL and soleus muscles. However, normalization to muscle cross sectional area further demonstrated a 13% decrease in maximum isometric specific force in the EDL and an even greater decrease (17%) in maximum isometric specific force in the soleus. Time to peak tension and half relaxation time were also significantly slowed in both the EDL and the solei from C-26 mice compared to controls. Since, in addition to postural control, the oxidative

The Progress of T Cell Immunity Related to Prognosis in Gastric Cancer

OpenAIRE

Ming Wei; Duo Shen; Sachin Mulmi Shrestha; Juan Liu; Junyi Zhang; Ying Yin

2018-01-01

Gastric cancer is the fifth most common malignancy all over the world, and the factors that can affect progress and prognosis of the gastric cancer patients are various, such as TNM stages, invasive depth, and lymph node metastasis ratio. T cell immunity is important component of human immunity system and immunity responding to tumor and dysfunction or imbalance of T cell immunity will lead to serious outcomes for body. T cell immunity includes many different types of cells, CD4+ T cell, CD8+...

Methods for the assessment of peripheral muscle fatigue and its energy and metabolic determinants in COPD.

Science.gov (United States)

Rondelli, Rafaella Rezende; Dal Corso, Simone; Simões, Alexandre; Malaguti, Carla

2009-11-01

It has been well established that, in addition to the pulmonary involvement, COPD has systemic consequences that can lead to peripheral muscle dysfunction, with greater muscle fatigue, lower exercise tolerance and lower survival in these patients. In view of the negative repercussions of early muscle fatigue in COPD, the objective of this review was to discuss the principal findings in the literature on the metabolic and bioenergy determinants of muscle fatigue, its functional repercussions, as well as the methods for its identification and quantification. The anatomical and functional substrate of higher muscle fatigue in COPD appears to include lower levels of high-energy phosphates, lower mitochondrial density, early lactacidemia, higher serum ammonia and reduced muscle perfusion. These alterations can be revealed by contraction failure, decreased firing rates of motor units and increased recruitment of motor units in a given activity, which can be functionally detected by a reduction in muscle strength, power and endurance. This review article also shows that various types of muscle contraction regimens and protocols have been used in order to detect muscle fatigue in this population. With this understanding, rehabilitation strategies can be developed in order to improve the resistance to muscle fatigue in this population.

The Nature of Fatigue in Chronic Fatigue Syndrome.

Science.gov (United States)

Olson, Karin; Zimka, Oksana; Stein, Eleanor

2015-10-01

In this article, we report the findings of our study on the nature of fatigue in patients diagnosed with chronic fatigue syndrome. Using ethnoscience as a design, we conducted a series of unstructured interviews and card sorts to learn more about how people with chronic fatigue syndrome describe fatigue. Participants (N = 14) described three distinct domains: tiredness, fatigue, and exhaustion. Most participants experienced tiredness prior to diagnosis, fatigue during daily life, and exhaustion after overexertion. We also discuss participants' ability to adapt to a variety of stressors and prevent shifts to exhaustion, and relate our findings to stress theory and other current research. Primary strategies that promoted adaptation to stressors included pacing and extended rest periods. These findings can aid health care professionals in detecting impending shifts between tiredness, fatigue, and exhaustion and in improving adaptive strategies, thereby improving quality of life. © The Author(s) 2015.

Physiological Aging: Links Among Adipose Tissue Dysfunction, Diabetes, and Frailty.

Science.gov (United States)

Stout, Michael B; Justice, Jamie N; Nicklas, Barbara J; Kirkland, James L

2017-01-01

Advancing age is associated with progressive declines in physiological function that lead to overt chronic disease, frailty, and eventual mortality. Importantly, age-related physiological changes occur in cellularity, insulin-responsiveness, secretory profiles, and inflammatory status of adipose tissue, leading to adipose tissue dysfunction. Although the mechanisms underlying adipose tissue dysfunction are multifactorial, the consequences result in secretion of proinflammatory cytokines and chemokines, immune cell infiltration, an accumulation of senescent cells, and an increase in senescence-associated secretory phenotype (SASP). These processes synergistically promote chronic sterile inflammation, insulin resistance, and lipid redistribution away from subcutaneous adipose tissue. Without intervention, these effects contribute to age-related systemic metabolic dysfunction, physical limitations, and frailty. Thus adipose tissue dysfunction may be a fundamental contributor to the elevated risk of chronic disease, disability, and adverse health outcomes with advancing age. ©2017 Int. Union Physiol. Sci./Am. Physiol. Soc.

The Role of the Immune System in Autism Spectrum Disorder.

Science.gov (United States)

Meltzer, Amory; Van de Water, Judy

2017-01-01

Autism is a neurodevelopmental disorder characterized by deficits in communication and social skills as well as repetitive and stereotypical behaviors. While much effort has focused on the identification of genes associated with autism, research emerging within the past two decades suggests that immune dysfunction is a viable risk factor contributing to the neurodevelopmental deficits observed in autism spectrum disorders (ASD). Further, it is the heterogeneity within this disorder that has brought to light much of the current thinking regarding the subphenotypes within ASD and how the immune system is associated with these distinctions. This review will focus on the two main axes of immune involvement in ASD, namely dysfunction in the prenatal and postnatal periods. During gestation, prenatal insults including maternal infection and subsequent immunological activation may increase the risk of autism in the child. Similarly, the presence of maternally derived anti-brain autoantibodies found in ~20% of mothers whose children are at risk for developing autism has defined an additional subphenotype of ASD. The postnatal environment, on the other hand, is characterized by related but distinct profiles of immune dysregulation, inflammation, and endogenous autoantibodies that all persist within the affected individual. Further definition of the role of immune dysregulation in ASD thus necessitates a deeper understanding of the interaction between both maternal and child immune systems, and the role they have in diagnosis and treatment.

Schizophrenia and the immune system: pathophysiology, prevention, and treatment.

Science.gov (United States)

Richard, Michelle D; Brahm, Nancy C

2012-05-01

Published evidence on established and theoretical connections between immune system dysfunction and schizophrenia is reviewed, with a discussion of developments in the search for immunologically-targeted treatments. A growing body of evidence indicates that immunologic influences may play an important role in the etiology and course of schizophrenia. A literature search identified more than 100 articles pertaining to suspected immunologic influences on schizophrenia published over the past 15 years. Schizophrenia researchers have explored a wide range of potential immune system-related causal or contributory factors, including neurobiological and neuroanatomical disorders, genetic abnormalities, and environmental influences such as maternal perinatal infection. Efforts to establish an immunologic basis for schizophrenia and identify reliable immune markers continue to be hindered by sampling challenges and methodological problems. In aggregate, the available evidence indicates that at least some cases of schizophrenia have an immunologic component, suggesting that immune-focused prevention strategies (e.g., counseling of pregnant women to avoid immune stressors) and close monitoring of at-risk children are appropriate. While antipsychotics remain the standard treatments for schizophrenia, a variety of drugs with immunologic effects have been investigated as adjunctive therapies, with variable and sometimes conflicting results; these include the cyclooxygenase-2 inhibitor celecoxib, immune-modulating agents (e.g., azathioprine and various anticytokine agents such as atlizumab, anakinra, and tumor necrosis factor-α blockers), and an investigational anti-interferon-γ agent. The published evidence indicates that immune system dysfunction related to genetic, environmental, and neurobiological influences may play a role in the etiology of schizophrenia in a subset of patients.

The status of and future research into Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: the need of accurate diagnosis, objective assessment, and acknowledging biological and clinical subgroups

Science.gov (United States)

Twisk, Frank N. M.

2014-01-01

Although Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) are used interchangeably, the diagnostic criteria define two distinct clinical entities. Cognitive impairment, (muscle) weakness, circulatory disturbances, marked variability of symptoms, and, above all, post-exertional malaise: a long-lasting increase of symptoms after a minor exertion, are distinctive symptoms of ME. This latter phenomenon separates ME, a neuro-immune illness, from chronic fatigue (syndrome), other disorders and deconditioning. The introduction of the label, but more importantly the diagnostic criteria for CFS have generated much confusion, mostly because chronic fatigue is a subjective and ambiguous notion. CFS was redefined in 1994 into unexplained (persistent or relapsing) chronic fatigue, accompanied by at least four out of eight symptoms, e.g., headaches and unrefreshing sleep. Most of the research into ME and/or CFS in the last decades was based upon the multivalent CFS criteria, which define a heterogeneous patient group. Due to the fact that fatigue and other symptoms are non-discriminative, subjective experiences, research has been hampered. Various authors have questioned the physiological nature of the symptoms and qualified ME/CFS as somatization. However, various typical symptoms can be assessed objectively using standardized methods. Despite subjective and unclear criteria and measures, research has observed specific abnormalities in ME/CFS repetitively, e.g., immunological abnormalities, oxidative and nitrosative stress, neurological anomalies, circulatory deficits and mitochondrial dysfunction. However, to improve future research standards and patient care, it is crucial that patients with post-exertional malaise (ME) and patients without this odd phenomenon are acknowledged as separate clinical entities that the diagnosis of ME and CFS in research and clinical practice is based upon accurate criteria and an objective assessment of characteristic symptoms

Triactome: neuro-immune-adipose interactions. Implication in vascular biology

Directory of Open Access Journals (Sweden)

George Nikov Chaldakov

2014-04-01

Full Text Available Understanding how the precise interactions of nerves, immune cells and adipose tissue account for cardiovascular and metabolic biology is a central aim of biomedical research at present. A long standing paradigm holds that the vascular wall is composed of three concentric tissue coats (tunicae: intima, media, and adventitia. However, large- and medium-sized arteries, where usually atherosclerotic lesions develop, are consistently surrounded by periadventitial adipose tissue, we recently designated tunica adiposa (in brief, adiposa like intima, media, adventitia. According to present paradigm, atherosclerosis is an immune-mediated inflammatory disease featured by endothelial dysfunction/intimal thickening, medial atrophy and adventitial lesions associated with adipose dysfunction, whereas hypertension is characterized by hyperinnervation-associated medial thickening due to smooth muscle cell hypertrophy/hyperplasia. Periadventitial adipose tissue expansion is associated with increased infiltration of immune cells, both adipocytes and immunocytes secreting pro-inflammatory and anti-inflammatory (metabotrophic signaling proteins collectively dubbed adipokines. However, the role of perivascular nerves and their interactions with immune cells and paracrine adipose tissue is not yet evaluated in such an integrated way. The present review attempts to briefly highlight the findings in basic and translational sciences in this area focusing on neuro-immune-adipose interactions, herein referred to as triactome. Triactome-targeted pharmacology may provide a novel therapeutic approach in cardiovascular disease.

Psychosocial factors involved in memory and cognitive failures in people with myalgic encephalomyelitis/chronic fatigue syndrome

Directory of Open Access Journals (Sweden)

Attree EA

2014-02-01

Full Text Available Elizabeth A Attree,1 Megan A Arroll,1 Christine P Dancey,1 Charlene Griffith,1 Amolak S Bansal1,2 1Chronic Illness Research Team, School of Psychology, University of East London, London, UK; 2Department of Immunology and the Sutton CFS Service, St Helier Hospital, Carshalton, UK Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS is characterized by persistent emotional, mental, and physical fatigue accompanied by a range of neurological, autonomic, neuroendocrine, immune, and sleep problems. Research has shown that psychosocial factors such as anxiety and depression as well as the symptoms of the illness, have a significant impact on the quality of life of people with ME/CFS. In addition, individuals may suffer from deficits in memory and concentration. This study set out to explore the relationships between variables which have been found to contribute to cognitive performance, as measured by prospective and retrospective memory, and cognitive failures. Methods: Eighty-seven people with ME/CFS answered questionnaires measuring fatigue, depression, anxiety, social support, and general self-efficacy. These were used in a correlational design (multiple regression to predict cognitive function (self-ratings on prospective and retrospective memory, and cognitive failures. Results: Our study found that fatigue, depression, and general self-efficacy were directly associated with cognitive failures and retrospective (but not prospective memory. Conclusion: Although it was not possible in this study to determine the cause of the deficits, the literature in this area leads us to suggest that although the pathophysiological mechanisms of ME/CFS are unclear, abnormalities in the immune system, including proinflammatory cytokines, can lead to significant impairments in cognition. We suggest that fatigue and depression may be a result of the neurobiological effects of ME/CFS and in addition, that the neurobiological effects of the illness

An immune origin of type 2 diabetes?

DEFF Research Database (Denmark)

Kolb, H; Mandrup-Poulsen, Thomas

2005-01-01

Subclinical, low-grade systemic inflammation has been observed in patients with type 2 diabetes and in those at increased risk of the disease. This may be more than an epiphenomenon. Alleles of genes encoding immune/inflammatory mediators are associated with the disease, and the two major...... environmental factors the contribute to the risk of type 2 diabetes-diet and physical activity-have a direct impact on levels of systemic immune mediators. In animal models, targeting of immune genes enhanced or suppressed the development of obesity or diabetes. Obesity is associated with the infiltration...... and proinflammatory activity of macrophages in adipose tissue, and immune mediators may be important regulators of insulin resistance, mitochondrial function, ectopic lipid storage and beta cell dysfunction or death. Intervention studies targeting these pathways would help to determine the contribution...

Does stress affect the joints? Daily stressors, stress vulnerability, immune and HPA axis activity, and short-term disease and symptom fluctuations in rheumatoid arthritis.

Science.gov (United States)

Evers, Andrea W M; Verhoeven, Elisabeth W M; van Middendorp, Henriët; Sweep, Fred C G J; Kraaimaat, Floris W; Donders, A Rogier T; Eijsbouts, Agnes E; van Laarhoven, Antoinette I M; de Brouwer, Sabine J M; Wirken, Lieke; Radstake, Timothy R D J; van Riel, Piet L C M

2014-09-01

Both stressors and stress vulnerability factors together with immune and hypothalamus-pituitary-adrenal (HPA) axis activity components have been considered to contribute to disease fluctuations of chronic inflammatory diseases, such as rheumatoid arthritis (RA). The aim of the present study was to investigate whether daily stressors and worrying as stress vulnerability factor as well as immune and HPA axis activity markers predict short-term disease activity and symptom fluctuations in patients with RA. In a prospective design, daily stressors, worrying, HPA axis (cortisol) and immune system (interleukin (IL)-1β, IL-6, IL-8, interferon (IFN)-γ, tumour necrosis factor α) markers, clinical and self-reported disease activity (disease activity score in 28 joints, RA disease activity index), and physical symptoms of pain and fatigue were monitored monthly during 6 months in 80 RA patients. Multilevel modelling indicated that daily stressors predicted increased fatigue in the next month and that worrying predicted increased self-reported disease activity, swollen joint count and pain in the next month. In addition, specific cytokines of IL-1β and IFN-γ predicted increased fatigue 1 month later. Overall, relationships remained relatively unchanged after controlling for medication use, disease duration and demographic variables. No evidence was found for immune and HPA axis activity markers as mediators of the stress-disease relationship. Daily stressors and the stress-vulnerability factor worrying predict indicators of the short-term course of RA disease activity and fatigue and pain, while specific cytokines predict short-term fluctuations of fatigue. These stress-related variables and immune markers seem to affect different aspects of disease activity or symptom fluctuations independently in RA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Melanoma NOS1 expression promotes dysfunctional IFN signaling.

Science.gov (United States)

Liu, Qiuzhen; Tomei, Sara; Ascierto, Maria Libera; De Giorgi, Valeria; Bedognetti, Davide; Dai, Cuilian; Uccellini, Lorenzo; Spivey, Tara; Pos, Zoltan; Thomas, Jaime; Reinboth, Jennifer; Murtas, Daniela; Zhang, Qianbing; Chouchane, Lotfi; Weiss, Geoffrey R; Slingluff, Craig L; Lee, Peter P; Rosenberg, Steven A; Alter, Harvey; Yao, Kaitai; Wang, Ena; Marincola, Francesco M

2014-05-01

In multiple forms of cancer, constitutive activation of type I IFN signaling is a critical consequence of immune surveillance against cancer; however, PBMCs isolated from cancer patients exhibit depressed STAT1 phosphorylation in response to IFN-α, suggesting IFN signaling dysfunction. Here, we demonstrated in a coculture system that melanoma cells differentially impairs the IFN-α response in PBMCs and that the inhibitory potential of a particular melanoma cell correlates with NOS1 expression. Comparison of gene transcription and array comparative genomic hybridization (aCGH) between melanoma cells from different patients indicated that suppression of IFN-α signaling correlates with an amplification of the NOS1 locus within segment 12q22-24. Evaluation of NOS1 levels in melanomas and IFN responsiveness of purified PBMCs from patients indicated a negative correlation between NOS1 expression in melanomas and the responsiveness of PBMCs to IFN-α. Furthermore, in an explorative study, NOS1 expression in melanoma metastases was negatively associated with patient response to adoptive T cell therapy. This study provides a link between cancer cell phenotype and IFN signal dysfunction in circulating immune cells.

Immune System Dysregulation, Viral Reactivation and Stress During Short-Duration Space Flight

Science.gov (United States)

Crucian, Brian; Mehta, Satish; Stowe, Raymond; Uchakin, Peter; Quiriarte, Heather; Pierson, Duane; Sams, Clarence

2010-01-01

This slide presentation reviews a study that was conducted to ascertain if the immune system dysregulation, viral reactivation and stress from short duration space flight were a result of the stress of landing and readjustment to gravity. The objectives of the study were to replace several recent immune studies with one comprehensive study that will include in-flight sampling; address lack of in-flight data: (i.e., determine the in-flight status of immunity, physiological stress, viral immunity/reactivation); determine the clinical risk related to immune dysregulation for exploration class spaceflight; and determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

Immune System Dysregulation and Herpesvirus Reactivation Persist During Long-Duration Spaceflight

Science.gov (United States)

Crucian, B. E.; Mehta, S.; Stowe, R. P.; Uchakin, P.; Quiriarte, H.; Pierson, D.; Sams, C. F.

2011-01-01

This poster presentation reviews a study that is designed to address immune system dysregulation and the risk to crewmembers in long duration exploration class missions. This study will address these objectives: (1) Determine the status of adaptive immunity physiological stress, viral immunity, latent herpesvirus reactivation in astronauts during 6 month missions to the International Space Station; (2) determine the clinical risk related to immune dysregulation for exploration class spaceflight; and (3) determine an appropriate monitoring strategy for spaceflight-associated immune dysfunction that could be used for the evaluation of countermeasures. The study anticipates 17 subjects, and for this presentation, (midpoint study data) 10 subjects are reviewed.

Perceived Fatigue Interference and Depressed Mood: Comparison of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients with Fatigued Breast Cancer Survivors.

Science.gov (United States)

Hall, Daniel L; Antoni, Michael H; Lattie, Emily G; Jutagir, Devika R; Czaja, Sara J; Perdomo, Dolores; Lechner, Suzanne C; Stagl, Jamie M; Bouchard, Laura C; Gudenkauf, Lisa M; Traeger, Lara; Fletcher, MaryAnn; Klimas, Nancy G

Persistent fatigue and depressive symptoms are both highly prevalent among patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) as well as breast cancer survivors. This study aimed to assess and directly compare perceptions of fatigue as highly interfering in one's daily functioning in both patient populations to better understand their relationships with depressed mood. Participants were 95 female CFS/ME patients and 67 females who were approximately 5 years post-treatment for stage 0-III breast cancer presenting with clinically elevated fatigue severity. Self-report measures were obtained on participants' fatigue-related interference in daily functioning and fatigue severity as well as depressed mood. Hierarchical regression was used to test effects controlling for relevant demographic, psychosocial, and medical covariates. CFS/ME patients endorsed greater depressed mood and fatigue interference than did fatigued breast cancer survivors, p's fatigued breast cancer survivors (β=.18, p =.19). CFS/ME patients reported elevated fatigue symptoms and depression relative to fatigued breast cancer survivors. In the former group, greater depressed mood was highly and significantly associated with greater fatigue-related inference in daily activities. Potential targets for cognitive behavioral interventions are discussed.

The Identification of Fatigue Resistant and Fatigue Susceptible Individuals

National Research Council Canada - National Science Library

Harrison, Richard; Chaiken, Scott; Harville, Donald; Fischer, Joseph; Fisher, Dion; Whitmore, Jeff

2008-01-01

The present study was designed to target two specific areas regarding fatigue. The primary purpose was to begin investigations into possible genetic markers linked to fatigue resistance and fatigue susceptibility...

Relationship between female pelvic floor dysfunction and sexual dysfunction: an observational study.

Science.gov (United States)

Bortolami, Arianna; Vanti, Carla; Banchelli, Federico; Guccione, Andrew A; Pillastrini, Paolo

2015-05-01

The ability to express one's sexuality and engage in sexual activity requires multisystemic coordination involving many psychological functions as well as the integrity of the nervous, hormonal, vascular, immune, and neuromuscular body structures and functions. The purpose of this study was to investigate the associations among pelvic floor function, sexual function, and demographic and clinical characteristics in a population of women initiating physical therapy evaluation and treatment for pelvic floor-related dysfunctions (urinary incontinence, pelvic organ prolapse, vulvodynia, vaginismus, and constipation). We consented and collected completed demographic data and data related to symptoms and clinical condition on 85 consecutive patients in an outpatient physical therapy clinic. Clinical and anthropometric characteristics were analyzed descriptively. Analysis of variance and linear regression analyses were used to analyze Female Sexual Function Index (FSFI) scale ratings, whereas zero-inflated beta-binomial regression was applied to the pain subscale. Main outcome measure was FSFI score, whereas the secondary outcome measure was the FSFI subscale score related to pain. Women in our sample were 38 years old on average, 33% of whom had given birth and 82% of whom had high tone pelvic floor. Being in the middle-tercile age group and exhibiting low pelvic floor tone (Beta = 6.8; 95% confidence interval [CI] = [1.4; 12.0]) were significantly associated with lower levels of sexual dysfunction. Women with low tone pelvic floor also reported lower pain (odds ratio = 4.0; 95% CI = [1.6; 9.6]), whereas younger aged and physically unsatisfied subjects were more likely not to have sexual activity in the month prior to scale measurement. In female patients with pelvic floor muscle dysfunction undergoing physical therapy and rehabilitation, sexual dysfunction appears to be significantly correlated with age and high pelvic floor muscle tone. © 2015

The Role of the Immune System in Obesity and Insulin Resistance

Directory of Open Access Journals (Sweden)

Payal S. Patel

2013-01-01

Full Text Available The innate immune system provides organisms with rapid and well-coordinated protection from foreign pathogens. However, under certain conditions of metabolic dysfunction, components of the innate immune system may be activated in the absence of external pathogens, leading to pathologic consequences. Indeed, there appears to be an intimate relationship between metabolic diseases and immune dysfunction; for example, macrophages are prime players in the initiation of a chronic inflammatory state in obesity which leads to insulin resistance. In response to increases in free fatty acid release from obese adipose depots, M1-polarized macrophages infiltrate adipose tissues. These M1 macrophages trigger inflammatory signaling and stress responses within cells that signal through JNK or IKKβ pathways, leading to insulin resistance. If overnutrition persists, mechanisms that counteract inflammation (such as M2 macrophages and PPAR signaling are suppressed, and the inflammation becomes chronic. Although macrophages are a principal constituent of obese adipose tissue inflammation, other components of the immune system such as lymphocytes and mast cells also contribute to the inflammatory cascade. Thus it is not merely an increased mass of adipose tissue that directly leads to attenuation of insulin action, but rather adipose tissue inflammation activated by the immune system in obese individuals that leads to insulin resistance.

Hepatic Mitochondrial Dysfunction and Immune Response in a Murine Model of Peanut Allergy

Directory of Open Access Journals (Sweden)

Giovanna Trinchese

2018-06-01

Full Text Available Background: Evidence suggests a relevant role for liver and mitochondrial dysfunction in allergic disease. However, the role of hepatic mitochondrial function in food allergy is largely unknown. We aimed to investigate hepatic mitochondrial dysfunction in a murine model of peanut allergy. Methods: Three-week-old C3H/HeOuJ mice were sensitized by the oral route with peanut-extract (PNT. We investigated: 1. the occurrence of effective sensitization to PNT by analysing acute allergic skin response, anaphylactic symptoms score, body temperature, serum mucosal mast cell protease-1 (mMCP-1 and anti-PNT immunoglobulin E (IgE levels; 2. hepatic involvement by analysing interleukin (IL-4, IL-5, IL-13, IL-10 and IFN-γ mRNA expression; 3. hepatic mitochondrial oxidation rates and efficiency by polarography, and hydrogen peroxide (H2O2 yield, aconitase and superoxide dysmutase activities by spectrophotometry. Results: Sensitization to PNT was demonstrated by acute allergic skin response, anaphylactic symptoms score, body temperature decrease, serum mMCP-1 and anti-peanut IgE levels. Liver involvement was demonstrated by a significant increase of hepatic Th2 cytokines (IL-4, IL-5 and IL-13 mRNA expression. Mitochondrial dysfunction was demonstrated by lower state 3 respiration rate in the presence of succinate, decreased fatty acid oxidation in the presence of palmitoyl-carnitine, increased yield of ROS proven by the inactivation of aconitase enzyme and higher H2O2 mitochondrial release. Conclusions: We provide evidence of hepatic mitochondrial dysfunction in a murine model of peanut allergy. These data could open the way to the identification of new mitochondrial targets for innovative preventive and therapeutic strategies against food allergy.

Fatigue testing of wood composites for aerogenerator blades. Pt. 11: Assessment of fatigue damage accumulation using a fatigue modulus approach

Energy Technology Data Exchange (ETDEWEB)

Hacker, C L; Ansell, M P [Bath Univ. (United Kingdom)

1996-12-31

Stress-strain hysteresis loops have been captured during fatigue tests performed at R=10 (compression-compression) and R=0.1 (tension-tension) on Khaya epoxy wood composites. A fatigue modulus approach, proposed by Hwang and Han in 1989, has been applied to the data and a relationship established between the initial change in fatigue modulus and fatigue life. By following changes in fatigue modulus during the first 100 test cycles it is possible to predict the life of the sample allowing rapid evaluation of the fatigue performance of wood composites. Fatigue modulus values have also been calculated for hysteresis loops captured during complex load - time history tests. Similar trends in change in fatigue modulus suggest that this approach could be used in complex loading conditions to evaluate fatigue damage accumulation and predict fatigue life. (Author)

Tumor-altered dendritic cell function: implications for anti-tumor immunity

Directory of Open Access Journals (Sweden)

Kristian Michael Hargadon

2013-07-01

Full Text Available Dendritic cells are key regulators of both innate and adaptive immunity, and the array of immunoregulatory functions exhibited by these cells is dictated by their differentiation, maturation, and activation status. Although a major role for these cells in the induction of immunity to pathogens has long been appreciated, data accumulated over the last several years has demonstrated that DC are also critical regulators of anti-tumor immune responses. However, despite the potential for stimulation of robust anti-tumor immunity by DC, tumor-altered DC function has been observed in many cancer patients and tumor-bearing animals and is often associated with tumor immune escape. Such dysfunction has significant implications for both the induction of natural anti-tumor immune responses as well as the efficacy of immunotherapeutic strategies that target endogenous DC in situ or that employ exogenous DC as part of anti-cancer immunization maneuvers. In this review, the major types of tumor-altered DC function will be described, with emphasis on recent insights into the mechanistic bases for the inhibition of DC differentiation from hematopoietic precursors, the altered programming of DC precursors to differentiate into myeloid-derived suppressor cells or tumor-associated macrophages, the suppression of DC maturation and activation, and the induction of immunoregulatory DC by tumors, tumor-derived factors, and tumor-associated cells within the milieu of the tumor microenvironment. The impact of these tumor-altered cells on the quality of the overall anti-tumor immune response will also be discussed. Finally, this review will also highlight questions concerning tumor-altered DC function that remain unanswered, and it will address factors that have limited advances in the study of this phenomenon in order to focus future research efforts in the field on identifying strategies for interfering with tumor-associated DC dysfunction and improving DC-mediated anti

Perceived Fatigue Interference and Depressed Mood: Comparison of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients with Fatigued Breast Cancer Survivors

Science.gov (United States)

Hall, Daniel L.; Antoni, Michael H.; Lattie, Emily G.; Jutagir, Devika R.; Czaja, Sara J.; Perdomo, Dolores; Lechner, Suzanne C.; Stagl, Jamie M.; Bouchard, Laura C.; Gudenkauf, Lisa M.; Traeger, Lara; Fletcher, MaryAnn; Klimas, Nancy G.

2015-01-01

Objective Persistent fatigue and depressive symptoms are both highly prevalent among patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) as well as breast cancer survivors. This study aimed to assess and directly compare perceptions of fatigue as highly interfering in one’s daily functioning in both patient populations to better understand their relationships with depressed mood. Methods Participants were 95 female CFS/ME patients and 67 females who were approximately 5 years post-treatment for stage 0-III breast cancer presenting with clinically elevated fatigue severity. Self-report measures were obtained on participants’ fatigue-related interference in daily functioning and fatigue severity as well as depressed mood. Hierarchical regression was used to test effects controlling for relevant demographic, psychosocial, and medical covariates. Results CFS/ME patients endorsed greater depressed mood and fatigue interference than did fatigued breast cancer survivors, p’sfatigued breast cancer survivors (β=.18, p=.19). Conclusions CFS/ME patients reported elevated fatigue symptoms and depression relative to fatigued breast cancer survivors. In the former group, greater depressed mood was highly and significantly associated with greater fatigue-related inference in daily activities. Potential targets for cognitive behavioral interventions are discussed. PMID:26180660

Housebound versus nonhousebound patients with myalgic encephalomyelitis and chronic fatigue syndrome.

Science.gov (United States)

Pendergrast, Tricia; Brown, Abigail; Sunnquist, Madison; Jantke, Rachel; Newton, Julia L; Strand, Elin Bolle; Jason, Leonard A

2016-12-01

The objective of this study was to examine individuals with myalgic encephalomyelitis and chronic fatigue syndrome who are confined to their homes due to severe symptomatology. The existing literature fails to address differences between this group, and less severe, nonhousebound patient populations. Participants completed the DePaul Symptom Questionnaire, a measure of myalgic encephalomyelitis and chronic fatigue syndrome symptomology, and the SF-36, a measure of health impact on physical/mental functioning. ANOVAs and, where appropriate, MANCOVAS were used to compare housebound and nonhousebound patients with myalgic encephalomyelitis and chronic fatigue syndrome across areas of functioning, symptomatology, and illness onset characteristics. Findings indicated that the housebound group represented one quarter of the sample, and were significantly more impaired with regards to physical functioning, bodily pain, vitality, social functioning, fatigue, postexertional malaise, sleep, pain, neurocognitive, autonomic, neuroendocrine, and immune functioning compared to individuals who were not housebound. Findings indicated that housebound patients have more impairment on functional and symptom outcomes compared to those who were not housebound. Understanding the differences between housebound and not housebound groups holds implications for physicians and researchers as they develop interventions intended for patients who are most severely affected by this chronic illness. © The Author(s) 2016.

Contributions of pulmonary hypertension to HIV-related cardiac dysfunction

Directory of Open Access Journals (Sweden)

Godsent C. Isiguzo

2013-09-01

Conclusion: Immune-suppression affects the cardiac function adversely and coexisting pulmonary hypertension contributes to poor systolic and diastolic function in affected patients. The subtle nature of presentation of pulmonary hypertension and other cardiac dysfunctions in HIV/AIDS patients demand a high-index of suspicion and early intervention if detected, to ensure better care for these emerging threats to our patients.

Impaired immune function in children and adults with Fanconi anemia.

Science.gov (United States)

Myers, Kasiani C; Sauter, Sharon; Zhang, Xue; Bleesing, Jacob J; Davies, Stella M; Wells, Susanne I; Mehta, Parinda A; Kumar, Ashish; Marmer, Daniel; Marsh, Rebecca; Brown, Darron; Butsch Kovacic, Melinda

2017-11-01

Fanconi anemia (FA) is a rare genetic disorder characterized by genome instability, bone marrow failure, and cancer predisposition. Previously, small studies have reported heterogeneous immune dysfunction in FA. We performed a detailed immunologic assessment in a large FA cohort who have not undergone bone marrow transplantation or developed malignancies. Comprehensive quantitative and functional immunologic assessment of 29 FA individuals was compared to healthy age-matched controls. Compared to non-FA persons of similar ages, FA individuals showed lower absolute total B cells (P candida (P = 0.019), were diminished in FA. Phytohemagglutinin responses and plasma cytokines were normal. Within FA subjects, adults and older children (≥10 years) exhibited higher CD8 + T cells than younger children (P = 0.004). Documented atypical infections were infrequent, although oral human papilloma virus (HPV) prevalence was higher (31% positive) in FA. Overall, these results demonstrate a high rate of significant humoral and cellular immune dysfunction. Continued longitudinal study of immune function is critical to understand evolution with age, bone marrow failure, and cancer development. © 2017 Wiley Periodicals, Inc.

Fatigue data compilation and evaluation of fatigue on design

International Nuclear Information System (INIS)

Nyilas, A.

1985-05-01

The aim of this report is a review of the available fatigue data of various materials necessary for the design of large superconducting magnets for fusion. One of the primary objectives of this work is to present a broad outline of the low temperature fatigue data of relevant materials within the scope of available data. Besides the classical fatigue data of materials the fatigue crack propagation measurements are outlined widely. The existing recommendations for the design of cryogenic structures are described. A brief introduction of fracture mechanics as well as a historical background of the development of our present day understanding of fatigue has been done. (orig.) [de

Associations among human papillomavirus, inflammation, and fatigue in patients with head and neck cancer.

Science.gov (United States)

Xiao, Canhua; Beitler, Jonathan J; Higgins, Kristin A; Glazer, Toby; Huynh, Linh Kha; Paul, Sudeshna; Felger, Jennifer C; Wommack, Evanthia C; Saba, Nabil F; Shin, Dong M; Bruner, Deborah W; Miller, Andrew H

2018-05-09

Human papillomavirus (HPV) infection has contributed to an increased incidence of squamous cell carcinoma of the head and neck (SCCHN). Fatigue is a major side effect of SCCHN and its treatment. However, to the authors' knowledge, the association between HPV and fatigue has not been examined to date, nor is it known whether HPV influences biological mechanisms of fatigue, including inflammation. Patients with SCCHN who were without distant metastasis were assessed at baseline (pre-radiotherapy) and 1 month and 3 months postradiotherapy. Fatigue was measured using the Multidimensional Fatigue Inventory. Peripheral inflammation was assessed by plasma C-reactive protein (CRP), interleukin 1 receptor antagonist (IL-1ra), soluble tumor necrosis factor receptor 2 (sTNFR2), and IL-6. Mixed effect models were used to examine associations. A total of 94 patients who were newly diagnosed were enrolled; 53% had HPV-related tumors. Patients with HPV-unrelated tumors had higher fatigue and higher plasma CRP, sTNFR2, and IL-6 over time, especially at baseline and 3 months after intensity-modulated radiotherapy compared with those with HPV-related tumors (all P < .05). However, fatigue and plasma sTNFR2 increased more significantly from baseline to 1 month after radiotherapy in the HPV-related group compared with the HPV-unrelated group (both P < .01). Controlling for significant covariates, HPV status and inflammation were found to be independent predictors of fatigue over time. HPV status is an important marker of vulnerability to the behavioral and immune consequences of SCCHN and its treatment, providing support for different symptom management strategies. Special emphasis should be placed on addressing marked persistent fatigue in patients with HPV-unrelated tumors, whereas attention should be paid to the large increases in fatigue during treatment among patients with HPV-related tumors. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Pharmacological treatments for fatigue in patients with multiple sclerosis: A systematic review and meta-analysis.

Science.gov (United States)

Yang, Ting-Ting; Wang, Li; Deng, Xiao-Yang; Yu, Gang

2017-09-15

Multiple sclerosis (MS) is a chronic immune-mediated inflammatory disease. Fatigue is the most common symptom of MS patients, affecting >80% subjects. Medical treatment is an important method for managing fatigue. Currently, although many drugs have been tested in treatment of MS fatigue, the efficacy of these drugs remain largely unclear. We researched available literatures in PubMed, Embase, Medline, Google Scholar, Cochrane Library (August 31, 2016). Search terms included multiple sclerosis, fatigue, medication treatments, amantadine, modafinil, aspirin, acetyl-l-carnitine, pemoline, 4-aminopyridine and randomized controlled trial (RCT). Two researchers were required to independently assess the quality of literatures, and finish data extraction. Meta-analysis was conducted using RevMan 5.3 software. A total of 11 RCTs involving 723 patients were included. The therapeutic effects were quantified by different scales, such as Modified Fatigue Impact Scale (MFIS) or Fatigue Severity Scale (FSS). Here, meta-analysis suggested that amantadine, not modafinil, was effective for treating the fatigue in MS. Moreover, two studies implied that l-carnitine might have similar therapeutic effect with amantadine. However, the reliability of this finding was greatly weakened by the limited sample sizes. Additionally, current data could not answer whether treatment of MS fatigue using aspirin or 4-aminopyridine was beneficial. Finally, we found that all drugs except pemoline were relatively safe for treating MS fatigue. Current limited data suggest that amantadine may be the only drug that has relatively sufficient evidences in treatment of fatigue symptoms in MS. Further RCT studies recruiting larger samples sizes are required to validate the therapeutic effect of these candidate drugs. Copyright © 2017. Published by Elsevier B.V.

The innate immune response during urinary tract infection and pyelonephritis.

Science.gov (United States)

Spencer, John David; Schwaderer, Andrew L; Becknell, Brian; Watson, Joshua; Hains, David S

2014-07-01

Despite its proximity to the fecal flora, the urinary tract is considered sterile. The precise mechanisms by which the urinary tract maintains sterility are not well understood. Host immune responses are critically important in the antimicrobial defense of the urinary tract. During recent years, considerable advances have been made in our understanding of the mechanisms underlying immune homeostasis of the kidney and urinary tract. Dysfunctions in these immune mechanisms may result in acute disease, tissue destruction and overwhelming infection. The objective of this review is to provide an overview of the innate immune response in the urinary tract in response to microbial assault. In doing so, we focus on the role of antimicrobial peptides-a ubiquitous component of the innate immune response.

Activation of cell-mediated immunity in depression: association with inflammation, melancholia, clinical staging and the fatigue and somatic symptom cluster of depression.

Science.gov (United States)

Maes, Michael; Mihaylova, Ivana; Kubera, Marta; Ringel, Karl

2012-01-10

Depression is characterized by activation of cell-mediated immunity (CMI), including increased neopterin levels, and increased pro-inflammatory cytokines (PICs), such as interleukin-1 (IL-1) and tumor necrosis factor-α (TNFα). These PICs may induce depressive, melancholic and chronic fatigue (CF) symptoms. We examined serum neopterin and plasma PIC levels in depressive subgroups in relation to the depressive subtypes and the melancholic and CF symptoms of depression. Participants were 85 patients with depression and in 26 normal controls. Severity of depression was assessed with the Hamilton Depression Rating Scale (HDRS) and severity of CF with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale. Serum neopterin was significantly higher in depressed patients and in particular in those with melancholia. There were positive correlations between serum neopterin, the plasma PICs and the number of previous depressive episodes. Neopterin and TNFα were associated with melancholia, while both PICs were associated with CF. Melancholia-group membership was predicted by the HDRS and neopterin, and CF group membership by age, the FF score and serum TNFα. Depression and melancholia are accompanied by CMI activation, suggesting that neopterin plays a role in their pathophysiology, e.g. through activation of oxidative and nitrosative stress and apoptosis pathways. The intertwined CMI and inflammatory responses are potentially associated with the onset of depression and with the melancholic and CF symptoms of depression. Exposure to previous depressive episodes may magnify the size of CMI and PIC responses, possibly increasing the likelihood of new depressive episodes. CMI activation and inflammation may contribute to the staging or recurrence of depression. Copyright © 2011 Elsevier Inc. All rights reserved.

Fatigue approach for addressing environmental effects in fatigue usage calculation

Energy Technology Data Exchange (ETDEWEB)

Wilhelm, Paul; Rudolph, Juergen [AREVA GmbH, Erlangen (Germany); Steinmann, Paul [Erlangen-Nuremberg Univ., erlangen (Germany). Chair of Applied Mechanics

2015-04-15

Laboratory tests consider simple trapezoidal, triangle, and sinusoidal signals. However, actual plant components are characterized by complex loading patterns and periods of holds. Fatigue tests in water environment show, that the damage from a realistic strain variation or the presence of hold-times within cyclic loading results in an environmental reduction factor (Fen) only half that of a simple waveform. This study proposes a new fatigue approach for addressing environmental effects in fatigue usage calculation for class 1 boiler and pressure vessel reactor components. The currently accepted method of fatigue assessment has been used as a base model and all cycles, which have been comparable with realistic fatigue tests, have been excluded from the code-based fatigue calculation and evaluated directly with the test data. The results presented show that the engineering approach can successfully be integrated in the code-based fatigue assessment. The cumulative usage factor can be reduced considerably.

Fatigue approach for addressing environmental effects in fatigue usage calculation

International Nuclear Information System (INIS)

Wilhelm, Paul; Rudolph, Juergen; Steinmann, Paul

2015-01-01

Laboratory tests consider simple trapezoidal, triangle, and sinusoidal signals. However, actual plant components are characterized by complex loading patterns and periods of holds. Fatigue tests in water environment show, that the damage from a realistic strain variation or the presence of hold-times within cyclic loading results in an environmental reduction factor (Fen) only half that of a simple waveform. This study proposes a new fatigue approach for addressing environmental effects in fatigue usage calculation for class 1 boiler and pressure vessel reactor components. The currently accepted method of fatigue assessment has been used as a base model and all cycles, which have been comparable with realistic fatigue tests, have been excluded from the code-based fatigue calculation and evaluated directly with the test data. The results presented show that the engineering approach can successfully be integrated in the code-based fatigue assessment. The cumulative usage factor can be reduced considerably.

Predictors and Trajectories of Morning Fatigue Are Distinct from Evening Fatigue

Science.gov (United States)

Wright, Fay; Melkus, Gail D’Eramo; Hammer, Marilyn; Schmidt, Brian L.; Knobf, M. Tish; Paul, Steven M.; Cartwright, Frances; Mastick, Judy; Cooper, Bruce A.; Chen, Lee-May; Melisko, Michelle; Levine, Jon D.; Kober, Kord; Aouizerat, Bradley E.; Miaskowski, Christine

2015-01-01

Context Fatigue is the most common symptom in oncology patients during chemotherapy (CTX). Little is known about the predictors of interindividual variability in initial levels and trajectories of morning fatigue severity in these patients. Objectives An evaluation was done to determine which demographic, clinical, and symptom characteristics were associated with initial levels as well as the trajectories of morning fatigue and to compare findings with our companion paper on evening fatigue. Methods A sample of outpatients with breast, gastrointestinal, gynecological, and lung cancer (N=586) completed demographic and symptom questionnaires a total of six times over two cycles of CTX. Fatigue severity was evaluated using the Lee Fatigue Scale. Hierarchical linear modeling (HLM) was used to answer the study objectives. Results A large amount of interindividual variability was found in the morning fatigue trajectories. A piecewise model fit the data best. Patients with higher body mass index (BMI), who did not exercise regularly, with a lower functional status, and who had higher levels of state anxiety, sleep disturbance and depressive symptoms, reported higher levels of morning fatigue at enrollment. Variations in the trajectories of morning fatigue were predicted by the patients’ ethnicity and younger age. Conclusion The modifiable risk factors that were associated with only morning fatigue were BMI, exercise, and state anxiety. Modifiable risk factors that were associated with both morning and evening fatigue included functional status, depressive symptoms, and sleep disturbance. Using this information, clinicians can identify patients at higher risk for more severe morning fatigue and evening fatigue, provide individualized patient education, and tailor interventions to address the modifiable risk factors. PMID:25828559

Effects of fatigue from sleep deprivation on experimental periodontitis in rats.

Science.gov (United States)

Nakada, T; Kato, T; Numabe, Y

2015-02-01

Factors such as vascularization of the periodontium, inflammatory reactions and immune response affect the oral environment and ecology, decreasing host resistance and promoting the development of symptoms and the advancement of periodontal disease. Fatigue also influences the hypothalamic-pituitary-adrenal axis and reports relate it to systemic resistance. The aim of this study was to evaluate whether fatigue is a modifying factor for periodontal disease in rats. We divided 24 3-wk-old male Sprague-Dawley rats randomly into the following four groups: control; fatigue (deep sleep deprivation for 7 d); infection (rats inoculated with carboxymethyl cellulose containing periodontopathic bacteria); and compound (combined fatigue and infection conditions). Weight, serum corticosterone levels, serum albumin levels, interleukin-1β and tumor necrosis factor-α expression levels and distance from the cement-enamel junction to the alveolar bone crest were measured at baseline, and on the 36th (before sleep deprivation), 43rd (immediately after sleep deprivation) and 57th d (end of experiment). Immediately after sleep deprivation and at the end of the experiment, weight gain in the fatigue and compound groups was significantly lower than in controls (p sleep deprivation, serum corticosterone levels were significantly higher in the fatigue and compound groups than in controls (p sleep deprivation, gene expression of interleukin-1β was significantly higher in the infection and compound groups than in controls (p < 0.05). Moreover, gene expression of tumor necrosis factor-α was significantly higher in the compound group than in controls (p < 0.05). At the end of the experiment, the distance from the cement-enamel junction to the alveolar bone crest was significantly higher in the infection and compound groups than in controls (p < 0.05). Moreover, the distance was significantly higher in the compound group than in the infection group. Fatigue worsened systemic health in rats

SI:FatiguePro 4 Advanced Approach for Fatigue Monitoring

International Nuclear Information System (INIS)

Evon, Keith; Gilman, Tim; Carney, Curt

2012-01-01

Many nuclear plants are making commitments to implement fatigue monitoring systems in support of license renewal. Current fatigue monitoring systems use the methodology of ASME Code Subarticle NB-3200, which is a design code intended to compute a bounding cumulative usage factor (CUF). The first generation of fatigue monitoring software utilized a simplified, single stress term assumption and classical stress cycle-counting methods that take order into account such as Rainflow or Ordered Overall Range counting. Recently, the NRC has indicated in Regulatory Issue Summary 2008-30 that any fatigue analyses in support of License Renewal should use ASME Code Section III methodologies considering all six stress components. In addition, fatigue calculations for the license renewal term are required to consider the effects of environment. The implementation of a six stress term NB-3200 fatigue calculation to a Boiling Water Reactor (BWR) feedwater nozzle, including environmental effects, is the topic of this paper. Differences in results between the advanced methodology and the simplified methodology are discussed. (author)

Are nurses able to assess fatigue, exertion fatigue and types of fatigue in residential home patients?

NARCIS (Netherlands)

Tiesinga, L.J.; Dijkstra, Ate; Dassen, T.W.N.; Halfens, R.J.G.; van den Heuvel, W.J.A.

Although fatigue is recognized as a subjective, generalized, extensive and disabling health care problem with a relatively high prevalence among the chronically ill, there have been no studies to show whether nurses caring for fatigued subjects are able to accurately assess the level of fatigue that

Necrotizing herpetic retinopathies. A spectrum of herpes virus-induced diseases determined by the immune state of the host.

Science.gov (United States)

Guex-Crosier, Y; Rochat, C; Herbort, C P

1997-12-01

Necrotizing herpetic retinopathies (NHR), a new spectrum of diseases induced by viruses of the herpes family (herpes simplex virus, varicella-zoster virus and cytomegalovirus), includes acute retinal necrosis (ARN) occurring in apparently immunocompetent patients and progressive outer retinal necrosis (PORN) described in severely immuno-compromised patients. Signs of impaired cellular immunity were seen in 16% of ARN patients in a review of 216 reported cases, indicating that immune dysfunction is not only at the origin of PORN but might also be at the origin of ARN. The aim of this study was to correlate clinical findings in NHR patients with their immunologic parameters. Charts from patients with the diagnosis of ARN or PORN seen from 1990 to 1995 were reviewed. Clinical characteristics and disease patterns were correlated with immunological parameters taking into account CD4 lymphocyte rate in AIDS patients and blood-lymphocyte subpopulation determination by flow cytometry, cutaneous delayed type hypersensitivity testing and lymphocytic proliferation rate to seven antigens in HIV-negative patients. During the period considered, 11 patients and 7 patients fulfilled the criteria of ARN and PORN respectively. Immune dysfunctions were identified in most patients. Mild type of ARN and classical ARN were associated with discrete immune dysfunctions, ARN with features of PORN was seen in more immunodepressed patients and classical PORN was always seen in severely immunodepressed HIV patients. Our findings suggest that NHR is a continuous spectrum of diseases induced by herpes viruses, whose clinical expression depends on the immune state of the host going from mild or classical ARN at one end in patients with non-detectable or slight immune dysfunction to PORN in severely immunodepressed patients at the other end and with intermediary forms between these extremes.

The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation.

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Mendes, Fernando; Domingues, Cátia; Rodrigues-Santos, Paulo; Abrantes, Ana Margarida; Gonçalves, Ana Cristina; Estrela, Jéssica; Encarnação, João; Pires, Ana Salomé; Laranjo, Mafalda; Alves, Vera; Teixo, Ricardo; Sarmento, Ana Bela; Botelho, Maria Filomena; Rosa, Manuel Santos

2016-04-01

Immune surveillance seems to represent an effective tumor suppressor mechanism. However, some cancer cells survive and become variants, being poorly immunogenic and able to enter a steady-state phase. These cells become functionally dormant or remain hidden clinically throughout. Neoplastic cells seem to be able to instruct immune cells to undergo changes promoting malignancy. Radiotherapy may act as a trigger of the immune response. After radiotherapy a sequence of reactions occurs, starting in the damage of oncogenic cells by multiple mechanisms, leading to the immune system positive feedback against the tumor. The link between radiotherapy and the immune system is evident. T cells, macrophages, Natural Killer cells and other immune cells seem to have a key role in controlling the tumor. T cells may be dysfunctional and remain in a state of T cell exhaustion, nonetheless, they often retain a high potential for successful defense against cancer, being able to be mobilized to become highly functional. The lack of clinical trials on a large scale makes data a little robust, in spite of promising information, there are still many variables in the studies relating to radiation and immune system. The clarification of the mechanisms underlying immune response to radiation exposure may contribute to treatment improvement, gain of life quality and span of patients. Copyright © 2016 Elsevier B.V. All rights reserved.

TREM-1 Promotes Pancreatitis-Associated Intestinal Barrier Dysfunction

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Shengchun Dang

2012-01-01

Full Text Available Severe acute pancreatitis (SAP can cause intestinal barrier dysfunction (IBD, which significantly increases the disease severity and risk of mortality. We hypothesized that the innate immunity- and inflammatory-related protein-triggering receptor expressed on myeloid cells-1 (TREM-1 contributes to this complication of SAP. Thus, we investigated the effect of TREM-1 pathway modulation on a rat model of pancreatitis-associated IBD. In this study we sought to clarify the role of TREM-1 in the pathophysiology of intestinal barrier dysfunction in SAP. Specifically, we evaluated levels of serum TREM-1 and membrane-bound TREM-1 in the intestine and pancreas from an animal model of experimentally induced SAP. TREM-1 pathway blockade by LP17 treatment may suppress pancreatitis-associated IBD and ameliorate the damage to the intestinal mucosa barrier.

Crosstalk between cancer and the neuro-immune system.

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Kuol, Nyanbol; Stojanovska, Lily; Apostolopoulos, Vasso; Nurgali, Kulmira

2018-02-15

In the last decade, understanding of cancer initiation and progression has been given much attention with studies mainly focusing on genetic abnormalities. Importantly, cancer cells can influence their microenvironment and bi-directionally communicate with other systems such as the immune system. The nervous system plays a fundamental role in regulating immune responses to a range of disease states including cancer. Its dysfunction influences the progression of cancer. The role of the immune system in tumor progression is of relevance to the nervous system since they can bi-directionally communicate via neurotransmitters and neuropeptides, common receptors, and, cytokines. However, cross-talk between these cells is highly complex in nature, and numerous variations are possible according to the type of cancer involved. The neuro-immune interaction is essential in influencing cancer development and progression. Copyright © 2017 Elsevier B.V. All rights reserved.

Chronic Fatigue Syndrome (CFS) and Cancer Related Fatigue (CRF): two "fatigue" syndromes with overlapping symptoms and possibly related aetiologies.

Science.gov (United States)

Rovigatti, Ugo

2012-12-01

In July 2010, at the Muscle Fatigue Meeting, I presented an overview of Chronic Fatigue Syndrome and Cancer Related Fatigue, emphasizing a critical interpretation of the potential association between Chronic Fatigue Syndrome and Cancer Related Fatigue and a newly discovered retrovirus: Xenotropic Murine Related Virus. Since this association was hotly debated at that time, I suggested at the Meeting that it was wrong and most likely due to the identification of the wrong virus culprit. Today, 20 months after the Meeting, the first part of our prediction has turned out to be correct, as Xenotropic Murine Related Virus was shown to be a laboratory-created artefact. Still, the potential association of fatigue-syndromes with an infection (most likely viral) is sustained by a plethora of evidence and this overview will initially summarize data suggesting prior viral infection(s). The principal hypothesized mechanisms for both peripheral and central Chronic Fatigue Syndrome/Cancer Related Fatigue will be then summarized, also indicating plausible associations and triggering factors. All evidence accrued so far suggests that further research work should be performed in this interesting area and in order to identify an infectious agent for Chronic Fatigue Syndrome/Cancer Related Fatigue. One candidate RNA virus, Micro-Foci inducing Virus, will be described in this overview. Copyright © 2012 Elsevier B.V. All rights reserved.

Fatigue in adults with post-infectious fatigue syndrome: a qualitative content analysis.

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Stormorken, Eva; Jason, Leonard A; Kirkevold, Marit

2015-01-01

Fatigue is a major problem among individuals with post-infectious fatigue syndrome (PIFS), also known as chronic fatigue syndrome or myalgic encephalomyelitis. It is a complex phenomenon that varies across illnesses. From a nursing perspective, knowledge and understanding of fatigue in this illness is limited. Nurses lack confidence in caring for these patients and devalue their professional role. The aim of this study was to explore in-depth the experiences of fatigue among individuals with PIFS. A detailed description of the phenomenon of fatigue is presented. Increased knowledge would likely contribute to more confident nurses and improved nursing care. A qualitative study with open interviews was employed. In-depth interviews with patients were fully transcribed and underwent a qualitative content analysis. A maximum variation sample of 26 affected adults between 26-59 years old was recruited from a population diagnosed at a fatigue outpatient clinic. The fatigue was a post-exertional, multidimensional, fluctuating phenomenon with varying degrees of severity and several distinct characteristics and was accompanied by concomitant symptoms. Fatigue was perceived to be an all-pervasive complex experience that substantially reduced the ability to function personally or professionally. A range of trigger mechanisms evoked or worsened the fatigue, but the affected were not always aware of what triggered it. There was an excessive increase in fatigue in response to even minor activities. An increase in fatigue resulted in the exacerbation of other concomitant symptoms. The term fatigue does not capture the participants' experiences, which are accompanied by a considerable symptom burden that contributes to the illness experience and the severe disability. Although some aspects of the fatigue experience have been reported previously, more were added in our study, such as the dimension of awakening fatigue and the characteristic beyond time, when time passes unnoticed

Study on the effect of prior fatigue and creep-fatigue damage on the fatigue and creep characteristics of 316 FR stainless steel. 2nd report. The effect of prior creep-fatigue damage on the creep and fatigue characteristics

International Nuclear Information System (INIS)

Yamauchi, Masafumi; Chuman, Yasuharu; Otani, Tomomi; Takahashi, Yukio

2001-01-01

The effect of prior creep-fatigue damage on the creep and the fatigue characteristics was studied to investigate the creep-fatigue life evaluation procedure of 316FR stainless steel. Creep and fatigue tests were conducted at 550degC by using the specimen exposed to prior creep-fatigue cycles at the same temperature and interrupted at 1/4 Nf, 1/2 Nf and 3/4 Nf cycle. The creep and fatigue strength of the pre-damaged material showed monotonic reduction with the prior creep-fatigue damage compared with the virgin material. The creep ductility also showed monotonic reduction with the prior creep-fatigue damage. These results were evaluated by the stress-based Time Fraction Rule and the strain-based Ductility Exhaustion Method. The result showed that the application of the Ductility Exhaustion Method to the creep-fatigue damage evaluation is more promising than the Time Fraction Rule. (author)

Seafarer fatigue

DEFF Research Database (Denmark)

Jepsen, Jørgen Riis; Zhao, Zhiwei; van Leeuwen, Wessel M. A.

2015-01-01

Background: The consequences of fatigue for the health and safety of seafarers has caused concern in the industry and among academics, and indicates the importance of further research into risk factors and preventive interventions at sea. This review gives an overview of the key issues relating...... to seafarer fatigue. Materials and methods: A literature study was conducted aiming to collect publications that address risk factors for fatigue, short-term and long-term consequences for health and safety, and options for fatigue mitigation at sea. Due to the limited number of publications that deals...... with seafarers, experiences from other populations sharing the same exposures (e.g. shift work) were also included when appropriate. Results: Work at sea involves multiple risk factors for fatigue, which in addition to acute effects (e.g., impaired cognition, accidents) contributes through autonomic, immunologic...

Fatigue processes in thermoplastic fibres; Les mecanismes de fatigue dans les fibres thermoplastiques

Energy Technology Data Exchange (ETDEWEB)

Herrera Ramirez, J.M.

2004-09-15

The present study examines and compares the behaviour of the two types of PA66 fibres and two types of PET fibres under fatigue loading up to failure, and the correlation between the fibres (nano)structures and their structural heterogeneities, with fatigue lifetimes. Several techniques have been used to analyze the materials, such as scanning electron microscopy (SEM), microanalysis (EDS), differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD) and micro-Raman spectroscopy. A meticulous analysis by scanning electron microscopy of the fracture morphology of fibres broken in tension and in fatigue, as well as a study of the fatigue life, were undertaken. The fatigue process occurs when the cyclic load amplitude is sufficiently large, however a condition for fatigue failure is that the minimum load each cycle must be lower than a threshold stress level. Failure under fatigue conditions leads to distinctive fracture morphologies which are very different from those seen after tensile or creep failure and this allows easy identification of the fatigue process. The fibres have been analyzed in the as received state and after fatigue failure in order to observe the microstructural changes resulting from the fatigue loading. The results will be compared with those obtained for fibres loaded under conditions where the fatigue process was hindered. The role of the microstructure of the fibres in determining fatigue will be discussed in this work and the possibility of improving their resistance to fatigue or eliminating the fatigue process will be discussed. (author)

Overexpression of antioxidant enzymes in diaphragm muscle does not alter contraction-induced fatigue or recovery

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McClung, Joseph M.; DeRuisseau, Keith C.; Whidden, Melissa A.; Van Remmen, Holly; Richardson, Arlan; Song, Wook; Vrabas, Ioannis S.; Powers, Scott K.

2010-01-01

Low levels of reactive oxygen species (ROS) production are necessary to optimize muscle force production in unfatigued muscle. In contrast, sustained high levels of ROS production have been linked to impaired muscle force production and contraction-induced skeletal muscle fatigue. Using genetically engineered mice, we tested the hypothesis that the independent transgenic overexpression of catalase (CAT), copper/zinc superoxide dismutase (CuZnSOD; SOD1) or manganese superoxide dismutase (MnSOD; SOD2) antioxidant enzymes would negatively affect force production in unfatigued diaphragm muscle but would delay the development of muscle fatigue and enhance force recovery after fatiguing contractions. Diaphragm muscle from wild-type littermates (WT) and from CAT, SOD1 and SOD2 overexpressing mice were subjected to an in vitro contractile protocol to investigate the force–frequency characteristics, the fatigue properties and the time course of recovery from fatigue. The CAT, SOD1 and SOD2 overexpressors produced less specific force (in N cm−2) at stimulation frequencies of 20–300 Hz and produced lower maximal tetanic force than WT littermates. The relative development of muscle fatigue and recovery from fatigue were not influenced by transgenic overexpression of any antioxidant enzyme. Morphologically, the mean cross-sectional area (in μm2) of diaphragm myofibres expressing myosin heavy chain type IIA was decreased in both CAT and SOD2 transgenic animals, and the percentage of non-contractile tissue increased in diaphragms from all transgenic mice. In conclusion, our results do not support the hypothesis that overexpression of independent antioxidant enzymes protects diaphragm muscle from contraction-induced fatigue or improves recovery from fatigue. Moreover, our data are consistent with the concept that a basal level of ROS is important to optimize muscle force production, since transgenic overexpression of major cellular antioxidants is associated with

The role of central and peripheral muscle fatigue in postcancer fatigue: a randomized controlled trial.

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Prinsen, Hetty; van Dijk, Johannes P; Zwarts, Machiel J; Leer, Jan Willem H; Bleijenberg, Gijs; van Laarhoven, Hanneke W M

2015-02-01

Postcancer fatigue is a frequently occurring problem, impairing quality of life. Little is known about (neuro)physiological factors determining postcancer fatigue. It may be hypothesized that postcancer fatigue is characterized by low peripheral muscle fatigue and high central muscle fatigue. The aims of this study were to examine whether central and peripheral muscle fatigue differ between fatigued and non-fatigued cancer survivors and to examine the effect of cognitive behavioral therapy (CBT) on peripheral and central muscle fatigue of fatigued cancer survivors in a randomized controlled trial. Sixteen fatigued patients in the intervention group (CBT) and eight fatigued patients in the waiting list group were successfully assessed at baseline and six months later. Baseline measurements of 20 fatigued patients were compared with 20 non-fatigued patients. A twitch interpolation technique and surface electromyography were applied, respectively, during sustained contraction of the biceps brachii muscle. Muscle fiber conduction velocity (MFCV) and central activation failure (CAF) were not significantly different between fatigued and non-fatigued patients. Change scores of MFCV and CAF were not significantly different between patients in the CBT and waiting list groups. Patients in the CBT group reported a significantly larger decrease in fatigue scores than patients in the waiting list group. Postcancer fatigue is neither characterized by abnormally high central muscle fatigue nor by low peripheral muscle fatigue. These findings suggest a difference in the underlying physiological mechanism of postcancer fatigue vs. other fatigue syndromes. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Retinoic Acid and Its Role in Modulating Intestinal Innate Immunity

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Paulo Czarnewski

2017-01-01

Full Text Available Vitamin A (VA is amongst the most well characterized food-derived nutrients with diverse immune modulatory roles. Deficiency in dietary VA has not only been associated with immune dysfunctions in the gut, but also with several systemic immune disorders. In particular, VA metabolite all-trans retinoic acid (atRA has been shown to be crucial in inducing gut tropism in lymphocytes and modulating T helper differentiation. In addition to the widely recognized role in adaptive immunity, increasing evidence identifies atRA as an important modulator of innate immune cells, such as tolerogenic dendritic cells (DCs and innate lymphoid cells (ILCs. Here, we focus on the role of retinoic acid in differentiation, trafficking and the functions of innate immune cells in health and inflammation associated disorders. Lastly, we discuss the potential involvement of atRA during the plausible crosstalk between DCs and ILCs.

Side Effects: Fatigue

Science.gov (United States)

Fatigue is a common side effect of many cancer treatments such as chemotherapy, radiation therapy, immunotherapy, and surgery. Anemia and pain can also cause fatigue. Learn about symptoms and way to manage fatigue.

Obesity, Fat Mass and Immune System: Role for Leptin

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Vera Francisco

2018-06-01

Full Text Available Obesity is an epidemic disease characterized by chronic low-grade inflammation associated with a dysfunctional fat mass. Adipose tissue is now considered an extremely active endocrine organ that secretes cytokine-like hormones, called adipokines, either pro- or anti-inflammatory factors bridging metabolism to the immune system. Leptin is historically one of most relevant adipokines, with important physiological roles in the central control of energy metabolism and in the regulation of metabolism-immune system interplay, being a cornerstone of the emerging field of immunometabolism. Indeed, leptin receptor is expressed throughout the immune system and leptin has been shown to regulate both innate and adaptive immune responses. This review discusses the latest data regarding the role of leptin as a mediator of immune system and metabolism, with particular emphasis on its effects on obesity-associated metabolic disorders and autoimmune and/or inflammatory rheumatic diseases.

Myoelectrical manifestation of fatigue less prominent in patients with cancer related fatigue.

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Katarzyna Kisiel-Sajewicz

Full Text Available PURPOSE: A lack of fatigue-related muscle contractile property changes at time of perceived physical exhaustion and greater central than peripheral fatigue detected by twitch interpolation technique have recently been reported in cancer survivors with fatigue symptoms. Based on these observations, it was hypothesized that compared to healthy people, myoelectrical manifestation of fatigue in the performing muscles would be less significant in these individuals while sustaining a prolonged motor task to self-perceived exhaustion (SPE since their central fatigue was more prominent. The purpose of this study was to test this hypothesis by examining electromyographic (EMG signal changes during fatiguing muscle performance. METHODS: Twelve individuals who had advanced solid cancer and cancer-related fatigue (CRF, and 12 age- and gender-matched healthy controls performed a sustained elbow flexion at 30% maximal voluntary contraction till SPE. Amplitude and mean power frequency (MPF of EMG signals of the biceps brachii, brachioradialis, and triceps brachii muscles were evaluated when the individuals experienced minimal, moderate, and severe fatigue. RESULTS: CRF patients perceived physical "exhaustion" significantly sooner than the controls. The myoelectrical manifestation of muscular fatigue assessed by EMG amplitude and MPF was less significant in CRF than controls. The lower MPF even at minimal fatigue stage in CRF may indicate pathophysiologic condition of the muscle. CONCLUSIONS: CRF patients experience less myoelectrical manifestation of muscle fatigue than healthy individuals near the time of SPE. The data suggest that central nervous system fatigue plays a more important role in limiting endurance-type of motor performance in patients with CRF.

A randomized controlled trial of qigong exercise on fatigue symptoms, functioning, and telomerase activity in persons with chronic fatigue or chronic fatigue syndrome.

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Ho, Rainbow T H; Chan, Jessie S M; Wang, Chong-Wen; Lau, Benson W M; So, Kwok Fai; Yuen, Li Ping; Sham, Jonathan S T; Chan, Cecilia L W

2012-10-01

Chronic fatigue is common in the general population. Complementary therapies are often used by patients with chronic fatigue or chronic fatigue syndrome to manage their symptoms. This study aimed to assess the effect of a 4-month qigong intervention program among patients with chronic fatigue or chronic fatigue syndrome. Sixty-four participants were randomly assigned to either an intervention group or a wait list control group. Outcome measures included fatigue symptoms, physical functioning, mental functioning, and telomerase activity. Fatigue symptoms and mental functioning were significantly improved in the qigong group compared to controls. Telomerase activity increased in the qigong group from 0.102 to 0.178 arbitrary units (p chronic fatigue and chronic fatigue syndrome.

Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies.

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Broce, Iris; Karch, Celeste M; Wen, Natalie; Fan, Chun C; Wang, Yunpeng; Tan, Chin Hong; Kouri, Naomi; Ross, Owen A; Höglinger, Günter U; Muller, Ulrich; Hardy, John; Momeni, Parastoo; Hess, Christopher P; Dillon, William P; Miller, Zachary A; Bonham, Luke W; Rabinovici, Gil D; Rosen, Howard J; Schellenberg, Gerard D; Franke, Andre; Karlsen, Tom H; Veldink, Jan H; Ferrari, Raffaele; Yokoyama, Jennifer S; Miller, Bruce L; Andreassen, Ole A; Dale, Anders M; Desikan, Rahul S; Sugrue, Leo P

2018-01-01

Converging evidence suggests that immune-mediated dysfunction plays an important role in the pathogenesis of frontotemporal dementia (FTD). Although genetic studies have shown that immune-associated loci are associated with increased FTD risk, a systematic investigation of genetic overlap between immune-mediated diseases and the spectrum of FTD-related disorders has not been performed. Using large genome-wide association studies (GWASs) (total n = 192,886 cases and controls) and recently developed tools to quantify genetic overlap/pleiotropy, we systematically identified single nucleotide polymorphisms (SNPs) jointly associated with FTD-related disorders-namely, FTD, corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and amyotrophic lateral sclerosis (ALS)-and 1 or more immune-mediated diseases including Crohn disease, ulcerative colitis (UC), rheumatoid arthritis (RA), type 1 diabetes (T1D), celiac disease (CeD), and psoriasis. We found up to 270-fold genetic enrichment between FTD and RA, up to 160-fold genetic enrichment between FTD and UC, up to 180-fold genetic enrichment between FTD and T1D, and up to 175-fold genetic enrichment between FTD and CeD. In contrast, for CBD and PSP, only 1 of the 6 immune-mediated diseases produced genetic enrichment comparable to that seen for FTD, with up to 150-fold genetic enrichment between CBD and CeD and up to 180-fold enrichment between PSP and RA. Further, we found minimal enrichment between ALS and the immune-mediated diseases tested, with the highest levels of enrichment between ALS and RA (up to 20-fold). For FTD, at a conjunction false discovery rate enriched in microglia/macrophages compared to other central nervous system cell types. The main study limitation is that the results represent only clinically diagnosed individuals. Also, given the complex interconnectedness of the HLA region, we were not able to define the specific gene or genes on Chr 6 responsible for our pleiotropic signal. We

Bilateral Vestibular Dysfunction Associated With Chronic Exposure to Military Jet Propellant Type-Eight Jet Fuel

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Terry D. Fife

2018-05-01

Full Text Available We describe three patients diagnosed with bilateral vestibular dysfunction associated with the jet propellant type-eight (JP-8 fuel exposure. Chronic exposure to aromatic and aliphatic hydrocarbons, which are the main constituents of JP-8 military aircraft jet fuel, occurred over 3–5 years’ duration while working on or near the flight line. Exposure to toxic hydrocarbons was substantiated by the presence of JP-8 metabolite n-hexane in the blood of one of the cases. The presenting symptoms were dizziness, headache, fatigue, and imbalance. Rotational chair testing confirmed bilateral vestibular dysfunction in all the three patients. Vestibular function improved over time once the exposure was removed. Bilateral vestibular dysfunction has been associated with hydrocarbon exposure in humans, but only recently has emphasis been placed specifically on the detrimental effects of JP-8 jet fuel and its numerous hydrocarbon constituents. Data are limited on the mechanism of JP-8-induced vestibular dysfunction or ototoxicity. Early recognition of JP-8 toxicity risk, cessation of exposure, and customized vestibular therapy offer the best chance for improved balance. Bilateral vestibular impairment is under-recognized in those chronically exposed to all forms of jet fuel.

Random non-proportional fatigue tests with planar tri-axial fatigue testing machine

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T. Inoue

2016-10-01

Full Text Available Complex stresses, which occur on the mechanical surfaces of transport machinery in service, bring a drastic degradation in fatigue life. However, it is hard to reproduce such complex stress states for evaluating the fatigue life with conventional multiaxial fatigue machines. We have developed a fatigue testing machine that enables reproduction of such complex stresses. The testing machine can reproduce arbitrary in-plane stress states by applying three independent loads to the test specimen using actuators which apply loads in the 0, 45, and 90 degree directions. The reproduction was tested with complex stress data obtained from the actual operation of transport machinery. As a result, it was found that the reproduced stress corresponded to the measured stress with an error range of less than 10 %. Then, we made a comparison between measured fatigue lives under random non-proportional loading conditions and predicted fatigue lives. It was found that predicted fatigue lives with cr, stress on critical plane, were over a factor of 10 against measured fatigue lives. On the other hand, predicted fatigue lives with ma, stress in consideration of a non-proportional level evaluated by using amplitude and direction of principal stress, were within a factor of 3 against measured fatigue lives

An overview of fatigue

International Nuclear Information System (INIS)

Mc Evily, A.J.

1987-01-01

Four topics are briefly discussed in this paper: fatigue crack initiation and growth in a nickel-base superalloy single crystal, the environment effect on near-threshold fatigue crack growth behaviour, the role of crack closure in load-interaction effects in fatigue crack growth, and the nature of creep-fatigue interactions, if any, during fatigue crack growth. (Author)

Fatigue with HIV/AIDS

Science.gov (United States)

... 21, 2014 Select a Language: Fact Sheet 551 Fatigue WHAT IS FATIGUE? IS FATIGUE IMPORTANT? HOW DO ... It can be physical or psychological. With physical fatigue , your muscles cannot do things as easily as ...

Multi-purpose fatigue sensor. Part 1. Uniaxial and multiaxial fatigue

Directory of Open Access Journals (Sweden)

M.V. Karuskevich

2016-10-01

Full Text Available The paper describes the key principles and results of preliminary experiments aimed at the development of new technique for the fatigue life prediction under conditions of biaxial cyclic tension. The foundations of the method were developed early by the numerous tests with monitoring the process of surface deformation relief formation, which is proved to be an indicator of accumulated fatigue damage under uniaxial fatigue. The employed phenomenon was early applied for the development of a family of uniaxial loading fatigue sensors. The formation of strain induced relief has been recently taken into consideration as a part of damage accumulation criteria under biaxial fatigue as well. The home-made testing machine has been designed to implement combined bending and torsion loading that simulates loads experienced by an aircraft wing skin. The experimental evidences on formation and evolution of the deformation relief revealed under conditions of combined loading, supports the proposed concept of biaxial fatigue sensor

Evidence for sensitized fatigue pathways in patients with chronic fatigue syndrome.

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Staud, Roland; Mokthech, Meriem; Price, Donald D; Robinson, Michael E

2015-04-01

Patients with chronic fatigue syndrome (CFS) frequently demonstrate intolerance to physical exertion that is often reported as increased and long-lasting fatigue. Because no specific metabolic alterations have been identified in CFS patients, we hypothesized that sensitized fatigue pathways become activated during exercise corresponding with increased fatigue. After exhausting handgrip exercise, muscle metabolites were trapped in the forearm tissues of 39 CFS patients and 29 normal control (NC) by sudden occlusion for up to 5 minutes. A nonocclusive condition of similar duration was used as control. Repeated fatigue and pain ratings were obtained before and after exercise. Mechanical and heat hyperalgesia were assessed by quantitative sensory testing. All subjects fulfilled the 1994 Fukuda Criteria for CFS. Normal control and CFS subjects exercised for 6.6 (2.4) and 7.0 (2.7) minutes (P > 0.05). Forearm occlusion lasted for 4.7 (1.3) and 4.9 (1.8) minutes in NC and CFS subjects, respectively (P > 0.05). Although fatigue ratings of CFS subjects increased from 4.8 (2.0) to 5.6 (2.1) visual analogue scale (VAS) units during forearm occlusion, they decreased from 5.0 (1.8) to 4.8 (2.0) VAS units during the control condition without occlusion (P = 0.04). A similar time course of fatigue ratings was observed in NC (P > 0.05), although their ratings were significantly lower than those of CFS subjects (P fatigue in CFS patients consistent with sensitization of fatigue pathways. Future interventions that reduce sensitization of fatigue pathways in CFS patients may be of therapeutic benefit.

Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa.

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Dantzer, Robert

2018-01-01

Because of the compartmentalization of disciplines that shaped the academic landscape of biology and biomedical sciences in the past, physiological systems have long been studied in isolation from each other. This has particularly been the case for the immune system. As a consequence of its ties with pathology and microbiology, immunology as a discipline has largely grown independently of physiology. Accordingly, it has taken a long time for immunologists to accept the concept that the immune system is not self-regulated but functions in close association with the nervous system. These associations are present at different levels of organization. At the local level, there is clear evidence for the production and use of immune factors by the central nervous system and for the production and use of neuroendocrine mediators by the immune system. Short-range interactions between immune cells and peripheral nerve endings innervating immune organs allow the immune system to recruit local neuronal elements for fine tuning of the immune response. Reciprocally, immune cells and mediators play a regulatory role in the nervous system and participate in the elimination and plasticity of synapses during development as well as in synaptic plasticity at adulthood. At the whole organism level, long-range interactions between immune cells and the central nervous system allow the immune system to engage the rest of the body in the fight against infection from pathogenic microorganisms and permit the nervous system to regulate immune functioning. Alterations in communication pathways between the immune system and the nervous system can account for many pathological conditions that were initially attributed to strict organ dysfunction. This applies in particular to psychiatric disorders and several immune-mediated diseases. This review will show how our understanding of this balance between long-range and short-range interactions between the immune system and the central nervous

Clinical neurophysiology of fatigue.

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Zwarts, M J; Bleijenberg, G; van Engelen, B G M

2008-01-01

Fatigue is a multidimensional concept covering both physiological and psychological aspects. Chronic fatigue is a typical symptom of diseases such as cancer, multiple sclerosis (MS), Parkinson's disease (PD) and cerebrovascular disorders but is also presented by people in whom no defined somatic disease has been established. If certain criteria are met, chronic fatigue syndrome can be diagnosed. The 4-item Abbreviated Fatigue Questionnaire allows the extent of the experienced fatigue to be assessed with a high degree of reliability and validity. Physiological fatigue has been well defined and originates in both the peripheral and central nervous system. The condition can be assessed by combining force and surface-EMG measurements (including frequency analyses and muscle-fibre conduction estimations), twitch interpolation, magnetic stimulation of the motor cortex and analysis of changes in the readiness potential. Fatigue is a well-known phenomenon in both central and peripheral neurological disorders. Examples of the former conditions are multiple sclerosis, Parkinson's disease and stroke. Although it seems to be a universal symptom of many brain disorders, the unique characteristics of the concomitant fatigue also point to a specific relationship with several of these syndromes. As regards neuromuscular disorders, fatigue has been reported in patients with post-polio syndrome, myasthenia gravis, Guillain-Barré syndrome, facioscapulohumeral dystrophy, myotonic dystrophy and hereditary motor and sensory neuropathy type-I. More than 60% of all neuromuscular patients suffer from severe fatigue, a prevalence resembling that of patients with MS. Except for several rare myopathies with specific metabolic derangements leading to exercise-induced muscle fatigue, most studies have not identified a prominent peripheral cause for the fatigue in this population. In contrast, the central activation of the diseased neuromuscular system is generally found to be suboptimal. The

Immunity to community: what can immune pathways tell us about disease patterns in corals?

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Mydlarz, L. D.; Fuess, L.; Pinzon, J. C.; Weil, E.

2016-02-01

Predicting species composition and abundances is one of the most fundamental questions in ecology. This question is even more pressing in marine ecology and coral reefs since communities are changing at a rapid pace due to climate-related changes. Increases in disease prevalence and severity are just some of the consequences of these environmental changes. Particularly in coral reef ecosystems, diseases are increasing and driving region-wide population collapses. It has become clear, however, that not all reefs or coral species are affected by disease equally. In fact, the Caribbean is a concentrated area for diseases. The patterns in which disease manifests itself on an individual reef are also proving interesting, as not all coral species are affected by disease equally. Some species are host to different diseases, but seem to successfully fight them reducing mortality. Other species are disproportionately infected on any given reef and experience high mortality due to disease. We are interested in the role immunity can play in directing these patterns and are evaluating coral immunity using several novel approaches. We exposed 4 species of corals with different disease susceptibilities to immune stimulators and quantified of coral immunity using a combination of full transcriptome sequencing and protein activity assays for gene to phenotype analysis. We also mapped gene expression changes onto immune pathways (i.e. melanin-cascade, antimicrobial peptide synthesis, complement cascade, lectin-opsonization) to evaluate expression of immune pathways between species. In our preliminary data we found many immune genes in the disease susceptible Orbicella faveolata underwent changes in gene expression opposite of the predictions and may disply `dysfunctional' patterns of expression. We will present expression data for 4 species of coral and assess how these transcriptional and protein immune responses are related to disease susceptibility in nature, thus scaling up

Immunopathophysiology of inflammatory bowel disease: how genetics link barrier dysfunction and innate immunity to inflammation.

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Mehta, Minesh; Ahmed, Shifat; Dryden, Gerald

2017-08-01

Inflammatory bowel diseases (IBD) comprise a distinct set of clinical symptoms resulting from chronic or relapsing immune activation and corresponding inflammation within the gastrointestinal (GI) tract. Diverse genetic mutations, encoding important aspects of innate immunity and mucosal homeostasis, combine with environmental triggers to create inappropriate, sustained inflammatory responses. Recently, significant advances have been made in understanding the interplay of the intestinal epithelium, mucosal immune system, and commensal bacteria as a foundation of the pathogenesis of inflammatory bowel disease. Complex interactions between specialized intestinal epithelial cells and mucosal immune cells determine different outcomes based on the environmental input: the development of tolerance in the presence of commensal bacterial or the promotion of inflammation upon recognition of pathogenic organisms. This article reviews key genetic abnormalities involved in inflammatory and homeostatic pathways that enhance susceptibility to immune dysregulation and combine with environmental triggers to trigger the development of chronic intestinal inflammation and IBD.

Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

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Ashton Kevin J

2011-05-01

Full Text Available Abstract Background Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME is characterised by severe prolonged fatigue, and decreases in cognition and other physiological functions, resulting in severe loss of quality of life, difficult clinical management and high costs to the health care system. To date there is no proven pathomechanism to satisfactorily explain this disorder. Studies have identified abnormalities in immune function but these data are inconsistent. We investigated the profile of markers of immune function (including novel markers in CFS/ME patients. Methods We included 95 CFS/ME patients and 50 healthy controls. All participants were assessed on natural killer (NK and CD8+T cell cytotoxic activities, Th1 and Th2 cytokine profile of CD4+T cells, expression of vasoactive intestinal peptide receptor 2 (VPACR2, levels of NK phenotypes (CD56bright and CD56dim and regulatory T cells expressing FoxP3 transcription factor. Results Compared to healthy individuals, CFS/ME patients displayed significant increases in IL-10, IFN-γ, TNF-α, CD4+CD25+ T cells, FoxP3 and VPACR2 expression. Cytotoxic activity of NK and CD8+T cells and NK phenotypes, in particular the CD56bright NK cells were significantly decreased in CFS/ME patients. Additionally granzyme A and granzyme K expression were reduced while expression levels of perforin were significantly increased in the CFS/ME population relative to the control population. These data suggest significant dysregulation of the immune system in CFS/ME patients. Conclusions Our study found immunological abnormalities which may serve as biomarkers in CFS/ME patients with potential for an application as a diagnostic tool.

Reduced Electromyographic Fatigue Threshold after Performing a Cognitive Fatiguing Task.

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Ferris, Justine R; Tomlinson, Mary A; Ward, Tayler N; Pepin, Marie E; Malek, Moh H

2018-02-22

Cognitive fatigue tasks performed prior to exercise may reduce exercise capacity. The electromyographic fatigue threshold (EMGFT) is the highest exercise intensity that can be maintained without significant increase in the EMG amplitude versus time relationship. To date, no studies have examined the effect of cognitive fatigue on the estimation of the EMGFT. The purpose of this study, therefore, was to determine whether or not cognitive fatigue prior to performing exercise reduces the estimated EMGFT. Eight healthy college-aged men were recruited from a university student population and visited the laboratory on multiple occasions. In a randomized order, subjects performed either the cognitive fatigue task (AX Continuous Performance Test; AX-CPT) for 60 min on one visit (experimental condition) or watched a video on trains for 60 min on the other visit (control condition). After each condition, subjects performed the incremental single-leg knee-extensor ergometry test while the EMG amplitude was recorded from the rectus femoris muscle and heart rate was monitored throughout. Thereafter, the EMGFT was calculated for each participant for each visit and compared using paired samples t-test. For exercise outcomes, there were no significant mean differences for maximal power output between the two conditions (control: 51 ± 5 vs. fatigue: 50 ± 3 W), but a significant decrease in EMGFT between the two conditions (control: 31 ± 3 vs. fatigue: 24 ± 2 W; p = 0.013). Moreover, maximal heart rate was significantly different between the two conditions (control: 151 ± 5 vs. fatigue: 132 ± 6; p = 0.027). These results suggest that performing the cognitive fatiguing task reduces the EMGFT with a corresponding reduction in maximal heart rate response.

Sepsis-induced myocardial dysfunction and myocardial protection from ischemia/reperfusion injury.

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McDonough, Kathleen H; Virag, Jitka Ismail

2006-01-01

Sepsis, bacteremia and inflammation cause myocardial depression. The mechanism of the dysfunction is not clearly established partly because dysfunction can be elicited by many different mechanisms which can all manifest in disruption of myocardial mechanical function. In addition the models of sepsis and bacteremia and inflammation may vary drastically in the sequence of the coordinated immune response to the inflammatory or septic stimulus. Patterns of cytokine expression can vary as can other responses of the immune system. Patterns of neurohumoral activation in response to the stress of sepsis or bacteremia or inflammation can also vary in both magnitude of response and temporal sequence of response. Stress induced activation of the sympathetic nervous system and humoral responses to stress have a wide range of intensity that can be elicited. The fairly uniform response of the myocardium indicating cardiac dysfunction is surprisingly constant. Systolic performance, as measured by stroke volume or cardiac output and pressure work as estimated by ventricular pressure, are impaired when myocardial contraction is compromised. At times, diastolic function, assessed by ventricular relaxation and filling, is impaired. In addition to the dysfunction that occurs, there is a longer term response of the myocardium to sepsis, and this response is similar to that which is elicited in the heart by multiple brief ischemia/reperfusion episodes and by numerous pharmacological agents as well as heat stress and modified forms of lipopolysaccharide. The myocardium develops protection after an initial stress such that during a second stress, the myocardium does not exhibit as much damage as does a non-protected heart. Many agents can induce this protection which has been termed preconditioning. Both early preconditioning (protection that is measurable min to hours after the initial stimulus) and late preconditioning (protection that is measurable hours to days after the initial

The Nature of Self-Regulatory Fatigue and "Ego Depletion": Lessons From Physical Fatigue.

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Evans, Daniel R; Boggero, Ian A; Segerstrom, Suzanne C

2015-07-30

Self-regulation requires overriding a dominant response and leads to temporary self-regulatory fatigue. Existing theories of the nature and causes of self-regulatory fatigue highlight physiological substrates such as glucose, or psychological processes such as motivation, but these explanations are incomplete on their own. Historically, theories of physical fatigue demonstrate a similar pattern of useful but incomplete explanations, as recent views of physical fatigue emphasize the roles of both physiological and psychological factors. In addition to accounting for multiple inputs, these newer views also explain how fatigue can occur even in the presence of sufficient resources. Examining these newer theories of physical fatigue can serve as a foundation on which to build a more comprehensive understanding of self-regulatory fatigue that integrates possible neurobiological underpinnings of physical and self-regulatory fatigue, and suggests the possible function of self-regulatory fatigue. © 2015 by the Society for Personality and Social Psychology, Inc.

Aberrant Resting-State Functional Connectivity in the Salience Network of Adolescent Chronic Fatigue Syndrome.

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Laura Anne Wortinger

Full Text Available Neural network investigations are currently absent in adolescent chronic fatigue syndrome (CFS. In this study, we examine whether the core intrinsic connectivity networks (ICNs are altered in adolescent CFS patients. Eighteen adolescent patients with CFS and 18 aged matched healthy adolescent control subjects underwent resting-state functional magnetic resonance imaging (rfMRI. Data was analyzed using dual-regression independent components analysis, which is a data-driven approach for the identification of independent brain networks. Intrinsic connectivity was evaluated in the default mode network (DMN, salience network (SN, and central executive network (CEN. Associations between network characteristics and symptoms of CFS were also explored. Adolescent CFS patients displayed a significant decrease in SN functional connectivity to the right posterior insula compared to healthy comparison participants, which was related to fatigue symptoms. Additionally, there was an association between pain intensity and SN functional connectivity to the left middle insula and caudate that differed between adolescent patients and healthy comparison participants. Our findings of insula dysfunction and its association with fatigue severity and pain intensity in adolescent CFS demonstrate an aberration of the salience network which might play a role in CFS pathophysiology.

Continuous fatigue crack monitoring of bridges: Long-Term Electrochemical Fatigue Sensor (LTEFS)

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Moshier, Monty A.; Nelson, Levi; Brinkerhoff, Ryan; Miceli, Marybeth

2016-04-01

Fatigue cracks in steel bridges degrade the load-carrying capacity of these structures. Fatigue damage accumulation caused by the repetitive loading of everyday truck traffic can cause small fatigue cracks initiate. Understanding the growth of these fatigue cracks is critical to the safety and reliability of our transportation infrastructure. However, modeling fatigue in bridges is difficult due to the nature of the loading and variations in connection integrity. When fatigue cracks reach critical lengths failures occur causing partial or full closures, emergency repairs, and even full structural failure. Given the aging US highway and the trend towards asset management and life extension, the need for reliable, cost effective sensors and monitoring technologies to alert bridge owners when fatigue cracks are growing is higher than ever. In this study, an innovative Long-Term Electrochemical Fatigue Sensor (LTEFS) has been developed and introduced to meet the growing NDT marketplace demand for sensors that have the ability to continuously monitor fatigue cracks. The performance of the LTEFS has been studied in the laboratory and in the field. Data was collected using machined specimens with different lengths of naturally initiated fatigue cracks, applied stress levels, applied stress ratios, and for both sinusoidal and real-life bridge spectrum type loading. The laboratory data was evaluated and used to develop an empirically based algorithm used for crack detection. Additionally, beta-tests on a real bridge structure has been completed. These studies have conclusively demonstrated that LTEFS holds great potential for long-term monitoring of fatigue cracks in steel structures

Fatigue Perceived by Multiple Sclerosis Patients Is Associated With Muscle Fatigue

NARCIS (Netherlands)

Steens, Anneke; de Vries, Astrid; Hemmen, Jolien; Heersema, Thea; Heerings, Marco; Maurits, Natasha; Zijdewind, Inge

Background. Fatigue is a debilitating symptom in multiple sclerosis (MS). Previous studies showed no association between fatigue as perceived by the patient and physiological measures of fatigability. Objective. The authors investigated associations between perceived fatigue and measures of

Anti-fatigue and vasoprotective effects of quercetin-3-O-gentiobiose on oxidative stress and vascular endothelial dysfunction induced by endurance swimming in rats.

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Lin, Yin; Liu, Hua-Liang; Fang, Jie; Yu, Chen-Huan; Xiong, Yao-Kang; Yuan, Ke

2014-06-01

Chronic fatigue accumulation increases the incidence of cardiovascular disease while the treatment of antioxidants could prevent this development. We have previously shown that quercetin-3-O-gentiobiose (QG), a flavonoid isolated from tonic herb Okra, possesses anti-oxidative properties. In the present study, the protective effects of QG were evaluated in a rat model of load-induced endurance swimming. Oral administration of QG at the doses of 25-75mg/kg could significantly improve the endurance capability of rats to fatigue along with decrease serum lactic acid and blood urea nitrogen levels were decreased. Moreover, QG could alleviate vascular impairments, enhance the activities of antioxidant enzymes and attenuate the levels of inflammatory cytokines (MCP-1, IL-6 and TNF-α). The results indicated that QG had anti-fatigue and vasoprotective effects and represented a potential agent for the treatment of aortic pathology involved with fatigue- and related syndrome. Copyright © 2014 Elsevier Ltd. All rights reserved.

Self-reported post-exertional fatigue in Gulf War veterans: roles of autonomic testing

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Li, Mian; Xu, Changqing; Yao, Wenguo; Mahan, Clare M.; Kang, Han K.; Sandbrink, Friedhelm; Zhai, Ping; Karasik, Pamela A.

2014-01-01

To determine if objective evidence of autonomic dysfunction exists from a group of Gulf War veterans with self-reported post-exertional fatigue, we evaluated 16 Gulf War ill veterans and 12 Gulf War controls. Participants of the ill group had self- reported, unexplained chronic post-exertional fatigue and the illness symptoms had persisted for years until the current clinical study. The controls had no self-reported post-exertional fatigue either at the time of initial survey nor at the time of the current study. We intended to identify clinical autonomic disorders using autonomic and neurophysiologic testing in the clinical context. We compared the autonomic measures between the 2 groups on cardiovascular function at both baseline and head-up tilt, and sudomotor function. We identified 1 participant with orthostatic hypotension, 1 posture orthostatic tachycardia syndrome, 2 distal small fiber neuropathy, and 1 length dependent distal neuropathy affecting both large and small fiber in the ill group; whereas none of above definable diagnoses was noted in the controls. The ill group had a significantly higher baseline heart rate compared to controls. Compound autonomic scoring scale showed a significant higher score (95% CI of mean: 1.72–2.67) among ill group compared to controls (0.58–1.59). We conclude that objective autonomic testing is necessary for the evaluation of self-reported, unexplained post-exertional fatigue among some Gulf War veterans with multi-symptom illnesses. Our observation that ill veterans with self-reported post-exertional fatigue had objective autonomic measures that were worse than controls warrants validation in a larger clinical series. PMID:24431987

Cumulative fatigue and creep-fatigue damage at 3500C on recrystallized zircaloy 4

International Nuclear Information System (INIS)

Brun, G.; Pelchat, J.; Floze, J.C.; Galimberti, M.

1985-06-01

An experimental programme undertaken by C.E.A., E.D.F. and FRAGEMA with the aim of characterizing the fatigue and creep fatigue behaviour of zircaloy-4 following annealing treatments (recrystallized, stress-delived) is in progress. The results given below concern only recrystallized material. Cyclic properties, low-cycle fatigue curves and creep behaviour laws under stresses have been established. Sequential tests of pure fatigue and creep-fatigue were performed. The cumulative life fractions at fracture depend on the sequence of leading, stress history and number of cycles of prestressing. The MINER's rule appears to be conservative with regard to a low-high loading sequence whereas it is not for the reverse high-low loading sequences. Fatigue and creep damage are not interchangeable. Pre-creep improves the fatigue resistance. Pre-fatigue improves the creep strength as long as the beneficial effect of cyclic hardening overcomes the damaging effect of surface cracking. The introduction of a tension hold time into the fatigue cycle slightly increases cyclic hardening and reduces the number of cycles to failure. For hold times of less than one hour, the sum of fatigue and creep life fractions is closed to one

Fatigue and creep-fatigue in sodium of 316 L stainless-steel

International Nuclear Information System (INIS)

Ardellier, A.

1981-03-01

The present paper describes test-facility developed to perform low-cycle fatigue and creep-fatigue interaction in sodium on stainless steel - 316 L . Fatigue life in sodium and in air are compared. A beneficial effect in sodium is noted

Taltirelin alleviates fatigue-like behavior in mouse models of cancer-related fatigue.

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Dougherty, John P; Wolff, Brian S; Cullen, Mary J; Saligan, Leorey N; Gershengorn, Marvin C

2017-10-01

Fatigue affects most cancer patients and has numerous potential causes, including cancer itself and cancer treatment. Cancer-related fatigue (CRF) is not relieved by rest, can decrease quality of life, and has no FDA-approved therapy. Thyrotropin-releasing hormone (TRH) has been proposed as a potential novel treatment for CRF, but its efficacy against CRF remains largely untested. Thus, we tested the TRH analog, taltirelin (TAL), in mouse models of CRF. To model fatigue, we used a mouse model of chemotherapy, a mouse model of radiation therapy, and mice bearing colon 26 carcinoma tumors. We used the treadmill fatigue test to assess fatigue-like behavior after treatment with TAL. Additionally, we used wild-type and TRH receptor knockout mice to determine which TRH receptor was necessary for the actions of TAL. Tumor-bearing mice displayed muscle wasting and all models caused fatigue-like behavior, with mice running a shorter distance in the treadmill fatigue test than controls. TAL reversed fatigue-like behavior in all three models and the mouse TRH 1 receptor was necessary for the effects of TAL. These data suggest that TAL may be useful in alleviating fatigue in all cancer patients and provide further support for evaluating TAL as a potential therapy for CRF in humans. Published by Elsevier Ltd.

Alpha1A-adrenergic receptor-directed autoimmunity induces left ventricular damage and diastolic dysfunction in rats.

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Katrin Wenzel

Full Text Available BACKGROUND: Agonistic autoantibodies to the alpha(1-adrenergic receptor occur in nearly half of patients with refractory hypertension; however, their relevance is uncertain. METHODS/PRINCIPAL FINDINGS: We immunized Lewis rats with the second extracellular-loop peptides of the human alpha(1A-adrenergic receptor and maintained them for one year. Alpha(1A-adrenergic antibodies (alpha(1A-AR-AB were monitored with a neonatal cardiomyocyte contraction assay by ELISA, and by ERK1/2 phosphorylation in human alpha(1A-adrenergic receptor transfected Chinese hamster ovary cells. The rats were followed with radiotelemetric blood pressure measurements and echocardiography. At 12 months, the left ventricles of immunized rats had greater wall thickness than control rats. The fractional shortening and dp/dt(max demonstrated preserved systolic function. A decreased E/A ratio in immunized rats indicated a diastolic dysfunction. Invasive hemodynamics revealed increased left ventricular end-diastolic pressures and decreased dp/dt(min. Mean diameter of cardiomyocytes showed hypertrophy in immunized rats. Long-term blood pressure values and heart rates were not different. Genes encoding sarcomeric proteins, collagens, extracellular matrix proteins, calcium regulating proteins, and proteins of energy metabolism in immunized rat hearts were upregulated, compared to controls. Furthermore, fibrosis was present in immunized hearts, but not in control hearts. A subset of immunized and control rats was infused with angiotensin (Ang II. The stressor raised blood pressure to a greater degree and led to more cardiac fibrosis in immunized, than in control rats. CONCLUSIONS/SIGNIFICANCE: We show that alpha(1A-AR-AB cause diastolic dysfunction independent of hypertension, and can increase the sensitivity to Ang II. We suggest that alpha(1A-AR-AB could contribute to cardiovascular endorgan damage.

Effects of mental fatigue on the development of physical fatigue: a neuroergonomic approach.

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Mehta, Ranjana K; Parasuraman, Raja

2014-06-01

The present study used a neuroergonomic approach to examine the interaction of mental and physical fatigue by assessing prefrontal cortex activation during submaximal fatiguing handgrip exercises. Mental fatigue is known to influence muscle function and motor performance, but its contribution to the development of voluntary physical fatigue is not well understood. A total of 12 participants performed separate physical (control) and physical and mental fatigue (concurrent) conditions at 30% of their maximal handgrip strength until exhaustion. Functional near infrared spectroscopy was employed to measure prefrontal cortex activation, whereas electromyography and joint steadiness were used simultaneously to quantify muscular effort. Compared to the control condition, blood oxygenation in the bilateral prefrontal cortex was significantly lower during submaximal fatiguing contractions associated with mental fatigue at exhaustion, despite comparable muscular responses. The findings suggest that interference in the prefrontal cortex may influence motor output during tasks that require both physical and cognitive processing. A neuroergonomic approach involving simultaneous monitoring of brain and body functions can provide critical information on fatigue development that may be overlooked during traditional fatigue assessments.

An Endotoxin Tolerance Signature Predicts Sepsis and Organ Dysfunction at Initial Clinical Presentation

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Olga M. Pena

2014-11-01

Interpretation: Our data support an updated model of sepsis pathogenesis in which endotoxin tolerance-mediated immune dysfunction (cellular reprogramming is present throughout the clinical course of disease and related to disease severity. Thus endotoxin tolerance might offer new insights guiding the development of new therapies and diagnostics for early sepsis.

Modelling fatigue and the use of fatigue models in work settings.

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Dawson, Drew; Ian Noy, Y; Härmä, Mikko; Akerstedt, Torbjorn; Belenky, Gregory

2011-03-01

In recent years, theoretical models of the sleep and circadian system developed in laboratory settings have been adapted to predict fatigue and, by inference, performance. This is typically done using the timing of prior sleep and waking or working hours as the primary input and the time course of the predicted variables as the primary output. The aim of these models is to provide employers, unions and regulators with quantitative information on the likely average level of fatigue, or risk, associated with a given pattern of work and sleep with the goal of better managing the risk of fatigue-related errors and accidents/incidents. The first part of this review summarises the variables known to influence workplace fatigue and draws attention to the considerable variability attributable to individual and task variables not included in current models. The second part reviews the current fatigue models described in the scientific and technical literature and classifies them according to whether they predict fatigue directly by using the timing of prior sleep and wake (one-step models) or indirectly by using work schedules to infer an average sleep-wake pattern that is then used to predict fatigue (two-step models). The third part of the review looks at the current use of fatigue models in field settings by organizations and regulators. Given their limitations it is suggested that the current generation of models may be appropriate for use as one element in a fatigue risk management system. The final section of the review looks at the future of these models and recommends a standardised approach for their use as an element of the 'defenses-in-depth' approach to fatigue risk management. Copyright © 2010 Elsevier Ltd. All rights reserved.

The nature of self-regulatory fatigue and “ego depletion”: Lessons from physical fatigue

Science.gov (United States)

Evans, Daniel R.; Boggero, Ian A.; Segerstrom, Suzanne C.

2016-01-01

Self-regulation requires overriding a dominant response, and leads to temporary self-regulatory fatigue. Existing theories of the nature and causes of self-regulatory fatigue highlight physiological substrates such as glucose or psychological processes such as motivation, but these explanations are incomplete on their own. Historically, theories of physical fatigue demonstrate a similar pattern of useful but incomplete explanations, as recent views of physical fatigue emphasize the roles of both physiological and psychological factors. In addition to accounting for multiple inputs, these newer views also explain how fatigue can occur even in the presence of sufficient resources. Examining these newer theories of physical fatigue can serve as a foundation on which to build a more comprehensive understanding of self-regulatory fatigue that integrates possible neurobiological underpinnings of physical and self-regulatory fatigue, and suggests the possible function of self-regulatory fatigue. PMID:26228914

Modulating effects of bioactive water Naftussya from layers Truskavets’ and Pomyarky on some metabolic and biophysic parameters at humans with dysfunction of neuro-endocrine-immune complex

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Anatoliy I Gozhenko

2016-12-01

Full Text Available Background. Previously we have been carry out comparative investigation immediate effects of Bioactive Water Naftussya from layers Truskavets’, Pomyarky and Skhidnyts’a on neuro-endocrine-immune complex at men with its dysfunction. The aim of this study is the influence of the use of the course of Bioactive Water Naftussya from layers Truskavets’ and Pomyarky on some metabolic and biophysical parameters at similar patients. Materials and methods. The object of observation were 20 volunteers: ten women and ten men aged 33-76 years without clinical diagnose but with dysfunction of neuro-endocrine-immune complex and metabolism. In daily urine and venous blood we determined the content of electrolytes, nitrogenous metabolites and lipids, recorded conductivity of acupuncture points, rate of electronegative nuclei of buccal epithelium as well as parameters of gas discharge vizualisation (GDV. After examination volunteers within 7 days used bioactive water Naftussya (250 mL three times a day from Truskavets’ or Pomyarky layer, then repeated the tests listed. Results. Weekly use of Bioactive Water Naftussya increases in the normal level of plasma chloride and sodium, normalizes low level of bicarbonate and decreases within the normal levels of potassium and phosphate. Urinary excretion of sodium and chloride increases while excretion and concentration of uric acid decreases, as the urine concentration of phosphates. The index lithogenicity urine decreased from 112% to 103% norm standard. Initially reduced level of plasma triacylglycerides increases, while decreases in the normal level of cholesterol in low-density lipoprotein composition. Among the biophysical parameters detected increase in the normal conductivity acupuncture points Pg (ND at right side, which represent the nervous system, and left shift the ratio between the conductivity of acupuncture points MC (AVL, which represents the immune system. Increases electrokinetic index of

Chronic fatigue syndrome and impaired peripheral pulse characteristics on orthostasis–a new potential diagnostic biomarker

International Nuclear Information System (INIS)

Allen, John; Murray, Alan; Di Maria, Costanzo; Newton, Julia L

2012-01-01

Autonomic nervous system dysfunction is frequently reported in chronic fatigue syndrome (CFS) with orthostatic intolerance, a common symptom that can be objectively assessed. The frequent finding of autonomic dysfunction and symptoms on standing has the potential to provide a diagnostic biomarker in chronic fatigue. In this study we explored the clinical value of non-invasive optical multi-site photoplethysmography (PPG) technology to assess cardiovascular responses to standing. Multi-site PPG pulses were collected from tissue pads of the ears, fingers and toes of 14 patients with CFS and 14 age-matched sedentary subjects using a measurement protocol of a 10 min baseline (subject supine) followed by 3 min of tilting on a tilt table (head-up to 70°). Percentage change in pulse timing (pulse transit time, PTTf) and pulse amplitude (AMP) at each site were calculated using beat-to-beat pulse wave analysis. A significant reduction in the overall pulse timing response to controlled standing was found for the CFS group (using summed absolute percentage change in PTTf for ear, finger and toe sites, median change of 26% for CFS and 37% for control with p = 0.002). There were no significant differences between subject groups for the AMP measure at any site. Changes in AMP with tilt were, however, weakly significantly and negatively correlated with fatigue severity (p < 0.05). Receiver operating characteristic (ROC) analysis of timing measures produced an area under the curve of 0.81. Experimental linear discriminant classification analysis comparing both timing and amplitude measures produced an overall diagnostic accuracy of 82%. Pulse wave abnormalities have been observed in CFS and represent a potential objective measure to help differentiate between CFS patients and healthy controls. (paper)

The concept of fatigue fracture toughness in fatigue delamination growth behavior

NARCIS (Netherlands)

Yao, L.; Alderliesten, R.C.; Benedictus, R.

2015-01-01

This paper provides a study on mode I fatigue delamination growth in composite laminates using energy principles. Experimental data has been obtained from fatigue tests conducted on Double Cantilever Beam (DCB) specimens at various stress ratios. A concept of fatigue fracture toughness is proposed

Stress Hyperglycemia, Insulin Treatment, and Innate Immune Cells

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Fangming Xiu

2014-01-01

Full Text Available Hyperglycemia (HG and insulin resistance are the hallmarks of a profoundly altered metabolism in critical illness resulting from the release of cortisol, catecholamines, and cytokines, as well as glucagon and growth hormone. Recent studies have proposed a fundamental role of the immune system towards the development of insulin resistance in traumatic patients. A comprehensive review of published literatures on the effects of hyperglycemia and insulin on innate immunity in critical illness was conducted. This review explored the interaction between the innate immune system and trauma-induced hypermetabolism, while providing greater insight into unraveling the relationship between innate immune cells and hyperglycemia. Critical illness substantially disturbs glucose metabolism resulting in a state of hyperglycemia. Alterations in glucose and insulin regulation affect the immune function of cellular components comprising the innate immunity system. Innate immune system dysfunction via hyperglycemia is associated with a higher morbidity and mortality in critical illness. Along with others, we hypothesize that reduction in morbidity and mortality observed in patients receiving insulin treatment is partially due to its effect on the attenuation of the immune response. However, there still remains substantial controversy regarding moderate versus intensive insulin treatment. Future studies need to determine the integrated effects of HG and insulin on the regulation of innate immunity in order to provide more effective insulin treatment regimen for these patients.

The problem of fatigue in patients suffering from neoplastic disease

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Agnieszka Kolak

2017-06-01

Full Text Available Modern therapeutic management of patients with cancer is associated with many adverse side effects, including fatigue defined as weariness, burnout, lassitude, malaise, apathy, impatience, and/or inability to perform daily activities. It occurs frequently before the diagnosis of cancer and may persist for a long time after the end of cancer therapy. It is a common problem that occurs regardless of the type of cancer and applied therapeutic procedure. The appearance of this symptom significantly affects the quality of life of patients and often reduces the effectiveness of implemented treatment. The symptom of fatigue occurs among approximately 80% of patients treated with chemotherapy and/or radiotherapy, as well as among more than 75% of patients with metastatic disease. Causes of fatigue include metabolic and immune system disorders as well as increased level of tumour necrosis factor  (TNF-. Recent studies also indicate a significant contribution of other cytokines, especially pro-inflammatory ones, i.e. interleukin-1 (IL-1, interleukin-6 (IL-6, soluble tumour necrosis factor receptor type II (sTNF type II and C-reactive protein (CRP. A patient reporting fatigue should be properly diagnosed and thoroughly interviewed by doctors. Patients are mostly treated non-pharmacologically (by means of physical exercise and psychotherapy and pharmacologically (by applying methylphenidate and methylprednisolone. What is also extremely important is proper education of the patient and their closest family/friends on the symptoms, which significantly reduces anxiety and stress. On the other hand therapeutic management hinders the subjectivity of feeling and lack of standardised scales to rate symptoms.

Experiences of Fatigue at Sea

DEFF Research Database (Denmark)

Zhao, Zhiwei; Jepsen, Jørgen Riis; Chen, Zhonglong

2016-01-01

Fatigue has negative impacts on the general working population as well as on seafarers. In order to study seafarers’ fatigue, a questionnaire-base survey was conducted to gain information about potential risk factors for fatigue and construct indexes indicating fatigue. The study applies T-test t......-test to compare strata of seafarers to analyse work and sleep patterns in global seafaring. Qualitative analysis are also employed to explore the impacts of fatigue on seafarer’s occupational health and safety.......Fatigue has negative impacts on the general working population as well as on seafarers. In order to study seafarers’ fatigue, a questionnaire-base survey was conducted to gain information about potential risk factors for fatigue and construct indexes indicating fatigue. The study applies T...

Innate immune reconstitution with suppression of HIV-1.

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Scully, Eileen P; Lockhart, Ainsley; Garcia-Beltran, Wilfredo; Palmer, Christine D; Musante, Chelsey; Rosenberg, Eric; Allen, Todd M; Chang, J Judy; Bosch, Ronald J; Altfeld, Marcus

2016-03-17

Progressive HIV-1 infection leads to both profound immune suppression and pathologic inflammation in the majority of infected individuals. While adaptive immune dysfunction, as evidenced by CD4 + T cell depletion and exhaustion, has been extensively studied, less is known about the functional capacity of innate immune cell populations in the context of HIV-1 infection. Given the broad susceptibility to opportunistic infections and the dysregulated inflammation observed in progressive disease, we hypothesized that there would be significant changes in the innate cellular responses. Using a cohort of patients with multiple samplings before and after antiretroviral therapy (ART) initiation, we demonstrated increased responses to innate immune stimuli following viral suppression, as measured by the production of inflammatory cytokines. Plasma viral load itself had the strongest association with this change in innate functional capacity. We further identified epigenetic modifications in the TNFA promoter locus in monocytes that are associated with viremia, suggesting a molecular mechanism for the observed changes in innate immune function following initiation of ART. These data indicate that suppression of HIV-1 viremia is associated with changes in innate cellular function that may in part determine the restoration of protective immune responses.

CD16(+) monocytes with smooth muscle cell characteristics are reduced in human renal chronic transplant dysfunction

NARCIS (Netherlands)

Boersema, M.; van den Born, Joost; van Ark, J.; Harms, Geertruida; Seelen, M. A.; van Dijk, M. C. R. F.; van Goor, H.; Navis, G. J.; Popa, E. R.; Hillebrands, J. L.

In chronic transplant dysfunction (CTD), persistent (allo)immune-mediated inflammation eventually leads to tissue remodeling including neointima formation in intragraft arteries. We previously showed that recipient-derived neointimal alpha-SMA(+) smooth muscle-like cells are present in human renal

Adrenal Fatigue

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... Search Featured Resource New Mobile App DOWNLOAD Adrenal Fatigue October 2017 Download PDFs English Editors Irina Bancos, MD Additional Resources Mayo Clinic What is adrenal fatigue? The term “adrenal fatigue” has been used to ...

Neuromuscular fatigue during exercise: Methodological considerations, etiology and potential role in chronic fatigue.

Science.gov (United States)

Twomey, Rosie; Aboodarda, Saied Jalal; Kruger, Renata; Culos-Reed, Susan Nicole; Temesi, John; Millet, Guillaume Y

2017-04-01

The term fatigue is used to describe a distressing and persistent symptom of physical and/or mental tiredness in certain clinical populations, with distinct but ultimately complex, multifactorial and heterogenous pathophysiology. Chronic fatigue impacts on quality of life, reduces the capacity to perform activities of daily living, and is typically measured using subjective self-report tools. Fatigue also refers to an acute reduction in the ability to produce maximal force or power due to exercise. The classical measurement of exercise-induced fatigue involves neuromuscular assessments before and after a fatiguing task. The limitations and alternatives to this approach are reviewed in this paper in relation to the lower limb and whole-body exercise, given the functional relevance to locomotion, rehabilitation and activities of daily living. It is suggested that under some circumstances, alterations in the central and/or peripheral mechanisms of fatigue during exercise may be related to the sensations of chronic fatigue. As such, the neurophysiological correlates of exercise-induced fatigue are briefly examined in two clinical examples where chronic fatigue is common: cancer survivors and people with multiple sclerosis. This review highlights the relationship between objective measures of fatigability with whole-body exercise and perceptions of fatigue as a priority for future research, given the importance of exercise in relieving symptoms of chronic fatigue and/or overall disease management. As chronic fatigue is likely to be specific to the individual and unlikely to be due to a simple biological or psychosocial explanation, tailored exercise programmes are a potential target for therapeutic intervention. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Double-Blind, Randomized Study of the Effects of Influenza Vaccination on the Specific Antibody Response and Clinical Course of Patients with Chronic Fatigue Syndrome

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Kenna M Sleigh

2000-01-01

Full Text Available OBJECTIVE: To determine whether influenza immunization is associated with early side effects, a deleterious impact on the illness course and depressed antibody response in patients with chronic fatigue syndrome (CFS.

Optimal Fatigue Testing

DEFF Research Database (Denmark)

Faber, Michael Havbro; Sørensen, John Dalsgaard; Kroon, I. B.

1993-01-01

life experiments for the same purpose. The methodology is basedon modern probabilistic concepts amd classical decision theory. The special case where the fatigue life experiments are given in terms of SN curves is considered in Particular. The proposed techniques are illustrated by an example.......This paper considers the reassessment of the reliability of tubular joints subjected to fatigue load. The reassessment is considered in two parts namely the task of utilizing new experimental data on fatigue life to update the reliability of the tubular joint ant the task of planning new fatigue...

Fatigue-Arrestor Bolts

Science.gov (United States)

Onstott, Joseph W.; Gilster, Mark; Rodriguez, Sergio; Larson, John E.; Wickham, Mark D.; Schoonover, Kevin E.

1995-01-01

Bolts that arrest (or, more precisely, retard) onset of fatigue cracking caused by inelastic strains developed. Specifically developed to be installed in flange holes of unrestrained rocket engine nozzle. Fanges sometimes used to bolt nozzle to test stand; however, when rocket engine operated without this restraint, region around bolt holes experience severe inelastic strains causing fatigue cracking. Interference fits introduce compressive preloads that retard fatigue by reducing ranges of strains. Principle of these fatigue-arrestor bolts also applicable to holes in plates made of other materials and/or used for different purposes.

Application of a unified fatigue modelling to some thermomechanical fatigue problems

International Nuclear Information System (INIS)

Dang, K. van; Maitournam, H.; Moumni, Z.

2005-01-01

Fatigue under thermomechanical loadings is an important topic for nuclear industries. For instance, thermal fatigue cracking is observed in the mixing zones of the nuclear reactor. Classical computations using existing methods based on strain amplitude or fracture mechanics are not sufficiently predictive. In this paper an alternative approach is proposed based on a multiscale modelling thanks to shakedown hypothesis. Examples of predictive results are presented. Finally an application to the RHR problem is discussed. Main ideas of the fatigue modelling: Following an idea of Professor D. Drucker who wrote in 1963 'when applied to the microstructure there is a hope that the concept of endurance limit and shakedown are related, and that fatigue failure can be related to energy dissipated in idealized material when shakedown does not occur.' we have developed a theory of fatigue based on this concept which is different from classical fatigue approaches. Many predictive applications have been already done particularly for the automotive industry. Fatigue resistance of structures undergoing thermomechanical loadings in the high cycle regime as well as in the low cycle regime are calculated using this modelling. However, this fatigue theory is until now rarely used in nuclear engineering. After recalling the main points of the theory, we shall present some relevant applications which were done in different industrial sectors. We shall apply this modelling to the prediction of thermal cracking observed in the mixing zones of RHR. (authors)

Fatigue Reliability and Calibration of Fatigue Design Factors for Offshore Wind Turbines

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Sergio Márquez-Domínguez

2012-06-01

Full Text Available Consequences of failure of offshore wind turbines (OWTs is in general lower than consequences of failure of, e.g., oil & gas platforms. It is reasonable that lower fatigue design factors can be applied for fatigue design of OWTs when compared to other fixed offshore structures. Calibration of appropriate partial safety factors/Fatigue Design Factors (FDF for steel substructures for OWTs is the scope of this paper. A reliability-based approach is used and a probabilistic model has been developed, where design and limit state equations are established for fatigue failure. The strength and load uncertainties are described by stochastic variables. SN and fracture mechanics approaches are considered for to model the fatigue life. Further, both linear and bi-linear SN-curves are formulated and various approximations are investigated. The acceptable reliability level for fatigue failure of OWTs is discussed and results are presented for calibrated optimal fatigue design factors. Further, the influence of inspections is considered in order to extend and maintain a given target safety level.

Low cycle fatigue and creep fatigue behavior of alloy 617 at high temperature

International Nuclear Information System (INIS)

Cabet, Celine; Carroll, Laura; Wright, Richard

2013-01-01

Alloy 617 is the leading candidate material for an intermediate heat exchanger (IHX) application of the very high temperature nuclear reactor (VHTR), expected to have an outlet temperature as high as 950 C. Acceptance of Alloy 617 in Section III of the ASME Code for nuclear construction requires a detailed understanding of the creep-fatigue behavior. Initial creep-fatigue work on Alloy 617 suggests a more dominant role of environment with increasing temperature and/or hold times evidenced through changes in creep-fatigue crack growth mechanisms and failure life. Continuous cycle fatigue and creep-fatigue testing of Alloy 617 was conducted at 950 C and 0.3% and 0.6% total strain in air to simulate damage modes expected in a VHTR application. Continuous cycle fatigue specimens exhibited transgranular cracking. Intergranular cracking was observed in the creep-fatigue specimens and the addition of a hold time at peak tensile strain degraded the cycle life. This suggests that creep-fatigue interaction occurs and that the environment may be partially responsible for accelerating failure. (authors)

Random non-proportional fatigue tests with planar tri-axial fatigue testing machine

OpenAIRE

Inoue, T.; Nagao, R.; Takeda, N.

2016-01-01

Complex stresses, which occur on the mechanical surfaces of transport machinery in service, bring a drastic degradation in fatigue life. However, it is hard to reproduce such complex stress states for evaluating the fatigue life with conventional multiaxial fatigue machines. We have developed a fatigue testing machine that enables reproduction of such complex stresses. The testing machine can reproduce arbitrary in-plane stress states by applying three independent loads to the test specimen u...

Role of the Ca2+-Calcineurin-Nuclear Factor of Activated T cell Pathway in Mitofusin-2-Mediated Immune Function of Jurkat Cells

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Xiu-Ping Xu

2018-01-01

Conclusions: Our findings suggest that MFN2 may regulate T cell immune functions primarily through the Ca2+-calcineurin-NFAT pathway. MFN2 may represent a potential therapeutic target for T cell immune dysfunction-related diseases.

Aflatoxin-Related Immune Dysfunction in Health and in Human Immunodeficiency Virus Disease

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Yi Jiang

2008-01-01

Full Text Available Both aflatoxin and the human immunodeficiency virus (HIV cause immune suppression and millions of HIV-infected people in developing countries are chronically exposed to aflatoxin in their diets. We investigated the possible interaction of aflatoxin and HIV on immune suppression by comparing immune parameters in 116 HIV positive and 80 aged-matched HIV negative Ghanaians with high (≥0.91 pmol/mg albumin and low (<0.91 pmol/mg albumin aflatoxin B1 albumin adduct (AF-ALB levels. AF-ALB levels and HIV viral load were measured in plasma and the percentages of leukocyte immunophenotypes and cytokine expression were determined using flow cytometry. The cross-sectional comparisons found that (1 among both HIV positive and negative participants, high AF-ALB was associated with lower perforin expression on CD8+ T-cells (P=.012; (2 HIV positive participants with high AF-ALB had significantly lower percentages of CD4+ T regulatory cells (Tregs; P=.009 and naive CD4+ T cells (P=.029 compared to HIV positive participants with low AF-ALB; and (3 HIV positive participants with high AF-ALB had a significantly reduced percentage of B-cells (P=.03 compared to those with low AF-ALB. High AF-ALB appeared to accentuate some HIV associated changes in T-cell phenotypes and in B-cells in HIV positive participants.

Mediators of the effects on fatigue of pragmatic rehabilitation for chronic fatigue syndrome.

Science.gov (United States)

Wearden, Alison J; Emsley, Richard

2013-10-01

To examine potential mediators of the effect of pragmatic rehabilitation on improvements in fatigue following a randomized controlled trial for patients with chronic fatigue syndrome (CFS/ME) in primary care (IRCTN 74156610). Patients fulfilled the Oxford criteria for CFS. Ninety-five patients were randomized to pragmatic rehabilitation and 100 to general practitioner (GP) treatment as usual. The outcome was the Chalder fatigue scale score (0123 scoring) at end of treatment (20 weeks) and 1-year follow up (70 weeks). First, the effect of treatment on potential mediators was assessed. Then fatigue was regressed on significant mediators, treatment allocation, and baseline measures of fatigue and significant mediators. Reduction in limiting activities at 20 weeks mediated the positive effect of pragmatic rehabilitation on fatigue at 70 weeks (mediated effect size = -2.64, SE = 0.81, p = .001, proportion of effect mediated = 82.0%). Reduction in catastrophizing at 20 weeks mediated the positive effect of pragmatic rehabilitation on fatigue at 70 weeks (mediated effect size = -1.39, SE = 0.61, p = .023, proportion of effect mediated = 43.2%). Reductions in 70-week measures of fear avoidance, embarrassment avoidance, limiting activities, and all-or-nothing behavior all mediated improvement in fatigue at 70 weeks, although the causal direction of these cross-sectional effects cannot be determined. There were no between-group differences on measures of exercise capacity (a timed step test). Improvements in fatigue following pragmatic rehabilitation are related to changes in behavioral responses to and beliefs about fatigue.

Immune response against the coiled coil domain of Sjögren's syndrome associated autoantigen Ro52 induces salivary gland dysfunction.

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Sroka, Magdalena; Bagavant, Harini; Biswas, Indranil; Ballard, Abigail; Deshmukh, Umesh S

2018-01-31

The structural domains of Ro52, termed the RING, B-box, coiled coil (CC) and B30.2/SPRY are targets of anti-Ro52 in multiple autoimmune disorders. In Sjögren's syndrome patients, the presence of anti-Ro52 is associated with higher disease severity, and in mice, they induce salivary gland hypofunction. This study was undertaken to investigate whether immune responses against different domains of Ro52, influences salivary gland disease in mice. Female NZM2758 mice were immunised with Ro52 domains expressed as recombinant fusion proteins with maltose binding protein (MBP) [MBP-RING-B-box, MBP-CC, MBP-CC(ΔC19), MBP-B30.2/SPRY]. Sera from immunised mice were studied for IgG antibodies to Ro52 by immunoprecipitation, and to salivary gland cells by immunofluorescence. Pilocarpine-induced saliva production was measured to evaluate salivary gland function. Submandibular glands were investigated by histopathology for inflammation and by immune-histochemistry for IgG deposition. Mice immunised with different Ro52-domains had comparable reactivity to Ro52 and to salivary gland cells. However, only mice immunised with the CC domain and its C-terminal truncated version CC(ΔC19) showed a significant drop in saliva production. None of the mice developed severe salivary gland inflammation. The salivary gland hypofunction significantly correlated with increased intra-lobar IgG deposits in the submandibular salivary glands. Our data demonstrate that epitope specificity of anti-Ro52 antibodies plays a critical role in the induction of glandular dysfunction. Clearly, screening Sjögren's syndrome patients for relative levels of Ro52 domain specific antibodies will be more informative for associating anti-Ro52 with clinical measures of the disorder.

MODELS OF FATIGUE LIFE CURVES IN FATIGUE LIFE CALCULATIONS OF MACHINE ELEMENTS – EXAMPLES OF RESEARCH

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Grzegorz SZALA

2014-03-01

Full Text Available In the paper there was attempted to analyse models of fatigue life curves possible to apply in calculations of fatigue life of machine elements. The analysis was limited to fatigue life curves in stress approach enabling cyclic stresses from the range of low cycle fatigue (LCF, high cycle fatigue (HCF, fatigue limit (FL and giga cycle fatigue (GCF appearing in the loading spectrum at the same time. Chosen models of the analysed fatigue live curves will be illustrated with test results of steel and aluminium alloys.

Associations of Body Mass Index and Physical Activity With Sexual Dysfunction in Breast Cancer Survivors.

Science.gov (United States)

Paiva, Carlos Eduardo; Rezende, Fabiana Faria; Paiva, Bianca Sakamoto Ribeiro; Mauad, Edmundo Carvalho; Zucca-Matthes, Gustavo; Carneseca, Estela Cristina; Syrjänen, Kari Juhani; Schover, Leslie R

2016-11-01

Sexual dysfunction is a common and distressing consequence of breast cancer (BC) treatment. In the present study, we investigated the sexual functioning of BC patients and its association with women's personal characteristics and cancer treatments. In this cross-sectional study, sexual function was assessed using the Female Sexual Function Index (FSFI). The health-related quality of life (HRQOL) was measured using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and its breast module BR-23. Of the 235 participants approached, 216 participants were included in the study. Of these, 63 patients reported no sexual activity in the last month and thus were analyzed only in relation to the sexual desire domain of FSFI. A total of 154 (71.3 %) patients were classified with hypoactive sexual desire disorder (HSDD). From those patients reporting sexual activity in the last month, 63.3 % (97 out of 153) were classified with sexual dysfunction. Using hierarchical logistic regression, the variance explained (change in R 2 ) by the addition of body mass index (BMI) and mild to moderate physical activity in the prediction models of sexual dysfunction and HSDD were 6.8 and 7.2 %, respectively. Age, BMI, and physical activity were independently associated with sexual dysfunction and HSDD. Additionally, BC patients with sexual dysfunction reported lower scores on global HRQOL, role functioning, and fatigue. Based on our findings, BC survivors should be encouraged to practice regular physical activity and to lose weight in order to avoid sexual dysfunction. However, future clinical trials are needed to confirm these findings.

The uremic environment and muscle dysfunction in man and rat

DEFF Research Database (Denmark)

Harrison, Adrian Paul; Nielsen, Arne Høj; Eidemak, I.

2006-01-01

Background: Patients reaching end-stage renal disease experience debilitating fatigue, with progression of this disease, rendering patients dysfunctional in their everyday lives. Methods: In vivo measurements of muscle function, assessed using surface electromyography (EMG), were made on 25...... patients prior to and after a session of hemodialysis (HD) treatment, alongside in vitro measurements of muscle function in isolated rat muscles incubated in normal or uremic conditions approximating to those found in uremic rats (rat uremic: RU) or uremic humans (human uremic: HU). Results: HD...... significantly affected plasma values, e.g. reducing urea (69%), creatinine (62%), potassium (23%) and phosphate (48%) concentrations in patients (all pimproved the EMG frequency of 2nd dorsal interosseous (fast-twitch) (p

Maternal stress, nutrition and physical activity: Impact on immune function, CNS development and psychopathology.

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Marques, Andrea Horvath; Bjørke-Monsen, Anne-Lise; Teixeira, Antônio L; Silverman, Marni N

2015-08-18

Evidence suggests that maternal and fetal immune dysfunction may impact fetal brain development and could play a role in neurodevelopmental disorders, although the definitive pathophysiological mechanisms are still not completely understood. Stress, malnutrition and physical inactivity are three maternal behavioral lifestyle factors that can influence immune and central nervous system (CNS) functions in both the mother and fetus, and may therefore, increase risk for neurodevelopmental/psychiatric disorders. First, we will briefly review some aspects of maternal-fetal immune system interactions and development of immune tolerance. Second, we will discuss the bidirectional communication between the immune system and CNS and the pathways by which immune dysfunction could contribute to neurodevelopmental disorders. Third, we will discuss the effects of prenatal stress and malnutrition (over and undernutrition) on perinatal programming of the CNS and immune system, and how this might influence neurodevelopment. Finally, we will discuss the beneficial impact of physical fitness during pregnancy on the maternal-fetal unit and infant and how regular physical activity and exercise can be an effective buffer against stress- and inflammatory-related disorders. Although regular physical activity has been shown to promote neuroplasticity and an anti-inflammatory state in the adult, there is a paucity of studies evaluating its impact on CNS and immune function during pregnancy. Implementing stress reduction, proper nutrition and ample physical activity during pregnancy and the childbearing period may be an efficient strategy to counteract the impact of maternal stress and malnutrition/obesity on the developing fetus. Such behavioral interventions could have an impact on early development of the CNS and immune system and contribute to the prevention of neurodevelopmental and psychiatric disorders. Further research is needed to elucidate this relationship and the underlying

[Research Progress on the Interaction Effects and Its Neural Mechanisms between Physical Fatigue and Mental Fatigue].

Science.gov (United States)

Zhang, Lixin; Zhang, Chuncui; He, Feng; Zhao, Xin; Qi, Hongzhi; Wan, Baikun; Ming, Dong

2015-10-01

Fatigue is an exhaustion state caused by prolonged physical work and mental work, which can reduce working efficiency and even cause industrial accidents. Fatigue is a complex concept involving both physiological and psychological factors. Fatigue can cause a decline of concentration and work performance and induce chronic diseases. Prolonged fatigue may endanger life safety. In most of the scenarios, physical and mental workloads co-lead operator into fatigue state. Thus, it is very important to study the interaction influence and its neural mechanisms between physical and mental fatigues. This paper introduces recent progresses on the interaction effects and discusses some research challenges and future development directions. It is believed that mutual influence between physical fatigue and mental fatigue may occur in the central nervous system. Revealing the basal ganglia function and dopamine release may be important to explore the neural mechanisms between physical fatigue and mental fatigue. Future effort is to optimize fatigue models, to evaluate parameters and to explore the neural mechanisms so as to provide scientific basis and theoretical guidance for complex task designs and fatigue monitoring.

Fatigue Damage in Wood

DEFF Research Database (Denmark)

Clorius, Christian Odin; Pedersen, Martin Bo Uhre; Hoffmeyer, Preben

1996-01-01

An investigation of fatigue failure in wood subjected to load cycles in compression parallel to grain is presented. Fatigue failure is found to depend both on the total time under load and on the number of cycles.Recent accelerated fatigue research on wood is reviewed, and a discrepancy between...... to 10 Hz are used. The number of cycles to failure is found to be a poor measure of the fatigue performance of wood. Creep, maximum strain, stiffness and work are monitored throughout the fatigue tests. Accumulated creep is suggested identified with damage and a correlation between stiffness reduction...

Chemotherapy-Induced Fatigue Correlates With Higher Fatigue Scores Before Treatment.

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Araújo, José Klerton Luz; Giglio, Adriana Del; Munhoz, Bruna Antenusse; Fonseca, Fernando Luiz Affonso; Cruz, Felipe Melo; Giglio, Auro Del

2017-06-01

Cancer chemotherapy can induce fatigue in about 20% to 30% of patients. So far, there is very little information as to the predictors of chemotherapy-induced fatigue (CIF). We evaluated potential predictors of CIF in a sample of patients with cancer with several types of solid tumors scheduled to receive chemotherapy according to institutional protocols. Before their first and second chemotherapy cycles, patients answered to the Brief Fatigue Inventory (BFI), Chalder, Mini Nutritional Assessment (MNA), Stress thermometer, and HADS questionnaires as well as provided blood samples for inflammatory markers. We evaluated 52 patients, 37 (71%) were female and mean age was 53 years. The most common tumors were breast cancer 21 (40%) and gastrointestinal tumors 12 (23%). Although 14 (25.2%) patients had an increase in their fatigue BFI scores equal or above 3 points from baseline, we observed no significant overall differences between BFI scores before and after chemotherapy. The only 2 factors associated with an increase of 3 points in the BFI scores after chemotherapy were race and higher baseline BFI levels. By multivariate analysis, overall BFI and Chalder scores after chemotherapy also correlated significantly with their respective baseline scores before treatment. HADS scores before treatment correlated with overall BFI scores postchemotherapy, whereas MNA scores before chemotherapy and female sex correlated with higher Chalder scores after treatment. We conclude that fatigue induced by chemotherapy is common and consistently associated with higher fatigue scores before treatment. Screening for fatigue before chemotherapy may help to identify patients who are prone to develop CIF.

Modafinil May Alleviate Poststroke Fatigue

DEFF Research Database (Denmark)

Poulsen, Mai Bang; Damgaard, Bodil; Zerahn, Bo

2015-01-01

was randomized, double-blinded, and placebo-controlled. Patients were treated with 400-mg modafinil or placebo for 90 days. Assessments were done at inclusion, 30, 90, and 180 days. The primary end point was fatigue at 90 days measured by the Multidimensional Fatigue Inventory-20 general fatigue domain......BACKGROUND AND PURPOSE: Poststroke fatigue is common and reduces quality of life. Current evidence for intervention is limited, and this is the first placebo-controlled trial to investigate treatment of poststroke fatigue with the wakefulness promoting drug modafinil. METHODS: The trial....... Secondary end points included the Fatigue Severity Scale, the Montreal Cognitive Assessment, the modified Rankin Scale and the Stroke-specific quality of Life questionnaire. Adult patients with a recent stroke achieving a score of ≥12 on the Multidimensional Fatigue Inventory-20 general fatigue domain were...

Kv1.1 knock-in ataxic mice exhibit spontaneous myokymic activity exacerbated by fatigue, ischemia and low temperature.

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Brunetti, Orazio; Imbrici, Paola; Botti, Fabio Massimo; Pettorossi, Vito Enrico; D'Adamo, Maria Cristina; Valentino, Mario; Zammit, Christian; Mora, Marina; Gibertini, Sara; Di Giovanni, Giuseppe; Muscat, Richard; Pessia, Mauro

2012-09-01

Episodic ataxia type 1 (EA1) is an autosomal dominant neurological disorder characterized by myokymia and attacks of ataxic gait often precipitated by stress. Several genetic mutations have been identified in the Shaker-like K(+) channel Kv1.1 (KCNA1) of EA1 individuals, including V408A, which result in remarkable channel dysfunction. By inserting the heterozygous V408A, mutation in one Kv1.1 allele, a mouse model of EA1 has been generated (Kv1.1(V408A/+)). Here, we investigated the neuromuscular transmission of Kv1.1(V408A/+) ataxic mice and their susceptibility to physiologically relevant stressors. By using in vivo preparations of lateral gastrocnemius (LG) nerve-muscle from Kv1.1(+/+) and Kv1.1(V408A/+) mice, we show that the mutant animals exhibit spontaneous myokymic discharges consisting of repeated singlets, duplets or multiplets, despite motor nerve axotomy. Two-photon laser scanning microscopy from the motor nerve, ex vivo, revealed spontaneous Ca(2+) signals that occurred abnormally only in preparations dissected from Kv1.1(V408A/+) mice. Spontaneous bursting activity, as well as that evoked by sciatic nerve stimulation, was exacerbated by muscle fatigue, ischemia and low temperatures. These stressors also increased the amplitude of compound muscle action potential. Such abnormal neuromuscular transmission did not alter fiber type composition, neuromuscular junction and vascularization of LG muscle, analyzed by light and electron microscopy. Taken together these findings provide direct evidence that identifies the motor nerve as an important generator of myokymic activity, that dysfunction of Kv1.1 channels alters Ca(2+) homeostasis in motor axons, and also strongly suggest that muscle fatigue contributes more than PNS fatigue to exacerbate the myokymia/neuromyotonia phenotype. More broadly, this study points out that juxtaparanodal K(+) channels composed of Kv1.1 subunits exert an important role in dampening the excitability of motor nerve axons during

Vascular Endothelial Dysfunction in Inflammatory Bowel Diseases: Pharmacological and Nonpharmacological Targets

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Antonietta Gerarda Gravina

2018-01-01

Full Text Available Inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis, are chronic inflammatory conditions involving primarily the gastrointestinal tract. However, they may be also associated with systemic manifestations and comorbidities. The relationship between chronic inflammation and endothelial dysfunction has been extensively demonstrated. Mucosal immunity and gastrointestinal physiology are modified in inflammatory bowel diseases, and these modifications are mainly sustained by alterations of endothelial function. The key elements involved in this process are cytokines, inflammatory cells, growth factors, nitric oxide, endothelial adhesion molecules, and coagulation cascade factors. In this review, we discuss available data in literature concerning endothelial dysfunction in patients affected by inflammatory bowel disease and we focus our attention on both pharmacological and nonpharmacological therapeutic targets.

The effect of creep cavitation on the fatigue life under creep-fatigue interaction

International Nuclear Information System (INIS)

Nam, S.W.

1995-01-01

Low cycle fatigue tests have been carried out with three different materials (1Cr-Mo-V steel, 12Cr-Mo-V steel and 304 stainless steel) for the investigation of the effect of surface roughness on the fatigue life. To see the effect systematically, we have chosen those materials which may or may not form grain boundary cavities.Test results show that the continuous fatigue life of 1Cr-Mo-V steel and aged 304 stainless steel with a rough surface is decreased compared with that of the specimens with a smooth surface. These two alloys are found to have no grain boundary cavities formed under creep-fatigue test conditions. On the contrary, the fatigue life of 12Cr-Mo-V steel and solutionized 304 stainless steel in which grain boundary cavities are formed under creep-fatigue test conditions is not influenced by the states of surface roughness.The characteristic test results strongly confirm that the fatigue life of the specimen under creep-fatigue interaction, during which creep cavities are forming, may be controlled by the cavity nucleation and growth processes rather than the process of surface crack initiation. ((orig.))

Herpes zoster-associated voiding dysfunction in hematopoietic malignancy patients.

Science.gov (United States)

Imafuku, Shinichi; Takahara, Masakazu; Uenotsuchi, Takeshi; Iwato, Koji; Furue, Masutaka

2008-01-01

Voiding dysfunction is a rare but important complication of lumbo-sacral herpes zoster. Although the symptoms are transient, the clinical impact on immunocompromised patients cannot be overlooked. To clarify the time course of voiding dysfunction in herpes zoster, 13 herpes zoster patients with voiding dysfunction were retrospectively analyzed. Of 13 patients, 12 had background disease, and six of these were hematopoietic malignancies; four of these patients were hematopoietic stem cell transplant (HSCT) recipients. Ten patients had sacral lesions, two had lumbar, and one had thoracic lesions. Interestingly, patients with severe rash, or with hematopoietic malignancy had later onset of urinary retention than did patients with mild skin symptoms (Mann-Whitney U analysis, P = 0.053) or with other background disease (P = 0.0082). Patients with severe skin rash also had longer durations (P = 0.035). In one case, acute urinary retention occurred as late as 19 days after the onset of skin rash. In immune compromised subjects, attention should be paid to patients with herpes zoster in the lumbo-sacral area for late onset of acute urinary retention even after the resolution of skin symptoms.

Fatigue and fatigue-related symptoms in patients treated for different causes of hypothyroidism.

Science.gov (United States)

Louwerens, Marloes; Appelhof, Bente C; Verloop, Herman; Medici, Marco; Peeters, Robin P; Visser, Theo J; Boelen, Anita; Fliers, Eric; Smit, Johannes W A; Dekkers, Olaf M

2012-12-01

Research on determinants of well-being in patients on thyroid hormone replacement therapy is warranted, as persistent fatigue-related complaints are common in this population. In this study, we evaluated the impact of different states of hypothyroidism on fatigue and fatigue-related symptoms. Furthermore, the relationship between fatigue and the TSH receptor (TSHR)-Asp727Glu polymorphism, a common genetic variant of the TSHR, was analyzed. A cross-sectional study was performed in 278 patients (140 patients treated for differentiated thyroid carcinoma (DTC) and 138 with autoimmune hypothyroidism (AIH)) genotyped for the TSHR-Asp727Glu polymorphism. The multidimensional fatigue inventory (MFI-20) was used to assess fatigue, with higher MFI-20 scores indicating more fatigue-related complaints. MFI-20 scores were related to disease status and Asp727Glu polymorphism status. AIH patients scored significantly higher than DTC patients on all five MFI-20 subscales (P<0.001), independent of clinical and thyroid hormone parameters. The frequency of the TSHR-Glu727 allele was 7.2%. Heterozygous DTC patients had more favorable MFI-20 scores than wild-type DTC patients on four of five subscales. The modest effect of the TSHR-Asp727Glu polymorphism on fatigue was found in DTC patients only. AIH patients had significantly higher levels of fatigue compared with DTC patients, which could not be attributed to clinical or thyroid hormone parameters. The modest effect of the TSHR-Asp727Glu polymorphism on fatigue in DTC patients should be confirmed in other cohorts.

Oxidative stress and mitochondrial dysfunction in infected pregnant

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Нана Мерабівна Пасієшвілі

2015-04-01

Full Text Available The infected pregnant women have been various perinatal complications. The aim of the work was to clarify the role of oxidative stress and mitochondrial dysfunction in the development of perinatal complications in infected pregnant.Methods. The study included 68 pregnant women with signs of maternal-fetal infection (MFI and 30 pregnant women who were found infected (control group. Later pregnant with MFI were divided into 2 groups: the first included 30 women who received traditional antibacterial and antiviral therapy, the second group consisted of 28 women who were additionally given an immunomodulator in combination with ozone therapy.Results. During pregnancy with MFI it is characterized the thrombophilic disorders, break immune homeostasis pregnant, endothelial dysfunction, which adversely affects perinatal indicators.Conclusions. The use of immunomodulators and ozone therapy in the complex treatment of MFI is pathogenetically substantiated effective treatment of oxidative stress and mitochondrial toxicity in the prevention of perinatal complications in infected women

Myalgic Encephalomyelitis, Chronic Fatigue Syndrome, and Systemic Exertion Intolerance Disease: Three Distinct Clinical Entities

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Frank N.M. Twisk

2018-04-01

Full Text Available Many researchers consider chronic fatigue syndrome (CFS to be a synonym of Myalgic Encephalomyelitis (ME. However, the case criteria of ME and CFS define two distinct clinical entities. Although some patients will meet both case criteria, other patients can meet the diagnosis of ME and not fulfil the case criteria for CFS, while the diagnosis of CFS is largely insufficient to be qualified as a ME patient. ME is a neuromuscular disease with distinctive muscular symptoms, including prolonged muscle weakness after exertion, and neurological signs implicating cerebral dysfunction, including cognitive impairment and sensory symptoms. The only mandatory symptom of CFS is chronic fatigue. Chronic fatigue must be accompanied by at least four out of eight nonspecific symptoms: substantial impairment in short-term memory or concentration, a sore throat, tender lymph nodes, muscle pain, multijoint pain, a new type of headaches, unrefreshing sleep, and postexertional “malaise” lasting more than 24 h. So, regardless whether the name ME is appropriate or not, ME is not synonymous to CFS. That is not a matter of opinion, but a matter of definition. Due to the definitions of ME and CFS, “ME/CFS” does not exist and cannot be replaced by a new clinical entity (SEID: Systemic Exertion Intolerance Disease, as recently suggested.

The Association of IFI27 Expression and Fatigue Intensification during Localized Radiation Therapy: Implication of a Para-Inflammatory Bystander Response

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Leorey N. Saligan

2013-08-01

Full Text Available The mechanisms behind fatigue intensification during cancer therapy remain elusive. The interferon alpha-inducible protein 27 (IFI27 was the most up-regulated gene based on our previous microarray data in fatigued men with non-metastatic prostate cancer receiving localized external beam radiation therapy (EBRT. The purpose of this study was to confirm the IFI27 up-regulation and determine its association with fatigue intensification during EBRT. Peripheral blood samples and fatigue scores were collected at three time points—prior to EBRT, at midpoint, and at completion of EBRT. Confirmatory quantitative real time polymerase chain reaction (qPCR and enzyme-linked immunosorbent assay (ELISA were utilized to verify the microarray results. Subjects were a total of 40 Caucasian men with prostate cancer; 20 scheduled for EBRT (65.6 ± 7.5 years old, and 20 on active surveillance as controls (62.8 ± 6.1 years old. Significant IFI27 expression overtime during EBRT was confirmed by qPCR (p < 0.5, which correlated with fatigue scores during EBRT (R = −0.90, p = 0.006. Alterations in mechanisms associated with immune response and mitochondrial function that explain the up-regulation of IFI27 may provide an understanding of the pathways related to the intensification of fatigue during localized radiation therapy.

Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy

Science.gov (United States)

Hotchkiss, Richard S.; Monneret, Guillaume; Payen, Didier

2014-01-01

Sepsis — severe life-threatening infection with organ dysfunction — initiates a complex interplay of host pro- and anti-inflammatory processes. In a real sense, sepsis can be considered a race to the death between the pathogens and the host immune system. It is the proper balance between the often competing pro- and anti-inflammatory pathways that determines the fate of the individual. Although the field of sepsis research has witnessed the failure of many highly-touted clinical trials, a better understanding of the pathophysiological basis of the disorder and the mechanisms responsible for the associated pro- and anti-inflammatory responses is leading to a novel approach to treat this highly lethal condition. Biomarker-guided immunotherapy administered to patients at the proper immune phase of sepsis represents a potential major advance in the treatment of sepsis and more broadly in the field of infectious disease. PMID:24232462

Comparison of Fatigue Properties and Fatigue Crack Growth Rates of Various Implantable Metals

Science.gov (United States)

Okazaki, Yoshimitsu

2012-01-01

The fatigue strength, effects of a notch on the fatigue strength, and fatigue crack growth rate of Ti-15Zr-4Nb-4Ta alloy were compared with those of other implantable metals. Zr, Nb, and Ta are important alloying elements for Ti alloys for attaining superior long-term corrosion resistance and biocompatibility. The highly biocompatible Ti-15Zr-4Nb-4Ta alloy exhibited an excellent balance between strength and ductility. Its notched tensile strength was much higher than that of a smooth specimen. The strength of 20% cold-worked commercially pure (C.P.) grade 4 Ti was close to that of Ti alloy. The tension-to-tension fatigue strength of an annealed Ti-15Zr-4Nb-4Ta rod at 107 cycles was approximately 740 MPa. The fatigue strength of this alloy was much improved by aging treatment after solution treatment. The fatigue strengths of C.P. grade 4 Ti and stainless steel were markedly improved by 20% cold working. The fatigue strength of Co-Cr-Mo alloy was markedly increased by hot forging. The notch fatigue strengths of 20% cold-worked C.P. grade 4 Ti, and annealed and aged Ti-15Zr-4Nb-4Ta, and annealed Ti-6Al-4V alloys were less than those of the smooth specimens. The fatigue crack growth rate of Ti-15Zr-4Nb-4Ta was the same as that of Ti-6Al-4V. The fatigue crack growth rate in 0.9% NaCl was the same as that in air. Stainless steel and Co-Cr-Mo-Ni-Fe alloy had a larger stress-intensity factor range (ΔK) than Ti alloy.

Fatigue Assessment of Nickel-Titanium Peripheral Stents: Comparison of Multi-Axial Fatigue Models

Science.gov (United States)

Allegretti, Dario; Berti, Francesca; Migliavacca, Francesco; Pennati, Giancarlo; Petrini, Lorenza

2018-02-01

Peripheral Nickel-Titanium (NiTi) stents exploit super-elasticity to treat femoropopliteal artery atherosclerosis. The stent is subject to cyclic loads, which may lead to fatigue fracture and treatment failure. The complexity of the loading conditions and device geometry, coupled with the nonlinear material behavior, may induce multi-axial and non-proportional deformation. Finite element analysis can assess the fatigue risk, by comparing the device state of stress with the material fatigue limit. The most suitable fatigue model is not fully understood for NiTi devices, due to its complex thermo-mechanical behavior. This paper assesses the fatigue behavior of NiTi stents through computational models and experimental validation. Four different strain-based models are considered: the von Mises criterion and three critical plane models (Fatemi-Socie, Brown-Miller, and Smith-Watson-Topper models). Two stents, made of the same material with different cell geometries are manufactured, and their fatigue behavior is experimentally characterized. The comparison between experimental and numerical results highlights an overestimation of the failure risk by the von Mises criterion. On the contrary, the selected critical plane models, even if based on different damage mechanisms, give a better fatigue life estimation. Further investigations on crack propagation mechanisms of NiTi stents are required to properly select the most reliable fatigue model.

Fatigue Assessment of Nickel-Titanium Peripheral Stents: Comparison of Multi-Axial Fatigue Models

Science.gov (United States)

Allegretti, Dario; Berti, Francesca; Migliavacca, Francesco; Pennati, Giancarlo; Petrini, Lorenza

2018-03-01

Peripheral Nickel-Titanium (NiTi) stents exploit super-elasticity to treat femoropopliteal artery atherosclerosis. The stent is subject to cyclic loads, which may lead to fatigue fracture and treatment failure. The complexity of the loading conditions and device geometry, coupled with the nonlinear material behavior, may induce multi-axial and non-proportional deformation. Finite element analysis can assess the fatigue risk, by comparing the device state of stress with the material fatigue limit. The most suitable fatigue model is not fully understood for NiTi devices, due to its complex thermo-mechanical behavior. This paper assesses the fatigue behavior of NiTi stents through computational models and experimental validation. Four different strain-based models are considered: the von Mises criterion and three critical plane models (Fatemi-Socie, Brown-Miller, and Smith-Watson-Topper models). Two stents, made of the same material with different cell geometries are manufactured, and their fatigue behavior is experimentally characterized. The comparison between experimental and numerical results highlights an overestimation of the failure risk by the von Mises criterion. On the contrary, the selected critical plane models, even if based on different damage mechanisms, give a better fatigue life estimation. Further investigations on crack propagation mechanisms of NiTi stents are required to properly select the most reliable fatigue model.

MicroRNA-155 attenuates late sepsis-induced cardiac dysfunction through JNK and β-arrestin 2.

Science.gov (United States)

Zhou, Yu; Song, Yan; Shaikh, Zahir; Li, Hui; Zhang, Haiju; Caudle, Yi; Zheng, Shouhua; Yan, Hui; Hu, Dan; Stuart, Charles; Yin, Deling

2017-07-18

Cardiac dysfunction is correlated with detrimental prognosis of sepsis and contributes to a high risk of mortality. After an initial hyperinflammatory reaction, most patients enter a protracted state of immunosuppression (late sepsis) that alters both innate and adaptive immunity. The changes of cardiac function in late sepsis are not yet known. MicroRNA-155 (miR-155) is previously found to play important roles in both regulations of immune activation and cardiac function. In this study, C57BL/6 mice were operated to develop into early and late sepsis phases, and miR-155 mimic was injected through the tail vein 48 h after cecal ligation and puncture (CLP). The effect of miR-155 on CLP-induced cardiac dysfunction was explored in late sepsis. We found that increased expression of miR-155 in the myocardium protected against cardiac dysfunction in late sepsis evidenced by attenuating sepsis-reduced cardiac output and enhancing left ventricular systolic function. We also observed that miR-155 markedly reduced the infiltration of macrophages and neutrophils into the myocardium and attenuated the inflammatory response via suppression of JNK signaling pathway. Moreover, overexpression of β-arrestin 2 (Arrb2) exacerbated the mice mortality and immunosuppression in late sepsis. Furthermore, transfection of miR-155 mimic reduced Arrb2 expression, and then restored immunocompetence and improved survival in late septic mice. We conclude that increased miR-155 expression through systemic administration of miR-155 mimic attenuates cardiac dysfunction and improves late sepsis survival by targeting JNK associated inflammatory signaling and Arrb2 mediated immunosuppression.

[Epidemiology of fatigue in general practice].

Science.gov (United States)

Fuhrer, R

1994-11-01

The epidemiology of fatigue is not well known in France, and this study reports on factors associated with fatigue in a sample of 3,784 general practice patients. Prevalence rates according to several definitions of fatigue are presented and factors are examined that have been reported to be associated with fatigue. Although 41.2% of the sample report having experienced symptoms of fatigue for at least three days, only 7.6% declare fatigue as a reason for consulting a doctor. Women report more symptoms of fatigue, but they do not consult more often than men for this reason. Age is strongly correlated with fatigue, but this is found only for men. Socioprofessional category bears no relationship to fatigue as a reason for consultation, however, the diagnosis of fatigue is more often attributed to professionals and upper management than it is to office staff or skilled and unskilled workers. We do find a strong relationship between depressive symptomatology as measured by the Center for Epidemiologic Studies (CES-D) and fatigue; nonetheless, fatigue is neither sensitive nor specific to the diagnosis of depression.

High-intensity resistance training in multiple sclerosis - An exploratory study of effects on immune markers in blood and cerebrospinal fluid, and on mood, fatigue, health-related quality of life, muscle strength, walking and cognition.

Science.gov (United States)

Kierkegaard, Marie; Lundberg, Ingrid E; Olsson, Tomas; Johansson, Sverker; Ygberg, Sofia; Opava, Christina; Holmqvist, Lotta Widén; Piehl, Fredrik

2016-03-15

High-intensity resistance training is unexplored in people with multiple sclerosis. To evaluate effects of high-intensity resistance training on immune markers and on measures of mood, fatigue, health-related quality of life, muscle strength, walking and cognition. Further, to describe participants' opinion and perceived changes of the training. Twenty patients with relapsing-remitting multiple sclerosis performed high-intensity resistance training at an intensity of 80% of one-repetition maximum, twice a week for 12 weeks. Blood and optional cerebrospinal fluid samples, and data on secondary outcome measures were collected before and after intervention. A study-specific questionnaire was used for capturing participants' opinion. Seventeen participants completed the study. Plasma cytokine levels of tumor necrosis factor were significantly decreased post-intervention (p=0.001). Exploratory cytokine analyses in cerebrospinal fluid (n=8) did not reveal major changes. Significant and clinically important improvements were found in fatigue (p=0.001) and health-related quality of life (p=0.004). Measures of mood (p=0.002), muscle strength (p ≤ 0.001), walking speed (p=0.013) and cognition (p=0.04) were also improved. A majority of participants evaluated the training as very good and perceived changes to the better. High-intensity resistance training in persons with relapsing remitting multiple sclerosis with low disability had positive effects on peripheral pro-inflammatory cytokine levels, led to clinically relevant improvements in measures of fatigue and health-related quality of life, and was well tolerated. These results provide a basis for a larger randomized trial. Copyright © 2016 Elsevier B.V. All rights reserved.

Investigation of the effects of vanilloids in chronic fatigue syndrome.

Science.gov (United States)

Sarvaiya, Kuldeep; Goswami, Sunita

2016-10-01

To assess the effectiveness of TRPV1 modulators in animal model of Chronic fatigue syndrome (CFS). To assess central and peripheral behavioral activity of TRPV1 modulators. CFS was induced by forcing the rats to swim for 10min for 21 consecutive days. The rats were treated with capsaicin (TRPV1 agonist, 2.5mg/kg) and n-tert-butylcyclohexanol (TRPV1 antagonist, 10mg/kg) for 21days 30min before the exposure to stress procedure. The behavioral consequence of CFS was measured in terms of immobility time, grip strength, locomotor activity, and anxiety level using Rota rod, Actophotometer, and Elevated plus maze model respectively. The other parameters include Plasma corticosterone, adrenal gland and spleen weight, complete blood count, blood urea niterogen (BUN), Lactate dehydrogenase (LDH), Lipid peroxidation, catalase and reduced glutathione (GSH). TRPV1 modulators reversed (pchronic fatigue syndrome. The mechanism of action can be attributed to inhibition of TRPV1 channel and thereby modulating pain perception, neuroendocrine function, oxidative stress and immune function. Copyright © 2016 Elsevier Inc. All rights reserved.

Prolonged unexplained fatigue in paediatrics

NARCIS (Netherlands)

Bakker, R.J.

2010-01-01

Prolonged Unexplained Fatigue in Paediatrics. Fatigue, as the result of mental or physical exertion, will disappear after rest, drinks and food. Fatigue as a symptom of illness will recover with the recovering of the illness. But when fatigue is ongoing for a long time, and not the result of

Assessment of early onset of driver fatigue using multimodal fatigue measures in a static simulator.

Science.gov (United States)

Jagannath, M; Balasubramanian, Venkatesh

2014-07-01

Driver fatigue is an important contributor to road accidents. This paper reports a study that evaluated driver fatigue using multimodal fatigue measures, i.e., surface electromyography (sEMG), electroencephalography (EEG), seat interface pressure, blood pressure, heart rate and oxygen saturation level. Twenty male participants volunteered in this study by performing 60 min of driving on a static simulator. Results from sEMG showed significant physical fatigue (ρ fatigue. This will help us understand the influence of physical and mental fatigue on driver during monotonous driving. Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Fatigue and fatigue-related symptoms in patients treated for different causes of hypothyroidism

NARCIS (Netherlands)

Louwerens, M.; Appelhof, B.C.; Verloop, H.; Medici, M.; Peeters, R.P.; Visser, T.J.; Boelen, A.; Fliers, E.; Smit, J.W.A.; Dekkers, O.M.

2012-01-01

OBJECTIVE: Research on determinants of well-being in patients on thyroid hormone replacement therapy is warranted, as persistent fatigue-related complaints are common in this population. In this study, we evaluated the impact of different states of hypothyroidism on fatigue and fatigue-related

Fatigue and fatigue-related symptoms in patients treated for different causes of hypothyroidism

NARCIS (Netherlands)

Louwerens, Marloes; Appelhof, Bente C.; Verloop, Herman; Medici, Marco; Peeters, Robin P.; Visser, Theo J.; Boelen, Anita; Fliers, Eric; Smit, Johannes W. A.; Dekkers, Olaf M.

2012-01-01

Objective: Research on determinants of well-being in patients on thyroid hormone replacement therapy is warranted, as persistent fatigue-related complaints are common in this population. In this study, we evaluated the impact of different states of hypothyroidism on fatigue and fatigue-related

Fucoidan Supplementation Improves Exercise Performance and Exhibits Anti-Fatigue Action in Mice

Directory of Open Access Journals (Sweden)

Yi-Ming Chen

2014-12-01

Full Text Available Fucoidan (FCD is a well-known bioactive constituent of seaweed extract that possess a wide spectrum of activities in biological systems, including anti-cancer, anti-inflammation and modulation of immune systems. However, evidence on the effects of FCD on exercise performance and physical fatigue is limited. Therefore, we investigated the potential beneficial effects of FCD on ergogenic and anti-fatigue functions following physiological challenge. Male ICR mice from three groups (n = 8 per group were orally administered FCD for 21 days at 0, 310 and 620 mg/kg/day, which were, respectively, designated the vehicle, FCD-1X and FCD-2X groups. The results indicated that the FCD supplementations increased the grip strength (p = 0.0002 and endurance swimming time (p = 0.0195 in a dose-depend manner. FCD treatments also produced dose-dependent decreases in serum levels of lactate (p < 0.0001 and ammonia (p = 0.0025, and also an increase in glucose level (p < 0.0001 after the 15-min swimming test. In addition, FCD supplementation had few subchronic toxic effects. Therefore, we suggest that long-term supplementation with FCD can have a wide spectrum of bioactivities on health promotion, performance improvement and anti-fatigue.

Hyperthermia and fatigue

DEFF Research Database (Denmark)

Nybo, Lars

2008-01-01

The present review addresses mechanisms of importance for hyperthermia-induced fatigue during short intense activities and prolonged exercise in the heat. Inferior performance during physical activities with intensities that elicit maximal oxygen uptake is to a large extent related to perturbation...... of the cardiovascular function, which eventually reduces arterial oxygen delivery to the exercising muscles. Accordingly, aerobic energy turnover is impaired and anaerobic metabolism provokes peripheral fatigue. In contrast, metabolic disturbances of muscle homeostasis are less important during prolonged exercise...... in the heat, because increased oxygen extraction compensates for the reduction in systemic blood flow. The decrease in endurance seems to involve changes in the function of the central nervous system (CNS) that lead to fatigue. The CNS fatigue appears to be influenced by neurotransmitter activity...

Fatigue Experiences Among OCD Outpatients.

Science.gov (United States)

Pasquini, Massimo; Piacentino, Daria; Berardelli, Isabella; Roselli, Valentina; Maraone, Annalisa; Tarsitani, Lorenzo; Biondi, Massimo

2015-12-01

Patients with OCD are impaired in multiple domains of functioning and quality of life. While associated psychopathology complaints and neuropsychological deficits were reported, the subjective experience of general fatigue and mental fatigue was scarcely investigated. In this single-center case-control study we compared 50 non-depressed OCD outpatients consecutively recruited and 50 panic disorder (PD) outpatients, to determine whether they experienced fatigue differently. Assessment consisted of structured clinical interview for DSM-IV criteria by using the SCID-I and the SCID-II. Symptom severity was assessed using the Yale-Brown Obsessive-Compulsive Scale, the Hamilton Anxiety Rating Scale, the Hamilton Depression Rating Scale, the Clinical Global Impressions Scale, severity and the Global Assessment of Functioning Scale. Fatigue was assessed by using the Multidimensional Fatigue Inventory (MFI). Regarding MFI physical fatigue, an OR of 0.196 (95 % CI 0.080-0.478) was found, suggesting that its presence is associated with lower odds of OCD compared to PD. The same can be said for MFI mental fatigue, as an OR of 0.138 (95 % CI 0.049-0.326) was found, suggesting that its presence is associated with lower odds of OCD. Notably, OCD patients with OCDP co-morbidity reported higher scores of mental fatigue. In this study fatigue, including mental fatigue, seems not to be a prominent experience among adult non-depressed OCD patients.

Fatigue Crack Topography.

Science.gov (United States)

1984-01-01

alloys (2). [--I Fig. 6. Fatigue fracture in Nitrile- butadien rubber ( NBR ). Fig. 7. The characteristic features of fatigue fracture in press moulded...in plastics and even in rubber . It follows therefore, that fatigue fractures must also occur in the mineral layers of our earth or in the rock on...effective until the weakest point yields and forms a crack. To get a feeling for this process, you can imagine that the stressed article is made of rubber

Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury

Science.gov (United States)

De Simoni, Sara; Jenkins, Peter O; Bourke, Niall J; Fleminger, Jessica J; Jolly, Amy E; Patel, Maneesh C; Leech, Robert; Sharp, David J

2018-01-01

Abstract Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with

Plasma neuropeptide Y: a biomarker for symptom severity in chronic fatigue syndrome

Directory of Open Access Journals (Sweden)

Harvey Jeanna M

2010-12-01

Full Text Available Abstract Background Chronic fatigue syndrome (CFS is a complex, multi-symptom illness with a multisystem pathogenesis involving alterations in the nervous, endocrine and immune systems. Abnormalities in stress responses have been identified as potential triggers or mediators of CFS symptoms. This study focused on the stress mediator neuropeptide Y (NPY. We hypothesized that NPY would be a useful biomarker for CFS. Methods The CFS patients (n = 93 were from the Chronic Fatigue and Related Disorders Clinic at the University of Miami and met the 1994 case definition of Fukuda and colleagues. Healthy sedentary controls (n = 100 were from NIH or VA funded studies. Another fatiguing, multi-symptom illness, Gulf War Illness (GWI, was also compared to CFS. We measured NPY in plasma using a radioimmunoassay (RIA. Psychometric measures, available for a subset of CFS patients included: Perceived Stress Scale, Profile of Mood States, ATQ Positive & Negative Self-Talk Scores, the COPE, the Beck Depression Inventory, Fatigue Symptom Inventory, Cognitive Capacity Screening Examination, Medical Outcomes Survey Short Form-36, and the Quality of Life Scale. Results Plasma NPY was elevated in CFS subjects, compared to controls (p = .000 and to GWI cases (p = .000. Receiver operating characteristics (ROC curve analyses indicated that the predictive ability of plasma NPY to distinguish CFS patients from healthy controls and from GWI was significantly better than chance alone. In 42 patients with CFS, plasma NPY had significant correlations ( Conclusions This study is the first in the CFS literature to report that plasma NPY is elevated compared to healthy controls and to a fatigued comparison group, GWI patients. The significant correlations of NPY with stress, negative mood, general health, depression and cognitive function strongly suggest that this peptide be considered as a biomarker to distinguish subsets of CFS.

The role of tissue renin angiotensin aldosterone system in the development of endothelial dysfunction and arterial stiffness

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Annayya R Aroor

2013-10-01

Full Text Available Epidemiological studies support the notion that arterial stiffness is an independent predictor of adverse cardiovascular events contributing significantly to systolic hypertension, impaired ventricular-arterial coupling and diastolic dysfunction, impairment in myocardial oxygen supply and demand, and progression of kidney disease. Although arterial stiffness is associated with aging, it is accelerated in the presence of obesity and diabetes. The prevalence of arterial stiffness parallels the increase of obesity that is occurring in epidemic proportions and is partly driven by a sedentary life style and consumption of a high fructose, high salt and high fat western diet. Although the underlying mechanisms and mediators of arterial stiffness are not well understood, accumulating evidence supports the role of insulin resistance and endothelial dysfunction. The local tissue renin angiotensin aldosterone system (RAAS in the vascular tissue and immune cells and perivascular adipose tissue is recognized as an important element involved in endothelial dysfunction which contributes significantly to arterial stiffness. Activation of vascular RAAS is seen in humans and animal models of obesity and diabetes, and associated with enhanced oxidative stress and inflammation in the vascular tissue. The cross talk between angiotensin and aldosterone underscores the importance of mineralocorticoid receptors in modulation of insulin resistance, decreased bioavailability of nitric oxide, endothelial dysfunction and arterial stiffness. In addition, both innate and adaptive immunity are involved in this local tissue activation of RAAS. In this review we will attempt to present a unifying mechanism of how environmental and immunological factors are involved in this local tissue RAAS activation, and the role of this process in the development of endothelial dysfunction and arterial stiffness and targeting tissue RAAS activation.

Thermal fatigue appears to be more damaging than uniaxial isothermal fatigue for the austentic stainless steels, and application of multiaxial fatigue criteria

Energy Technology Data Exchange (ETDEWEB)

Fissolo, Antoine; Gourdin, Cedric [DM2S/SEMT/LISN, Gif sur Yvette (France); Vincent, Ludovic [DMN/SRMA/LCD, Gif sur Yvette (France)

2009-07-01

For nuclear reactor components, uniaxial isothermal fatigue curves are used to estimate the crack initiation under thermal fatigue. However, such approach would be not sufficient in some cases where cracking was observed. To investigate differences between uniaxial and thermal fatigue damage, tests have been carried out at CEA using the thermal fatigue devices SPLASH and FAT3D: a bi-dimensional (2-D) loading status is obtained in SPLASH, whereas a tri-dimensional (3-D) loading status is obtained in FAT3D. All the analysed tests clearly show that crack initiation in thermal fatigue is faster than in uniaxial isothermal fatigue conditions: for identical levels of strain, the number of cycles required to achieve crack initiation is significantly lower. The enhanced damaging effect probably results from a pure mechanical origin: a nearly perfect biaxial state corresponds to an increased hydrostatic stress. Consequently, multiaxial fatigue criteria must be applied. The Zamrik's strain criterion and the energy criterion proposed by Ecole Polytechnique provide the best estimations. In that framework, the proposed new method coupling both RCC-MR strain estimations and Zamrik's criterion appears to be more promising for the designer. (orig.)

Thermal fatigue appears to be more damaging than uniaxial isothermal fatigue for the austentic stainless steels, and application of multiaxial fatigue criteria

International Nuclear Information System (INIS)

Fissolo, Antoine; Gourdin, Cedric; Vincent, Ludovic

2009-01-01

For nuclear reactor components, uniaxial isothermal fatigue curves are used to estimate the crack initiation under thermal fatigue. However, such approach would be not sufficient in some cases where cracking was observed. To investigate differences between uniaxial and thermal fatigue damage, tests have been carried out at CEA using the thermal fatigue devices SPLASH and FAT3D: a bi-dimensional (2-D) loading status is obtained in SPLASH, whereas a tri-dimensional (3-D) loading status is obtained in FAT3D. All the analysed tests clearly show that crack initiation in thermal fatigue is faster than in uniaxial isothermal fatigue conditions: for identical levels of strain, the number of cycles required to achieve crack initiation is significantly lower. The enhanced damaging effect probably results from a pure mechanical origin: a nearly perfect biaxial state corresponds to an increased hydrostatic stress. Consequently, multiaxial fatigue criteria must be applied. The Zamrik's strain criterion and the energy criterion proposed by Ecole Polytechnique provide the best estimations. In that framework, the proposed new method coupling both RCC-MR strain estimations and Zamrik's criterion appears to be more promising for the designer. (orig.)

Mechanisms of PD-L1/PD-1-mediated CD8 T-cell dysfunction in the context of aging-related immune defects in the Eµ-TCL1 CLL mouse model.

Science.gov (United States)

McClanahan, Fabienne; Riches, John C; Miller, Shaun; Day, William P; Kotsiou, Eleni; Neuberg, Donna; Croce, Carlo M; Capasso, Melania; Gribben, John G

2015-07-09

T-cell defects, immune suppression, and poor antitumor immune responses are hallmarks of chronic lymphocytic leukemia (CLL), and PD-1/PD-L1 inhibitory signaling has emerged as a major immunosuppressive mechanism. However, the effect of different microenvironments and the confounding influence of aging are poorly understood. The current study uses the Eμ-TCL1 mouse model, which replicates human T-cell defects, as a preclinical platform to longitudinally examine patterns of T-cell dysfunction alongside developing CLL and in different microenvironments, with a focus on PD-1/PD-L1 interactions. The development of CLL was significantly associated with changes in T-cell phenotype across all organs and function. Although partly mirrored in aging wild-type mice, CLL-specific T-cell changes were identified. Murine CLL cells highly expressed PD-L1 and PD-L2 in all organs, with high PD-L1 expression in the spleen. CD3(+)CD8(+) T cells from leukemic and aging healthy mice highly expressed PD-1, identifying aging as a confounder, but adoptive transfer experiments demonstrated CLL-specific PD-1 induction. Direct comparisons of PD-1 expression and function between aging CLL mice and controls identified PD-1(+) T cells in CLL as a heterogeneous population with variable effector function. This is highly relevant for therapeutic targeting of CD8(+) T cells, showing the potential of reprogramming and selective subset expansion to restore antitumor immunity. © 2015 by The American Society of Hematology.

Evidence for a heritable predisposition to Chronic Fatigue Syndrome

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Bateman Lucinda

2011-05-01

Full Text Available Abstract Background Chronic Fatigue Syndrome (CFS came to attention in the 1980s, but initial investigations did not find organic causes. Now decades later, the etiology of CFS has yet to be understood, and the role of genetic predisposition in CFS remains controversial. Recent reports of CFS association with the retrovirus xenotropic murine leukemic virus-related virus (XMRV or other murine leukemia related retroviruses (MLV might also suggest underlying genetic implications within the host immune system. Methods We present analyses of familial clustering of CFS in a computerized genealogical resource linking multiple generations of genealogy data with medical diagnosis data of a large Utah health care system. We compare pair-wise relatedness among cases to expected relatedness in the Utah population, and we estimate risk for CFS for first, second, and third degree relatives of CFS cases. Results We observed significant excess relatedness of CFS cases compared to that expected in this population. Significant excess relatedness was observed for both close (p Conclusions These analyses provide strong support for a heritable contribution to predisposition to Chronic Fatigue Syndrome. A population of high-risk CFS pedigrees has been identified, the study of which may provide additional understanding.

[The role of immune system in the control of cancer development and growth].

Science.gov (United States)

Sütő, Gábor

2016-06-01

The role of immune system is the maintenace of the integritiy of the living organism. The elements of the immune system are connected by several ways forming a complex biological network. This network senses the changes of the inner and outer environment and works out the most effective response against infections and tumors. Dysfunction of the immune system leads to the development of cancer development and chronic inflammatory diseases. Modulation of the checkpoints of the immune system opened new perspecitves in the treatment of rheumatological and oncological diseases as well. Beside the potent antiinflammatory activity, new therapies are able to stimulate anticancer activity of the immune system. The result of these recent developments is a better outcome of malignant diseases, which had an unfavorable outcome in the past. Orv. Hetil., 2016, 157(Suppl. 2), 3-8.

Fatigue evaluation algorithms: Review

Energy Technology Data Exchange (ETDEWEB)

Passipoularidis, V.A.; Broendsted, P.

2009-11-15

A progressive damage fatigue simulator for variable amplitude loads named FADAS is discussed in this work. FADAS (Fatigue Damage Simulator) performs ply by ply stress analysis using classical lamination theory and implements adequate stiffness discount tactics based on the failure criterion of Puck, to model the degradation caused by failure events in ply level. Residual strength is incorporated as fatigue damage accumulation metric. Once the typical fatigue and static properties of the constitutive ply are determined,the performance of an arbitrary lay-up under uniaxial and/or multiaxial load time series can be simulated. The predictions are validated against fatigue life data both from repeated block tests at a single stress ratio as well as against spectral fatigue using the WISPER, WISPERX and NEW WISPER load sequences on a Glass/Epoxy multidirectional laminate typical of a wind turbine rotor blade construction. Two versions of the algorithm, the one using single-step and the other using incremental application of each load cycle (in case of ply failure) are implemented and compared. Simulation results confirm the ability of the algorithm to take into account load sequence effects. In general, FADAS performs well in predicting life under both spectral and block loading fatigue. (author)

Innate Immunity and Saliva in Candida albicans–mediated Oral Diseases

Science.gov (United States)

Salvatori, O.; Puri, S.; Tati, S.; Edgerton, M.

2016-01-01

The oral cavity is a unique niche where Candida albicans infections occur in immunocompetent as well as immunosuppressed individuals. Here we critically review the significance of human innate immune response in preventing oral candidiasis. One important line of defense against oropharyngeal candidiasis is the oral microbiota that prevents infection by competing for space and nutrients as well as by secreting antagonistic molecules and triggering local inflammatory responses. C. albicans is able to induce mucosal defenses through activation of immune cells and production of cytokines. Also, saliva contains various proteins that affect C. albicans growth positively by promoting mucosal adherence and negatively through immune exclusion and direct fungicidal activity. We further discuss the role of saliva in unifying host innate immune defenses against C. albicans as a communicating medium and how C. albicans overgrowth in the oral cavity may be a result of aberrations ranging from microbial dysbiosis and salivary dysfunction to epithelial damage. Last we underscore select oral diseases in which C. albicans is a contributory microorganism in immune-competent individuals. PMID:26747422

Examining fatigue in COPD

DEFF Research Database (Denmark)

Al-Shair, Khaled; Muellerova, Hana; Yorke, Janelle

2012-01-01

ABSTRACT: INTRODUCTION: Fatigue is a disruptive symptom that inhibits normal functional performance of COPD patients in daily activities. The availability of a short, simple, reliable and valid scale would improve assessment of the characteristics and influence of fatigue in COPD. METHODS......: At baseline, 2107 COPD patients from the ECLIPSE cohort completed the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scale. We used well-structured classic method, the principal components analysis (PCA) and Rasch analysis for structurally examining the 13-item FACIT-F. RESULTS: Four items...... were less able to capture fatigue characteristics in COPD and were deleted. PCA was applied to the remaining 9 items of the modified FACIT-F and resulted in three interpretable dimensions: i) general (5 items); ii) functional ability (2 items); and iii) psychosocial fatigue (2 items). The modified...

High temperature creep-fatigue design

International Nuclear Information System (INIS)

Tavassoli, A. A. F.; Fournier, B.; Sauzay, M.

2010-01-01

Generation IV fission and future fusion reactors envisage development of more efficient high temperature concepts where materials performances are key to their success. This paper examines different types of high temperature creep-fatigue interactions and their implications on design rules for the structural materials retained in both programmes. More precisely, the paper examines current status of design rules for the stainless steel type 316L(N), the conventional Modified 9Cr-1Mo martensitic steel and the low activation Eurofer steel. Results obtained from extensive high temperature creep, fatigue and creep-fatigue tests performed on these materials and their welded joints are presented. These include sequential creep-fatigue and relaxation creep-fatigue tests with hold times in tension, in compression or in both. Effects of larger plastic deformations on fatigue properties are studied through cyclic creep tests or fatigue tests with extended hold time in creep. In most cases, mechanical test results are accompanied with microstructural and fractographic observations. In the case of martensitic steels, the effect of oxidation is examined by performing creep-fatigue tests on identical specimens in vacuum. Results obtained are analyzed and their implications on design allowable and creep-fatigue interaction diagrams are presented. While reasonable confidence is found in predicting creep-fatigue damage through existing code procedures for austenitic stainless steels, effects of cyclic softening and coarsening of microstructure of martensitic steels throughout the fatigue life on materials properties need to be taken into account for more precise damage calculations. In the long-term, development of ferritic/martensitic steels with stable microstructure, such as ODS steels, is proposed. (authors)

High temperature creep-fatigue design

Energy Technology Data Exchange (ETDEWEB)

Tavassoli, A. A. F.; Fournier, B.; Sauzay, M. [CEA Saclay, DEN DMN, F-91191 Gif Sur Yvette (France)

2010-07-01

Generation IV fission and future fusion reactors envisage development of more efficient high temperature concepts where materials performances are key to their success. This paper examines different types of high temperature creep-fatigue interactions and their implications on design rules for the structural materials retained in both programmes. More precisely, the paper examines current status of design rules for the stainless steel type 316L(N), the conventional Modified 9Cr-1Mo martensitic steel and the low activation Eurofer steel. Results obtained from extensive high temperature creep, fatigue and creep-fatigue tests performed on these materials and their welded joints are presented. These include sequential creep-fatigue and relaxation creep-fatigue tests with hold times in tension, in compression or in both. Effects of larger plastic deformations on fatigue properties are studied through cyclic creep tests or fatigue tests with extended hold time in creep. In most cases, mechanical test results are accompanied with microstructural and fractographic observations. In the case of martensitic steels, the effect of oxidation is examined by performing creep-fatigue tests on identical specimens in vacuum. Results obtained are analyzed and their implications on design allowable and creep-fatigue interaction diagrams are presented. While reasonable confidence is found in predicting creep-fatigue damage through existing code procedures for austenitic stainless steels, effects of cyclic softening and coarsening of microstructure of martensitic steels throughout the fatigue life on materials properties need to be taken into account for more precise damage calculations. In the long-term, development of ferritic/martensitic steels with stable microstructure, such as ODS steels, is proposed. (authors)

Translating Fatigue to Human Performance

Science.gov (United States)

Enoka, Roger M.; Duchateau, Jacques

2016-01-01

Despite flourishing interest in the topic of fatigue—as indicated by the many presentations on fatigue at the 2015 annual meeting of the American College of Sports Medicine—surprisingly little is known about its impact on human performance. There are two main reasons for this dilemma: (1) the inability of current terminology to accommodate the scope of the conditions ascribed to fatigue, and (2) a paucity of validated experimental models. In contrast to current practice, a case is made for a unified definition of fatigue to facilitate its management in health and disease. Based on the classic two-domain concept of Mosso, fatigue is defined as a disabling symptom in which physical and cognitive function is limited by interactions between performance fatigability and perceived fatigability. As a symptom, fatigue can only be measured by self-report, quantified as either a trait characteristic or a state variable. One consequence of such a definition is that the word fatigue should not be preceded by an adjective (e.g., central, mental, muscle, peripheral, and supraspinal) to suggest the locus of the changes responsible for an observed level of fatigue. Rather, mechanistic studies should be performed with validated experimental models to identify the changes responsible for the reported fatigue. As indicated by three examples (walking endurance in old adults, time trials by endurance athletes, and fatigue in persons with multiple sclerosis) discussed in the review, however, it has proven challenging to develop valid experimental models of fatigue. The proposed framework provides a foundation to address the many gaps in knowledge of how laboratory measures of fatigue and fatigability impact real-world performance. PMID:27015386

The role of immune mechanisms in Tourette syndrome.

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Martino, Davide; Zis, Panagiotis; Buttiglione, Maura

2015-08-18

Tourette syndrome (TS) is a childhood-onset tic disorder associated with abnormal development of brain networks involved in the sensory and motor processing. An involvement of immune mechanisms in its pathophysiology has been proposed. Animal models based on active immunization with bacterial or viral mimics, direct injection of cytokines or patients' serum anti-neuronal antibodies, and transgenic approaches replicated stereotyped behaviors observed in human TS. A crucial role of microglia in the neural-immune crosstalk within TS and related disorders has been proposed by animal models and confirmed by recent post mortem studies. With analogy to autism, genetic and early life environmental factors could foster the involvement of immune mechanisms to the abnormal developmental trajectories postulated in TS, as well as lead to systemic immune dysregulation in this condition. Clinical studies demonstrate an association between TS and immune responses to pathogens like group A Streptococcus (GAS), although their role as risk-modifiers is still undefined. Overactivity of immune responses at a systemic level is suggested by clinical studies exploring cytokine and immunoglobulin levels, immune cell subpopulations, and gene expression profiling of peripheral lymphocytes. The involvement of autoantibodies, on the other hand, remains uncertain and warrants more work using live cell-based approaches. Overall, a body of evidence supports the hypothesis that disease mechanisms in TS, like other neurodevelopmental illnesses (e.g. autism), may involve dysfunctional neural-immune cross-talk, ultimately leading to altered maturation of brain pathways controlling different behavioral domains and, possibly, differences in organising immune and stress responses. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Determinants of seafarers’ fatigue

DEFF Research Database (Denmark)

Bøggild Dohrmann, Solveig; Leppin, Anja

2017-01-01

in the review. The main reason for exclusion was fatigue not being the outcome variable. Results: Most evidence was available for work time-related factors suggesting that working nights was most fatiguing, that fatigue levels were higher toward the end of watch or shift, and that the 6-h on–6-h off watch...

Nutritional strategies to optimize dairy cattle immunity.

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Sordillo, L M

2016-06-01

Dairy cattle are susceptible to increased incidence and severity of both metabolic and infectious diseases during the periparturient period. A major contributing factor to increased health disorders is alterations in bovine immune mechanisms. Indeed, uncontrolled inflammation is a major contributing factor and a common link among several economically important infectious and metabolic diseases including mastitis, retained placenta, metritis, displaced abomasum, and ketosis. The nutritional status of dairy cows and the metabolism of specific nutrients are critical regulators of immune cell function. There is now a greater appreciation that certain mediators of the immune system can have a reciprocal effect on the metabolism of nutrients. Thus, any disturbances in nutritional or immunological homeostasis can provide deleterious feedback loops that can further enhance health disorders, increase production losses, and decrease the availability of safe and nutritious dairy foods for a growing global population. This review will discuss the complex interactions between nutrient metabolism and immune functions in periparturient dairy cattle. Details of how either deficiencies or overexposure to macro- and micronutrients can contribute to immune dysfunction and the subsequent development of health disorders will be presented. Specifically, the ways in which altered nutrient metabolism and oxidative stress can interact to compromise the immune system in transition cows will be discussed. A better understanding of the linkages between nutrition and immunity may facilitate the design of nutritional regimens that will reduce disease susceptibility in early lactation cows. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Immune Cells Link Obesity-associated Type 2 Diabetes and Periodontitis

Science.gov (United States)

Zhu, M.; Nikolajczyk, B.S.

2014-01-01

The clinical association between obesity-associated type 2 diabetes (T2D) and periodontitis, coupled with the increasing prevalence of these diseases, justifies studies to identify mechanisms responsible for the vicious feed-forward loop between systemic and oral disease. Changes in the immune system are critical for both obesity-associated T2D and periodontitis and therefore may link these diseases. Recent studies at the intersection of immunology and metabolism have greatly advanced our understanding of the role the immune system plays in the transition between obesity and obesity-associated T2D and have shown that immune cells exhibit similar functional changes in obesity/T2D and periodontitis. Furthermore, myeloid and lymphoid cells likely synergize to promote obesity/T2D-associated periodontitis despite complexities introduced by disease interaction. Thus the groundwork is being laid for researchers to exploit existing models to understand immune cell dysfunction and break the devastating relationship between obesity-associated T2D and oral disease. PMID:24393706

Are There Any Natural Remedies That Reduce Chronic Fatigue Associated with Chronic Fatigue Syndrome?

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... natural remedies that reduce chronic fatigue associated with chronic fatigue syndrome? Answers from Brent A. Bauer, M.D. Researchers ... a variety of natural products for effectiveness against chronic fatigue syndrome. Most results have been disappointing. A few remedies — ...

Anti-Fatigue Effects of the Unique Polysaccharide Marker of Dendrobium officinale on BALB/c Mice.

Science.gov (United States)

Wei, Wei; Li, Zhi-Peng; Zhu, Tong; Fung, Hau-Yee; Wong, Tin-Long; Wen, Xin; Ma, Dik-Lung; Leung, Chung-Hang; Han, Quan-Bin

2017-01-18

Dendrobium officinale extract shows potent anti-fatigue effects; however, the active substance responsible for these effects remains undetermined. A glucomannan with a huge molecular size of 730 kDa, called DOP, was identified as the unique authentication marker of this expensive herb. DOP exhibited immunomodulating effects on macrophages and lymphocytes in our previous study. Clinical reports also showed that people with fatigue syndrome have a disturbed immune system. Because DOP is the unique and dominant component of D. officinale , we hypothesize that DOP may also have anti-fatigue activity. The present study aims to evaluate the anti-fatigue activity of DOP on BALB/c mice, with Rhodiola rosea extract as a positive control. DOP and Rhodiola rosea extract were orally administered at doses of 50 mg/kg and 100 mg/kg, respectively, for four weeks, and the anti-fatigue activity of DOP on BALB/c mice was evaluated using the weight-loaded swimming test. The contents of lactic dehydrogenase (LDH), creatine phosphokinase (CK), triglyceride (TG), blood urea nitrogen (BUN), superoxide dismutase (SOD), malondialdehyde (MDA), lactic acid (LD), and glutathione peroxidase (GSH-Px) in serum, glycogen of liver and gastrocnemius muscle were also determined. Their effects on variability of T cells and B cells were determined by using tetrazolium compound (MTS) method. The weight-loaded swimming exercise caused fatigue syndrome, mainly including the decreases of serum SOD/GSH-Px and gastrocnemius glycogen, as well as the increases of LDH, BUN, MDA, CK, TG, and LD in serum. All of these indicators of fatigue were inhibited to a certain extent by both DOP and Rhodiola rosea extract; however, the effects of DOP were much stronger than those of Rhodiola rosea extract. Compared to the positive control, mice dosed with DOP showed increases in endurance, body weight, and food intake. Furthermore, DOP-feeding mice significantly increased the cell variability of T lymphocytes and B

Anti-Fatigue Effects of the Unique Polysaccharide Marker of Dendrobium officinale on BALB/c Mice

Directory of Open Access Journals (Sweden)

Wei Wei

2017-01-01

Full Text Available Dendrobium officinale extract shows potent anti-fatigue effects; however, the active substance responsible for these effects remains undetermined. A glucomannan with a huge molecular size of 730 kDa, called DOP, was identified as the unique authentication marker of this expensive herb. DOP exhibited immunomodulating effects on macrophages and lymphocytes in our previous study. Clinical reports also showed that people with fatigue syndrome have a disturbed immune system. Because DOP is the unique and dominant component of D. officinale, we hypothesize that DOP may also have anti-fatigue activity. The present study aims to evaluate the anti-fatigue activity of DOP on BALB/c mice, with Rhodiola rosea extract as a positive control. DOP and Rhodiola rosea extract were orally administered at doses of 50 mg/kg and 100 mg/kg, respectively, for four weeks, and the anti-fatigue activity of DOP on BALB/c mice was evaluated using the weight-loaded swimming test. The contents of lactic dehydrogenase (LDH, creatine phosphokinase (CK, triglyceride (TG, blood urea nitrogen (BUN, superoxide dismutase (SOD, malondialdehyde (MDA, lactic acid (LD, and glutathione peroxidase (GSH-Px in serum, glycogen of liver and gastrocnemius muscle were also determined. Their effects on variability of T cells and B cells were determined by using tetrazolium compound (MTS method. The weight-loaded swimming exercise caused fatigue syndrome, mainly including the decreases of serum SOD/GSH-Px and gastrocnemius glycogen, as well as the increases of LDH, BUN, MDA, CK, TG, and LD in serum. All of these indicators of fatigue were inhibited to a certain extent by both DOP and Rhodiola rosea extract; however, the effects of DOP were much stronger than those of Rhodiola rosea extract. Compared to the positive control, mice dosed with DOP showed increases in endurance, body weight, and food intake. Furthermore, DOP-feeding mice significantly increased the cell variability of T lymphocytes

Influence of diabetes mellitus on immunity to human tuberculosis.

Science.gov (United States)

Kumar Nathella, Pavan; Babu, Subash

2017-09-01

Type 2 diabetes mellitus(DM) is a major risk factor for the development of active pulmonary tuberculosis (TB), with development of DM pandemic in countries where TB is also endemic. Understanding the impact of DM on TB and the determinants of co-morbidity is essential in responding to this growing public health problem with improved therapeutic approaches. Despite the clinical and public health significance posed by the dual burden of TB and DM, little is known about the immunological and biochemical mechanisms of susceptibility. One possible mechanism is that an impaired immune response in patients with DM facilitates either primary infection with Mycobacterium tuberculosis or reactivation of latent TB. Diabetes is associated with immune dysfunction and alterations in the components of the immune system, including altered levels of specific cytokines and chemokines. Some effects of DM on adaptive immunity that are potentially relevant to TB defence have been identified in humans. In this review, we summarize current findings regarding the alterations in the innate and adaptive immune responses and immunological mechanisms of susceptibility of patients with DM to M. tuberculosis infection and disease. © 2017 John Wiley & Sons Ltd.

Compressive Fatigue in Wood

DEFF Research Database (Denmark)

Clorius, Christian Odin; Pedersen, Martin Bo Uhre; Hoffmeyer, Preben

1999-01-01

An investigation of fatigue failure in wood subjected to load cycles in compression parallel to grain is presented. Small clear specimens of spruce are taken to failure in square wave formed fatigue loading at a stress excitation level corresponding to 80% of the short term strength. Four...... frequencies ranging from 0.01 Hz to 10 Hz are used. The number of cycles to failure is found to be a poor measure of the fatigue performance of wood. Creep, maximum strain, stiffness and work are monitored throughout the fatigue tests. Accumulated creep is suggested identified with damage and a correlation...

Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies.

Directory of Open Access Journals (Sweden)

Iris Broce

2018-01-01

Full Text Available Converging evidence suggests that immune-mediated dysfunction plays an important role in the pathogenesis of frontotemporal dementia (FTD. Although genetic studies have shown that immune-associated loci are associated with increased FTD risk, a systematic investigation of genetic overlap between immune-mediated diseases and the spectrum of FTD-related disorders has not been performed.Using large genome-wide association studies (GWASs (total n = 192,886 cases and controls and recently developed tools to quantify genetic overlap/pleiotropy, we systematically identified single nucleotide polymorphisms (SNPs jointly associated with FTD-related disorders-namely, FTD, corticobasal degeneration (CBD, progressive supranuclear palsy (PSP, and amyotrophic lateral sclerosis (ALS-and 1 or more immune-mediated diseases including Crohn disease, ulcerative colitis (UC, rheumatoid arthritis (RA, type 1 diabetes (T1D, celiac disease (CeD, and psoriasis. We found up to 270-fold genetic enrichment between FTD and RA, up to 160-fold genetic enrichment between FTD and UC, up to 180-fold genetic enrichment between FTD and T1D, and up to 175-fold genetic enrichment between FTD and CeD. In contrast, for CBD and PSP, only 1 of the 6 immune-mediated diseases produced genetic enrichment comparable to that seen for FTD, with up to 150-fold genetic enrichment between CBD and CeD and up to 180-fold enrichment between PSP and RA. Further, we found minimal enrichment between ALS and the immune-mediated diseases tested, with the highest levels of enrichment between ALS and RA (up to 20-fold. For FTD, at a conjunction false discovery rate < 0.05 and after excluding SNPs in linkage disequilibrium, we found that 8 of the 15 identified loci mapped to the human leukocyte antigen (HLA region on Chromosome (Chr 6. We also found novel candidate FTD susceptibility loci within LRRK2 (leucine rich repeat kinase 2, TBKBP1 (TBK1 binding protein 1, and PGBD5 (piggyBac transposable element

Fatigue after Stroke: The Patient's Perspective

Directory of Open Access Journals (Sweden)

Victoria Louise Barbour

2012-01-01

Full Text Available Background. Fatigue after stroke is common and distressing to patients. Aims. Our aims were to explore patients' perceptions of post-stroke fatigue, including the causes of fatigue and the factors that alleviate fatigue, in a mixed methods study. Results. We interviewed 15 patients who had had a stroke and were inpatients on stroke rehabilitation wards. A substantial proportion of patients reported that their fatigue started at the time of their stroke. Various different factors were reported to improve fatigue, including exercise, good sleep, rehabilitation and rest. Fatigue influences patients' sense of “control” after their stroke. Conclusion. Our results are consistent with the possibility that poststroke fatigue might be triggered by factors that occur at the time of the stroke (e.g., the stroke lesion itself, or admission to hospital and then exacerbated by poor sleep and boredom. These factors should be considered when developing complex interventions to improve post-stroke fatigue.

The role of the immune system in neurodegenerative disorders: Adaptive or maladaptive?

Science.gov (United States)

Doty, Kevin R; Guillot-Sestier, Marie-Victoire; Town, Terrence

2015-08-18

Neurodegenerative diseases share common features, including catastrophic neuronal loss that leads to cognitive or motor dysfunction. Neuronal injury occurs in an inflammatory milieu that is populated by resident and sometimes, infiltrating, immune cells - all of which participate in a complex interplay between secreted inflammatory modulators and activated immune cell surface receptors. The importance of these immunomodulators is highlighted by the number of immune factors that have been associated with increased risk of neurodegeneration in recent genome-wide association studies. One of the more difficult tasks for designing therapeutic strategies for immune modulation against neurodegenerative diseases is teasing apart beneficial from harmful signals. In this regard, learning more about the immune components of these diseases has yielded common themes. These unifying concepts should eventually enable immune-based therapeutics for treatment of Alzheimer׳s and Parkinson׳s diseases and amyotrophic lateral sclerosis. Targeted immune modulation should be possible to temper maladaptive factors, enabling beneficial immune responses in the context of neurodegenerative diseases. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease. Copyright © 2014 Elsevier B.V. All rights reserved.

The Progress of T Cell Immunity Related to Prognosis in Gastric Cancer.

Science.gov (United States)

Wei, Ming; Shen, Duo; Mulmi Shrestha, Sachin; Liu, Juan; Zhang, Junyi; Yin, Ying

2018-01-01

Gastric cancer is the fifth most common malignancy all over the world, and the factors that can affect progress and prognosis of the gastric cancer patients are various, such as TNM stages, invasive depth, and lymph node metastasis ratio. T cell immunity is important component of human immunity system and immunity responding to tumor and dysfunction or imbalance of T cell immunity will lead to serious outcomes for body. T cell immunity includes many different types of cells, CD4+ T cell, CD8+ T cell, memory cell, and so on, and each of them has special function on antitumor response or tumor immune escape which is revealed in lung cancer, colorectal cancer, breast cancer, ovarian cancer, and so on. But its correlation with gastric cancer is not clear. Our review was preformed to explore the relationship between the progress and prognosis of gastric cancer (GC) and T cell immunity. According to recent researches, T cell immunity may have an important role in the progress and prognosis of GCs, but its function is affected by location, category, related molecule, and interaction between the cells, and some effects still are controversial. More researches are needed to clarify this correlation.

Fretting fatigue life estimation using fatigue damage gradient correction factor in various contact configurations

Energy Technology Data Exchange (ETDEWEB)

Hwang, Dong Hyeon; Cho, Sung-San [Hongik University, Seoul (Korea, Republic of)

2017-03-15

A fretting fatigue life estimation method that takes into account the stress gradient effect was developed by the authors [Journal of Mechanical Science and Technology, 28 (2014) 2153-2159]. In the developed method, fatigue damage value at the cracking location is corrected with fatigue damage gradient and the corrected value is compared directly with the plain fatigue data for life estimation. In other words, the correction factor is the ratio of plain fatigue damage to fretting fatigue damage at the same life and a function of fatigue damage gradient. Since reliability of the method was verified only for cylinder-on-flat contact configuration in the previous study, the present study extends application of the method to flat-on-flat contact configurations by developing the correction factor for both the contact configuration. Fretting fatigue experiments were conducted to obtain fatigue life data for various fretting pads. Finite element analyses were conducted to evaluate the Smith-Watson-Topper (SWT) fatigue damage parameter in the cracking region. It is revealed that the SWT parameter in fat-on-flat contact configuration decreases exponentially away from the surface as in cylinder-on-flat contact configuration, and thus the SWT gradient at the surface can be evaluated reliably. Moreover, it is found that decrease in the SWT parameter around the cracking location can be expressed by piecewise exponential curves. If the gradient of SWT at the surface is used as a representative value of SWT gradient, it is impossible to establish functional relationship between the SWT gradient and the correction factor for both the contact configurations although it was possible for cylinder-on-flat contact configuration. However, if weighted average of the SWT gradient values obtained from each exponential curve in the piecewise exponential curve is used as a representative value, the correction factor for both the contact configurations becomes a function of the SWT gradient

Fatigue in soccer

DEFF Research Database (Denmark)

Mohr, Magni; Krustrup, Peter; Bangsbo, Jens

2005-01-01

This review describes when fatigue may develop during soccer games and the potential physiological mechanisms that cause fatigue in soccer. According to time?-?motion analyses and performance measures during match-play, fatigue or reduced performance seems to occur at three different stages......, acidity or the breakdown of creatine phosphate. Instead, it may be related to disturbances in muscle ion homeostasis and an impaired excitation of the sarcolemma. Soccer players' ability to perform maximally is inhibited in the initial phase of the second half, which may be due to lower muscle...... concentrations in a considerable number of individual muscle fibres. In a hot and humid environment, dehydration and a reduced cerebral function may also contribute to the deterioration in performance. In conclusion, fatigue or impaired performance in soccer occurs during various phases in a game, and different...

Role of the Immune System in Hypertension.

Science.gov (United States)

Rodriguez-Iturbe, Bernardo; Pons, Hector; Johnson, Richard J

2017-07-01

High blood pressure is present in more than one billion adults worldwide and is the most important modifiable risk factor of death resulting from cardiovascular disease. While many factors contribute to the pathogenesis of hypertension, a role of the immune system has been firmly established by a large number of investigations from many laboratories around the world. Immunosuppressive drugs and inhibition of individual cytokines prevent or ameliorate experimental hypertension, and studies in genetically-modified mouse strains have demonstrated that lymphocytes are necessary participants in the development of hypertension and in hypertensive organ injury. Furthermore, immune reactivity may be the driving force of hypertension in autoimmune diseases. Infiltration of immune cells, oxidative stress, and stimulation of the intrarenal angiotensin system are induced by activation of the innate and adaptive immunity. High blood pressure results from the combined effects of inflammation-induced impairment in the pressure natriuresis relationship, dysfunctional vascular relaxation, and overactivity of the sympathetic nervous system. Imbalances between proinflammatory effector responses and anti-inflammatory responses of regulatory T cells to a large extent determine the severity of inflammation. Experimental and human studies have uncovered autoantigens (isoketal-modified proteins and heat shock protein 70) of potential clinical relevance. Further investigations on the immune reactivity in hypertension may result in the identification of new strategies for the treatment of the disease. Copyright © 2017 the American Physiological Society.

Low cycle fatigue: high cycle fatigue damage accumulation in a 304L austenitic stainless steel

International Nuclear Information System (INIS)

Lehericy, Y.

2007-05-01

The aim of this study was to evaluate the consequences of a Low Cycle Fatigue pre-damage on the subsequent fatigue limit of a 304L stainless steel. The effects of hardening and severe roughness (grinding) have also been investigated. In a first set of tests, the evolution of the surface damage induced by the different LCF pre-cycling was characterized. This has permitted to identify mechanisms and kinetics of damage in the plastic domain for different surface conditions. Then, pre-damaged samples were tested in the High Cycle Fatigue domain in order to establish the fatigue limits associated with each level of pre-damage. Results evidence that, in the case of polished samples, an important number of cycles is required to initiate surface cracks ant then to affect the fatigue limit of the material but, in the case of ground samples, a few number of cycles is sufficient to initiate cracks and to critically decrease the fatigue limit. The fatigue limit of pre-damaged samples can be estimated using the stress intensity factor threshold. Moreover, this detrimental effect of severe surface conditions is enhanced when fatigue tests are performed under a positive mean stress (author)

Reduction of fatigue in Sjögren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study.

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Dass, S; Bowman, S J; Vital, E M; Ikeda, K; Pease, C T; Hamburger, J; Richards, A; Rauz, S; Emery, P

2008-11-01

Primary Sjögren syndrome (pSS) causes significant systemic symptoms including fatigue as well as glandular dysfunction. There are currently no effective systemic therapies; however, open label series have suggested that rituximab may be beneficial for systemic and glandular manifestations. Therefore, we performed a double blind, placebo-controlled, randomised pilot study of the efficacy of rituximab in reducing fatigue in pSS. A total of 17 patients with pSS and a score on fatigue visual analogue scale (VAS) >50 were randomised to receive either 2 infusions of rituximab 1 g or placebo; patients also received oral and intravenous steroids. Outcome measures included: the proportion of patients with >20% reduction in fatigue VAS, changes in pSS related symptoms, health related quality of life and immunological parameters of pSS. These were measured 6 months after therapy. There was significant improvement from baseline in fatigue VAS in the rituximab group (p<0.001) in contrast to the placebo group (p = 0.147). There was a significant difference between the groups at 6 months in the social functioning score of SF-36 (p = 0.01) and a trend to significant difference in the mental health domain score of SF-36 (p = 0.06). There was one episode of serum sickness in the rituximab treated group. This is the first double blind study of rituximab in pSS to show benefit; further studies are justified.

Pharmaceutical composition and drug effect of synthetic Bacopa monnieri L. health promoting agent from the perspective of resistance fatigue.

Science.gov (United States)

Chen, Zhidan; Yan, Yanqin

2017-09-01

Bacopa monnieri has effect on the nervous system, digestive system and blood circulation systems. In this paper, the authors conducted pharmacological analysis on Bacopa monniera and its innovative pharmaceutical preparation of promote motor function. The extract of the drug has some effect on relieving the fatigue and providing the movement function. By analyzing the composition and efficacy of Chinese herbal extracts, it can be seen that these drugs have obvious effect on improving immunity. Experimental results show that the agent can increase the liver glycogen energy reserves, reduce Bla and BUN levels, balance and energy metabolism of muscle cells in the environment, it plays a positive role to improve the exercise capacity and exercise fatigue.

Visual perception of fatigued lifting actions.

Science.gov (United States)

Fischer, Steven L; Albert, Wayne J; McGarry, Tim

2012-12-01

Fatigue-related changes in lifting kinematics may expose workers to undue injury risks. Early detection of accumulating fatigue offers the prospect of intervention strategies to mitigate such fatigue-related risks. In a first step towards this objective, this study investigated whether fatigue detection was accessible to visual perception and, if so, what was the key visual information required for successful fatigue discrimination. Eighteen participants were tasked with identifying fatigued lifts when viewing 24 trials presented using both video and point-light representations. Each trial comprised a pair of lifting actions containing a fresh and a fatigued lift from the same individual presented in counter-balanced sequence. Confidence intervals demonstrated that the frequency of correct responses for both sexes exceeded chance expectations (50%) for both video (68%±12%) and point-light representations (67%±10%), demonstrating that fatigued lifting kinematics are open to visual perception. There were no significant differences between sexes or viewing condition, the latter result indicating kinematic dynamics as providing sufficient information for successful fatigue discrimination. Moreover, results from single viewer investigation reported fatigue detection (75%) from point-light information describing only the kinematics of the box lifted. These preliminary findings may have important workplace applications if fatigue discrimination rates can be improved upon through future research. Copyright © 2012 Elsevier B.V. All rights reserved.

Corrosion fatigue of steels

International Nuclear Information System (INIS)

Spaehn, H.; Wagner, G.H.

1976-01-01

Corrosion fatigue phenomena can be classified into two main groups according to the electrochemical state of the metal surface in the presence of electrolytes: the active and the passive state with an important sub-group of corrosion fatigue in the unstable passive state. The allowable stress for structures exposed to the conjoint action of corrosion and fatigue is influenced by many factors: kind of media, number of cycles, frequency, mean stress, size, notches, loading mode, alloy composition and mechanical strength. A critical literature review shows contradictory results if a classification by the electrochemical surface state is not applied. Case histories and counter measures illustrate the practical importance of corrosion fatigue in many branches of industry as well as the urgent need for a better knowledge about the mutual influence of the phenomena to get rules by which the engineer can appraise the risk of corrosion fatigue. (orig.) [de

Muscle Deoxygenation Causes Muscle Fatigue

Science.gov (United States)

Murthy, G.; Hargens, A. R.; Lehman, S.; Rempel, D.

1999-01-01

Muscle fatigue is a common musculoskeletal disorder in the work place, and may be a harbinger for more disabling cumulative trauma disorders. Although the cause of fatigue is multifactorial, reduced blood flow and muscle oxygenation may be the primary factor in causing muscle fatigue during low intensity muscle exertion. Muscle fatigue is defined as a reduction in muscle force production, and also occurs among astronauts who are subjected to postural constraints while performing lengthy, repetitive tasks. The objectives of this research are to: 1) develop an objective tool to study the role of decreased muscle oxygenation on muscle force production, and 2) to evaluate muscle fatigue during prolonged glovebox work.

Targeted overexpression of mitochondrial catalase protects against cancer chemotherapy-induced skeletal muscle dysfunction.

Science.gov (United States)

Gilliam, Laura A A; Lark, Daniel S; Reese, Lauren R; Torres, Maria J; Ryan, Terence E; Lin, Chien-Te; Cathey, Brook L; Neufer, P Darrell

2016-08-01

The loss of strength in combination with constant fatigue is a burden on cancer patients undergoing chemotherapy. Doxorubicin, a standard chemotherapy drug used in the clinic, causes skeletal muscle dysfunction and increases mitochondrial H2O2 We hypothesized that the combined effect of cancer and chemotherapy in an immunocompetent breast cancer mouse model (E0771) would compromise skeletal muscle mitochondrial respiratory function, leading to an increase in H2O2-emitting potential and impaired muscle function. Here, we demonstrate that cancer chemotherapy decreases mitochondrial respiratory capacity supported with complex I (pyruvate/glutamate/malate) and complex II (succinate) substrates. Mitochondrial H2O2-emitting potential was altered in skeletal muscle, and global protein oxidation was elevated with cancer chemotherapy. Muscle contractile function was impaired following exposure to cancer chemotherapy. Genetically engineering the overexpression of catalase in mitochondria of muscle attenuated mitochondrial H2O2 emission and protein oxidation, preserving mitochondrial and whole muscle function despite cancer chemotherapy. These findings suggest mitochondrial oxidants as a mediator of cancer chemotherapy-induced skeletal muscle dysfunction. Copyright © 2016 the American Physiological Society.

Effect of ratchet strain on fatigue and creep–fatigue strength of Mod.9Cr–1Mo steel

International Nuclear Information System (INIS)

Ando, Masanori; Isobe, Nobuhiro; Kikuchi, Koichi; Enuma, Yasuhiro

2012-01-01

Highlights: ► Uniaxial fatigue and creep–fatigue tests with superimposed strain were performed. ► Variety of superimposed strain were applied as ratchet strain in the tests. ► Effect of superimposed strain on fatigue and creep–fatigue life is negligible. ► A cyclic softening character reducing the effect of superimposed strain. - Abstract: The effect of ratcheting deformation on fatigue and creep–fatigue life in Mod.9Cr–1Mo steel was investigated. Uniaxial fatigue and creep–fatigue testing with superimposed strain were performed to evaluate the effect of ratcheting deformation on the failure cycle. In a series of tests, a specific amount of superimposed strain was accumulated in each cycle. The accumulated strain as ratcheting deformation, cycles to reach the accumulated strain, and test temperatures were varied in the tests. In the fatigue tests with superimposed strain at 550 °C, slight reductions of failure lives were observed. All of the numbers of cycles to failure in the fatigue tests with superimposed strain were within a factor of 1.5 of that of the fatigue test without superimposed strain at 550 °C. The apparent relationship between failure cycles and testing parameters was not observed. In fatigue tests with superimposed strain at 550 °C, maximum mean stress was insignificant and generated in early cycles because Mod.9Cr–1Mo steel exhibits cyclic softening characteristics. It was assumed that suppression of mean stress generation by cyclic softening reduces the effect of ratcheting strain. Conversely, failure lives were increased by accumulated strain in the test conducted at 450 °C because of stress–strain hysteresis loop shrinkage caused by cyclic softening induced by the accumulated strain. In the creep–fatigue tests with superimposed strain, test results indicated that the accumulated stain was negligible. It was concluded that the effect of ratcheting deformation on fatigue and creep–fatigue life is negligible as long

All Fatigue is Not Created Equal: The Association of Fatigue and Its Subtypes on Pain Interference in Orofacial Pain.

Science.gov (United States)

Boggero, Ian A; Rojas-Ramirez, Marcia V; Carlson, Charles R

2017-03-01

Fatigue is known to be a pathway through which depression, psychological distress, pain intensity, and sleep disturbance influence pain interference, but the independent effects of fatigue on pain interference after controlling for these variables remains unknown. In addition, no study to date has tested whether fatigue subtypes of general fatigue, mental fatigue, emotional fatigue, physical fatigue, or vigor differentially predict pain interference. The current study tested these associations using archival medical data of 2133 chronic orofacial pain patients, who completed a battery of psychological questionnaires at the time of their first appointment at an orofacial pain clinic. Hierarchical linear regression analysis revealed that after controlling for depression, psychological distress, sleep disturbance, pain intensity, and demographic variables, fatigue predicted higher pain interference (B=0.70, SE=0.17, Ppain interference after controlling for the aforementioned variables. The findings suggest that fatigue is an important independent predictor of pain interference and not merely a mediator. These findings also suggest that not all fatigue is created equal. Interventions aimed at reducing pain interference should target specific fatigue symptoms of physical fatigue and vigor. Future research investigating the independent associations of fatigue subtypes on pain outcomes may help clarify the nature of the interrelationships between pain and fatigue.

Impacts of obesity and stress on neuromuscular fatigue development and associated heart rate variability.

Science.gov (United States)

Mehta, R K

2015-02-01

Obesity and stress are independently associated with decrements in neuromuscular functions. The present study examined the interplay of obesity and stress on neuromuscular fatigue and associated heart rate variability (HRV). Forty-eight non-obese (18.5obese (30⩽BMI) adults performed repetitive handgrip exertions at 30% of their maximum strength until exhaustion in the absence and presence of a mental arithmetic stressor. Dependent measures included gold standard fatigue indicators (endurance time and rate of strength loss), perceived effort and mental demand, heart rate and temporal (RMSSD: root mean square of successive differences between N-N intervals) and spectral (LF/HF: ratio of low to high frequency) indices of HRV. Stress negatively affected endurance time (Pobesity × stress interactions were found on endurance time (P=0.0073), rate of strength loss (P=0.027) and perceived effort (P=0.026), indicating that stress increased fatigability, particularly in the obese group. Both obesity (P=0.001) and stress (P=0.033) independently lowered RMSSD. Finally, stress increased LF/HF ratio (P=0.028) and the interaction of stress and obesity (P=0.008) indicated that this was augmented in the obese group. The present study provides the first evidence that stress-related neuromuscular fatigue development is accelerated in obese individuals. In addition, the stress condition resulted in poorer HRV indices, which is indicative of autonomic dysfunction, particularly in the obese group. These findings indicate that workers are more susceptible to fatigue in high-stress work environments, particularly those with higher BMI, which can increase the risk of musculoskeletal injuries as well as cardiovascular diseases in this population.

Thermal fatigue strength estimation of 2.25Cr-1Mo steel under creep-fatigue interaction

International Nuclear Information System (INIS)

Kuwahara, Kazuo; Nitta, Akihito; Kitamura, Takayuki

1980-01-01

A 2-1/4Cr-1Mo steel is one of principal materials for high temperature equipments in nuclear and thermal power plants. The authors experimentally analyzed the high temperature fatigue strength and creep strength of a 2-1/4 Cr-1Mo steel main steam pipe which had been used in a thermal plant for operation up to 130,000 hours, and pointed out that the strain-range vs. life curves crossed each other due to the difference of temperature-strain phase in thermal fatigue. This suggests that it is difficult to estimate thermal fatigue life of steel materials having been subjected to different temperature-strain phase on the basis of isothermal low-cycle fatigue life at the upper limit temperature of thermal fatigue, and that it is urgently required to establish an appropriate method of evaluating thermal fatigue life. The authors attempted to prove that the strain range partitioning method used for the evaluation of thermal fatigue life in SUS 304 steels is applicable to this 2-1/4Cr-1Mo steel. Consequently, it was found that the thermal fatigue life could be estimated within a factor of 2.5 by the application of this method. (author)

Fatigue and radiotherapy. A literature review; Fatigue et radiotherapie. Revue de la litterature

Energy Technology Data Exchange (ETDEWEB)

Dilhuydy, J.M.; Ouhtatou, F.; Laporte, C.; Nguyen, T.V.F.; Vendrely, V. [Institut Bergonie Centre Regional de Lutte Contre le Cancer, 33 - Bordeaux (France); Dilhuydy, J.M. [Federation Nationale des Centres de Lutte Contre le Cancer, FNCLCC, Groupe Rehabilitation, 75 - Paris (France); Dilhuydy, M.S. [Hopital Saint-Andre, Service de Medecine Interne, 33 - Bordeaux (France)

2001-11-01

Fatigue is a common complaint for the cancer patient during and after radiotherapy, according to the published studies. Fatigue is a subjective symptom mostly underestimated by oncologists and other care givers. Etiology is complex, poorly understood in spite of obvious causes like insomnia, nausea, pain, depression, psychological distress, anemia, hypothyroidism, menopause disturbances, treatment adverse effects. Fatigue presents multi-factorial and multidimensional aspects. To evaluate it, many tools can be used as single-item, unidimensional and multidimensional instruments. Practically, the open discussion with the patient throughout radiotherapy is essential to define it. Taking charge fatigue requires its acknowledgement by radiotherapist, treatment of associated symptoms with a multidisciplinary approach. (authors)

Development and characterization of fatigue resistant aramid reinforced aluminium laminates (ARALL) for fatigue critical aircraft components

International Nuclear Information System (INIS)

Qaiser, M. H.; Umar, S.; Nauman, S.

2013-01-01

The structural weight of an aircraft has always been a controlling parameter that governs its fuel efficiency and transport capacity. In pursuit of achieving light-weight aircraft structures, high design stress levels have to be adopted and materials with high specific strength such as Aluminum etc. are to be deployed. However, an extensive spectrum of fatigue load exists at the aircraft wings and other aerodynamic components that may cause initiation and propagation of fatigue cracks and concludes in a catastrophic rupture. Fatigue is therefore the limiting design parameter in such cases and materials with high fatigue resistance are then required. A major improvement in the fatigue behavior was observed by laminating Kevlar fibers with Aluminum using epoxy. ARALL (Aramid Reinforced Aluminum Laminates) is a fatigue resistant hybrid composite that consists of layers of thin high strength aluminum alloy sheets surface bonded with aramid fibers. The intact aramid fibers tie up the fatigue cracks, thus reducing the stress intensity factor at the crack tip as a result of which the fatigue properties of can be enhanced with orders of magnitude as compared to monolithic high strength Aluminum alloy sheets. Significant amount of weight savings can be achieved in fatigue critical components in comparison with the traditional materials used in aircraft. (author)

Development and characterization of fatigue resistant Aramid reinforced aluminium laminates (ARALL) for fatigue Critical aircraft components

Science.gov (United States)

Qaiser, M. H.; Umar, S.; Nauman, S.

2014-06-01

The structural weight of an aircraft has always been a controlling parameter that governs its fuel efficiency and transport capacity. In pursuit of achieving light-weight aircraft structures, high design stress levels have to be adopted and materials with high specific strength such as Aluminum etc. are to be deployed. However, an extensive spectrum of fatigue load exists at the aircraft wings and other aerodynamic components that may cause initiation and propagation of fatigue cracks and concludes in a catastrophic rupture. Fatigue is therefore the limiting design parameter in such cases and materials with high fatigue resistance are then required. A major improvement in the fatigue behavior was observed by laminating Kevlar fibers with Aluminum using epoxy. ARALL (Aramid Reinforced ALuminum Laminates) is a fatigue resistant hybrid composite that consists of layers of thin high strength aluminum alloy sheets surface bonded with aramid fibers. The intact aramid fibers tie up the fatigue cracks, thus reducing the stress intensity factor at the crack tip as a result of which the fatigue properties of can be enhanced with orders of magnitude as compared to monolithic high strength Aluminum alloy sheets. Significant amount of weight savings can be achieved in fatigue critical components in comparison with the traditional materials used in aircraft.

Development and characterization of fatigue resistant Aramid reinforced aluminium laminates (ARALL) for fatigue Critical aircraft components

International Nuclear Information System (INIS)

Qaiser, M H; Umar, S; Nauman, S

2014-01-01

The structural weight of an aircraft has always been a controlling parameter that governs its fuel efficiency and transport capacity. In pursuit of achieving light-weight aircraft structures, high design stress levels have to be adopted and materials with high specific strength such as Aluminum etc. are to be deployed. However, an extensive spectrum of fatigue load exists at the aircraft wings and other aerodynamic components that may cause initiation and propagation of fatigue cracks and concludes in a catastrophic rupture. Fatigue is therefore the limiting design parameter in such cases and materials with high fatigue resistance are then required. A major improvement in the fatigue behavior was observed by laminating Kevlar fibers with Aluminum using epoxy. ARALL (Aramid Reinforced ALuminum Laminates) is a fatigue resistant hybrid composite that consists of layers of thin high strength aluminum alloy sheets surface bonded with aramid fibers. The intact aramid fibers tie up the fatigue cracks, thus reducing the stress intensity factor at the crack tip as a result of which the fatigue properties of can be enhanced with orders of magnitude as compared to monolithic high strength Aluminum alloy sheets. Significant amount of weight savings can be achieved in fatigue critical components in comparison with the traditional materials used in aircraft

Inflammatory fatigue and sickness behaviour - lessons for the diagnosis and management of chronic fatigue syndrome.

Science.gov (United States)

Arnett, S V; Clark, I A

2012-12-10

Persistent and severe fatigue is a common part of the presentation of a diverse range of disease processes. There is a growing body of evidence indicating a common inflammatory pathophysiology underlying many conditions where fatigue is a primary patient concern, including chronic fatigue syndrome. This review explores current models of how inflammatory mediators act on the central nervous system to produce fatigue and sickness behaviour, and the commonality of these processes in conditions as diverse as surgical trauma, infection, various cancers, inflammatory bowel disease, connective tissue diseases and autoimmune diseases. We also discuss evidence indicating chronic fatigue syndrome may have important pathophysiological similarities with cytokine mediated sickness behaviour, and what lessons can be applied from sickness behaviour to chronic fatigue syndrome with regards to the diagnosis and management. Copyright © 2012 Elsevier B.V. All rights reserved.

Mental Fatigue Affects Visual Selective Attention

NARCIS (Netherlands)

Faber, Leon G.; Maurits, Natasha M.; Lorist, Monicque M.

2012-01-01

Mental fatigue is a form of fatigue, induced by continuous task performance. Mentally fatigued people often report having a hard time keeping their attention focussed and being easily distracted. In this study, we examined the relation between mental fatigue, as induced by time on task, and

Standard guide for fretting fatigue testing

CERN Document Server

American Society for Testing and Materials. Philadelphia

2010-01-01

1.1 This guide defines terminology and covers general requirements for conducting fretting fatigue tests and reporting the results. It describes the general types of fretting fatigue tests and provides some suggestions on developing and conducting fretting fatigue test programs. 1.2 Fretting fatigue tests are designed to determine the effects of mechanical and environmental parameters on the fretting fatigue behavior of metallic materials. This guide is not intended to establish preference of one apparatus or specimen design over others, but will establish guidelines for adherence in the design, calibration, and use of fretting fatigue apparatus and recommend the means to collect, record, and reporting of the data. 1.3 The number of cycles to form a fretting fatigue crack is dependent on both the material of the fatigue specimen and fretting pad, the geometry of contact between the two, and the method by which the loading and displacement are imposed. Similar to wear behavior of materials, it is important t...

Probabilistic Fatigue Damage Program (FATIG)

Science.gov (United States)

Michalopoulos, Constantine

2012-01-01

FATIG computes fatigue damage/fatigue life using the stress rms (root mean square) value, the total number of cycles, and S-N curve parameters. The damage is computed by the following methods: (a) traditional method using Miner s rule with stress cycles determined from a Rayleigh distribution up to 3*sigma; and (b) classical fatigue damage formula involving the Gamma function, which is derived from the integral version of Miner's rule. The integration is carried out over all stress amplitudes. This software solves the problem of probabilistic fatigue damage using the integral form of the Palmgren-Miner rule. The software computes fatigue life using an approach involving all stress amplitudes, up to N*sigma, as specified by the user. It can be used in the design of structural components subjected to random dynamic loading, or by any stress analyst with minimal training for fatigue life estimates of structural components.

Classifying post-stroke fatigue: Optimal cut-off on the Fatigue Assessment Scale.

Science.gov (United States)

Cumming, Toby B; Mead, Gillian

2017-12-01

Post-stroke fatigue is common and has debilitating effects on independence and quality of life. The Fatigue Assessment Scale (FAS) is a valid screening tool for fatigue after stroke, but there is no established cut-off. We sought to identify the optimal cut-off for classifying post-stroke fatigue on the FAS. In retrospective analysis of two independent datasets (the '2015' and '2007' studies), we evaluated the predictive validity of FAS score against a case definition of fatigue (the criterion standard). Area under the curve (AUC) and sensitivity and specificity at the optimal cut-off were established in the larger 2015 dataset (n=126), and then independently validated in the 2007 dataset (n=52). In the 2015 dataset, AUC was 0.78 (95% CI 0.70-0.86), with the optimal ≥24 cut-off giving a sensitivity of 0.82 and specificity of 0.66. The 2007 dataset had an AUC of 0.83 (95% CI 0.71-0.94), and applying the ≥24 cut-off gave a sensitivity of 0.84 and specificity of 0.67. Post-hoc analysis of the 2015 dataset revealed that using only the 3 most predictive FAS items together ('FAS-3') also yielded good validity: AUC 0.81 (95% CI 0.73-0.89), with sensitivity of 0.83 and specificity of 0.75 at the optimal ≥8 cut-off. We propose ≥24 as a cut-off for classifying post-stroke fatigue on the FAS. While further validation work is needed, this is a positive step towards a coherent approach to reporting fatigue prevalence using the FAS. Copyright © 2017 Elsevier Inc. All rights reserved.

Fatigue Analysis of Large-scale Wind turbine

Directory of Open Access Journals (Sweden)

Zhu Yongli

2017-01-01

Full Text Available The paper does research on top flange fatigue damage of large-scale wind turbine generator. It establishes finite element model of top flange connection system with finite element analysis software MSC. Marc/Mentat, analyzes its fatigue strain, implements load simulation of flange fatigue working condition with Bladed software, acquires flange fatigue load spectrum with rain-flow counting method, finally, it realizes fatigue analysis of top flange with fatigue analysis software MSC. Fatigue and Palmgren-Miner linear cumulative damage theory. The analysis result indicates that its result provides new thinking for flange fatigue analysis of large-scale wind turbine generator, and possesses some practical engineering value.

Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatic tachycardia syndrome.

Science.gov (United States)

Lewis, I; Pairman, J; Spickett, G; Newton, J L

2013-05-01

A significant proportion of patients with chronic fatigue syndrome (CFS) also have postural orthostatic tachycardia syndrome (POTS). We aimed to characterize these patients and differentiate them from CFS patients without POTS in terms of clinical and autonomic features. A total of 179 patients with CFS (1994 Centers for Disease Control and Prevention criteria) attending one of the largest Department of Health-funded CFS clinical services were included in this study. Outcome measures were as follows: (i) symptom assessment tools including the fatigue impact scale, Chalder fatigue scale, Epworth sleepiness scale (ESS), orthostatic grading scale (OGS) and hospital anxiety and depression scale (HADS-A and -D, respectively), (ii) autonomic function analysis including heart rate variability and (iii) haemodynamic responses including left ventricular ejection time and systolic blood pressure drop upon standing. CFS patients with POTS (13%, n = 24) were younger (29 ± 12 vs. 42 ± 13 years, P fatigued (Chalder fatigue scale, 8 ± 4 vs. 10 ± 2, P = 0.002), less depressed (HADS-D, 6 ± 4 vs. 9 ± 4, P = 0.01) and had reduced daytime hypersomnolence (ESS, 7 ± 6 vs. 10 ± 5, P = 0.02), compared with patients without POTS. In addition, they exhibited greater orthostatic intolerance (OGS, 11 ± 5; P < 0.0001) and autonomic dysfunction. A combined clinical assessment tool of ESS ≤9 and OGS ≥9 identifies accurately CFS patients with POTS with 100% positive and negative predictive values. The presence of POTS marks a distinct clinical group of CFS patents, with phenotypic features differentiating them from those without POTS. A combination of validated clinical assessment tools can determine which CFS patients have POTS with a high degree of accuracy, and thus potentially identify those who require further investigation and consideration for therapy to control heart rate. © 2013 The Association for the Publication of the Journal of Internal Medicine.

Increased autoimmune activity against 5-HT: a key component of depression that is associated with inflammation and activation of cell-mediated immunity, and with severity and staging of depression.

Science.gov (United States)

Maes, Michael; Ringel, Karl; Kubera, Marta; Berk, Michael; Rybakowski, Janusz

2012-02-01

Depression is characterized by inflammation and cell-mediated immune (CMI) activation and autoimmune reactions directed against a multitude of self-epitopes. There is evidence that the inflammatory response in depression causes dysfunctions in the metabolism of 5-HT, e.g. lowering the 5-HT precursor tryptophan, and upregulating 5-HT receptor mRNA. This study has been undertaken to examine autoimmune activity directed against 5-HT in relation to CMI activation and inflammation. 5-HT antibodies were examined in major depressed patients (n=109) versus normal controls (n=35) in relation to serum neopterin and lysozyme, and plasma pro-inflammatory cytokines (PIC), i.e. interleukin-1 (IL-1) and tumor necrosis factor-α (TNFα). Severity of depression was assessed with the Hamilton Depression Rating Scale (HDRS) and severity of fatigue and somatic symptoms with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale. The incidence of anti-5-HT antibody activity was significantly higher in depressed patients (54.1%), and in particular in those with melancholia (82.9%), than in controls (5.7%). Patients with positive 5-HT antibodies showed increased serum neopterin and lysozyme, and plasma TNFα and IL-1; higher scores on the HDRS and FF scales, and more somatic symptoms, including malaise and neurocognitive dysfunctions. There was a significant association between autoimmune activity to 5-HT and the number of previous depressive episodes. The autoimmune reactions directed against 5-HT might play a role in the pathophysiology of depression and the onset of severe depression. The strong association between autoimmune activity against 5-HT and inflammation/CMI activation is explained by multiple, reciprocal pathways between these factors. Exposure to previous depressive episodes increases the incidence of autoimmune activity directed against 5-HT, which in turn may increase the likelihood to develop new depressive episodes. These findings suggest that sensitization

Fatigue analysis of aluminum drill pipes

Directory of Open Access Journals (Sweden)

João Carlos Ribeiro Plácido

2005-12-01

Full Text Available An experimental program was performed to investigate the fundamental fatigue mechanisms of aluminum drill pipes. Initially, the fatigue properties were determined through small-scale tests performed in an optic-mechanical fatigue apparatus. Additionally, full-scale fatigue tests were carried out with three aluminum drill pipe specimens under combined loading of cyclic bending and constant axial tension. Finally, a finite element model was developed to simulate the stress field along the aluminum drill pipe during the fatigue tests and to estimate the stress concentration factors inside the tool joints. By this way, it was possible to estimate the stress values in regions not monitored during the fatigue tests.

Sleep Dysfunction and Gastrointestinal Diseases.

Science.gov (United States)

Khanijow, Vikesh; Prakash, Pia; Emsellem, Helene A; Borum, Marie L; Doman, David B

2015-12-01

Sleep deprivation and impaired sleep quality have been associated with poor health outcomes. Many patients experience sleep disturbances, which can increase the risk of medical conditions such as hypertension, obesity, stroke, and heart disease as well as increase overall mortality. Recent studies have suggested that there is a strong association between sleep disturbances and gastrointestinal diseases. Proinflammatory cytokines, such as tumor necrosis factor, interleukin-1, and interleukin-6, have been associated with sleep dysfunction. Alterations in these cytokines have been seen in certain gastrointestinal diseases, such as gastroesophageal reflux disease, inflammatory bowel disease, liver disorders, and colorectal cancer. It is important for gastroenterologists to be aware of the relationship between sleep disorders and gastrointestinal illnesses to ensure good care for patients. This article reviews the current research on the interplay between sleep disorders, immune function, and gastrointestinal diseases.

Flexural fatigue life prediction of closed hat-section using materially nonlinear axial fatigue characteristics

Science.gov (United States)

Razzaq, Zia

1989-01-01

Straight or curved hat-section members are often used as structural stiffeners in aircraft. For instance, they are employed as stiffeners for the dorsal skin as well as in the aerial refueling adjacent area structure in F-106 aircraft. The flanges of the hat-section are connected to the aircraft skin. Thus, the portion of the skin closing the hat-section interacts with the section itself when resisting the stresses due to service loads. The flexural fatigue life of such a closed section is estimated using materially nonlinear axial fatigue characteristics. It should be recognized that when a structural shape is subjected to bending, the fatigue life at the neutral axis is infinity since the normal stresses are zero at that location. Conversely, the fatigue life at the extreme fibers where the normal bending stresses are maximum can be expected to be finite. Thus, different fatigue life estimates can be visualized at various distances from the neural axis. The problem becomes compounded further when significant portions away from the neutral axis are stressed into plastic range. A theoretical analysis of the closed hat-section subjected to flexural cyclic loading is first conducted. The axial fatigue characteristics together with the related axial fatigue life formula and its inverted form given by Manson and Muralidharan are adopted for an aluminum alloy used in aircraft construction. A closed-form expression for predicting the flexural fatigue life is then derived for the closed hat-section including materially nonlinear action. A computer program is written to conduct a study of the variables such as the thicknesses of the hat-section and the skin, and the type of alloy used. The study has provided a fundamental understanding of the flexural fatigue life characteristics of a practical structural component used in aircraft when materially nonlinear action is present.

Fatigue of vanadium--hydrogen alloys

International Nuclear Information System (INIS)

Lee, K.S.; Stoloff, N.S.

1975-01-01

Hydrogen contents near and above the room temperature solubility limit increase the high cycle fatigue life but decrease low cycle life of polycrystalline vanadium. Changes in endurance limit with hydrides may be a consequence of decreased cyclic strain hardening coefficient, n'. 132 ppM hydrogen in solution has only a slightly beneficial effect on stress controlled fatigue life and essentially no effect on low cycle fatigue life. Unalloyed vanadium exhibits profuse striations, while hydrides produce cleavage cracks in fatigued samples. 10 fig

Evaluation of micro fatigue crack growth under equi-biaxial stress by membranous pressure fatigue test

International Nuclear Information System (INIS)

Iida, Satoshi; Abe, Shigeki; Nakamura, Takao; Kamaya, Masayuki

2014-01-01

For preventing nuclear power plant (NPP) accidents, NPPs are required to ensure system safety in long term safe operation under aging degradation. Now, fatigue accumulation is one of major ageing phenomena and are evaluated to ensure safety by design fatigue curve that are based on the results of uniaxial fatigue tests. On the other hand, thermal stress that occurs in piping of actual components is not uniaxial but equi-biaxial. For accurate evaluation, it is required to conform real circumstance. In this study, membranous pressure fatigue test was conducted to simulated equi-biaxial stress. Crack initiation and crack growth were examined by replica investigation. Calculation result of equivalent stress intensity factor shows crack growth under equi-biaxial stress is faster than under uniaxial stress. It is concluded that equi-biaxial fatigue behavior should be considered in the evaluation of fatigue crack initiation and crack growth. (author)

Muscle injections with lidocaine improve resting fatigue and pain in patients with chronic fatigue syndrome

Directory of Open Access Journals (Sweden)

Staud R

2017-06-01

Full Text Available Roland Staud,1 Taylor Kizer,1 Michael E Robinson2 1Department of Medicine, College of Medicine, 2Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA Objective: Patients with chronic fatigue syndrome (CFS complain of long-lasting fatigue and pain which are not relieved by rest and worsened by physical exertion. Previous research has implicated metaboreceptors of muscles to play an important role for chronic fatigue and pain. Therefore, we hypothesized that blocking impulse input from deep tissues with intramuscular lidocaine injections would improve not only the pain but also fatigue of CFS patients. Methods: In a double-blind, placebo-controlled study, 58 CFS patients received 20 mL of 1% lidocaine (200 mg or normal saline once into both trapezius and gluteal muscles. Study outcomes included clinical fatigue and pain, depression, and anxiety. In addition, mechanical and heat hyperalgesia were assessed and serum levels of lidocaine were obtained after the injections. Results: Fatigue ratings of CFS patients decreased significantly more after lidocaine compared to saline injections (p = 0.03. In contrast, muscle injections reduced pain, depression, and anxiety (p < 0.001, but these changes were not statistically different between lidocaine and saline (p > 0.05. Lidocaine injections increased mechanical pain thresholds of CFS patients (p = 0.04 but did not affect their heat hyperalgesia. Importantly, mood changes or lidocaine serum levels did not significantly predict fatigue reductions. Conclusion: These results demonstrate that lidocaine injections reduce clinical fatigue of CFS patients significantly more than placebo, suggesting an important role of peripheral tissues for chronic fatigue. Future investigations will be necessary to evaluate the clinical benefits of such interventions. Keywords: muscle injections, lidocaine, metaboreceptor, chronic fatigue 

Fatigue Analysis of a Mono-Tower Platform

DEFF Research Database (Denmark)

Kirkegaard, Poul Henning; Sørensen, John Dalsgaard; Brincker, Rune

In this paper, a fatigue reliability analysis of a Mono-tower platform is presented. The failure mode, fatigue failure in the butt welds, is investigated with two different models. The one with the fatigue strength expressed through SN relations, the other with the fatigue strength expressed thro...... of the natural period, damping ratio, current, stress Spectrum and parameters describing the fatigue strength. Further, soil damping is shown to be significant for the Mono-tower.......In this paper, a fatigue reliability analysis of a Mono-tower platform is presented. The failure mode, fatigue failure in the butt welds, is investigated with two different models. The one with the fatigue strength expressed through SN relations, the other with the fatigue strength expressed...... through linear-elastic fracture mechanics (LEFM). In determining the cumulative fatigue damage, Palmgren-Miner's rule is applied. Element reliability as well as systems reliability is estimated using first-order reliability methods (FORM). The sensitivity of the systems reliability to various parameters...

Complement activation, endothelial dysfunction, insulin resistance and chronic heart failure

DEFF Research Database (Denmark)

Bjerre, M.; Kistorp, C.; Hansen, T.K.

2010-01-01

Objectives. Patients with chronic heart failure (CHF) have an exaggerated immune response, endothelial damage/dysfunction, and increased risk of diabetes mellitus (DM). The inter-relationship(s) between indices of complement activation (soluble membrane attack complex, sMAC), inflammation (hs...... to ischemic heart disease (IHD) as compared with CHF patients with non-ischemic ethiology (p = 0.02), but were not predictive of survival or progression of CHF. A moderate strong relation between sMAC and sEsel levels was found beta = 0.33 (p ... damaging of the heart tissue...

Epigenetic Targets for Reversing Immune Defects Caused by Alcohol Exposure

Science.gov (United States)

Curtis, Brenda J.; Zahs, Anita; Kovacs, Elizabeth J.

2013-01-01

Alcohol consumption alters factors that modify gene expression without changing the DNA code (i.e., epigenetic modulators) in many organ systems, including the immune system. Alcohol enhances the risk for developing several serious medical conditions related to immune system dysfunction, including acute respiratory distress syndrome (ARDS), liver cancer, and alcoholic liver disease (ALD). Binge and chronic drinking also render patients more susceptible to many infectious pathogens and advance the progression of HIV infection by weakening both innate and adaptive immunity. Epigenetic mechanisms play a pivotal role in these processes. For example, alcohol-induced epigenetic variations alter the developmental pathways of several types of immune cells (e.g., granulocytes, macrophages, and T-lymphocytes) and through these and other mechanisms promote exaggerated inflammatory responses. In addition, epigenetic mechanisms may underlie alcohol’s ability to interfere with the barrier functions of the gut and respiratory systems, which also contribute to the heightened risk of infections. Better understanding of alcohol’s effects on these epigenetic processes may help researchers identify new targets for the development of novel medications to prevent or ameliorate alcohol’s detrimental effects on the immune system. PMID:24313169

The role of autonomic function in exercise-induced endogenous analgesia : a case-control study in myalgic encephalomyelitis/chronic fatigue syndrome and healthy people

OpenAIRE

Van Oosterwijck, Jessica; Marusic, Uros; De Wandele, Inge; Paul, Lorna; Meeus, Mira; Moorkens, Greta; Lambrecht, Luc; Danneels, Lieven; Nijs, Jo

2017-01-01

BACKGROUND: Patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are unable to activate brain-orchestrated endogenous analgesia (or descending inhibition) in response to exercise. This physiological impairment is currently regarded as one factor explaining post-exertional malaise in these patients. Autonomic dysfunction is also a feature of ME/CFS. OBJECTIVES: This study aims to examine the role of the autonomic nervous system in exercise-induced analgesia in healthy...

Biaxial fatigue of metals the present understanding

CERN Document Server

Schijve, Jaap

2016-01-01

Problems of fatigue under multiaxial fatigue loads have been addressed in a very large number of research publications. The present publication is primarily a survey of biaxial fatigue under constant amplitude loading on metal specimens. It starts with the physical understanding of the fatigue phenomenon under biaxial fatigue loads. Various types of proportional and non-proportional biaxial fatigue loads and biaxial stress distributions in a material are specified. Attention is paid to the fatigue limit, crack nucleation, initial micro crack growth and subsequent macro-crack in different modes of crack growth. The interference between the upper and lower surfaces of a fatigue crack is discussed. Possibilities for predictions of biaxial fatigue properties are analysed with reference to the similarity concept. The significance of the present understanding for structural design problems is considered. The book is completed with a summary of major observations.

Stimulation of dendritic cells enhances immune response after photodynamic therapy

Science.gov (United States)

Mroz, Pawel; Castano, Ana P.; Hamblin, Michael R.

2009-02-01

Photodynamic therapy (PDT) involves the administration of photosensitizers followed by illumination of the primary tumor with red light producing reactive oxygen species that cause vascular shutdown and tumor cell necrosis and apoptosis. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, priming of the immune system to recognize tumor-associated antigens (TAA). The induction of specific CD8+ Tlymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. This process is however, often sub-optimal, in part due to tumor-induced DC dysfunction. Instead of DC that can become mature and activated and have a potent antigen-presenting and immune stimulating phenotype, immature dendritic cells (iDC) are often found in tumors and are part of an immunosuppressive milieu including regulatory T-cells and immunosuppressive cytokines such as TGF-beta and IL10. We here report on the use of a potent DC activating agent, an oligonucleotide (ODN) that contains a non-methylated CpG motif and acts as an agonist of toll like receptor (TLR) 9. TLR activation is a danger signal to notify the immune system of the presence of invading pathogens. CpG-ODN (but not scrambled non-CpG ODN) increased bone-marrow DC activation after exposure to PDT-killed tumor cells, and significantly increased tumor response to PDT and mouse survival after peri-tumoral administration. CpG may be a valuable immunoadjuvant to PDT especially for tumors that produce DC dysfunction.

Fatigue Strength of Weathering Steel

Czech Academy of Sciences Publication Activity Database

Kunz, Ludvík; Lukáš, Petr; Klusák, Jan

2012-01-01

Roč. 18, č. 1 (2012), s. 18-22 ISSN 1392-1320 Grant - others:GA MPO(CZ) FT/TA5/076 Institutional support: RVO:68081723 Keywords : fatigue of weathering steel * corrosion pits * fatigue notch factor Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 0.522, year: 2012

Importance of fatiguing, overtraining and chronic fatigue in athletes

Directory of Open Access Journals (Sweden)

Adam Piesik

2017-09-01

Full Text Available Each training that requires achieving a higher heart rate limit and/or increased concentration in time may cause fatigue, considered to be a natural defence mechanism of a body. In the case of excessive fatigue and insufficient time designated for rest and regeneration, an overtraining syndrome (OTS may develop. The main symptom of overtraining is increased fatigue that fails to become reversed in normal conditions of regeneration. Although authors are familiar with the overtraining syndrome and associated symptoms, as of today no diagnostic tool has been developed that may form a basis for a final diagnosis, and the diagnosis itself is frequently based on a subjective assessment of the athlete. Possible causes of the band overtraining syndrome are disorders of sodium, inflammatory processes resulting from physical activity and / or disorders of the autonomic nervous system.

Comparing Fatigue Life Estimations of Composite Wind Turbine Blades using different Fatigue Analysis Tools

DEFF Research Database (Denmark)

Ardila, Oscar Gerardo Castro; Lennie, Matthew; Branner, Kim

2015-01-01

In this paper, fatigue lifetime prediction of NREL 5MW reference wind turbine is presented. The fatigue response of materials used in selected blade cross sections was obtained by applying macroscopic fatigue approaches and assuming uniaxial stress states. Power production and parked load cases...... suggested by the IEC 61400-1 standard were studied employing different load time intervals and by using two novel fatigue tools called ALBdeS and BECAS+F. The aeroelastic loads were defined thought aeroelastic simulations performed with both FAST and HAWC2 tools. The stress spectra at each layer were...... calculated employing laminated composite theory and beam cross section methods. The Palmgren-Miner linear damage rule was used to calculate the accumulation damage. The theoretical results produced by both fatigue tools proved a prominent effect of analysed design load conditions on the estimated lifetime...

Endothelial function and dysfunction: clinical significance and assessment

Directory of Open Access Journals (Sweden)

Shaghayegh Haghjooyejavanmard

2008-08-01

Full Text Available

• Over the past two decades, investigators have increasingly recognized the importance of the endothelium as a centralregulator of vascular and body homeostasis. The endothelial lining represents an organ of 1.5 kg in an adult, which is distributed throughout the body. The endothelium is versatile and multifunctional. In addition to its role as a selective permeability barrier, it has many synthetic and metabolic properties, including modulation of vascular tone and blood flow, regulation of immune and inflammatory responses, and regulation of coagulation, fibrinolysis and thrombosis. Endothelial dysfunction (ED is a frequently used term, which can be referred to abnormalities in various physiological functions of the endothelium, and it is known as a key variable in the pathogenesis of several diseases and their complications. Finding suitable markers for endothelial damage or ED is certainly of interest. Established and emerging techniques to detect ED are divided into three large families of functional, cellular, and biochemical markers. Instead of performing single assessments, it may be much more valuable to determine various biological aspects of endothelium. It seems that there is likely a spectrum between normality, endothelial activation (by inflammatory cytokines, endothelial dysfunction (e.g., impairment of nitric oxide, resulting in loss of regulation of vascular tone and endothelial damage (e.g., atherosclerosis. In this review we review the importance of endothelium and its activation, biomarkers and dysfunction.
•  KEYWORDS: Endothelial function, endothelium, Disease.

Prevalence of fatigue and chronic fatigue syndrome in a primary care practice.

Science.gov (United States)

Bates, D W; Schmitt, W; Buchwald, D; Ware, N C; Lee, J; Thoyer, E; Kornish, R J; Komaroff, A L

1993-12-27

Our goals were to determine the prevalence of unusual, debilitating fatigue and the frequency with which it was associated with the chronic fatigue syndrome (CFS) or other physical or psychological illness in an outpatient clinic population. We prospectively evaluated a cohort of 1000 consecutive patients in a primary care clinic in an urban, hospital-based general medicine practice. The study protocol included a detailed history, physical examination, and laboratory and psychiatric testing. Five patients who came because of CFS studies were excluded. Of the remaining 995, 323 reported fatigue, and 271 (27%) complained of at least 6 months of unusual fatigue that interfered with their daily lives. Of the 271, self-report or record review revealed a medical or psychiatric condition that could have explained the fatigue in 186 (69%). Thus, 85 (8.5%) of 995 patients had a debilitating fatigue of at least 6 months' duration, without apparent cause. Of these patients, 48 refused further evaluation, and 11 were unavailable for follow-up; 26 completed the protocol. Three of the 26 were hypothyroid, and one had a major psychiatric disorder. Of the remaining 22 patients, three met Centers for Disease Control and Prevention criteria for CFS, four met British criteria, and 10 met the Australian case definition. The point prevalences of CFS were thus 0.3% (95% confidence interval [CI], 0% to 0.6%), 0.4% (95% CI, 0% to 0.8%), and 1.0% (95% CI, 0.4% to 1.6%) using the Centers for Disease Control and Prevention, British, and Australian case definitions, respectively. These estimates were conservative, because they assumed that none of the patients who refused evaluation or were unavailable for follow-up would meet criteria for CFS. While chronic, debilitating fatigue is common in medical outpatients, CFS is relatively uncommon. Prevalence depends substantially on the case definition used.

Work fatigue in urban bus drivers

Directory of Open Access Journals (Sweden)

Teresa Makowiec-Dąbrowska

2015-10-01

Full Text Available Background: Bus drivers are a special group of professional drivers who are at a very high risk of fatigue. The aim of the study was to examine whether the driver’s subjective assessment of fatigue allows for the determination of its level and identification of its causes. Material and Methods: The study group comprised 45 randomly selected bus drivers (mean age – 43.7±7.9 years, period of employment as drivers – 14.7±8.6 years. Examinations were performed in all subjects four times – before and after work on the “easy” route (outside the city center, small traffic intensity and before and after work on the “difficult” route (city center, heavy traffic. The fatigue test questionnaire, based on the list of symptoms of fatigue prepared by the Japan Research Committee of Fatigue, was used in the study. Results: The rating of fatigue after the work was significantly higher than that before the work. The profile of fatigue after work was not influenced by the type of route, but the assessment of most symptoms of fatigue reached a higher level after the “difficult” routes and the differences were statistically significant for 7 symptoms. Only the ratings of leg fatigue, feeling of heaviness, and the necessity to squint eyes and gaze with effort reached the higher levels after driving the “easy” routes. It has been found that the level of fatigue was significantly correlated with the job characteristics (driving time, the length of the route, number of stops, etc. and with the abundance of food ingested and type of beverage (coffee vs. others drunk prior to driving. Conclusions: The questionnaire used in our study to assess the subjective feeling of fatigue has proved to be a sensitive and useful tool for indicating the level and causes of fatigue. The relationship between the symptoms of fatigue and the characteristics of job and lifestyle shows that actions must be taken by both the employers and employees to prevent fatigue

Fatigue 󈨛. Volume 2,

Science.gov (United States)

1987-06-01

ROLAND STICKLER Absolute Fatigue Thresholds in Metallic 801 Materials - J.A. LEWIS Thermometrical Investigations on the Near 809 Threshold Fatigue...impurities reported by Semi- Alloys Inc. totaled less than 0.1%. Specimens were cast in a flat open aluminum mold. Each specimen was 6 mm thick and 12...and 2024-T351 Aluminum Alloy", in "Fatigue Crack Growth Threshold Concepts", D.L. Davidson, S. Suresh, editors, TMS-AIME. 1984, pp. 63-82. (2) Bailon

Oxidative Stress and COPD: The Impact of Oral Antioxidants on Skeletal Muscle Fatigue

Science.gov (United States)

Rossman, Matthew J.; Groot, H. Jonathan; Van Reese; Zhao, Jia; Amann, Markus; Richardson, Russell S.

2014-01-01

PURPOSE Oxidative stress may contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). This study sought to determine the effect of an acute oral antioxidant cocktail (AOC: vitamins C, E, and alpha-lipoic acid) on skeletal muscle function during dynamic quadriceps exercise in COPD. METHODS Ten patients with COPD performed knee extensor exercise to exhaustion and isotime trials following either the AOC or placebo (PL). Pre- to post-exercise changes in quadriceps maximal voluntary contractions (MVCs) and potentiated twitch forces (Qtw,pot) quantified quadriceps fatigue. RESULTS Under PL conditions, the plasma electron paramagnetic resonance (EPR) spectroscopy signal was inversely correlated with the forced expiratory volume in one second to forced vital capacity ratio (FEV1/FVC), an index of lung dysfunction (r=−0.61, p=0.02), and MVC force (r=−0.56, p=0.04). AOC consumption increased plasma ascorbate levels (10.1±2.2 to 24.1±3.8 ug/ml, p<0.05) and attenuated the area under the curve of the EPR spectroscopy free radical signal (11.6±3.7 to 4.8±2.2 AU, p<0.05), but did not alter endurance time or quadriceps fatigue. The ability of the AOC to decrease the EPR spectroscopy signal, however, was prominent in those with high basal free radicals (n=5, PL: 19.7±5.8 to AOC: 5.8±4.5 AU, p<0.05) with minimal effects in those with low levels (n=5, PL: 1.6±0.5 to AOC: 3.4±1.1 AU). DISCUSSION These data document a relationship between directly measured free radicals and lung dysfunction, and the ability of the AOC to decrease oxidative stress in COPD. Acute amelioration of free radicals, however, does not appear to impact dynamic quadriceps exercise performance. PMID:23299763

Thermal Acoustic Fatigue Apparatus

Data.gov (United States)

Federal Laboratory Consortium — The Thermal Acoustic Fatigue Apparatus (TAFA) is a progressive wave tube test facility that is used to test structures for dynamic response and sonic fatigue due to...

Factors related to fatigue; priority of interventions to reduce or eliminate fatigue and the exploration of a multidisciplinary research model for further study of fatigue

NARCIS (Netherlands)

Tiesinga, LJ; Dassen, TWN; Halfens, RJG; van den Heuvel, WJA

A growing interest in the health problem presented by fatigue, both in clinical practice and research, coupled with a decreasing number of reported studies on fatigue in the last decade, make an updated and systematic review of factors related to fatigue necessary. A search of the literature,

Fatigue and creep-fatigue strength of 304 steel under biaxial strain conditions

International Nuclear Information System (INIS)

Asayama, Tai; Aoto, Kazumi; Wada, Yusaku

1990-01-01

A series of fatigue and creep-fatigue tests were conducted with 304 stainless steel at 550degC under a variety of biaxial strain conditions. Fatigue life under nonproportional loading conditions showed a significant life reduction compared with that of proportional loading, and this life reduction was reasonably estimated by taking into account the strain paths along which the strain history is imposed. Furthermore, a marked life reduction was shown to occur under nonproportional loading by imposing a strain hold period at a peak tensile strain. This life reduction was evaluated by the linear damage rule. It was shown to be possible to estimate the fatigue damage and the creep damage under nonproportional loading by a linear damage rule by estimating a stress relaxation behavior by Mises-type equivalent stress or Huddleston-type equivalent stress. (author)

Immune thrombocytopenia and autoimmune thyroid disease: a controversial overlap

OpenAIRE

Marta, Guilherme Nader; de Campos, Fernando Peixoto Ferraz

2015-01-01

Immune thrombocytopenia (ITP) is an entity characterized by a platelet count of less than 100 × 109/L in the absence of other causes of thrombocytopenia, such as viral infections, rheumatic diseases, or drugs. Grave’s disease is also an autoimmune condition in which thrombocytopenia is often observed. Moreover, in the literature, many reports show a marked interference of the thyroid dysfunction (mainly hyperthyroidism) in the control of thrombocytopenia. Although this issue still remains deb...

A comparison of patients with Q fever fatigue syndrome and patients with chronic fatigue syndrome with a focus on inflammatory markers and possible fatigue perpetuating cognitions and behaviour.

Science.gov (United States)

Keijmel, Stephan P; Saxe, Johanna; van der Meer, Jos W M; Nikolaus, Stephanie; Netea, Mihai G; Bleijenberg, Gijs; Bleeker-Rovers, Chantal P; Knoop, Hans

2015-10-01

Comparison of Q fever fatigue syndrome (QFS) and chronic fatigue syndrome (CFS) patients, with a focus on markers of inflammation and fatigue-related cognitive-behavioural variables. Data from two independent prospective studies on QFS (n=117) and CFS (n=173), respectively, were pooled and analyzed. QFS patients were less often female, had a higher BMI, and had less often received treatment for depression before the onset of symptoms. After controlling for symptom duration and correcting for differences in diagnostic criteria for QFS and CFS with respect to the level of impairment and the presence of additional symptoms, differences in the proportion of females and BMI remained significant. After correction, QFS patients were also significantly older. In all analyses QFS patients were as fatigued and distressed as CFS patients, but reported less additional symptoms. QFS patients had stronger somatic attributions, and higher levels of physical activity. No differences were found with regard to inflammatory markers and in other fatigue-related cognitive-behavioural variables. The relationship between cognitive-behavioural variables and fatigue, previously established in CFS, could not be confirmed in QFS patients with the exception of the negative relationship between physical activity and fatigue. Differences and similarities between QFS and CFS patients were found. Although the relationship between perpetuating factors and fatigue previously established in CFS could not be confirmed in QFS patients, the considerable overlap in fatigue-related cognitive-behavioural variables and the relationship found between physical activity and fatigue may suggest that behavioural interventions could reduce fatigue severity in QFS patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Skeletal Muscle and Lymphocyte Mitochondrial Dysfunctions in Septic Shock Trigger ICU-Acquired Weakness and Sepsis-Induced Immunoparalysis

Directory of Open Access Journals (Sweden)

Quentin Maestraggi

2017-01-01

Full Text Available Fundamental events driving the pathological processes of septic shock-induced multiorgan failure (MOF at the cellular and subcellular levels remain debated. Emerging data implicate mitochondrial dysfunction as a critical factor in the pathogenesis of sepsis-associated MOF. If macrocirculatory and microcirculatory dysfunctions undoubtedly participate in organ dysfunction at the early stage of septic shock, an intrinsic bioenergetic failure, sometimes called “cytopathic hypoxia,” perpetuates cellular dysfunction. Short-term failure of vital organs immediately threatens patient survival but long-term recovery is also severely hindered by persistent dysfunction of organs traditionally described as nonvital, such as skeletal muscle and peripheral blood mononuclear cells (PBMCs. In this review, we will stress how and why a persistent mitochondrial dysfunction in skeletal muscles and PBMC could impair survival in patients who overcome the first acute phase of their septic episode. First, muscle wasting protracts weaning from mechanical ventilation, increases the risk of mechanical ventilator-associated pneumonia, and creates a state of ICU-acquired muscle weakness, compelling the patient to bed. Second, failure of the immune system (“immunoparalysis” translates into its inability to clear infectious foci and predisposes the patient to recurrent nosocomial infections. We will finally emphasize how mitochondrial-targeted therapies could represent a realistic strategy to promote long-term recovery after sepsis.

Hormone levels in radiotherapy treatment related fatigue

International Nuclear Information System (INIS)

Biswal, B.M.; Mallik, G.S.

2003-01-01

Radiotherapy is known to cause debilitating treatment related fatigue. Fatigue in general is a conglomeration of psychological, physical, hematological and unknown factors influencing the internal milieu of the cancer patient. Radiotherapy can add stress at the cellular and somatic level to aggravate further fatigue in cancer patients undergoing radiotherapy. Stress related hormones might be mediating in the development of fatigue. This is an ongoing prospective study to evaluate if the hormonal profile related to stress is influenced by radiotherapy treatment related fatigue. The study was conducted from September 2002 onwards in the division of Radiotherapy and Oncology of our Medical School. Previously untreated patients with histopathology proof of malignancy requiring external beam radiotherapy were considered for this study. Selection criteria were applied to exclude other causes of fatigue. Initial fatigue score was obtained using Pipers Fatigue Score questionnaire containing 23 questions, subsequently final fatigue score was obtained at the end of radiotherapy. Blood samples were obtained to estimate the levels of ACTH, TSH, HGH, and cortisol on the final assessment. The hormone levels were compared with resultant post radiotherapy fatigue score. At the time of reporting 50 patients were evaluable for the study. The total significant fatigue score was observed among 12 (24%) patients. The individual debilitating fatigue score were behavioral severity 14 (28%), affective meaning 14(28%), Sensory 13 (26%) and cognitive mood 10 (20%) respectively. From the analysis of hormonal profile, growth hormone level > 1 ng/mL and TSH <0.03 appears to be associated with high fatigue score (though statistically not significant); whereas there was no correlation with ACTH and serum cortisol level. In our prospective study severe radiotherapy treatment related fatigue was found among our patient population. Low levels of TSH and high levels of GH appear to be associated

Thermal fatigue of beryllium

International Nuclear Information System (INIS)

Deksnis, E.; Ciric, D.; Falter, H.

1995-01-01

Thermal fatigue life of S65c beryllium castellated to a geometry 6 x 6 x (8-10)mm deep has been tested for steady heat fluxes of 3 MW/m 2 to 5 MW/m 2 and under pulsed heat fluxes (10-20 MW/m 2 ) for which the time averaged heat flux is 5 MW/m 2 . These tests were carried out in the JET neutral beam test facility A test sequence with peak surface temperatures ≤ 600 degrees C produced no visible fatigue cracks. In the second series of tests, with T max ≤ 750 degrees C evidence for fatigue appeared after a minimum of 1350 stress cycles. These fatigue data are discussed in view of the observed lack of thermal fatigue in JET plasma operations with beryllium PFC. JET experience with S65b and S65c is reviewed; recent operations with Φ = 25 MW/m 2 and sustained melting/resolidification are also presented. The need for a failure criterion for finite element analyses of Be PFC lifetimes is discussed

Early life innate immune signatures of persistent food allergy.

Science.gov (United States)

Neeland, Melanie R; Koplin, Jennifer J; Dang, Thanh D; Dharmage, Shyamali C; Tang, Mimi L; Prescott, Susan L; Saffery, Richard; Martino, David J; Allen, Katrina J

2017-11-14

Food allergy naturally resolves in a proportion of food-allergic children without intervention; however the underlying mechanisms governing the persistence or resolution of food allergy in childhood are not understood. This study aimed to define the innate immune profiles associated with egg allergy at age 1 year, determine the phenotypic changes that occur with the development of natural tolerance in childhood, and explore the relationship between early life innate immune function and serum vitamin D. This study used longitudinally collected PBMC samples from a population-based cohort of challenge-confirmed egg-allergic infants with either persistent or transient egg allergy outcomes in childhood to phenotype and quantify the functional innate immune response associated with clinical phenotypes of egg allergy. We show that infants with persistent egg allergy exhibit a unique innate immune signature, characterized by increased numbers of circulating monocytes and dendritic cells that produce more inflammatory cytokines both at baseline and following endotoxin exposure when compared with infants with transient egg allergy. Follow-up analysis revealed that this unique innate immune signature continues into childhood in those with persistent egg allergy and that increased serum vitamin D levels correlate with changes in innate immune profiles observed in children who developed natural tolerance to egg. Early life innate immune dysfunction may represent a key immunological driver and predictor of persistent food allergy in childhood. Serum vitamin D may play an immune-modulatory role in the development of natural tolerance. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Fatigue and workload among Danish fishermen

DEFF Research Database (Denmark)

Remmen, Line Nørgaard; Herttua, Kimmo; Riss-Jepsen, Jørgen

2017-01-01

. Highest levels of fatigue were observed among fishermen at Danish seiners (mean 10.21), and fatigue scores decreased with more days at sea. However, none of these results were significant. Adjusted analyses showed that physical workload was significantly related to general fatigue (b = 0.20, 95% CI: 0...... was additionally significantly associated to the levels of physical and mental fatigue. Fishermen had a lower average score for all fatigue dimensions compared to those seen in general Danish working population. Prospective studies are required to assess whether the identified associations are causal....

Fatigue: Is it all neurochemistry?

Science.gov (United States)

Meeusen, Romain; Roelands, Bart

2018-02-01

Fatigue during exercise can be approached from different angles. Peripheral fatigue is usually described as an impairment located in the muscle and characterized by a metabolic end point, while central fatigue is defined as a failure of the central nervous system to adequately drive the muscle. The aim of the present narrative review paper is to look at the mechanisms involved in the occurrence of fatigue during prolonged exercise, predominantly from a brain neurochemical point of view. From studies in rodents it is clear that exercise increases the release of several neurotransmitters in different brain regions, and that the onset of fatigue can be manipulated when dopaminergic influx in the preoptic and anterior hypothalamus is increased, interfering with thermoregulation. This is however not as straightforward in humans, in which most studies manipulating brain neurotransmission failed to change the onset of fatigue in normal ambient temperatures. When the ambient temperature was increased, dopaminergic and combined dopaminergic and noradrenergic reuptake inhibition appeared to override a safety switch, allowing subjects to push harder and become much warmer, without changing their perception. In general, we can conclude that brain neurochemistry is clearly involved in the complex regulation of fatigue, but many other mediators also play a role.

Damage assessment of low-cycle fatigue by crack growth prediction. Fatigue life under cyclic thermal stress

International Nuclear Information System (INIS)

Kamaya, Masayuki

2013-01-01

The number of cycles to failure of specimens in fatigue tests can be estimated by predicting crack growth. Under a cyclic thermal stress caused by fluctuation of fluid temperature, due to the stress gradient in the thickness direction, the estimated fatigue life differs from that estimated for mechanical fatigue tests. In this paper, the influence of crack growth under cyclic thermal loading on the fatigue life was investigated. First, the thermal stress was derived by superposing analytical solutions, and then, the stress intensity factor was obtained by the weight function method. It was shown that the thermal stress depended not on the rate of the fluid temperature change but on the rise time, and the magnitude of the stress was increased as the rise time was decreased. The stress intensity factor under the cyclic thermal stress was smaller than that under the uniform stress distribution. The change in the stress intensity factor with the crack depth was almost the same regardless of the rise time. The estimated fatigue life under the cyclic thermal loading could be 1.6 times longer than that under the uniform stress distribution. The critical size for the fatigue life determination was assumed to be 3 mm for fatigue test specimens of 10 mm diameter. By evaluating the critical size by structural integrity analyses, the fatigue life was increased and the effect of the critical size on the fatigue life was more pronounced for the cyclic thermal stress. (author)

Fatigue, burnout, and chronic fatigue syndrome among employees on sick leave: do attributions make the difference?

NARCIS (Netherlands)

Huibers, M.J.H.; Beurskens, A.J.H.M.; Prins, J.B.; Kant, I.J.; Bazelmans, H.M.; Schayck, C.P. van; Knottnerus, J.A.; Bleijenberg, G.

2003-01-01

BACKGROUND: Persistent fatigue among employees, burnout, and chronic fatigue syndrome (CFS) are three fatigue conditions that share some characteristics in theory. However, these conditions have not been compared in empirical research, despite conceptual similarities. METHODS: This cross sectional

Fatigue property and fatigue cracks of ultra-fine grained copper processed by equal-channel angular pressing

Czech Academy of Sciences Publication Activity Database

Wang, Q.; Du, Z.; Liu, X.; Kunz, Ludvík

2011-01-01

Roč. 2011, č. 682 (2011), s. 231-237 ISSN 1013-9826 Institutional research plan: CEZ:AV0Z20410507 Keywords : ultrafine-grained copper * equal channel angular pressing * fatigue * fatigue cracks Subject RIV: JL - Materials Fatigue, Friction Mechanics

Noncontact fatigue crack evaluation using thermoelastic

Energy Technology Data Exchange (ETDEWEB)

Kim, Ji Min; An, Yun Kyu; Sohn, Hoon [KAIST, Daejeon (Korea, Republic of)

2012-12-15

This paper proposes a noncontact thermography technique for fatigue crack evaluation under a cyclic tensile loading. The proposed technique identifies and localizes an invisible fatigue crack without scanning, thus making it possible to instantaneously evaluate an incipient fatigue crack. Based on a thermoelastic theory, a new fatigue crack evaluation algorithm is proposed for the fatigue crack tip localization. The performance of the proposed algorithm is experimentally validated. To achieve this, the cyclic tensile loading is applied to a dog bone shape aluminum specimen using a universal testing machine, and the corresponding thermal responses induced by thermoelastic effects are captured by an infrared camera. The test results confirm that the fatigue crack is well identified and localized by comparing with its microscopic images.

Design fatigue curve for Hastelloy-X

International Nuclear Information System (INIS)

Nishiguchi, Isoharu; Muto, Yasushi; Tsuji, Hirokazu

1983-12-01

In the design of components intended for elevated temperature service as the experimental Very High-Temperature gas-cooled Reactor (VHTR), it is essential to prevent fatigue failure and creep-fatigue failure. The evaluation method which uses design fatigue curves is adopted in the design rules. This report discussed several aspects of these design fatigue curves for Hastelloy-X (-XR) which is considered for use as a heat-resistant alloy in the VHTR. Examination of fatigue data gathered by a literature search including unpublished data showed that Brinkman's equation is suitable for the design curve of Hastelloy-X (-XR), where total strain range Δ epsilon sub(t) is used as independent variable and fatigue life Nsub(f) is transformed into log(log Nsub(f)). (author)

Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

OpenAIRE

Maes, Michael; Kubera, Marta; Uytterhoeven, Marc; Vrydags, Nicolas; Bosmans, Eugene

2011-01-01

Summary Background There is evidence that myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by activation of immune, inflammatory, oxidative and nitrosative stress (IO&NS) pathways. The present study was carried out in order to examine whether ME/CFS is accompanied by increased levels of plasma peroxides and serum oxidized LDL (oxLDL) antibodies, two biomarkers of oxidative stress. Material/Methods Blood was collected from 56 patients with ME/CFS and 37 normal volun...

Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury.

Science.gov (United States)

De Simoni, Sara; Jenkins, Peter O; Bourke, Niall J; Fleminger, Jessica J; Hellyer, Peter J; Jolly, Amy E; Patel, Maneesh C; Cole, James H; Leech, Robert; Sharp, David J

2018-01-01

Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with measures of

Fatigue sensation induced by the sounds associated with mental fatigue and its related neural activities: revealed by magnetoencephalography

OpenAIRE

Ishii, Akira; Tanaka, Masaaki; Iwamae, Masayoshi; Kim, Chongsoo; Yamano, Emi; Watanabe, Yasuyoshi

2013-01-01

Background It has been proposed that an inappropriately conditioned fatigue sensation could be one cause of chronic fatigue. Although classical conditioning of the fatigue sensation has been reported in rats, there have been no reports in humans. Our aim was to examine whether classical conditioning of the mental fatigue sensation can take place in humans and to clarify the neural mechanisms of fatigue sensation using magnetoencephalography (MEG). Methods Ten and 9 healthy volunteers particip...

Fatigue Life Analysis and Prediction of 316L Stainless Steel Under Low Cycle Fatigue Loading

Energy Technology Data Exchange (ETDEWEB)

Oh, Hyeong; Myung, NohJun; Choi, Nak-Sam [Hanyang Univ., Seoul (Korea, Republic of)

2016-12-15

In this study, a strain-controlled fatigue test of widely-used 316L stainless steel with excellent corrosion resistance and mechanical properties was conducted, in order to assess its fatigue life. Low cycle fatigue behaviors were analyzed at room temperature, as a function of the strain amplitude and strain ratio. The material was hardened during the initial few cycles, and then was softened during the long post period, until failure occurred. The fatigue life decreased with increasing strain amplitude. Masing behavior in the hysteresis loop was shown under the low strain amplitude, whereas the high strain amplitude caused non-Masing behavior and reduced the mean stress. Low cycle fatigue life prediction based on the cyclic plastic energy dissipation theory, considering Masing and non-Masing effects, showed a good correlation with the experimental results.

The Immune System in Obesity: Developing Paradigms Amidst Inconvenient Truths.

Science.gov (United States)

Agrawal, Madhur; Kern, Philip A; Nikolajczyk, Barbara S

2017-08-15

Adipose tissue (AT) houses both innate and adaptive immune systems that are crucial for preserving AT function and metabolic homeostasis. In this review, we summarize recent information regarding progression of obesity-associated AT inflammation and insulin resistance. We additionally consider alterations in AT distribution and the immune system in males vs. females and among different racial populations. Innate and adaptive immune cell-derived inflammation drives insulin resistance both locally and systemically. However, new evidence also suggests that the immune system is equally vital for adipocyte differentiation and protection from ectopic lipid deposition. Furthermore, roles of anti-inflammatory immune cells such as regulatory T cells, "M2-like" macrophages, eosinophils, and mast cells are being explored, primarily due to promise of immunotherapeutic applications. Both immune responses and AT distribution are strongly influenced by factors like sex and race, which have been largely underappreciated in the field of metabolically-associated inflammation, or meta-flammation. More studies are required to recognize factors that switch inflammation from controlled to uncontrolled in obesity-associated pathogenesis and to integrate the combined effects of meta-flammation and immunometabolism. It is critical to recognize that the AT-associated immune system can be alternately beneficial and destructive; therefore, simply blocking immune responses early in obesity may not be the best clinical approach. The dearth of information on gender and race-associated disparities in metabolism, AT distribution, and the immune system suggest that a greater understanding of such differences will be critical to develop personalized treatments for obesity and the associated metabolic dysfunction.

Exploring nurse leader fatigue: a mixed methods study.

Science.gov (United States)

Steege, Linsey M; Pinekenstein, Barbara J; Arsenault Knudsen, Élise; Rainbow, Jessica G

2017-05-01

To describe hospital nurse leaders' experiences of fatigue. Fatigue is a critical challenge in nursing. Existing literature focuses on staff nurse fatigue, yet nurse leaders are exposed to high demands that may contribute to fatigue and associated risks to patient, nurse and organisational outcomes. A mixed method approach comprising semi-structured interviews and the Occupational Fatigue Exhaustion Recovery scale with 21 nurse administrators (10 nurse managers and 11 nurse executives) from hospitals in a Midwestern state. Most nurse leaders experience fatigue; nurse managers reported higher levels of chronic fatigue. Participants identified multiple sources of fatigue including 24 h accountability and intensity of role expectations, and used a combination of wellness, restorative, social support and boundary setting strategies to cope with fatigue. The consequences of nurse leader fatigue include an impact on decision-making, work-life balance and turnover intent. The high prevalence of nurse leader fatigue could impact the turnover intent of nurse administrators and quality of care. This study highlights the significance and consequences of nurse leader fatigue. As health care organisations continue to raise awareness and establish systems to reduce nurse fatigue, policies and programmes must be adapted to address nurse leader fatigue. © 2017 John Wiley & Sons Ltd.

Variable amplitude fatigue, modelling and testing

International Nuclear Information System (INIS)

Svensson, Thomas.

1993-01-01

Problems related to metal fatigue modelling and testing are here treated in four different papers. In the first paper different views of the subject are summarised in a literature survey. In the second paper a new model for fatigue life is investigated. Experimental results are established which are promising for further development of the mode. In the third paper a method is presented that generates a stochastic process, suitable to fatigue testing. The process is designed in order to resemble certain fatigue related features in service life processes. In the fourth paper fatigue problems in transport vibrations are treated

Metabolomic markers of fatigue: Association between circulating metabolome and fatigue in women with chronic widespread pain.

Science.gov (United States)

Freidin, Maxim B; Wells, Helena R R; Potter, Tilly; Livshits, Gregory; Menni, Cristina; Williams, Frances M K

2018-02-01

Fatigue is a sensation of unbearable tiredness that frequently accompanies chronic widespread musculoskeletal pain (CWP) and inflammatory joint disease. Its mechanisms are poorly understood and there is a lack of effective biomarkers for diagnosis and onset prediction. We studied the circulating metabolome in a population sample characterised for CWP to identify biomarkers showing specificity for fatigue. Untargeted metabolomic profiling was conducted on fasting plasma and serum samples of 1106 females with and without CWP from the TwinsUK cohort. Linear mixed-effects models accounting for covariates were used to determine relationships between fatigue and metabolites. Receiver operating curve (ROC)-analysis was used to determine predictive value of metabolites for fatigue. While no association between fatigue and metabolites was identified in twins without CWP (n=711), in participants with CWP (n=395), levels of eicosapentaenoate (EPA) ω-3 fatty acid were significantly reduced in those with fatigue (β=-0.452±0.116; p=1.2×10 -4 ). A significant association between fatigue and two other metabolites also emerged when BMI was excluded from the model: 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF), and C-glycosyltryptophan (p=1.5×10 -4 and p=3.1×10 -4 , respectively). ROC analysis has identified a combination of 15 circulating metabolites with good predictive potential for fatigue in CWP (AUC=75%; 95% CI 69-80%). The results of this agnostic metabolomics screening show that fatigue is metabolically distinct from CWP, and is associated with a decrease in circulating levels of EPA. Our panel of circulating metabolites provides the starting point for a diagnostic test for fatigue in CWP. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Dysfunctional stress responses in chronic pain.

Science.gov (United States)

Woda, Alain; Picard, Pascale; Dutheil, Frédéric

2016-09-01

Many dysfunctional and chronic pain conditions overlap. This review describes the different modes of chronic deregulation of the adaptive response to stress which may be a common factor for these conditions. Several types of dysfunction can be identified within the hypothalamo-pituitary-adrenal axis: basal hypercortisolism, hyper-reactivity, basal hypocortisolism and hypo-reactivity. Neuroactive steroid synthesis is another component of the adaptive response to stress. Dehydroepiandrosterone (DHEA) and its sulfated form DHEA-S, and progesterone and its derivatives are synthetized in cutaneous, nervous, and adipose cells. They are neuroactive factors that act locally. They may have a role in the localization of the symptoms and their levels can vary both in the central nervous system and in the periphery. Persistent changes in neuroactive steroid levels or precursors can induce localized neurodegeneration. The autonomic nervous system is another component of the stress response. Its dysfunction in chronic stress responses can be expressed by decreased basal parasympathethic activity, increased basal sympathetic activity or sympathetic hyporeactivity to a stressful stimulus. The immune and genetic systems also participate. The helper-T cells Th1 secrete pro-inflammatory cytokines such as IL-1-β, IL-2, IL-6, IL-8, IL-12, IFN-γ, and TNF-α, whereas Th2 secrete anti-inflammatory cytokines: IL-4, IL-10, IGF-10, IL-13. Chronic deregulation of the Th1/Th2 balance can occur in favor of anti- or pro-inflammatory direction, locally or systemically. Individual vulnerability to stress can be due to environmental factors but can also be genetically influenced. Genetic polymorphisms and epigenetics are the main keys to understanding the influence of genetics on the response of individuals to constraints. Copyright © 2016 Elsevier Ltd. All rights reserved.

Complex role for the immune system in initiation and progression of pancreatic cancer.

Science.gov (United States)

Inman, Kristin S; Francis, Amanda A; Murray, Nicole R

2014-08-28

The immune system plays a complex role in the development and progression of pancreatic cancer. Inflammation can promote the formation of premalignant lesions and accelerate pancreatic cancer development. Conversely, pancreatic cancer is characterized by an immunosuppressive environment, which is thought to promote tumor progression and invasion. Here we review the current literature describing the role of the immune response in the progressive development of pancreatic cancer, with a focus on the mechanisms that drive recruitment and activation of immune cells at the tumor site, and our current understanding of the function of the immune cell types at the tumor. Recent clinical and preclinical data are reviewed, detailing the involvement of the immune response in pancreatitis and pancreatic cancer, including the role of specific cytokines and implications for disease outcome. Acute pancreatitis is characterized by a predominantly innate immune response, while chronic pancreatitis elicits an immune response that involves both innate and adaptive immune cells, and often results in profound systemic immune-suppression. Pancreatic adenocarcinoma is characterized by marked immune dysfunction driven by immunosuppressive cell types, tumor-promoting immune cells, and defective or absent inflammatory cells. Recent studies reveal that immune cells interact with cancer stem cells and tumor stromal cells, and these interactions have an impact on development and progression of pancreatic ductal adenocarcinoma (PDAC). Finally, current PDAC therapies are reviewed and the potential for harnessing the actions of the immune response to assist in targeting pancreatic cancer using immunotherapy is discussed.

Real-Time Assessment of Fatigue in Patients With Multiple Sclerosis: How Does It Relate to Commonly Used Self-Report Fatigue Questionnaires?

Science.gov (United States)

Heine, Martin; van den Akker, Lizanne Eva; Blikman, Lyan; Hoekstra, Trynke; van Munster, Erik; Verschuren, Olaf; Visser-Meily, Anne; Kwakkel, Gert

2016-11-01

(1) To assess real-time patterns of fatigue; (2) to assess the association between a real-time fatigue score and 3 commonly used questionnaires (Checklist Individual Strength [CIS] fatigue subscale, Modified Fatigue Impact Scale (MFIS), and Fatigue Severity Scale [FSS]); and (3) to establish factors that confound the association between the real-time fatigue score and the conventional fatigue questionnaires in patients with multiple sclerosis (MS). Cross-sectional study. MS-specialized outpatient facility. Ambulant patients with MS (N=165) experiencing severe self-reported fatigue. Not applicable. A real-time fatigue score was assessed by sending participants 4 text messages on a particular day (How fatigued do you feel at this moment?; score range, 0-10). Latent class growth mixed modeling was used to determine diurnal patterns of fatigue. Regression analyses were used to assess the association between the mean real-time fatigue score and the CIS fatigue subscale, MFIS, and FSS. Significant associations were tested for candidate confounders (eg, disease severity, work status, sleepiness). Four significantly different fatigue profiles were identified by the real-time fatigue score, namely a stable high (n=79), increasing (n=57), stable low (n=16), and decreasing (n=13). The conventional questionnaires correlated poorly (rquestionnaires, ranging from 15.4% to 35%. Perceived fatigue showed 4 different diurnal patterns in patients with MS. Severity of sleepiness is an important confounder to take into account in the assessment of fatigue. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Acute hypopituitarism associated with periorbital swelling and cardiac dysfunction in a patient with pituitary tumor apoplexy: a case report.

Science.gov (United States)

Ohara, Nobumasa; Yoneoka, Yuichiro; Seki, Yasuhiro; Akiyama, Katsuhiko; Arita, Masataka; Ohashi, Kazumasa; Suzuki, Kazuo; Takada, Toshinori

2017-08-24

Pituitary tumor apoplexy is a rare clinical syndrome caused by acute hemorrhage or infarction in a preexisting pituitary adenoma. It typically manifests as an acute episode of headache, visual disturbance, mental status changes, cranial nerve palsy, and endocrine pituitary dysfunction. However, not all patients present with classical symptoms, so it is pertinent to appreciate the clinical spectrum of pituitary tumor apoplexy presentation. We report an unusual case of a patient with pituitary tumor apoplexy who presented with periorbital edema associated with hypopituitarism. An 83-year-old Japanese man developed acute anterior hypopituitarism; he showed anorexia, fatigue, lethargy, severe bilateral periorbital edema, and mild cardiac dysfunction in the absence of headache, visual disturbance, altered mental status, and cranial nerve palsy. Magnetic resonance imaging showed a 2.5-cm pituitary tumor containing a mixed pattern of solid and liquid components indicating pituitary tumor apoplexy due to hemorrhage in a preexisting pituitary adenoma. Replacement therapy with oral hydrocortisone and levothyroxine relieved his symptoms of central adrenal insufficiency, central hypothyroidism, periorbital edema, and cardiac dysfunction. Common causes of periorbital edema include infections, inflammation, trauma, allergy, kidney or cardiac dysfunction, and endocrine disorders such as primary hypothyroidism. In the present case, the patient's acute central hypothyroidism was probably involved in the development of both periorbital edema and cardiac dysfunction. The present case highlights the need for physicians to consider periorbital edema as an unusual predominant manifestation of pituitary tumor apoplexy.

Research on driver fatigue detection

Science.gov (United States)

Zhang, Ting; Chen, Zhong; Ouyang, Chao

2018-03-01

Driver fatigue is one of the main causes of frequent traffic accidents. In this case, driver fatigue detection system has very important significance in avoiding traffic accidents. This paper presents a real-time method based on fusion of multiple facial features, including eye closure, yawn and head movement. The eye state is classified as being open or closed by a linear SVM classifier trained using HOG features of the detected eye. The mouth state is determined according to the width-height ratio of the mouth. The head movement is detected by head pitch angle calculated by facial landmark. The driver's fatigue state can be reasoned by the model trained by above features. According to experimental results, drive fatigue detection obtains an excellent performance. It indicates that the developed method is valuable for the application of avoiding traffic accidents caused by driver's fatigue.

Damage assessment of low-cycle fatigue by crack growth prediction. Fatigue life under cyclic thermal stress

International Nuclear Information System (INIS)

Kamaya, Masayuki

2013-01-01

The number of cycles to failure of specimens in fatigue tests can be estimated by predicting crack growth. Under a cyclic thermal stress caused by fluctuation of fluid temperature, due to the stress gradient in the thickness direction, the estimated fatigue life differs from that estimated for mechanical fatigue tests. In this paper, the influence of crack growth under cyclic thermal loading on the fatigue life was investigated. First, the thermal stress was derived by superposing analytical solutions, and then, the stress intensity factor was obtained by the weight function method. It was shown that the thermal stress depended not on the rate of the fluid temperature change but on the rise time, and the magnitude of the stress was increased as the rise time was decreased. The stress intensity factor under the cyclic thermal stress was smaller than that under the uniform stress distribution. The change in the stress intensity factor with the crack depth did not depend on the heat transfer coefficient and only slightly depended on the rise time. The estimated fatigue life under the cyclic thermal loading could be 1.6 times longer than that under the uniform stress distribution. The critical size for the fatigue life determination was assumed to be 3 mm for fatigue test specimens of 10 mm diameter. By evaluating the critical size by structural integrity analyses, the fatigue life was increased and the effect of the critical size on the fatigue life was more pronounced for the cyclic thermal stress. (author)

A Preliminary Review of Fatigue Among Rail Staff

Directory of Open Access Journals (Sweden)

Jialin Fan

2018-05-01

Full Text Available Background: Fatigue is a severe problem in the rail industry, which may jeopardize train crew's health and safety. Nonetheless, a preliminary review of all empirical evidence for train crew fatigue is still lacking. The aim of the present paper is, therefore, to provide a preliminary description of occupational fatigue in the rail industry. This paper reviews the literature with the research question examining the risk factors associated with train crew fatigue, covering both papers published in refereed journals and reports from trade organizations and regulators. It assesses the progress of research on railway fatigue, including research on the main risk factors for railway fatigue, the association between fatigue and railway incidents, and how to better manage fatigue in the railway industry.Methods: Systematic searches were performed in both science and industry databases. The searches considered studies published before August 2017. The main exclusion criterion was fatigue not being directly measured through subjective or objective methods.Results: A total of 31 studies were included in the main review. The causes of fatigue included long working hours, heavy workload, early morning or night shifts, and insufficient sleep. Poor working environment, particular job roles, and individual differences also contributed to fatigue.Conclusion: Fatigue in the rail industry includes most of the features of occupational fatigue, and it is also subject to industry-specific factors. The effect of fatigue on well-being and the fatigued population in the railway industry are still not clear. Future studies can consider associations between occupational risk factors and perceived fatigue by examining the prevalence of fatigue and identifying the potential risk factors in staff within the railway industry.

Studies on fatigue life enhancement of pre-fatigued spring steel specimens using laser shock peening

International Nuclear Information System (INIS)

Ganesh, P.; Sundar, R.; Kumar, H.; Kaul, R.; Ranganathan, K.; Hedaoo, P.; Raghavendra, G.; Anand Kumar, S.; Tiwari, P.; Nagpure, D.C.; Bindra, K.S.; Kukreja, L.M.; Oak, S.M.

2014-01-01

Highlights: • Laser peening significantly extended fatigue life of pre-fatigued spring steel. • Increase in fatigue life of laser peened specimens was more than 15 times. • Black PVC tape is an effective coating for laser peening of ground surfaces. • Repeat peening repaired local surface melted regions on laser peened surface. • Technique is effective for life extension of in-service automobile parts. - Abstract: SAE 9260 spring steel specimens after enduring 50% of their mean fatigue life were subjected to laser shock peening using an in-house developed 2.5 J/7 ns pulsed Neodymium-doped Yttrium Aluminum Garnet (Nd:YAG) laser for studying their fatigue life enhancement. In the investigated range of process parameters, laser shock peening resulted in the extension of fatigue life of these partly fatigue damaged specimens by more than 15 times. Contributing factors for the enhanced fatigue life of laser peened specimens are: about 400 μm thick compressed surface layer with magnitude of surface stress in the range of −600 to −700 MPa, about 20% increase in surface hardness and unaltered surface finish. For laser peening of ground steel surface, an adhesive-backed black polyvinyl chloride (PVC) tape has been found to be a superior sacrificial coating than conventionally used black paint. The effect of repeated laser peening treatment was studied to repair locally surface melted regions and the treatment has been found to be effective in re-establishing desired compressive stress pattern on the erstwhile tensile-stressed surface

Low putamen activity associated with poor reward sensitivity in childhood chronic fatigue syndrome

Directory of Open Access Journals (Sweden)

Kei Mizuno, Ph.D.

2016-01-01

Full Text Available Motivational signals influence a wide variety of cognitive processes and components of behavioral performance. Cognitive dysfunction in patients with childhood chronic fatigue syndrome (CCFS may be closely associated with a low motivation to learn induced by impaired neural reward processing. However, the extent to which reward processing is impaired in CCFS patients is unclear. The aim of the present functional magnetic resonance imaging (fMRI study was to determine whether brain activity in regions related to reward sensitivity is impaired in CCFS patients. fMRI data were collected from 13 CCFS patients (mean age, 13.6 ± 1.0 years and 13 healthy children and adolescents (HCA (mean age, 13.7 ± 1.3 years performing a monetary reward task. Neural activity in high- and low-monetary-reward conditions was compared between CCFS and HCA groups. Severity of fatigue and the reward obtained from learning in daily life were evaluated by questionnaires. Activity of the putamen was lower in the CCFS group than in the HCA group in the low-reward condition, but not in the high-reward condition. Activity of the putamen in the low-reward condition in CCFS patients was negatively and positively correlated with severity of fatigue and the reward from learning in daily life, respectively. We previously revealed that motivation to learn was correlated with striatal activity, particularly the neural activity in the putamen. This suggests that in CCFS patients low putamen activity, associated with altered dopaminergic function, decreases reward sensitivity and lowers motivation to learn.

Therapeutic Targets for Neurodevelopmental Disorders Emerging from Animal Models with Perinatal Immune Activation

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Daisuke Ibi

2015-11-01

Full Text Available Increasing epidemiological evidence indicates that perinatal infection with various viral pathogens enhances the risk for several psychiatric disorders. The pathophysiological significance of astrocyte interactions with neurons and/or gut microbiomes has been reported in neurodevelopmental disorders triggered by pre- and postnatal immune insults. Recent studies with the maternal immune activation or neonatal polyriboinosinic polyribocytidylic acid models of neurodevelopmental disorders have identified various candidate molecules that could be responsible for brain dysfunction. Here, we review the functions of several candidate molecules in neurodevelopment and brain function and discuss their potential as therapeutic targets for psychiatric disorders.

Fatigue Reliability of Offshore Wind Turbine Systems

DEFF Research Database (Denmark)

Marquez-Dominguez, Sergio; Sørensen, John Dalsgaard

2012-01-01

of appropriate partial safety factors / fatigue design factors (FDF) for steel substructures of offshore wind turbines (OWTs). The fatigue life is modeled by the SN approach. Design and limit state equations are established based on the accumulated fatigue damage. The acceptable reliability level for optimal...... fatigue design of OWTs is discussed and results for reliability assessment of typical fatigue critical design of offshore steel support structures are presented....

Fatigue Reliability and Calibration of Fatigue Design Factors for Offshore Wind Turbines

DEFF Research Database (Denmark)

Dominguez, Sergio Marquez; Sørensen, John Dalsgaard

2012-01-01

Consequences of failure of offshore wind turbines (OWTs) are in general lower than consequences of failure of, e.g., oil & gas platforms. It is reasonable that lower fatigue design factors can be applied for fatigue design of OWTs when compared to other fixed offshore structures. Calibration...

Collect Available Creep-Fatigue Data and Study Existing Creep-Fatigue Evaluation Procedures for Grade 91 and Hastelloy XR

International Nuclear Information System (INIS)

Asayama, Tai; Tachibana, Yukio

2007-01-01

This report describes the results of investigation on Task 5 of DOE/ASME Materials Project based on a contract between ASME Standards Technology, LLC (ASME ST-LLC) and Japan Atomic Energy Agency (JAEA). Task 5 is to collect available creep-fatigue data and study existing creep-fatigue evaluation procedures for Grade 91 steel and Hastelloy XR. Part I of this report is devoted to Grade 91 steel. Existing creep-fatigue data were collected (Appendix A) and analyzed from the viewpoints of establishing a creep-fatigue procedure for VHTR design. A fair amount of creep-fatigue data has been obtained and creep-fatigue phenomena have been clarified to develop design standards mainly for fast breeder reactors. Following this, existing creep-fatigue procedures were studied and it was clarified that the creep-fatigue evaluation procedure of the ASME-NH has a lot of conservatisms and they were analyzed in detail from the viewpoints of the evaluation of creep damage of material. Based on the above studies, suggestions to improve the ASME-NH procedure along with necessary research and development items were presented. Part II of this report is devoted to Hastelloy XR. Existing creep-fatigue data used for development of the high temperature structural design guideline for High Temperature Gas-cooled Reactor (HTGR) were collected. Creep-fatigue evaluation procedure in the design guideline and its application to design of the intermediate heat exchanger (IHX) for High Temperature Engineering Test Reactor (HTTR) was described. Finally, some necessary research and development items in relation to creep-fatigue evaluation for Gen IV and VHTR reactors were presented.

Guide to safe work : fatigue management : an employer's guide to designing and implementing a fatigue management program. 2 ed.

Energy Technology Data Exchange (ETDEWEB)

NONE

2007-02-15

The impacts of fatigue on workplace safety are now commonly recognized. Many employers now wish to include fatigue management as part of their overall health and safety programs. This guide to fatigue management was written to help companies in the petroleum industry design and implement effective fatigue management programs that reduce incidents and injuries among employees. The guide provided information about workplace fatigue and discussed fatigue management issues and strategies. It was suggested that workplace culture can play a significant role in managing fatigue by allowing fatigue factors to be quickly recognized and managed. Employers who wish to build fatigue management programs should involve all levels of employees, and should consider all workplace practices and procedures. Consideration must also be given to the development of employee competency in managing fatigue. The guide included step-by-step recommendations for implementing a fatigue management program. It was concluded that the benefits of fatigue management include reduced worker absence and turnover, as well as avoiding the costs of safety incidents. 1 tab., 1 fig.

Fatigue failure by in-line flow-induced vibration and fatigue life evaluation

International Nuclear Information System (INIS)

Odahara, Satoru; Murakami, Yukitaka; Inoue, Masahiro; Sueoka, Atsuo

2004-01-01

The phenomenon of fatigue failure by the In-line flow-induced vibration was studied. A newly water-flow-induced vibration system was made and used to reproduce fatigue failure by flow-induced vibration. A medium carbon steel specimen was fixed to the experimental equipment. A small artificial hole was introduced onto the specimen surface. Fatigue crack initiated from the artificial hole. A small portable strain histogram recorder (Mini Rainflow Corder, MRC) developed in another project of the authors' team was used to acquire the service strain hisogram at a critical point of the specimen and to measure the variation of natural frequency. Cumulative fatigue damage D defined by the Modified Miner Rule was calculated by using the strain histogram at the initial stage of test. The value of D was almost unity in the case of In-line vibration, while the values of D in the case of the Cross-flow vibration ranged from 0.2 to 0.8. (author)

Creep fatigue assessment for EUROFER components

Energy Technology Data Exchange (ETDEWEB)

Özkan, Furkan, E-mail: oezkan.furkan@partner.kit.edu; Aktaa, Jarir

2015-11-15

Highlights: • Design rules for creep fatigue assessment are developed to EUROFER components. • Creep fatigue assessment tool is developed in FORTRAN code with coupling MAPDL. • Durability of the HCPB-TBM design is discussed under typical fusion reactor loads. - Abstract: Creep-fatigue of test blanket module (TBM) components built from EUROFER is evaluated based on the elastic analysis approach in ASME Boiler Pressure Vessel Code (BPVC). The required allowable number of cycles design fatigue curve and stress-to-rupture curve to estimate the creep-fatigue damage are used from the literature. Local stress, strain and temperature inputs for the analysis of creep-fatigue damage are delivered by the finite element code ANSYS utilizing the Mechanical ANSYS Parametric Design Language (MAPDL). A developed external FORTRAN code used as a post processor is coupled with MAPDL. Influences of different pulse durations (hold-times) and irradiation on creep-fatigue damage for the preliminary design of the Helium Cooled Pebble Bed Test Blanket Module (HCPB-TBM) are discussed for the First Wall component of the TBM box.

Fatigue design 1998

Energy Technology Data Exchange (ETDEWEB)

Marquis, G.; Solin, J. [eds.] [VTT Manufacturing Technology, Espoo (Finland)

1998-12-31

These preprints contain the presentations to be delivered at the Fatigue Design 1998 symposium held on May 26-29, 1998 in Espoo. Fatigue Design 1998 is the tenth in a series of VTT symposia addressing the challenge of fatigue of materials, components and structures. Previous international events were in 1992 and 1995. The key theme of the current meeting is `RELIABILITY`. The two volumes (VTT symposium 181-182) represent 56 contributions by authors representing 26 countries. Emphasis has been given to application oriented research topics that report new technologies, new uses of existing methods and case studies. The objective of the symposium is to bring together researchers and engineers to share experiences and new innovations in designing reliable components to resist alternating loads. (orig.)

IEA Joint Action. Wind turbine fatigue

Energy Technology Data Exchange (ETDEWEB)

Maribo Pedersen, B [ed.

1996-09-01

Fatigue research on wind turbine blade material has been an important issue over the years in many countries and in the E.U. As a result of the effort the knowledge on fatigue properties of fibre reinforced materials has been expanded enormously. Practical fatigue design properties are available for constant amplitude tests at ambient temperatures. A lack of knowledge can be shown in several other fields, such as variable amplitude and multi-axial testing and the influence of the environment and carbon fibres. Fatigue is seen as dominant for the blade design, improvements in both the load prediction and material fatigue properties should be strove for. In discussions with blade manufacturers and subsidy agencies (E.U. DGXII, NOVEM, ETSU, etc.) on the importance of continuous materials fatigue research the improvement in reliability should be stressed. (au)

Fatigue and damage tolerance scatter models

Science.gov (United States)

Raikher, Veniamin L.

1994-09-01

Effective Total Fatigue Life and Crack Growth Scatter Models are proposed. The first of them is based on the power form of the Wohler curve, fatigue scatter dependence on mean life value, cycle stress ratio influence on fatigue scatter, and validated description of the mean stress influence on the mean fatigue life. The second uses in addition are fracture mechanics approach, assumption of initial damage existence, and Paris equation. Simple formulas are derived for configurations of models. A preliminary identification of the parameters of the models is fulfilled on the basis of experimental data. Some new and important results for fatigue and crack growth scatter characteristics are obtained.

Fatigue Strength of Titanium Risers - Defect Sensitivity

Energy Technology Data Exchange (ETDEWEB)

Babalola, Olusegun Tunde

2001-07-01

This study is centred on assessment of the fatigue strength of titanium fusion welds for deep-water riser's applications. Deep-water risers are subjected to significant fatigue loading. Relevant fatigue data for titanium fusion welds are very scarce. Hence there is a need for fatigue data and life prediction models for such weldments. The study has covered three topics: Fatigue testing, Fractography and defect assessment, and Fracture Mechanics modelling of fatigue crack growth. Two series of welded grade of titanium consisting of 14 specimens in each series were fatigue tested under constant amplitude loading. Prior to fatigue testing, strain gauge measurements of some specimens was conducted to enable the definition of stress range in the fatigue assessment procedure. The results were compared with finite solid element analysis and related to fatigue stresses in a riser pipe wall. Distribution and geometry of internal and surface defects both in the as-welded and in the post-weld machined conditions were assessed using fractography. This served as a tool to determine the fatigue initiation point in the welds. Fracture mechanics was applied to model fatigue strength of titanium welds with initiation from weld defects. Two different stress intensity factor formulations for embedded eccentrically placed cracks were used for analysis of elliptical cracks with the major axis parallel and close to one of the free surfaces. The methods were combined to give a satisfactory model for crack growth analysis. The model analyses crack growth of elliptical and semi-elliptical cracks in two directions, with updating of the crack geometry. Fatigue strength assessment was conducted using two crack growth models, the Paris-Erdogan relation with no threshold and the Donahue et al. relation with an implied threshold. The model was validated against experimental data, with a discussion on the choice of crack growth model. (author)

Fatigue in cancer: A review of literature

Directory of Open Access Journals (Sweden)

Vijayakumar Narayanan

2009-01-01

Full Text Available Fatigue is a common symptom of advanced cancer limiting one′s activity and affecting the quality of life. It is a multidimensional symptom complex with subjective and objective components. Hence, its definition and assessment seems arbitrary, incomplete, and elusive. Components of fatigue often merge with other ′disease states′ as anemia, depression and so on, compounding difficulty to assess it separately. Fatigue has a high prevalence rate, and lasts longer in chronic diseases like cancer. Its association with treatment modalities like chemotherapy, radiotherapy alongside the primary disease process makes it seemingly ubiquitous in many cases. Systemic manifestation of cancer causes excess demand on body resources on cell repair, uncontrolled growth with metabolite accumulation causing fatigue. Co-morbid conditions of organic and psychological nature causes fatigue. There are many assessment tools for fatigue with different uses and objectives, simple and reproducible tools like Brief Fatigue Inventory, Edmonton Symptom assessment scale seem feasible in everyday practice. Management of fatigue is not straightforward and rewarding. Although treatment of cause appears to be an attractive option, it is not possible in all cases. Therapeutic agents targeting cytokine load is in early stages of study and available results are not favorable. Specific measures aimed at pain relief, prevention/treatment of sepsis, management of depression, avoidance of drugs causing fatigue, restoring the metabolic profile are important. Methyl phenidate, megestrol, and modafinil are some drugs with promising effect to treat fatigue, though confirmatory studies are yet to be established. Non-pharmacological methods are also helpful. Forewarning patients on upcoming fatigue, active regular exercise, and stress management are some of them. Fatigue being a multidimensional entity, single mode of therapy is insufficient. Combined modality tailored to individual

Fatigue Monitoring Tool for Airline Operators (FMT

Directory of Open Access Journals (Sweden)

Gislason Sigurdur Hrafn

2017-12-01

Full Text Available A Fatigue Monitoring Tool (FMT model was constructed for an operational airline in order to manage the fatigue levels of their crews in accordance with Fatigue Risk Management System (FRMS practices. This article describes the implementation of the Fatigue Monitoring Tool model and the airline’s aims to put the recent scientific findings on aviation fatigue into practical use. The model consists of proxy points allotted to various duties and rest periods.

Diagnostik der Fatigue bei Multipler Sklerose [Assessment of fatigue in multiple sclerosis

NARCIS (Netherlands)

Sander, C.; Voelter, H.U.; Schlake, H.P.; Eling, P.A.T.M.; Hildebrandt, H.

2017-01-01

Hintergrund: Fatigue ist eines der häufigsten Symptome bei Multipler Sklerose (MS) und hat deutliche Auswirkungen auf die Lebensqualität sowie die Berufstätigkeit. Die adäquate Messung der erlebten Fatigue ist aber auch heutzutage noch mit erheblicher Unsicherheit behaftet. Ziel der Arbeit: In dem

Nutritional support to maintain proper immune status during intense training.

Science.gov (United States)

Gleeson, Michael

2013-01-01

Prolonged exercise and heavy training are associated with depressed immune function which can increase the risk of picking up minor infections. To maintain robust immunity, athletes should eat a well-balanced diet sufficient to meet their energy, carbohydrate, protein, and micronutrient requirements. Dietary deficiencies of protein and specific micronutrients have long been associated with immune dysfunction and an adequate intake of iron, zinc, and vitamins A, D, E, B6 and B12 is particularly important in the maintenance of immune function. Consuming carbohydrate during prolonged strenuous exercise attenuates rises in stress hormones and appears to limit the degree of exercise-induced immune depression. Similar effects can be seen with daily ingestion of high-dose antioxidant vitamin supplements, though concerns have been expressed that excessive antioxidant intake may impair exercise training adaptations. It is safe to say with reasonable confidence that individual amino acids, colostrum, Echinacea, and zinc are unlikely to boost immunity or reduce infection risk in athletes. The ingestion of carbohydrate during exercise and daily consumption of probiotic and plant polyphenol (e.g. quercetin)-containing supplements or foodstuffs (e.g. non-alcoholic beer) currently offer the best chance of success. This approach is likely to be most effective for individuals who are particularly prone to illness. Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.

Decreased Numbers of CD57+CD3- Cells Identify Potential Innate Immune Differences in Patients with Autism Spectrum Disorder.

Science.gov (United States)

Siniscalco, Dario; Mijatovic, Tatjana; Bosmans, Eugene; Cirillo, Alessandra; Kruzliak, Peter; Lombardi, Vincent C; De Meirleir, Kenny; Antonucci, Nicola

2016-01-01

Autism spectrum disorders (ASD) are complex, and severe heterogeneous neurodevelopmental pathologies with accepted but complex immune system abnormalities. Additional knowledge regarding potential immune dysfunctions may provide a greater understanding of this malady. The aim of this study was to evaluate the CD57(+)CD3(-) mature lymphocyte subpopulation of natural killer cells as a marker of immune dysfunction in ASD. Three-color flow cytometry-based analysis of fresh peripheral blood samples from children with autism was utilized to measure CD57(+)CD3(-) lymphocytes. A reduction of CD57(+)CD3(-) lymphocyte count was recorded in a significant number of patients with autism. We demonstrated that the number of peripheral CD57(+)CD3(-) cells in children with autism often falls below the clinically accepted normal range. This implies that a defect in the counter-regulatory functions necessary for balancing pro-inflammatory cytokines exists, thus opening the way to chronic inflammatory conditions associated with ASD. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Possible use of repeated cold stress for reducing fatigue in Chronic Fatigue Syndrome: a hypothesis

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Shevchuk Nikolai A

2007-10-01

Full Text Available Abstract Background Physiological fatigue can be defined as a reduction in the force output and/or energy-generating capacity of skeletal muscle after exertion, which may manifest itself as an inability to continue exercise or usual activities at the same intensity. A typical example of a fatigue-related disorder is chronic fatigue syndrome (CFS, a disabling condition of unknown etiology and with uncertain therapeutic options. Recent advances in elucidating pathophysiology of this disorder revealed hypofunction of the hypothalamic-pituitary-adrenal axis and that fatigue in CFS patients appears to be associated with reduced motor neurotransmission in the central nervous system (CNS and to a smaller extent with increased fatigability of skeletal muscle. There is also some limited evidence that CFS patients may have excessive serotonergic activity in the brain and low opioid tone. Presentation of the hypothesis This work hypothesizes that repeated cold stress may reduce fatigue in CFS because brief exposure to cold may transiently reverse some physiological changes associated with this illness. For example, exposure to cold can activate components of the reticular activating system such as raphe nuclei and locus ceruleus, which can result in activation of behavior and increased capacity of the CNS to recruit motoneurons. Cold stress has also been shown to reduce the level of serotonin in most regions of the brain (except brainstem, which would be consistent with reduced fatigue according to animal models of exercise-related fatigue. Finally, exposure to cold increases metabolic rate and transiently activates the hypothalamic-pituitary-adrenal axis as evidenced by a temporary increase in the plasma levels of adrenocorticotropic hormone, beta-endorphin and a modest increase in cortisol. The increased opioid tone and high metabolic rate could diminish fatigue by reducing muscle pain and accelerating recovery of fatigued muscle, respectively. Testing

Serological profiling of the EBV immune response in Chronic Fatigue Syndrome using a peptide microarray.

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Madlen Loebel

Full Text Available Epstein-Barr-Virus (EBV plays an important role as trigger or cofactor for various autoimmune diseases. In a subset of patients with Chronic Fatigue Syndrome (CFS disease starts with infectious mononucleosis as late primary EBV-infection, whereby altered levels of EBV-specific antibodies can be observed in another subset of patients.We performed a comprehensive mapping of the IgG response against EBV comparing 50 healthy controls with 92 CFS patients using a microarray platform. Patients with multiple sclerosis (MS, systemic lupus erythematosus (SLE and cancer-related fatigue served as controls. 3054 overlapping peptides were synthesised as 15-mers from 14 different EBV proteins. Array data was validated by ELISA for selected peptides. Prevalence of EBV serotypes was determined by qPCR from throat washing samples.EBV type 1 infections were found in patients and controls. EBV seroarray profiles between healthy controls and CFS were less divergent than that observed for MS or SLE. We found significantly enhanced IgG responses to several EBNA-6 peptides containing a repeat sequence in CFS patients compared to controls. EBNA-6 peptide IgG responses correlated well with EBNA-6 protein responses. The EBNA-6 repeat region showed sequence homologies to various human proteins.Patients with CFS had a quite similar EBV IgG antibody response pattern as healthy controls. Enhanced IgG reactivity against an EBNA-6 repeat sequence and against EBNA-6 protein is found in CFS patients. Homologous sequences of various human proteins with this EBNA-6 repeat sequence might be potential targets for antigenic mimicry.

Clinical neurophysiology of fatigue.

NARCIS (Netherlands)

Zwarts, M.J.; Bleijenberg, G.; Engelen, B.G.M. van

2008-01-01

Fatigue is a multidimensional concept covering both physiological and psychological aspects. Chronic fatigue is a typical symptom of diseases such as cancer, multiple sclerosis (MS), Parkinson's disease (PD) and cerebrovascular disorders but is also presented by people in whom no defined somatic

A Brief Historic Overview of Clinical Disorders Associated with Tryptophan: The Relevance to Chronic Fatigue Syndrome (CFS and Fibromyalgia (FM.

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Adele Blankfield

2012-01-01

Full Text Available Last century there was a short burst of interest in the tryptophan related disorders of pellagra and related abnormalities that are usually presented in infancy. 1 , 2 Nutritional physiologists recognized that a severe human dietary deficiency of either tryptophan or the B group vitamins could result in central nervous system (CNS sequelae such as ataxia, cognitive dysfunction and dysphoria, accompanied by skin hyperpigmentation. 3 , 4 The current paper will focus on the emerging role of tryptophan in chronic fatigue syndrome (CFS and fibromyalgia (FM.

Fatigue damage of ultrafine-grain copper in very-high cycle fatigue region

Czech Academy of Sciences Publication Activity Database

Lukáš, Petr; Kunz, Ludvík; Navrátilová, Lucie; Bokůvka, O.

2011-01-01

Roč. 528, - (2011), s. 7036-7040 ISSN 0921-5093 R&D Projects: GA ČR GAP108/10/2001 Institutional research plan: CEZ:AV0Z20410507 Keywords : ultrafine-grained microstructure * ultrasonic fatigue * crack initiation * copper Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 2.003, year: 2011

Fatigue Reliability Analysis of a Mono-Tower Platform

DEFF Research Database (Denmark)

Kirkegaard, Poul Henning; Sørensen, John Dalsgaard; Brincker, Rune

1991-01-01

In this paper, a fatigue reliability analysis of a Mono-tower platform is presented. The failure mode, fatigue failure in the butt welds, is investigated with two different models. The one with the fatigue strength expressed through SN relations, the other with the fatigue strength expressed thro...... of the natural period, damping ratio, current, stress spectrum and parameters describing the fatigue strength. Further, soil damping is shown to be significant for the Mono-tower.......In this paper, a fatigue reliability analysis of a Mono-tower platform is presented. The failure mode, fatigue failure in the butt welds, is investigated with two different models. The one with the fatigue strength expressed through SN relations, the other with the fatigue strength expressed...... through linear-elastic fracture mechanics (LEFM). In determining the cumulative fatigue damage, Palmgren-Miner's rule is applied. Element reliability, as well as systems reliability, is estimated using first-order reliability methods (FORM). The sensitivity of the systems reliability to various parameters...

Risk factors of fatigue status among Chinese adolescents.

Science.gov (United States)

Jin, Yuelong; Peng, Baozhen; Li, Yijun; Song, Lei; He, Lianping; Fu, Rui; Wu, Qianqian; Fan, Qingxiu; Yao, Yingshui

2015-01-01

In recent years, fatigue is common among adolescents. The aim of this study is to evaluate fatigue status and find related factors of fatigue among students ranged from 13-26 years from Wuhu, China. This is a case-control, cross-sectional observational study. The students from six middle schools (high school? 26 years old?) in Wuhu city were recruited, Self-Rating Fatigue Scale (SFS) was used to measure the fatigue status among students ranged from 13-26 years, and some demographic characteristics of students also was determined. A total of 726 students are included in our study. A significant difference was observed between fatigue status and grade, a balanced diet, the partial eclipse, picky for food, lack of sleep, excessive fatigue, drinking (P sleep, drinking; grade while a balanced diet is the protective factor of fatigue. Therefore, the school should pay more attention to the fatigue among students in middle school in China, and take some properly measures to reduce the fatigue.

Gastric emptying in patients with chronic fatigue syndrome

International Nuclear Information System (INIS)

Sand, A.; Hulstaert, J.; Wanet, P.; Uyttersprot, A.; Meirleir, K. de

2002-01-01

Chronic fatigue syndrome (CFS) is a debilitating chronic illness of unknown cause characterized by mental fatigue and sensorimotor disturbances. Moreover, gastrointestinal symptoms (GI) are frequently noticed in those patients. A possible cause could be a dysfunction of the NANC neurotransmitter system in which Vasoactive Intestinal Polypeptide and NO plays an important role in the speed of the gastric relaxation. The Aim of this study was to determine the prevalence of gastric motility disorder in CFS patients. Materials and Methods: 51 patients affected by CFS (45 females and 6 males; mean age 38.5 ± 14.7 y) were prospectively studied by a gastric emptying scintigraphy and the results compared with a control population. The patients were categorized in two clinical groups according to the severity criteria of Holmes and Fukuda (H/F - or H/F +). The presence of GI symptoms was noticed for each patient. Gastric emptying was assessed by the standard procedure according to the guidelines of the Belgian Society of Nuclear Medicine. The acquisition of a series of 10 static images in anterior and posterior projections was started after a test meal (1 fried egg + 20 Mbq Tc99m sulfur colloids, 2 pieces of bread and 125 ml of water). Geometric means were calculated after correction for the half-life of Tc99m and the gastric half-emptying time (T1/2) was determined for each patient. Results: A significantly prolonged T 1/2 was found in CFS patients (97.8 ± 41.6 min) compared to our control population (70 ± 15 min) independently of the presence of associated GI symptoms. (p<0.01) There was also a close relationship between the T1/2 and severity of the CFS disease: the gastric emptying time of the two CFS groups (according to the H/F criteria) were respectively 78.9 and 112.9 min. which is highly significant. (p<0.05). Conclusion: We conclude that delayed gastric emptying is frequently encountered in patients with CFS (with mild or severe symptoms of gastroparesis) which

Sleep complaints and fatigue of airline pilots.

Science.gov (United States)

Reis, Cátia; Mestre, Catarina; Canhão, Helena; Gradwell, David; Paiva, Teresa

2016-01-01

This work aimed to determine daytime sleepiness and sleep complaints prevalence and the corresponding influence on perceived fatigue and to evaluate the influence of sociodemographic parameters and labour variables on sleep complaints, sleepiness and fatigue. A questionnaire was developed including socio-economic and labour issues and instruments, focused in sleep and fatigue. The response rate was 32% and the final sample had 435 pilots. The prevalence of sleep complaints was 34.9%, daytime sleepiness 59.3% and fatigue 90.6%. The high prevalence of sleep complaints, sleepiness and fatigue was disclosed in pilots, with those who fly short/medium having an added risk of fatigue.

Pomegranate extract and exercise provide additive benefits on improvement of immune function by inhibiting inflammation and oxidative stress in high-fat-diet-induced obesity in rats.

Science.gov (United States)

Zhao, Fei; Pang, Wentao; Zhang, Ziyi; Zhao, Jialong; Wang, Xin; Liu, Ye; Wang, Xun; Feng, Zhihui; Zhang, Yong; Sun, Wenyan; Liu, Jiankang

2016-06-01

Obesity is reported to be associated with immune dysfunction and a state of low-grade, chronic inflammation. Either pomegranate extract (PomE) or exercise (Ex) has been shown to have antiobesity, anti-inflammatory and antioxidant effects. Nevertheless, no study has addressed the additive benefits of PomE and Ex on the restoration of obesity-induced immune defects. The present work aims to study the effect of PomE and Ex as a combined intervention on immune function and the underlying mechanism involved in inflammation and oxidative stress in rats with high-fat-diet (HFD)-induced obesity. Our results demonstrate that the combination of PomE and Ex showed additive benefits on inhibition of HFD-induced body weight increase and improvement of HFD-induced immune dysfunction, including (a) attenuating the abnormality of histomorphology of the spleen, (b) increasing the ratio of the CD4+:CD8+ T cell subpopulations in splenocytes and peripheral blood mononuclear cells (PBMC), (c) inhibition of apoptosis in splenocytes and PBMC, (d) normalizing peritoneal macrophage phenotypes and (e) restoring immunomodulating factors in serum. We also find that immune dysfunction in HFD-fed rats was associated with increased inflammatory cytokine secretion and oxidative stress biomarkers, and that the combination of PomE and Ex effectively inhibited the inflammatory response and decreased oxidative damage. The effect of PomE and Ex as a combined intervention is greater than the effect of either PomE or Ex alone, showing that PomE and Ex may be additively effective in improving immune function in HFD-fed rats by inhibiting inflammation and decreasing oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

Recurrent pregnancy loss in patients with thyroid dysfunction

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Debanjali Sarkar

2012-01-01

Full Text Available Purpose of the Review: Thyroid disturbances are common in women during their reproductive years. Thyroid dysfunction interferes with human reproductive physiology, reduces the likelihood of pregnancy and adversely affects pregnancy outcome, thus becoming relevant in the algorithm of reproductive dysfunction. This review highlights the "gap" in knowledge regarding the contribution of thyroid dysfunction in reproduction. Literature Reviewed: Following implantation, the maintenance of the pregnancy is dependent on a multitude of endocrinological events that will eventually aid in the successful growth and development of the fetus. It is estimated that approximately 8-12% of all pregnancy losses are the result of endocrine factors. Autoimmune thyroid disease is present in around 4% of young females and up to 15% are at risk because they are thyroid antibody-positive. There is a strong relationship between thyroid immunity on one hand and infertility, miscarriage, and thyroid disturbances in pregnancy and postpartum, on the other hand. Even minimal hypothyroidism can increase rates of miscarriage and fetal death and may also have adverse effects on later cognitive development of the offspring. Hyperthyroidism during pregnancy may also have adverse consequences. Summary: Pregnant women with subclinical hypothyroidism or thyroid antibodies have an increased risk of complications, especially pre-eclampsia, perinatal mortality, and miscarriage. Universal screening for thyroid hormone abnormalities is not routinely recommended at present, but thyroid function must be examined in female with fetal loss or menstrual disturbances. Practitioners providing health care for women should be alert to thyroid disorders as an underlying etiology for recurrent pregnancy loss.

Immune senescence: relative contributions of age and cytomegalovirus infection.

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Andrea Mekker

Full Text Available Immune senescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterised by impaired protective immunity and decreased efficacy of vaccines. Recent clinical, epidemiological and immunological studies suggest that Cytomegalovirus (CMV infection may be associated with accelerated immune senescence, possibly by restricting the naïve T cell repertoire. However, direct evidence whether and how CMV-infection is implicated in immune senescence is still lacking. In this study, we have investigated whether latent mouse CMV (MCMV infection with or without thymectomy (Tx alters antiviral immunity of young and aged mice. After infection with lymphocytic choriomeningitis virus (LCMV or Vaccinia virus, specific antiviral T cell responses were significantly reduced in old, old MCMV-infected and/or Tx mice compared to young mice. Importantly, control of LCMV replication was more profoundly impaired in aged MCMV-infected mice compared to age-matched MCMV-naïve or young mice. In addition, latent MCMV infection was associated with slightly reduced vaccination efficacy in old Tx mice. In contrast to the prevailing hypothesis of a CMV-mediated restriction of the naïve T cell repertoire, we found similar naïve T cell numbers in MCMV-infected and non-infected mice, whereas ageing and Tx clearly reduced the naïve T cell pool. Instead, MCMV-infection expanded the total CD8(+ T cell pool by a massive accumulation of effector memory T cells. Based on these results, we propose a new model of increased competition between CMV-specific memory T cells and any 'de novo' immune response in aged individuals. In summary, our results directly demonstrate in a mouse model that latent CMV-infection impairs immunity in old age and propagates immune senescence.

Roughness Effects on Fretting Fatigue

Science.gov (United States)

Yue, Tongyan; Abdel Wahab, Magd

2017-05-01

Fretting is a small oscillatory relative motion between two normal loaded contact surfaces. It may cause fretting fatigue, fretting wear and/or fretting corrosion damage depending on various fretting couples and working conditions. Fretting fatigue usually occurs at partial slip condition, and results in catastrophic failure at the stress levels below the fatigue limit of the material. Many parameters may affect fretting behaviour, including the applied normal load and displacement, material properties, roughness of the contact surfaces, frequency, etc. Since fretting damage is undesirable due to contacting, the effect of rough contact surfaces on fretting damage has been studied by many researchers. Experimental method on this topic is usually focusing on rough surface effects by finishing treatment and random rough surface effects in order to increase fretting fatigue life. However, most of numerical models on roughness are based on random surface. This paper reviewed both experimental and numerical methodology on the rough surface effects on fretting fatigue.

Common Mathematical Model of Fatigue Characteristics

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Z. Maléř

2004-01-01

Full Text Available This paper presents a new common mathematical model which is able to describe fatigue characteristics in the whole necessary range by one equation only:log N = A(R + B(R ∙ log Sawhere A(R = AR2 + BR + C and B(R = DR2 + AR + F.This model was verified by five sets of fatigue data taken from the literature and by our own three additional original fatigue sets. The fatigue data usually described the region of N 104 to 3 x 106 and stress ratio of R = -2 to 0.5. In all these cases the proposed model described fatigue results with small scatter. Studying this model, following knowledge was obtained:– the parameter ”stress ratio R” was a good physical characteristic– the proposed model provided a good description of the eight collections of fatigue test results by one equation only– the scatter of the results through the whole scope is only a little greater than that round the individual S/N curve– using this model while testing may reduce the number of test samples and shorten the test time– as the proposed model represents a common form of the S/N curve, it may be used for processing uniform objective fatigue life results, which may enable mutual comparison of fatigue characteristics.

Brain SPECT of chronic fatigue syndrome (CFS): a blinded visual analysis

International Nuclear Information System (INIS)

Casse, R.; Chew, G.; Barnden, L.; DelFante, P.; Burnet, R.; Kwiatek, R.; Chew, J.; Behin-Ain, S.; Unger, S.

2002-01-01

Full text: Chronic fatigue syndrome (CFS) is a debilitating and complex disorder characterised by profound fatigue and neuropsychiatric dysfunction. Previous studies with cerebral perfusion SPECT (rCBF) scans have yielded conflicting results. Most were performed with inhomogeneous patient populations and the findings were not based on a blinded visual analysis. To address this, HMPAO SPECT on a triple head gamma camera was performed on a group of 59 subjects. This group included 32 subjects (16-61 years, 24F and 8M) with moderate CFS based on the Fukuda criteria not on medication and not depressed and 27 normal volunteers (20-56 years, 16F and 11 M). Two blinded reviewers (RC and GC) separately assessed the SPECT studies. 28 brain structures were scored as either definitely abnormal(1), possibly abnormal(2) or normal(3-5). Abnormal results were only found in the temporal lobes and brainstem. The results (Sensitivity/Specificity) based on scores 1 or 2, show that that abnormal score yielded acceptable specificity but low sensitivity. Scores 1 or 2 improved sensitivity but reduced the specificity. This shows that visual analysis of brain SPECT is not a reliable discriminant test for CFS, although quantitative analysis with statistical parametric mapping (SPM) has demonstrated significant abnormalities. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

Prevalence of fatigue in general practice.

Science.gov (United States)

Cullen, W; Kearney, Y; Bury, G

2002-01-01

Fatigue is an important symptom in general practice due to its association with physical, psychological and social problems. To determine the prevalence of fatigue as an unsolicited symptom during general practice consultations. A random sample of GPs practising in Ireland was invited to provide data on consultations held over one day. Data were recorded on the presence of fatigue as a main or supporting symptom, social and demographic characteristics. Data were recorded by 89 GPs on 1,428 consultations. The prevalence of fatigue was 25%. It was the main reason for attending the doctor in 6.5% and a secondary reason in 19%. Sixty-two per cent of patients were female and 48% were eligible for free GP services. The mean age was 47.1 years. The presence of fatigue was associated with: attending a female GP, being female, attending a GP who had been qualified for fewer years and attending the GP frequently. The prevalence of fatigue reported in this study is over three times higher than that reported in earlier work. Doctor characteristics appear to be as important as patient characteristics in determining fatigue.

Fatigue Lifetime of ADI from Ultimate Tensile Strength to Permanent Fatigue Limit

Czech Academy of Sciences Publication Activity Database

Zapletal, J.; Věchet, S.; Kohout, J.; Obrtlík, Karel

-, č. 1 (2008), s. 40-43 ISSN 0556-171X. [MSMF /5./. Brno, 27.06.2007-29.06.2007] R&D Projects: GA ČR GA106/03/1265 Institutional research plan: CEZ:AV0Z20410507 Keywords : austempered ductile iron * fatigue behaviour * S N curve Subject RIV: JL - Materials Fatigue , Friction Mechanics

Tissue Hypoperfusion, Hypercoagulopathy, and Kidney and Liver Dysfunction after Ingestion of a Naphazoline-Containing Antiseptic

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Yuko Ono

2017-01-01

Full Text Available Naphazoline is a peripheral α2-adrenergic receptor agonist commonly used as a topical decongestant. In Japan, over-the-counter antiseptics often contain naphazoline to effect local hemostasis. We present the first case involving the development of hypercoagulopathy, with kidney and liver dysfunction, following a naphazoline overdose. A 22-year-old Japanese woman with a history of depression ingested 160 mL of a commercially available antiseptic containing 0.1% naphazoline. Three days later, she was brought to the emergency department because of general fatigue, nausea, and vomiting. Physical examination revealed cool, pale extremities. Laboratory data showed evidence of severe kidney and liver dysfunction (creatinine, 9.2 mg/dL; alanine aminotransferase, 2948 IU/L, hypercoagulation (D-dimers, 58.3 μg/mL, and thrombocytopenia (platelet count, 90,000/μL. After infusion of normal saline, intravenous administration of alprostadil, and hemodiafiltration, her organ function completely recovered. Because both the kidney and liver express α2-adrenergic receptors, their failure was likely associated with naphazoline overdose-induced hypoperfusion. The most plausible causes of hypercoagulation are peripheral low perfusion and subsequent microthrombus formation. This case illustrates that severe organ dysfunction can occur following over-the-counter antiseptic ingestion and serves as a caution for both drug manufacturers and healthcare professionals.

Fatigue and fatigue-related symptoms in patients treated for different causes of hypothyroidism

NARCIS (Netherlands)

J.W.K. Louwerens; B.C. Appelhof (Bente); H. Verloop (Herman); M. Medici (Marco); R.P. Peeters (Robin); T.J. Visser (Theo); A. Boelen (Anita); E. Fliers (Eric); J.W.A. Smit (Jan); O.M. Dekkers (Olaf)

2012-01-01

textabstractObjective: Research on determinants of well-being in patients on thyroid hormone replacement therapy is warranted, as persistent fatigue-related complaints are common in this population. In this study, we evaluated the impact of different states of hypothyroidism on fatigue and

Fatigue proofing: The role of protective behaviours in mediating fatigue-related risk in a defence aviation environment.

Science.gov (United States)

Dawson, Drew; Cleggett, Courtney; Thompson, Kirrilly; Thomas, Matthew J W

2017-02-01

In the military or emergency services, operational requirements and/or community expectations often preclude formal prescriptive working time arrangements as a practical means of reducing fatigue-related risk. In these environments, workers sometimes employ adaptive or protective behaviours informally to reduce the risk (i.e. likelihood or consequence) associated with a fatigue-related error. These informal behaviours enable employees to reduce risk while continuing to work while fatigued. In this study, we documented the use of informal protective behaviours in a group of defence aviation personnel including flight crews. Semi-structured interviews were conducted to determine whether and which protective behaviours were used to mitigate fatigue-related error. The 18 participants were from aviation-specific trades and included aircrew (pilots and air-crewman) and aviation maintenance personnel (aeronautical engineers and maintenance personnel). Participants identified 147 ways in which they and/or others act to reduce the likelihood or consequence of a fatigue-related error. These formed seven categories of fatigue-reduction strategies. The two most novel categories are discussed in this paper: task-related and behaviour-based strategies. Broadly speaking, these results indicate that fatigued military flight and maintenance crews use protective 'fatigue-proofing' behaviours to reduce the likelihood and/or consequence of fatigue-related error and were aware of the potential benefits. It is also important to note that these behaviours are not typically part of the formal safety management system. Rather, they have evolved spontaneously as part of the culture around protecting team performance under adverse operating conditions. When compared with previous similar studies, aviation personnel were more readily able to understand the idea of fatigue proofing than those from a fire-fighting background. These differences were thought to reflect different cultural

Fatigue-free PZT-based nanocomposites

Energy Technology Data Exchange (ETDEWEB)

Hwang, H J; Sando, M [Nat. Ind. Res. Inst., Nagoya (Japan); Tajima, K [Synergy Ceramics Lab., Fine Ceramics Research Association, Nagoya (Japan); Niihara, K [ISIR, Osaka Univ., Mihogaoka, Ibaraki (Japan)

1999-03-01

The goal of this study is to fabricate fatigue-free piezoelectrics-based nanocomposites. Lead zirconate titanate (PZT) and metallic platinum (Pt) were selected as a matrix and secondary phase dispersoid. Fine Pt particles were homogeneously dispersed in the PZT matrix. Fatigue properties of the unpoled PZT-based nanocomposite under electrical cyclic loading were investigated. The electrical-field-induced crack growth was monitored by an optical microscope, and it depended on the number of cycles the sample was subjected to. Resistance to fatigue was significantly enhanced in the nanocomposite. The excellent fatigue behavior of the PZT/Pt nanocomposites may result from the grain boundary strenghtening due to the interaction between the matrix and Pt particles. (orig.) 8 refs.

Effects of loading sequences and size of repeated stress block of loads on fatigue life calculated using fatigue functions

International Nuclear Information System (INIS)

Schott, G.

1989-01-01

It is well-known that collective form, stress intensity and loading sequence of individual stresses as well as size of repeated stress blocks can influence fatigue life, significantly. The basic variant of the consecutive Woehler curve concept will permit these effects to be involved into fatigue life computation. The paper presented will demonstrate that fatigue life computations using fatigue functions reflect the loading sequence effect with multilevel loading precisely and provide reliable fatigue life data. Effects of size of repeated stress block and loading sequence on fatigue life as observed with block program tests can be reproduced using the new computation method. (orig.) [de

Chronic fatigue in cancer patients treated with radiotherapy

International Nuclear Information System (INIS)

Rucinska, M.; Wojtukiewicz, M.Z.; Tokajuk, P.

2004-01-01

Fatigue is one of the most prevalent and profound symptoms related to both malignancy and anti-neoplastic treatment. It is being reported in 60% to 80% of cancer patients. We review the correlation between the cancer-related fatigue syndrome and radiotherapy. In patients undergoing radiotherapy, fatigue is often cumulative and may reach its peak during the last weeks of treatment. The presence of fatigue prior to therapy initiation is the most important predictive factor of the occurrence of radiotherapy-related cancer fatigue syndrome. Occasionally, fatigue persists for a prolonged period of months and even years beyond radiotherapy. Anemia may be one of major causative factors responsible for the development of the cancer-related fatigue syndrome. Fatigue has an enormous physical, mental, emotional, and economic impact on cancer patients, their families and care-providers. The treatment of radiation-related fatigue remains unknown. The initial approach should cover efforts aimed at the correction of potential etiologies, especially anemia. Education concerning fatigue greatly benefits some patients. It seems that exercise may be beneficial in relieving fatigue, bearing in mind that the exercise program for cancer patients should be initiated gradually and significantly individualized. (author)

Postpartum fatigue in the active-duty military woman.

Science.gov (United States)

Rychnovsky, Jacqueline D

2007-01-01

(a) To describe fatigue levels in military active-duty women, (b) to describe the relationship among selected predictor variables of fatigue, and (c) to examine the relationship between predictor variables, fatigue levels, and performance (as measured by functional status) after childbirth. Based on the Theory of Unpleasant Symptoms, a longitudinal, prospective design. A large military medical facility in the southwest United States. A convenience sample of 109 military active-duty women. Postpartum fatigue. Women were found to be moderately fatigued across time, with no change in fatigue levels from 2 to 6 weeks after delivery. All variables correlated with fatigue during hospitalization and at 2 weeks after delivery, and depression, anxiety, maternal sleep, and functional status correlated with fatigue at 6 weeks after delivery. Regression analyses indicated that maternal anxiety predicted fatigue at 6 weeks after delivery. Over half the women had not regained full functional status when they returned to work, and 40% still displayed symptoms of postpartum depression and anxiety. Military women continue to experiencing postpartum fatigue when they return to the workplace. Future research is needed to examine issues surrounding fatigue and its associated variables during the first year after delivery.

Fatigue and creep-fatigue in sodium of 316 1 stainless steel

International Nuclear Information System (INIS)

Ardellier, A.

1982-01-01

Equipment and results obtained on type 316 L stainless stee1 at 450 0 C and 600 0 C with low-cycle fatique and creep fatigue tests are described. Comparison with runs in air on type 316 L stainless steel shows a better low-cycle fatigue behavior in a sodium environment. This beneficial effect can be attributed to the low oxygen content which limits the surface oxidazation

Capturing the post-exertional exacerbation of fatigue following physical and cognitive challenge in patients with chronic fatigue syndrome.

Science.gov (United States)

Keech, Andrew; Sandler, Carolina X; Vollmer-Conna, Ute; Cvejic, Erin; Lloyd, Andrew R; Barry, Benjamin K

2015-12-01

To design and validate an instrument to capture the characteristic post-exertional exacerbation of fatigue in patients with chronic fatigue syndrome (CFS). Firstly, patients with CFS (N=19) participated in five focus group discussions to jointly explore the nature of fatigue and dynamic changes after activity, and inform development of a self-report instrument - the Fatigue and Energy Scale (FES). The psychometric properties of the FES were then examined in two case-control challenge studies: a physically-demanding challenge (moderate-intensity aerobic exercise; N=10 patients), and a cognitively-demanding challenge (simulated driving; N=11 patients). Finally, ecological validity was evaluated by recording in association with tasks of daily living (N=9). Common descriptors for fatigue included 'exhaustion', 'tiredness', 'drained of energy', 'heaviness in the limbs', and 'foggy in the head'. Based on the qualitative data, fatigue was conceptualised as consisting of 'physical' and 'cognitive' dimensions. Analysis of the psychometric properties of the FES showed good sensitivity to the changing symptoms during a post-exertional exacerbation of fatigue following both physical exercise and driving simulation challenges, as well as tasks of daily living. The 'fatigue' experienced by patients with CFS covers both physical and cognitive components. The FES captured the phenomenon of a post-exertional exacerbation of fatigue commonly reported by patients with CFS. The characteristics of the symptom response to physical and cognitive challenges were similar. Both the FES and the challenge paradigms offer key tools to reliably investigate biological correlates of the dynamic changes in fatigue. Copyright © 2015 Elsevier Inc. All rights reserved.

Monitoring and Managing Fatigue in Basketball

Directory of Open Access Journals (Sweden)

Toby Edwards

2018-02-01

Full Text Available The sport of basketball exposes athletes to frequent high intensity movements including sprinting, jumping, accelerations, decelerations and changes of direction during training and competition which can lead to acute and accumulated chronic fatigue. Fatigue may affect the ability of the athlete to perform over the course of a lengthy season. The ability of practitioners to quantify the workload and subsequent fatigue in basketball athletes in order to monitor and manage fatigue levels may be beneficial in maintaining high levels of performance and preventing unfavorable physical and physiological training adaptations. There is currently limited research quantifying training or competition workload outside of time motion analysis in basketball. In addition, systematic research investigating methods to monitor and manage athlete fatigue in basketball throughout a season is scarce. To effectively optimize and maintain peak training and playing performance throughout a basketball season, potential workload and fatigue monitoring strategies need to be discussed.

Fatigue management considering LWR coolant environments

International Nuclear Information System (INIS)

Park, Heung Bae; Jin, Tae eun

2000-01-01

Design fatigue curve for structural material in the ASME Boiler and Pressure Vessel Code do not explicitly address the effects of reactor coolant environments on fatigue life. Environmentally assisted cracking (EAC) of low-alloy steels in light water reactor (LWR) coolant environments has been a concern ever since the early 1970's. And, recent fatigue test data indicate a significant decrease in fatigue lives of carbon steels, low-alloy steels and austenitic stainless steels in LWR coolant environments. For these reasons, fatigue of major components has been identified as a technical issue remaining to be resolved for life management and license renewal of nuclear power plants. In the present paper, results of recent investigations by many organizations are reviewed to provide technical justification to support the development of utility approach regarding the management of fatigue considering LWR coolant environments for the purpose of life management and license renewal of nuclear power plants. (author)

Fatigue characteristics of dual-phase steel sheets

Energy Technology Data Exchange (ETDEWEB)

Onn, Irwan Herman; Ahmad, Norhayati; Tamin, Mohd Nasir [Universiti Teknologi Malaysia, Skudai (Malaysia)

2015-01-15

Fatigue characteristics of dual-phase steel sheets, commonly used in automobile body construction were established. For this purpose, a series of fatigue tests, each at constant stress amplitude were conducted on 1.2 mm-thick, dual-phase DP600 steel sheet specimens with two different load ratios of minimum-to-maximum stress, R = 0.1 and -1. The resulting fatigue behavior is expressed in terms of fatigue strength-life (S-N) curves. Fatigue behavior of the steel sheets in the high-cycle fatigue region can be represented by Basquin's equation with coefficient and exponent value of 921.2 and 0.093, respectively. An endurance limit of 255 MPa is observed. In addition, fatigue strengths of the dual-phase steel sheets display lower magnitude than their bulk counterparts. Effect of mean stress on fatigue behavior of the steel sheets is well predicted by Walker's model. Exponential calibration factor is introduced to the models by SWT, Goodman and Morrow with comparable prediction to the Walker's model.

Fatigue Behavior of Inconel 718 TIG Welds

Science.gov (United States)

Alexopoulos, Nikolaos D.; Argyriou, Nikolaos; Stergiou, Vasillis; Kourkoulis, Stavros K.

2014-08-01

Mechanical behavior of reference and TIG-welded Inconel 718 specimens was examined in the present work. Tensile, constant amplitude fatigue, and fracture toughness tests were performed in ambient temperature for both, reference and welded specimens. Microstructure revealed the presence of coarse and fine-grained heat-affected zones. It has been shown that without any post-weld heat treatment, welded specimens maintained their tensile strength properties while their ductility decreased by more than 40%. It was found that the welded specimens had lower fatigue life and this decrease was a function of the applied fatigue maximum stress. A 30% fatigue life decrease was noticed in the high cycle fatigue regime for the welded specimens while this decrease exceeded 50% in the low cycle fatigue regime. Cyclic stress-strain curves showed that Inconel 718 experiences a short period of hardening followed by softening for all fatigue lives. Cyclic fatigue response of welded specimens' exhibited cyclically stable behavior. Finally, a marginal decrease was noticed in the Mode I fracture toughness of the welded specimens.

Prevalence of operator fatigue in winter maintenance operations.

Science.gov (United States)

Camden, Matthew C; Medina-Flintsch, Alejandra; Hickman, Jeffrey S; Bryce, James; Flintsch, Gerardo; Hanowski, Richard J

2018-02-02

Similar to commercial motor vehicle drivers, winter maintenance operators are likely to be at an increased risk of becoming fatigued while driving due to long, inconsistent shifts, environmental stressors, and limited opportunities for sleep. Despite this risk, there is little research concerning the prevalence of winter maintenance operator fatigue during winter emergencies. The purpose of this research was to investigate the prevalence, sources, and countermeasures of fatigue in winter maintenance operations. Questionnaires from 1043 winter maintenance operators and 453 managers were received from 29 Clear Road member states. Results confirmed that fatigue was prevalent in winter maintenance operations. Over 70% of the operators and managers believed that fatigue has a moderate to significant impact on winter maintenance operations. Approximately 75% of winter maintenance operators reported to at least sometimes drive while fatigued, and 96% of managers believed their winter maintenance operators drove while fatigued at least some of the time. Furthermore, winter maintenance operators and managers identified fatigue countermeasures and sources of fatigue related to winter maintenance equipment. However, the countermeasures believed to be the most effective at reducing fatigue during winter emergencies (i.e., naps) were underutilized. For example, winter maintenance operators reported to never use naps to eliminate fatigue. These results indicated winter maintenance operations are impacted by operator fatigue. These results support the increased need for research and effective countermeasures targeting winter maintenance operator fatigue. Copyright © 2018 Elsevier Ltd. All rights reserved.

Usefulness of multiple dimensions of fatigue in fibromyalgia.

Science.gov (United States)

Ericsson, Anna; Bremell, Tomas; Mannerkorpi, Kaisa

2013-07-01

To explore in which contexts ratings of multiple dimensions of fatigue are useful in fibromyalgia, and to compare multidimensional fatigue between women with fibromyalgia and healthy women. A cross-sectional study. The Multidimensional Fatigue Inventory (MFI-20), comprising 5 subscales of fatigue, was compared with the 1-dimensional subscale of fatigue from the Fibromyalgia Impact Questionnaire (FIQ) in 133 women with fibromyalgia (mean age 46 years; standard deviation 8.6), in association with socio-demographic and health-related aspects and analyses of explanatory variables of severe fatigue. The patients were also compared with 158 healthy women (mean age 45 years; standard deviation 9.1) for scores on MFI-20 and FIQ fatigue. The MFI-20 was associated with employment, physical activity and walking capacity (rs = -0.27 to -0.36), while FIQ fatigue was not. MFI-20 and FIQ fatigue were equally associated with pain, sleep, depression and anxiety (rs = 0.32-0.63). Regression analyses showed that the MFI-20 increased the explained variance (R2) for the models of pain intensity, sleep, depression and anxiety, by between 7 and 29 percentage points, compared with if FIQ fatigue alone was included in the models. Women with fibromyalgia rated their fatigue higher than healthy women for all subscales of the MFI-20 and the FIQ fatigue (p fibromyalgia. The patients reported higher levels on all fatigue dimensions in comparison with healthy women.

Multidimensional fatigue in pulmonary hypertension: prevalence, severity and predictors

Science.gov (United States)

Tartavoulle, Todd M.; Karpinski, Aryn C.; Aubin, Andrew; Kluger, Benzi M.; Distler, Oliver; Saketkoo, Lesley Ann

2018-01-01

Pulmonary hypertension is a potentially fatal disease. Despite pharmacological advances in pulmonary hypertension, fatigue remains common in patients with pulmonary hypertension. A convenience sample of 120 participants at an international patient conference completed the Multidimensional Fatigue Inventory (MFI)-20 scale. Data on New York Heart Association Functional Class, body mass index, oxygen use and medication type/use were also collected. There was a high prevalence of “severe” to “very severe” fatigue for each dimension: General Fatigue (60%), Physical Fatigue (55.8%), Reduced Activity (41.7%), Reduced Motivation (32.5%) and Mental Fatigue (27.5%). The mean±sd overall MFI-20 score was 58±5.1. Dimensions with the highest averaged levels were General Fatigue (13.40±3.61), Physical Fatigue (13.23±3.67) and Reduced Activity (11.33±4.16). Body mass index correlated with higher fatigue scores. Phosphodiesterase inhibitor plus endothelin receptor antagonist combination negatively predicted General Fatigue, Physical Fatigue, Reduced Motivation and Reduced Activity. Triple therapy was a significant predictor of General Fatigue, Physical Fatigue and Reduced Activity. There were no significant predictors of Mental Fatigue. Multidimensional fatigue is common and severe in patients with pulmonary hypertension. Phosphodiesterase inhibitor plus endothelin receptor antagonist combination resulted in lower scores in most fatigue dimensions. Comprehensive assessment of fatigue should be considered in the clinical care of patients with pulmonary hypertension and clinical research to develop formal interventions that target this disabling symptom. PMID:29577043