Effects of fatigue on immune function in nurses performing shift work.

PubMed

Nagai, Makie; Morikawa, Yuko; Kitaoka, Kazuyo; Nakamura, Koshi; Sakurai, Masaru; Nishijo, Muneko; Hamazaki, Yuko; Maruzeni, Shoko; Nakagawa, Hideaki

2011-01-01

We investigated the effects of fatigue on NK cell function and lymphocyte subpopulations in nurses performing shift work using a longitudinal design. Fifty-seven female nurses engaged in shift work at a hospital in Japan were selected for our study cohort. The hospital used a counterclockwise rotating three-shift system. Night shifts followed day shifts after a seven-hour interval. Immune parameters measured at the beginning of the day shift through to the end of the night shift were compared between two groups stratified by their level of fatigue. Statistical differences were evaluated after adjusting for baseline immune values and other demographic features. Subjective feelings of fatigue increased progressively from the beginning of day shifts to the end of night shifts. From the beginning of day shifts to the end of night shifts, NK cell activity and CD16(+)CD56(+) lymphocytes decreased, while CD3(+) and CD4(+) lymphocytes increased. The group with the greater increase in fatigue showed a larger decrease in NK cell activity and a larger increase in CD4(+)lymphocytes when compared with the group reporting less fatigue. These findings did not change after adjusting for demographic factors and sleep hours. Our data suggest that shift work has deleterious effects on NK cell function and that the effects depend on the degree of fatigue. Proper management of shift work may lessen fatigue in workers and also ameliorate many health problems experienced by shift workers.

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

PubMed

Aspler, Anne L; Bolshin, Carly; Vernon, Suzanne D; Broderick, Gordon

2008-09-26

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. 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. 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 < 0.05, patterns of co-expression in each group differed markedly. Significant co-expression of CD14+ monocyte with CD16+ neutrophil (p = 0.01) and CD19+ B cell sets (p = 0.00) characterized CFS and fatigue phenotype groups. Also in CFS was a significant negative correlation between CD8+ and both CD19+ up-regulated (p = 0.02) and NK gene sets (p = 0.08). These patterns were absent in controls. 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.

Immune dysfunction prior to Staphylococcus aureus bacteremia is a determinant of long-term mortality.

PubMed

Greenberg, Jared A; David, Michael Z; Hall, Jesse B; Kress, John P

2014-01-01

The clinical implications for patients who survive serious infections are not well understood. It has been hypothesized that the excess mortality for survivors of sepsis observed in epidemiological studies is due to increased vulnerability to subsequent infections. We undertook this study to identify characteristics of patients who are at high risk for death after surviving a common type of blood-stream infection. At a single academic medical center, 237 patients with Staphylococcus aureus bacteremia admitted during a three-year period were retrospectively identified. The primary outcomes were 30-day and 31 to 90-day mortality after the first positive blood culture. The primary predictor variable of interest was clinical immune dysfunction prior to bacteremia. The 30-day mortality was not significantly different for patients with and without prior immune dysfunction. However, during days 31 to 90, 11 patients (20%) with prior immune dysfunction compared to 10 patients (8.6%) without prior immune dysfunction died (OR 2.59, 95% CI 1.03-6.53, p = 0.04). In a Cox-proportional hazard model controlling for age, there was a significant association between prior immune dysfunction and greater 31 to 90 day mortality (HR 2.44, 95% CI 1.01-5.90, p = 0.05) and a non-significant trend towards occurrence of subsequent infections and greater 31 to 90 day mortality (HR 2.12, 95% CI 0.89-5.07, p = 0.09). Patients with prior immune dysfunction are at high risk for death 31 to 90 days, but not <30 days, after S. aureus bacteremia. Further investigation is needed to determine if this finding is due to poor prognosis of chronic disease or increased vulnerability to subsequent infections.

Immunophenotyping in post-giardiasis functional gastrointestinal disease and chronic fatigue syndrome.

PubMed

Hanevik, Kurt; Kristoffersen, Einar K; Sørnes, Steinar; Mørch, Kristine; Næss, Halvor; Rivenes, Ann C; Bødtker, Jørn E; Hausken, Trygve; Langeland, Nina

2012-10-14

A Giardia outbreak was associated with development of post-infectious functional gastrointestinal disorders (PI-FGID) and chronic fatigue syndrome (PI-CFS). Markers of immune dysfunction have given conflicting results in CFS and FGID patient populations. The aim of this study was to evaluate a wide selection of markers of immune dysfunction in these two co-occurring post-infectious syndromes. 48 patients, reporting chronic fatigue in a questionnaire study, were clinically evaluated five years after the outbreak and grouped according to Fukuda criteria for CFS (n=19) and idiopathic chronic fatigue (n=5) and Rome II criteria for FGIDs (n=54). 22 Giardia exposed non-fatigued individuals and 10 healthy unexposed individuals were recruited as controls. Peripheral blood lymphocyte subsets were analyzed by flow cytometry. In peripheral blood we found significantly higher CD8 T-cell levels in PI-FGID, and significantly lower NK-cell levels in PI-CFS patients. Severity of abdominal and fatigue symptoms correlated negatively with NK-cell levels. A tendency towards lower T-cell CD26 expression in FGID was seen. Patients with PI-CFS and/or PI-FGID 5 years after Giardia lamblia infection showed alterations in NK-cell and CD8-cell populations suggesting a possible immunological abnormality in these conditions. We found no significant changes in other markers examined in this well-defined group of PI-CFS and PI-FGID elicited by a gastrointestinal infection. Controlling for co-morbid conditions is important in evaluation of CFS-biomarkers.

Development and validation of immune dysfunction score to predict 28-day mortality of sepsis patients

PubMed Central

Fang, Wen-Feng; Douglas, Ivor S.; Chen, Yu-Mu; Lin, Chiung-Yu; Kao, Hsu-Ching; Fang, Ying-Tang; Huang, Chi-Han; Chang, Ya-Ting; Huang, Kuo-Tung; Wang, Yi-His; Wang, Chin-Chou

2017-01-01

Background Sepsis-induced immune dysfunction ranging from cytokines storm to immunoparalysis impacts outcomes. Monitoring immune dysfunction enables better risk stratification and mortality prediction and is mandatory before widely application of immunoadjuvant therapies. We aimed to develop and validate a scoring system according to patients’ immune dysfunction status for 28-day mortality prediction. Methods A prospective observational study from a cohort of adult sepsis patients admitted to ICU between August 2013 and June 2016 at Kaohsiung Chang Gung Memorial Hospital in Taiwan. We evaluated immune dysfunction status through measurement of baseline plasma Cytokine levels, Monocyte human leukocyte-DR expression by flow cytometry, and stimulated immune response using post LPS stimulated cytokine elevation ratio. An immune dysfunction score was created for 28-day mortality prediction and was validated. Results A total of 151 patients were enrolled. Data of the first consecutive 106 septic patients comprised the training cohort, and of other 45 patients comprised the validation cohort. Among the 106 patients, 21 died and 85 were still alive on day 28 after ICU admission. (mortality rate, 19.8%). Independent predictive factors revealed via multivariate logistic regression analysis included segmented neutrophil-to-monocyte ratio, granulocyte-colony stimulating factor, interleukin-10, and monocyte human leukocyte antigen-antigen D–related levels, all of which were selected to construct the score, which predicted 28-day mortality with area under the curve of 0.853 and 0.789 in the training and validation cohorts, respectively. Conclusions The immune dysfunction scoring system developed here included plasma granulocyte-colony stimulating factor level, interleukin-10 level, serum segmented neutrophil-to-monocyte ratio, and monocyte human leukocyte antigen-antigen D–related expression appears valid and reproducible for predicting 28-day mortality. PMID:29073262

A mechanism for trauma induced muscle wasting and immune dysfunction

NASA Astrophysics Data System (ADS)

Madihally, S.; Toner, M.; Yarmush, M.; Mitchell, R.

A diverse physiological conditions lead to a hypercatabolic state marked by the loss of proteins, primarily derived from skeletal muscle. The sustained loss of proteins results in loss of muscle mass and strength, poor healing, and long-term hospitalization. These problems are further compounded by the deterioration of immunity to infection which is a leading cause of morbidity and mortality of traumatic patients. In an attempt to understand the signal propagation mechanism(s), we tested the role of Interferon-? (IFN-? ) in an animal burn injury model; IFN-? is best conceptualized as a macrophage activating protein and known to modulate a variety of intracellular processes potentially relevant to muscle wasting and immune dysfunction. Mice congenitally -deficient in IFN-? , and IFN-? -Receptor, and wild type (WT) animals treated with IFN-? neutralizing antibody received either a 20% total body surface area burn or a control sham treatment. At days 1, 2, and 7 following treatment, skeletal muscle, peripheral blood, and spleen were harvested from both groups. Overall body weight, protein turnovers, changes in the lymphocyte subpopulations and alterations in the major histocompatibility complex I expression (MHC I) and proliferation capacity of lymphocytes was measured using mixed lymphocyte reaction (MLR). These results indicate that we can prevent both muscle wasting and immune dysfunction. Based on these observations and our previous other animal model results (using insulin therapy), a novel mechanism of interactions leading to muscle wasting and immune dysfunction will be discussed. Further, implications of these findings on future research and clinical therapies will be discussed in detail.

Epigenetic alterations are associated with monocyte immune dysfunctions in HIV-1 infection.

PubMed

Espíndola, Milena S; Soares, Luana S; Galvão-Lima, Leonardo J; Zambuzi, Fabiana A; Cacemiro, Maira C; Brauer, Verônica S; Marzocchi-Machado, Cleni M; de Souza Gomes, Matheus; Amaral, Laurence R; Martins-Filho, Olindo A; Bollela, Valdes R; Frantz, Fabiani G

2018-04-03

Monocytes are key cells in the immune dysregulation observed during human immunodeficiency virus (HIV) infection. The events that take place specifically in monocytes may contribute to the systemic immune dysfunction characterized by excessive immune activation in infected individuals, which directly correlates with pathogenesis and progression of the disease. Here, we investigated the immune dysfunction in monocytes from untreated and treated HIV + patients and associated these findings with epigenetic changes. Monocytes from HIV patients showed dysfunctional ability of phagocytosis and killing, and exhibited dysregulated cytokines and reactive oxygen species production after M. tuberculosis challenge in vitro. In addition, we showed that the expression of enzymes responsible for epigenetic changes was altered during HIV infection and was more prominent in patients that had high levels of soluble CD163 (sCD163), a newly identified plasmatic HIV progression biomarker. Among the enzymes, histone acetyltransferase 1 (HAT1) was the best epigenetic biomarker correlated with HIV - sCD163 high patients. In conclusion, we confirmed that HIV impairs effector functions of monocytes and these alterations are associated with epigenetic changes that once identified could be used as targets in therapies aiming the reduction of the systemic activation state found in HIV patients.

Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis.

PubMed

Brenu, Ekua Weba; Huth, Teilah K; Hardcastle, Sharni L; Fuller, Kirsty; Kaur, Manprit; Johnston, Samantha; Ramos, Sandra B; Staines, Don R; Marshall-Gradisnik, Sonya M

2014-04-01

Perturbations in immune processes are a hallmark of a number of autoimmune and inflammatory disorders. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is an inflammatory disorder with possible autoimmune correlates, characterized by reduced NK cell activity, elevations in regulatory T cells (Tregs) and dysregulation in cytokine levels. The purpose of this article is to examine innate and adaptive immune cell phenotypes and functional characteristics that have not been previously examined in CFS/ME patients. Thirty patients with CFS/ME and 25 non-fatigued controls were recruited for this study. Whole blood samples were collected from all participants for the assessment of cell phenotypes, functional properties, receptors, adhesion molecules, antigens and intracellular proteins using flow cytometric protocols. The cells investigated included NK cells, dendritic cells, neutrophils, B cells, T cells, γδT cells and Tregs. Significant changes were observed in B-cell subsets, Tregs, CD4(+)CD73(+)CD39(+) T cells, cytotoxic activity, granzyme B, neutrophil antigens, TNF-α and IFN-γ in the CFS/ME patients in comparison with the non-fatigued controls. Alterations in B cells, Tregs, NK cells and neutrophils suggest significant impairments in immune regulation in CFS/ME and these may have similarities to a number of autoimmune disorders.

Curcumin reverses T cell-mediated adaptive immune dysfunctions in tumor-bearing hosts.

PubMed

Bhattacharyya, Sankar; Md Sakib Hossain, Dewan; Mohanty, Suchismita; Sankar Sen, Gouri; Chattopadhyay, Sreya; Banerjee, Shuvomoy; Chakraborty, Juni; Das, Kaushik; Sarkar, Diptendra; Das, Tanya; Sa, Gaurisankar

2010-07-01

Immune dysfunction is well documented during tumor progression and likely contributes to tumor immune evasion. CD8(+) cytotoxic T lymphocytes (CTLs) are involved in antigen-specific tumor destruction and CD4(+) T cells are essential for helping this CD8(+) T cell-dependent tumor eradication. Tumors often target and inhibit T-cell function to escape from immune surveillance. This dysfunction includes loss of effector and memory T cells, bias towards type 2 cytokines and expansion of T regulatory (Treg) cells. Curcumin has previously been shown to have antitumor activity and some research has addressed the immunoprotective potential of this plant-derived polyphenol in tumor-bearing hosts. Here we examined the role of curcumin in the prevention of tumor-induced dysfunction of T cell-based immune responses. We observed severe loss of both effector and memory T-cell populations, downregulation of type 1 and upregulation of type 2 immune responses and decreased proliferation of effector T cells in the presence of tumors. Curcumin, in turn, prevented this loss of T cells, expanded central memory T cell (T(CM))/effector memory T cell (T(EM)) populations, reversed the type 2 immune bias and attenuated the tumor-induced inhibition of T-cell proliferation in tumor-bearing hosts. Further investigation revealed that tumor burden upregulated Treg cell populations and stimulated the production of the immunosuppressive cytokines transforming growth factor (TGF)-beta and IL-10 in these cells. Curcumin, however, inhibited the suppressive activity of Treg cells by downregulating the production of TGF-beta and IL-10 in these cells. More importantly, curcumin treatment enhanced the ability of effector T cells to kill cancer cells. Overall, our observations suggest that the unique properties of curcumin may be exploited for successful attenuation of tumor-induced suppression of cell-mediated immune responses.

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

PubMed

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.

Role of Dendritic Cells in Immune Dysfunction

NASA Technical Reports Server (NTRS)

Savary, Cherylyn A.

1998-01-01

The specific aims of the project were: (1) Application of the NASA bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC). (2) Compare the frequency and function of DC in normal donors and immunocompromised cancer patients. (3) Analyze the effectiveness of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in a murine model of experimental fungal disease. Our investigations have provided new insight into DC immunobiology and have led to the development of methodology to evaluate DC in blood of normal donors and patients. Information gained from these studies has broadened our understanding of possible mechanisms involved in the immune dysfunction of space travelers and earth-bound cancer patients, and could contribute to the design of novel therapies to restore/preserve immunity in these individuals. Several new avenues of investigation were also revealed. The results of studies completed during Round 2 are summarized.

Mitochondrial dysfunction as a trigger of innate immune responses and inflammation.

PubMed

West, A Phillip

2017-11-01

A growing literature indicates that mitochondria are key participants in innate immune pathways, functioning as both signaling platforms and contributing to effector responses. In addition to regulating antiviral signaling and antibacterial immunity, mitochondria are also important drivers of inflammation caused by sterile injury. Much research on mitochondrial control of immunity now centers on understanding how mitochondrial constituents released during cellular damage simulate the innate immune system. When mitochondrial integrity is compromised, mitochondrial damage-associated molecular patterns engage pattern recognition receptors, trigger inflammation, and promote pathology in an expanding list of diseases. Here, I review the emerging knowledge of mitochondrial dysfunction in innate immune responses and discuss how environmental exposures may induce mitochondrial damage to potentiate inflammation and human disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuro-immune dysfunction during brain aging: new insights in microglial cell regulation.

PubMed

Matt, Stephanie M; Johnson, Rodney W

2016-02-01

Microglia, the resident immune cells of the brain, are at the center of communication between the central nervous system and immune system. While these brain-immune interactions are balanced in healthy adulthood, the ability to maintain homeostasis during aging is impaired. Microglia develop a loss of integrated regulatory networks including aberrant signaling from other brain cells, immune sensors, and epigenetic modifiers. The low-grade chronic neuroinflammation associated with this dysfunctional activity likely contributes to cognitive deficits and susceptibility to age-related pathologies. A better understanding of the underlying mechanisms responsible for neuro-immune dysregulation with age is crucial for providing targeted therapeutic strategies to support brain repair and healthy aging. Copyright © 2015 Elsevier Ltd. All rights reserved.

A preliminary path analysis: Effect of psychopathological symptoms, mental and physical dysfunctions related to quality of life and body mass index on fatigue severity of Iranian patients with multiple sclerosis.

PubMed

Salehpoor, Ghasem; Hosseininezhad, Mozaffar; Rezaei, Sajjad

2012-01-01

Multiple sclerosis (MS) is a neurological disease with fatigue as most prevalent symptom. Psychopathological symptoms, physical and mental dysfunctions and body mass abnormalities potentially could deteriorate fatigue. Thus, in this study, we aimed at evaluating the effect of these factors on fatigue severity of MS patients. In this cross-sectional study, 162 patients with mean age of 34.1 ± 9.4 (16-58 years) were recruited by consecutive sampling. All the patients, after completing demographic information were evaluated using Persian versions of Fatigue Severity Scale (FSS), depression, anxiety and stress scale (DASS-21), and short form Health Survey Questionnaire (SF-36). Correlation analysis showed a significant relationship between fatigue severity and depression, anxiety, stress, physical component summary (PCS) and mental component summary (MCS) (P < 0.01). Findings of path analysis demonstrated that PCS is the only variable which has a direct effect on fatigue severity (β = -0.278, P < 0.05). Moreover, the strongest standard coefficient (β) belonged to cause and effect relationship between MCS and depression (β = -0.691, P < 0.0001). Present study made the role of psychopathological symptoms and physical and mental dysfunctions prominent in exacerbation of fatigue severity. Moreover, we can refer to more sensible effect of physical dysfunction related to life on fatigue.

Astrocyte atrophy and immune dysfunction in self-harming macaques.

PubMed

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.

The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: Focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis.

PubMed

Morris, Gerwyn; Stubbs, Brendon; Köhler, Cristiano A; Walder, Ken; Slyepchenko, Anastasiya; Berk, Michael; Carvalho, André F

2018-04-04

Sleep and circadian abnormalities are prevalent and burdensome manifestations of diverse neuro-immune diseases, and may aggravate the course of several neuropsychiatric disorders. The underlying pathophysiology of sleep abnormalities across neuropsychiatric disorders remains unclear, and may involve the inter-play of several clinical variables and mechanistic pathways. In this review, we propose a heuristic framework in which reciprocal interactions of immune, oxidative and nitrosative stress, and mitochondrial pathways may drive sleep abnormalities across potentially neuroprogressive disorders. Specifically, it is proposed that systemic inflammation may activate microglial cells and astrocytes in brain regions involved in sleep and circadian regulation. Activated glial cells may secrete pro-inflammatory cytokines (for example, interleukin-1 beta and tumour necrosis factor alpha), nitric oxide and gliotransmitters, which may influence the expression of key circadian regulators (e.g., the Circadian Locomotor Output Cycles Kaput (CLOCK) gene). Furthermore, sleep disruption may further aggravate oxidative and nitrosative, peripheral immune activation, and (neuro) inflammation across these disorders in a vicious pathophysiological loop. This review will focus on chronic fatigue syndrome, bipolar disorder, and multiple sclerosis as exemplars of neuro-immune disorders. We conclude that novel therapeutic targets exploring immune and oxidative & nitrosative pathways (p.e. melatonin and molecular hydrogen) hold promise in alleviating sleep and circadian dysfunction in these disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

Neuroendocrine and immune network re-modeling in chronic fatigue syndrome: an exploratory analysis.

PubMed

Fuite, Jim; Vernon, Suzanne D; Broderick, Gordon

2008-12-01

This work investigates the significance of changes in association patterns linking indicators of neuroendocrine and immune activity in patients with chronic fatigue syndrome (CFS). Gene sets preferentially expressed in specific immune cell isolates were integrated with neuroendocrine data from a large population-based study. Co-expression patterns linking immune cell activity with hypothalamic-pituitary-adrenal (HPA), thyroidal (HPT) and gonadal (HPG) axis status were computed using mutual information criteria. Networks in control and CFS subjects were compared globally in terms of a weighted graph edit distance. Local re-modeling of node connectivity was quantified by node degree and eigenvector centrality measures. Results indicate statistically significant differences between CFS and control networks determined mainly by re-modeling around pituitary and thyroid nodes as well as an emergent immune sub-network. Findings align with known mechanisms of chronic inflammation and support possible immune-mediated loss of thyroid function in CFS exacerbated by blunted HPA axis responsiveness.

Early immune responses are independent of RGC dysfunction in glaucoma with complement component C3 being protective.

PubMed

Harder, Jeffrey M; Braine, Catherine E; Williams, Pete A; Zhu, Xianjun; MacNicoll, Katharine H; Sousa, Gregory L; Buchanan, Rebecca A; Smith, Richard S; Libby, Richard T; Howell, Gareth R; John, Simon W M

2017-05-09

Various immune response pathways are altered during early, predegenerative stages of glaucoma; however, whether the early immune responses occur secondarily to or independently of neuronal dysfunction is unclear. To investigate this relationship, we used the Wld s allele, which protects from axon dysfunction. We demonstrate that DBA/2J .Wld s mice develop high intraocular pressure (IOP) but are protected from retinal ganglion cell (RGC) dysfunction and neuroglial changes that otherwise occur early in DBA/2J glaucoma. Despite this, immune pathways are still altered in DBA/2J .Wld s mice. This suggests that immune changes are not secondary to RGC dysfunction or altered neuroglial interactions, but may be directly induced by the increased strain imposed by high IOP. One early immune response following IOP elevation is up-regulation of complement C3 in astrocytes of DBA/2J and DBA/2J. Wld s mice. Unexpectedly, because the disruption of other complement components, such as C1Q, is protective in glaucoma, C3 deficiency significantly increased the number of DBA/2J eyes with nerve damage and RGC loss at an early time point after IOP elevation. Transcriptional profiling of C3-deficient cultured astrocytes implicated EGFR signaling as a hub in C3-dependent responses. Treatment with AG1478, an EGFR inhibitor, also significantly increased the number of DBA/2J eyes with glaucoma at the same early time point. These findings suggest that C3 protects from early glaucomatous damage, a process that may involve EGFR signaling and other immune responses in the optic nerve head. Therefore, therapies that target specific components of the complement cascade, rather than global inhibition, may be more applicable for treating human glaucoma.

Early immune responses are independent of RGC dysfunction in glaucoma with complement component C3 being protective

PubMed Central

Harder, Jeffrey M.; Braine, Catherine E.; Williams, Pete A.; Zhu, Xianjun; MacNicoll, Katharine H.; Sousa, Gregory L.; Buchanan, Rebecca A.; Smith, Richard S.; Howell, Gareth R.; John, Simon W. M.

2017-01-01

Various immune response pathways are altered during early, predegenerative stages of glaucoma; however, whether the early immune responses occur secondarily to or independently of neuronal dysfunction is unclear. To investigate this relationship, we used the Wlds allele, which protects from axon dysfunction. We demonstrate that DBA/2J.Wlds mice develop high intraocular pressure (IOP) but are protected from retinal ganglion cell (RGC) dysfunction and neuroglial changes that otherwise occur early in DBA/2J glaucoma. Despite this, immune pathways are still altered in DBA/2J.Wlds mice. This suggests that immune changes are not secondary to RGC dysfunction or altered neuroglial interactions, but may be directly induced by the increased strain imposed by high IOP. One early immune response following IOP elevation is up-regulation of complement C3 in astrocytes of DBA/2J and DBA/2J.Wlds mice. Unexpectedly, because the disruption of other complement components, such as C1Q, is protective in glaucoma, C3 deficiency significantly increased the number of DBA/2J eyes with nerve damage and RGC loss at an early time point after IOP elevation. Transcriptional profiling of C3-deficient cultured astrocytes implicated EGFR signaling as a hub in C3-dependent responses. Treatment with AG1478, an EGFR inhibitor, also significantly increased the number of DBA/2J eyes with glaucoma at the same early time point. These findings suggest that C3 protects from early glaucomatous damage, a process that may involve EGFR signaling and other immune responses in the optic nerve head. Therefore, therapies that target specific components of the complement cascade, rather than global inhibition, may be more applicable for treating human glaucoma. PMID:28446616

Chronic fatigue in Ehlers-Danlos syndrome-Hypermobile type.

PubMed

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.

Contractile dysfunctions in ATP-dependent K+ channel-deficient mouse muscle during fatigue involve excessive depolarization and Ca2+ influx through L-type Ca2+ channels.

PubMed

Cifelli, Carlo; Boudreault, Louise; Gong, Bing; Bercier, Jean-Philippe; Renaud, Jean-Marc

2008-10-01

Muscles deficient in ATP-dependent potassium (KATP) channels develop contractile dysfunctions during fatigue that may explain their apparently faster rate of fatigue compared with wild-type muscles. The objectives of this study were to determine: (1) whether the contractile dysfunctions, namely unstimulated force and depressed force recovery, result from excessive membrane depolarization and Ca2+ influx through L-type Ca2+ channels; and (2) whether reducing the magnitude of these two contractile dysfunctions reduces the rate of fatigue in KATP channel-deficient muscles. To reduce Ca2+ influx, we lowered the extracellular Ca2+ concentration ([Ca2+]o) from 2.4 to 0.6 mM or added 1 microM verapamil, an L-type Ca2+ channel blocker. Flexor digitorum brevis (FDB) muscles deficient in KATP channels were obtained by exposing wild-type muscles to 10 microM glibenclamide or by using FDB from Kir6.2-/- mice. Fatigue was elicited with one contraction per second for 3 min at 37 degrees C. In wild-type FDB, lowered [Ca2+]o or verapamil did not affect the decrease in peak tetanic force and unstimulated force during fatigue and force recovery following fatigue. In KATP channel-deficient FDB, lowered [Ca2+]o or verapamil slowed down the decrease in peak tetanic force recovery, reduced unstimulated force and improved force recovery. In Kir6.2-/- FDB, the rate of fatigue became slower than in wild-type FDB in the presence of verapamil. The cell membrane depolarized from -83 to -57 mV in normal wild-type FDB. The depolarizations in some glibenclamide-exposed fibres were similar to those of normal FDB, while in other fibres the cell membrane depolarized to -31 mV in 80 s, which was also the time when these fibres supercontracted. It is concluded that: (1) KATP channels are crucial in preventing excessive membrane depolarization and Ca2+ influx through L-type Ca2+ channels; and (2) they contribute to the decrease in force during fatigue.

Chemotherapy Necessitates Increased Immune Control of HHVs: A Cause of Persistent Inflammation Enabling Protracted Fatigue in Breast Cancer Survivors

DTIC Science & Technology

2014-10-01

14. ABSTRACT This work hypothesizes that chemotherapy can permanently alter the balance between the immune system and chronic herpes virus...infections. We predicted that herpes virus-driven inflammatory cytokines exacerbate cancer treatment related fatigue (CTRF). Here we report the significant...TERMS breast cancer, chemotherapy, immunology, human herpes viruses, survivor fatigue 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT

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

PubMed

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.

Extracellular vesicles are key intercellular mediators in the development of immune dysfunction to allergens in the airways.

PubMed

Shin, T-S; Kim, J H; Kim, Y-S; Jeon, S G; Zhu, Z; Gho, Yong Song; Kim, Yoon-Keun

2010-10-01

Previous evidence indicates that inhalation of lipopolysaccharide (LPS)-containing with allergens induced mixed Th1 and Th17 cell responses in the airways. Extracellular vesicles (EVs) are nanometer-sized spherical, lipid-bilayered structures and are recently in the public eye as an intercellular communicator in immune responses. To evaluate the role of EVs secreted by LPS inhalation in the development of airway immune dysfunction in response to allergens. Extracellular vesicles in bronchoalveolar lavage fluids of BALB/c mice were isolated and characterized 24 h after applications to the airway of 10 μg of LPS for 3 days. To evaluate the role of LPS-induced EVs on the development of airway immune dysfunction, in vivo and in vitro experiments were performed using the isolated LPS-induced EVs. The inhalation of LPS enhanced EVs release into the BAL fluid, when compared to the application of PBS. Airway sensitization with allergens and LPS-induced EVs resulted in a mixed Th1 and Th17 cell responses, although that with allergens and PBS-induced EVs induced immune tolerance. In addition, LPS-induced EVs enhanced the production of Th1- and Th17-polarizing cytokines (IL-12p70 and IL-6, respectively) by lung dendritic cells. Moreover, the immune responses induced by the LPS-induced EVs were blocked by denaturation of the EV-bearing proteins. These data suggest that EVs (especially, the protein components) secreted by LPS inhalation are a key intercellular communicator in the development of airway immune dysfunction to inhaled LPS-containing allergens.

Extracellular vesicles are key intercellular mediators in the development of immune dysfunction to allergens in the airways

PubMed Central

Shin, T-S; Kim, J H; Kim, Y-S; Jeon, S G; Zhu, Z; Gho, Y S; Kim, Y-K

2010-01-01

Background Previous evidence indicates that inhalation of lipopolysaccharide (LPS)-containing with allergens induced mixed Th1 and Th17 cell responses in the airways. Extracellular vesicles (EVs) are nanometer-sized spherical, lipid-bilayered structures and are recently in the public eye as an intercellular communicator in immune responses. Objective To evaluate the role of EVs secreted by LPS inhalation in the development of airway immune dysfunction in response to allergens. Methods Extracellular vesicles in bronchoalveolar lavage fluids of BALB/c mice were isolated and characterized 24 h after applications to the airway of 10 μg of LPS for 3 days. To evaluate the role of LPS-induced EVs on the development of airway immune dysfunction, in vivo and in vitro experiments were performed using the isolated LPS-induced EVs. Results The inhalation of LPS enhanced EVs release into the BAL fluid, when compared to the application of PBS. Airway sensitization with allergens and LPS-induced EVs resulted in a mixed Th1 and Th17 cell responses, although that with allergens and PBS-induced EVs induced immune tolerance. In addition, LPS-induced EVs enhanced the production of Th1- and Th17-polarizing cytokines (IL-12p70 and IL-6, respectively) by lung dendritic cells. Moreover, the immune responses induced by the LPS-induced EVs were blocked by denaturation of the EV-bearing proteins. Conclusion These data suggest that EVs (especially, the protein components) secreted by LPS inhalation are a key intercellular communicator in the development of airway immune dysfunction to inhaled LPS-containing allergens. PMID:20337607

Current insights into the innate immune system dysfunction in irritable bowel syndrome.

PubMed

Lazaridis, Nikolaos; Germanidis, Georgios

2018-01-01

Irritable bowel syndrome (IBS) is a functional bowel disorder associated with abdominal pain and alterations in bowel habits. The presence of IBS greatly impairs patients' quality of life and imposes a high economic burden on the community; thus, there is intense pressure to reveal its elusive pathogenesis. Many etiological mechanisms have been implicated, but the pathophysiology of the syndrome remains unclear. As a result, novel drug development has been slow and no pharmacological intervention is universally accepted. A growing evidence implicates the role of low-grade inflammation and innate immune system dysfunction, although contradictory results have frequently been presented. Mast cells (MC), eosinophils and other key immune cells together with their mediators seem to play an important role, at least in subgroups of IBS patients. Cytokine imbalance in the systematic circulation and in the intestinal mucosa may also characterize IBS presentation. Toll-like receptors and their emerging role in pathogen recognition have also been highlighted recently, as dysregulation has been reported to occur in patients with IBS. This review summarizes the current knowledge regarding the involvement of any immunological alteration in the development of IBS. There is substantial evidence to support innate immune system dysfunction in several IBS phenotypes, but additional studies are required to better clarify the underlying pathogenetic pathways. IBS heterogeneity could potentially be attributed to multiple causes that lead to different disease phenotypes, thus explaining the variability found between study results.

Current insights into the innate immune system dysfunction in irritable bowel syndrome

PubMed Central

Lazaridis, Nikolaos; Germanidis, Georgios

2018-01-01

Irritable bowel syndrome (IBS) is a functional bowel disorder associated with abdominal pain and alterations in bowel habits. The presence of IBS greatly impairs patients’ quality of life and imposes a high economic burden on the community; thus, there is intense pressure to reveal its elusive pathogenesis. Many etiological mechanisms have been implicated, but the pathophysiology of the syndrome remains unclear. As a result, novel drug development has been slow and no pharmacological intervention is universally accepted. A growing evidence implicates the role of low-grade inflammation and innate immune system dysfunction, although contradictory results have frequently been presented. Mast cells (MC), eosinophils and other key immune cells together with their mediators seem to play an important role, at least in subgroups of IBS patients. Cytokine imbalance in the systematic circulation and in the intestinal mucosa may also characterize IBS presentation. Toll-like receptors and their emerging role in pathogen recognition have also been highlighted recently, as dysregulation has been reported to occur in patients with IBS. This review summarizes the current knowledge regarding the involvement of any immunological alteration in the development of IBS. There is substantial evidence to support innate immune system dysfunction in several IBS phenotypes, but additional studies are required to better clarify the underlying pathogenetic pathways. IBS heterogeneity could potentially be attributed to multiple causes that lead to different disease phenotypes, thus explaining the variability found between study results. PMID:29507464

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

PubMed

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.

Dendritic cells modulate lung response to Pseudomonas aeruginosa in a murine model of sepsis-induced immune dysfunction.

PubMed

Pène, Frédéric; Zuber, Benjamin; Courtine, Emilie; Rousseau, Christophe; Ouaaz, Fatah; Toubiana, Julie; Tazi, Asmaa; Mira, Jean-Paul; Chiche, Jean-Daniel

2008-12-15

Host infection by pathogens triggers an innate immune response leading to a systemic inflammatory response, often followed by an immune dysfunction which can favor the emergence of secondary infections. Dendritic cells (DCs) link innate and adaptive immunity and may be centrally involved in the regulation of sepsis-induced immune dysfunction. We assessed the contribution of DCs to lung defense in a murine model of sublethal polymicrobial sepsis (cecal ligature and puncture, CLP). In this model, bone marrow-derived DCs (BMDCs) retained an immature phenotype, associated with decreased capacity of IL-12p70 release and impaired priming of T cell lymphocytes. Eight days after CLP surgery, we induced a secondary pulmonary infection through intratracheal instillation of 5 x 10(6) CFUs of Pseudomonas aeruginosa. Whereas all sham-operated mice survived, 80% of post-CLP mice died after secondary pneumonia. Post-CLP mice exhibited marked lung damage with early recruitment of neutrophils, cytokine imbalance with decreased IL-12p70 production, and increased IL-10 release, but no defective bacterial lung clearance, while systemic bacterial dissemination was almost constant. Concomitant intrapulmonary administration of exogenous BMDCs into post-CLP mice challenged with P. aeruginosa dramatically improved survival. BMDCs did not improve bacterial lung clearance, but delayed neutrophil recruitment, strongly attenuated the early peak of TNF-alpha and restored an adequate Il-12p70/IL-10 balance in post-CLP mice. Thus, adoptive transfer of BMDCs reversed sepsis-induced immune dysfunction in a relevant model of secondary P. aeruginosa pneumonia. Unexpectedly, the mechanism of action of BMDCs did not involve enhanced antibacterial activity, but occurred by dampening the pulmonary inflammatory response.

Implications of immune dysfunction on endometriosis associated infertility

PubMed Central

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

2017-01-01

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. PMID:27740937

Implications of immune dysfunction on endometriosis associated infertility.

PubMed

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.

PubMed

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.

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

PubMed Central

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

2012-01-01

Objectives 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. Methods 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. Results Having greater PSMS related to less fatigue (p = .019) and emotional distress (p < .001), greater diurnal cortisol slope (p = .023) and lower IL-2 levels (p = .043). PSMS and emotional distress related to fatigue 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. Discussion 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. PMID:22417946

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

PubMed

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 (p<.001), greater diurnal cortisol slope (p=.023) and lower IL-2 levels (p=.043). PSMS and emotional distress related to fatigue 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.

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

PubMed

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.

Chemotherapy Necessitates Increased Immune Control of HHVs: A Cause of Persistent Inflammation Enabling Protracted Fatigue in Breast Cancer Survivors

DTIC Science & Technology

2013-10-01

survivors. 15. SUBJECT TERMS breast cancer, chemotherapy, immunology, human herpes viruses, survivor fatigue 16. SECURITY CLASSIFICATION OF...hypothesizes that chemotherapy can permanently alter the balance between the immune system and chronic herpes virus infections and the resultant

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

PubMed

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.

Gut epithelial barrier dysfunction in human immunodeficiency virus-hepatitis C virus coinfected patients: Influence on innate and acquired immunity.

PubMed

Márquez, Mercedes; Fernández Gutiérrez del Álamo, Clotilde; Girón-González, José Antonio

2016-01-28

Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus (HIV)-infected patients have several non-acquired immunodeficiency syndrome (AIDS) related co-morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus (HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed.

Traditional Chinese Medicine for Chronic Fatigue Syndrome

PubMed Central

Chen, Rui; Moriya, Junji; Yamakawa, Jun-ichi; Takahashi, Takashi

2010-01-01

More and more patients have been diagnosed as having chronic fatigue syndrome (CFS) in recent years. Western drug use for this syndrome is often associated with many side-effects and little clinical benefit. As an alternative medicine, traditional Chinese medicine (TCM) has provided some evidences based upon ancient texts and recent studies, not only to offer clinical benefit but also offer insights into their mechanisms of action. It has perceived advantages such as being natural, effective and safe to ameliorate symptoms of CFS such as fatigue, disordered sleep, cognitive handicaps and other complex complaints, although there are some limitations regarding the diagnostic standards and methodology in related clinical or experimental studies. Modern mechanisms of TCM on CFS mainly focus on adjusting immune dysfunction, regulating abnormal activity in the hypothalamic-pituitary-adrenal (HPA) axis and serving as an antioxidant. It is vitally important for the further development to establish standards for ‘zheng’ of CFS, i.e. the different types of CFS pathogenesis in TCM, to perform randomized and controlled trials of TCM on CFS and to make full use of the latest biological, biochemical, molecular and immunological approaches in the experimental design. PMID:18955323

Immune System Dysfunction in the Elderly.

PubMed

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.

'Exercise to me is a scary word': perceptions of fatigue, sleep dysfunction, and exercise in people with fibromyalgia syndrome-a focus group study.

PubMed

Russell, D; Álvarez Gallardo, I C; Wilson, I; Hughes, C M; Davison, G W; Sañudo, B; McVeigh, J G

2018-03-01

Fibromyalgia syndrome (FMS) is a common and complex chronic pain condition. Exercise is recommended in the management of the FMS; however, people with FMS often find exercise exacerbates their condition and causes overwhelming fatigue. The objective of this study was to explore the perceptions of fatigue and sleep dysfunction, and exercise in people with FMS. Three, 60-90 min focus groups were conducted with people with FMS (n = 14). Participants were recruited from patient support groups who had experienced therapeutic exercise in the management of their condition. Focus groups were video and audio recorded and transcriptions analysed for thematic content by three independent evaluators. Fatigue, sleep dysfunction, and pain were universally reported by participants. The over-arching theme to emerge was a lack of understanding of the condition by others. A huge sense of loss was a major sub-theme and participants felt that they had fundamentally changed since the onset of FMS. Participants reported that they were unable to carry out their normal activities, including physical activity and exercise. The invisibility of FMS was associated with the lack of understanding by others, the sense of loss, and the impact of FMS. People with FMS perceive that there is a lack of understanding of the condition among health care professionals and the wider society. Those with FMS expressed a profound sense of loss of their former 'self'; part of this loss was the ability to engage in normal physical activity and exercise.

Nitroaspirin corrects immune dysfunction in tumor-bearing hosts and promotes tumor eradication by cancer vaccination

NASA Astrophysics Data System (ADS)

de Santo, Carmela; Serafini, Paolo; Marigo, Ilaria; Dolcetti, Luigi; Bolla, Manlio; del Soldato, Piero; Melani, Cecilia; Guiducci, Cristiana; Colombo, Mario P.; Iezzi, Manuela; Musiani, Piero; Zanovello, Paola; Bronte, Vincenzo

2005-03-01

Active suppression of tumor-specific T lymphocytes can limit the immune-mediated destruction of cancer cells. Of the various strategies used by tumors to counteract immune attacks, myeloid suppressors recruited by growing cancers are particularly efficient, often resulting in the induction of systemic T lymphocyte dysfunction. We have previously shown that the mechanism by which myeloid cells from tumor-bearing hosts block immune defense strategies involves two enzymes that metabolize L-arginine: arginase and nitric oxide (NO) synthase. NO-releasing aspirin is a classic aspirin molecule covalently linked to a NO donor group. NO aspirin does not possess direct antitumor activity. However, by interfering with the inhibitory enzymatic activities of myeloid cells, orally administered NO aspirin normalized the immune status of tumor-bearing hosts, increased the number and function of tumor-antigen-specific T lymphocytes, and enhanced the preventive and therapeutic effectiveness of the antitumor immunity elicited by cancer vaccination. Because cancer vaccines and NO aspirin are currently being investigated in independent phase I/II clinical trials, these findings offer a rationale to combine these treatments in subjects with advanced neoplastic diseases. arginase | immunosuppression | myeloid cells | nitric oxide | immunotherapy

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

PubMed

Enns, Murray W; Bernstein, Charles N; Kroeker, Kristine; Graff, Lesley; Walker, John R; Lix, Lisa M; Hitchon, Carol A; El-Gabalawy, Renée; Fisk, John D; Marrie, Ruth Ann

2018-01-01

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

PubMed Central

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 < 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. PMID:26332828

Chronic fatigue syndrome and fibromyalgia following immunization with the hepatitis B vaccine: another angle of the 'autoimmune (auto-inflammatory) syndrome induced by adjuvants' (ASIA).

PubMed

Agmon-Levin, Nancy; Zafrir, Yaron; Kivity, Shaye; Balofsky, Ari; Amital, Howard; Shoenfeld, Yehuda

2014-12-01

The objectives of this study were to gather information regarding demographic and clinical characteristics of patients diagnosed with either fibromyalgia (FM) or chronic fatigue (CFS) following hepatitis B vaccination (HBVv) and furthermore to apply the recently suggested criteria of autoimmune (auto-inflammatory) syndromes induced by adjuvants (ASIA), in the aim of identifying common characteristics that may suggest an association between fibromyalgia, chronic fatigue and HBV vaccination. Medical records of 19 patients with CFS and/or fibromyalgia following HBVv immunization were analyzed. All of which were immunized during 1990-2008 in different centers in the USA. All medical records were evaluated for demographics, medical history, the number of vaccine doses, as well as immediate and long term post-immunization adverse events and clinical manifestations. In addition, available blood tests, imaging results, treatments and outcomes were analyzed. ASIA criteria were applied to all patients. The mean age of patients was 28.6 ± 11 years, of which 68.4 % were females. 21.05 % had either personal or familial background of autoimmune disease. The mean latency period from the last dose of HBVv to onset of symptoms was 38.6 ± 79.4 days, ranging from days to a year. Eight (42.1 %) patients continued with the immunization program despite experiencing adverse events. Manifestations that were commonly reported included neurological manifestations (84.2 %), musculoskeletal (78.9 %), psychiatric (63.1 %), fatigue (63.1 %), gastrointestinal complains (58 %) and mucocutaneous manifestations (36.8 %). Autoantibodies were detected in 71 % of patients tested. All patients fulfilled the ASIA criteria. This study suggests that in some cases CFS and FM can be temporally related to immunization, as part of ASIA syndrome. The appearance of adverse event during immunization, the presence of autoimmune susceptibility and higher titers of autoantibodies all can be suggested as risk

Post-traumatic hypopituitarism and fatigue.

PubMed

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.

Effects of acupuncturing Pishu combined with Ginsenoside Rg3 on the immune function of rats with chronic fatigue.

PubMed

Zhang, Wenjing; Zhang, Yue; Ma, Xiande; Chen, Yiguo

2015-01-01

This study was designed to investigate the effects of acupuncturing Pishu combined with Ginsenoside Rg3 on the immune function of rats with chronic fatigue. Forty male SD rats were equally randomized into control group, chronic fatigue system group (CFS), Ginsenoside Rg3 (Rg3) group, acupuncture group and acupuncture combined with Ginsenoside Rg3 (A+Rg3) group. Rats with chronic fatigue were established by bounding and forced swimming in cold water once daily for 21 days except control group, then the rats in the acupuncture and A+Rg3 group were treated by manual acupuncture stimulation of bilateral "Pishu" once daily for 7 days. Ginsenoside Rg3 was administered by intravenous to the rats of the A+Rg3 and Rg3 group for 7 days in dosages of 2 mg/kg body weight, and two markers of physical fatigue were evaluated: body weight and blood lactic acid (LA). The percentages of CD3(+) lymphocytes, CD4(+) lymphocytes, and CD8(+) lymphocytes in the spleens of the rats were evaluated using flow cytometric analysis. Serum IFN-gamma (IFN-γ) and IL-4 contents were detected by ELISA. Increased body weight and reduced blood LA concentrations were found in the rat of Rg3 group and A+Rg3 group than that in CFS group. The rat of Rg3 group and A+Rg3 group also showed a significant increase in the percentage of CD4(+) lymphocytes and a significant decrease in the percentage of CD8(+) lymphocytes and correct CD4(+)/CD8(+) ratio. Compared with the CFS group, the level of IFN-γ in the Rg3, acupuncture and A+Rg3 groups was reduced and IL-4 was increased. Acupuncture and Rg3 can improve the immune system activity of CFS rats and acupuncturing Pishu combined with Rg3 was significantly superior compared with Rg3 and acupuncture, respectively.

Fatigue and neuromuscular diseases.

PubMed

Féasson, L; Camdessanché, J-P; El Mandhi, L; Calmels, P; Millet, G-Y

2006-07-01

To identify the role of fatigue, its evaluation and its causes in the pathophysiology context of acquired or hereditary neuromuscular diseases of the spinal anterior horn cell, peripheral nerve, neuromuscular junction and muscle. A literature review has been done on Medline with the following keywords: neuromuscular disease, peripheral neuropathy, myopathy, fatigue assessment, exercise intolerance, force assessment, fatigue scale and questionnaire, then with the terms: Fatigue Severity Scale, Chalder Fatigue Scale, Fatigue Questionnaire, Piper Fatigue Scale, electromyography and the combination of the word Fatigue with the following terms: Amyotrophic Lateral Sclerosis (ALS), Post-Polio Syndrome (PPS), Guillain-Barre Syndrome, Immune Neuropathy, Charcot-Marie-Tooth Disease, Myasthenia Gravis (MG), Metabolic Myopathy, Mitochondrial Myopathy, Muscular Dystrophy, Facioscapulohumeral Dystrophy, Myotonic Dystrophy. Fatigue is a symptom very frequently reported by patients. Fatigue is mainly evaluated by strength loss after an exercise, by change in electromyographic activity during a given exercise and by questionnaires that takes into account the subjective (psychological) part of fatigue. Due to the large diversity of motor disorders, there are multiple clinical expressions of fatigue that differ in their presentation, consequences and therapeutic approach. This review shows that fatigue has to be taken into account in patients with neuromuscular diseases. In this context, pathophysiology of fatigue often implies the motor component but the disease evolution and the physical obligates of daily life also induce an important psychological component.

Fatigue in older adults with stable heart failure.

PubMed

Stephen, Sharon A

2008-01-01

The purpose of this study was to describe fatigue and the relationships among fatigue intensity, self-reported functional status, and quality of life in older adults with stable heart failure. A descriptive, correlational design was used to collect quantitative data with reliable and valid instruments. Fifty-three eligible volunteers completed a questionnaire during an interview. Those with recent changes in their medical regimen, other fatigue-inducing illnesses, and isolated diastolic dysfunction were excluded. Fatigue intensity (Profile of Mood States fatigue subscale) was associated with lower quality of life, perceived health, and satisfaction with life. Fatigue was common, and no relationship was found between fatigue intensity and self-reported functional status. Marital status was the only independent predictor of fatigue. In stable heart failure, fatigue is a persistent symptom. Clinicians need to ask patients about fatigue and assess the impact on quality of life. Self-reported functional status cannot serve as a proxy measure for fatigue.

Overactivation of Mitogen-Activated Protein Kinase and Suppression of Mitofusin-2 Expression Are Two Independent Events in High Mobility Group Box 1 Protein–Mediated T Cell Immune Dysfunction

PubMed Central

Tang, Lu-ming; Zhao, Guang-ju; Zhu, Xiao-mei; Dong, Ning; Yu, Yan

2013-01-01

High mobility group box 1 protein (HMGB1), a critical proinflammatory cytokine, has recently been identified to be an immunostimulatory signal involved in sepsis-related immune dysfunction when released extracellularly, but the potential mechanism involved remains elusive. Here, we showed that the treatment with HMGB1 in vitro inhibited T lymphocyte immune response and expression of mitofusin-2 (Mfn-2; a member of the mitofusin family) in a dose- and time-dependent manner. Upregulation of Mfn-2 expression attenuated the suppressive effect of HMGB1 on T cell immune function. The phosphorylation of both extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) was markedly upregulated by treating with high amount of HMGB1, while pretreatment with ERK1/2 and p38 MAPK-specific inhibitors (U0126 and SB203580) could attenuate suppression of T cell immune function and nuclear factor of activated T cell (NFAT) activation induced by HMGB1, respectively. HMGB1-induced activity of ERK1/2 and p38 was not fully inhibited in the presence of U0126 or SB203580. Interestingly, overexpression of Mfn-2 had no marked effect on HMGB1-mediated activation of MAPK, but could attenuate the suppressive effect of HMGB1 on the activity of NFAT. Thus, the mechanisms involved in HMGB1-induced T cell immune dysfunction in vitro at least partly include suppression of Mfn-2 expression, overactivation of ERK1/2, p38 MAPK, and intervention of NFAT activation, while the protective effect of Mfn-2 on T cell immune dysfunction induced by HMGB1 is dependent on other signaling pathway associated with NFAT, but not MAPK. Taken together, we conclude that overactivation of MAPK and suppression of Mfn-2 expression are two independent events in HMGB1-mediated T cell immune dysfunction. PMID:23697559

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

PubMed

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, p<0.005 and r=-0.34, p<0.05). Purinergic P2RY1 was correlated only with PCF fatigue 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.

Differing Leukocyte Gene Expression Profiles Associated with Fatigue in Patients with Prostate Cancer versus Chronic Fatigue Syndrome

PubMed Central

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.

2013-01-01

Summary Background 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. Methods 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. Results 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, p<0.005 and r=−0.34, p<0.05). Purinergic P2RY1 was correlated only with PCF fatigue and pain severity (r= +0.43 and +0.59, p=0.025 and p=0.001). Conclusions 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. PMID:24054763

Kindling and Oxidative Stress as Contributors to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

PubMed Central

Jason, L. A.; Porter, N.; Herrington, J.; Sorenson, M.; Kubow, S.

2010-01-01

Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS) is one of the more complex illnesses involving multiple systems within the body. Onset of ME/CFS frequently occurs quickly, and many patients report a prior exposure to a viral infection. This debilitating illness can affect the immune, neuroendocrine, autonomic, and neurologic systems. Abnormal biological findings among some patients have included aberrant ion transport and ion channel activity, cortisol deficiency, sympathetic nervous system hyperactivity, EEG spike waves, left ventricular dysfunction in the heart, low natural killer cell cytotoxicity, and a shift from Th1 to Th2 cytokines. We propose that the kindling and oxidative stress theories provide a heuristic template for better understanding the at times conflicting findings regarding the etiology and pathophysiology of this illness. PMID:21253446

Cognitive dysfunction in adolescents with chronic fatigue: a cross-sectional study.

PubMed

Sulheim, Dag; Fagermoen, Even; Sivertsen, Øyvind Stople; Winger, Anette; Wyller, Vegard Bruun; Øie, Merete Glenne

2015-09-01

To compare cognitive function in adolescents with chronic fatigue with cognitive function in healthy controls (HC). Cross-sectional study. Paediatric department at Oslo University Hospital, Norway. 120 adolescents with chronic fatigue (average age 15.4 years; range 12-18) and 39 HC (average age 15.2 years; range 12-18). The adolescents completed a neurocognitive test battery measuring processing speed, working memory, cognitive inhibition, cognitive flexibility, verbal learning and verbal memory, and questionnaires addressing demographic data, depression symptoms, anxiety traits, fatigue and sleep problems. Parents completed the Behaviour Rating Inventory of Executive Function (BRIEF), which measures the everyday executive functions of children. Adolescents with chronic fatigue had impaired cognitive function compared to HC regarding processing speed (mean difference 3.3, 95% CI 1.1 to 5.5, p=0.003), working memory (-2.4, -3.7 to -1.1, p<0.001), cognitive inhibition response time (6.2, 0.8 to 11.7, p=0.025) and verbal learning (-1.7, -3.2 to -0.3, p=0.022). The BRIEF results indicated that everyday executive functions were significantly worse in the chronic fatigue group compared to the HC (11.2, 8.2 to 14.3, p<0.001). Group differences remained largely unaffected when adjusted for symptoms of depression, anxiety traits and sleep problems. Adolescents with chronic fatigue had impaired cognitive function of clinical relevance, measured by objective cognitive tests, in comparison to HC. Working memory and processing speed may represent core difficulties. 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.

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

PubMed

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

Endocrinological side-effects of immune checkpoint inhibitors.

PubMed

Torino, Francesco; Corsello, Salvatore M; Salvatori, Roberto

2016-07-01

Three mAbs targeting immune checkpoint proteins are available for the treatment of patients with melanoma, lung, and kidney cancer, and their use will likely expand in the future to additional tumor types. We here update the literature on the incidence and pathophysiology of endocrine toxicities induced by these agents, and discuss management guidance. Immune checkpoint inhibition may trigger autoimmune syndromes involving different organs, including several endocrine glands (pituitary, thyroid, adrenals, and endocrine pancreas). Hypophysitis is more frequently associated with ipilimumab, whereas the incidence of thyroid dysfunction is higher with nivolumab/pembrolizumab. Primary adrenal insufficiency can rarely occur with either treatment. Autoimmune diabetes is very rare. As hypophysitis and adrenalitis may be life-threatening, endocrinological evaluation is essential particularly in patients developing fatigue and other symptoms consistent with adrenal insufficiency. Corticosteroids should be promptly used when hypophysitis-induced adrenal insufficiency or adrenalitis are diagnosed, but not in thyroiditis or diabetes. No impact of corticosteroids on the efficacy/activity of immune checkpoint-inhibiting drugs is reported. Hormonal deficiencies are often permanent. In absence of predicting factors, accurate information to patients provided by the oncology care team is essential for early diagnosis and to limit the consequences of checkpoint inhibition-related endocrine toxicity.

Adolescent Fatigue, POTS, and Recovery: A Guide for Clinicians

PubMed Central

Kizilbash, Sarah J.; Ahrens, Shelley P.; Bruce, Barbara K.; Chelimsky, Gisela; Driscoll, Sherilyn W.; Harbeck-Weber, Cynthia; Lloyd, Robin M.; Mack, Kenneth J.; Nelson, Dawn E.; Ninis, Nelly; Pianosi, Paolo T.; Stewart, Julian M.; Weiss, Karen E.; Fischer, Philip R.

2018-01-01

Many teenagers who struggle with chronic fatigue have symptoms suggestive of autonomic dysfunction that may include lightheadedness, headaches, palpitations, nausea, and abdominal pain. Inadequate sleep habits and psychological conditions can contribute to fatigue, as can concurrent medical conditions. One type of autonomic dysfunction, postural orthostatic tachycardia syndrome, is increasingly being identified in adolescents with its constellation of fatigue, orthostatic intolerance, and excessive postural tachycardia (more than 40 beats/min). A family-based approach to care with support from a multidisciplinary team can diagnose, treat, educate, and encourage patients. Full recovery is possible with multi-faceted treatment. The daily treatment plan should consist of increased fluid and salt intake, aerobic exercise, and regular sleep and meal schedules; some medications can be helpful. Psychological support is critical and often includes biobehavioral strategies and cognitive–behavioral therapy to help with symptom management. More intensive recovery plans can be implemented when necessary. PMID:24819031

Integrated Immune

NASA Technical Reports Server (NTRS)

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

2010-01-01

This slide presentation reviews the program to replace several recent studies about astronaut immune systems with one comprehensive study that will include in-flight sampling. The study will address lack of in-flight data to determine the inflight status of immune systems, physiological stress, viral immunity, to determine the clinical risk related to immune dysregulation for exploration class spaceflight, and to determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

Nursing Fatigue: An Evidence-Based Practice Review for Oncology Nurses
.

PubMed

Ferris, Jordan

2015-12-01

Nursing fatigue is a current and well-researched topic. Many negative outcomes and consequences exist for patients and nurses that have been linked to nursing fatigue. Medical errors are one such consequence, and these errors have become one of the top three preventable deaths in the United States. Oncology nurses are not immune to fatigue, and the consequences of their fatigue can be much more harmful to patients.

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

PubMed

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.

Got worms? Perinatal exposure to helminths prevents persistent immune sensitization and cognitive dysfunction induced by early-life infection.

PubMed

Williamson, Lauren L; McKenney, Erin A; Holzknecht, Zoie E; Belliveau, Christine; Rawls, John F; Poulton, Susan; Parker, William; Bilbo, Staci D

2016-01-01

The incidence of autoimmune and inflammatory diseases has risen dramatically in post-industrial societies. "Biome depletion" - loss of commensal microbial and multicellular organisms such as helminths (intestinal worms) that profoundly modulate the immune system - may contribute to these increases. Hyperimmune-associated disorders also affect the brain, especially neurodevelopment, and increasing evidence links early-life infection to cognitive and neurodevelopmental disorders. We have demonstrated previously that rats infected with bacteria as newborns display life-long vulnerabilities to cognitive dysfunction, a vulnerability that is specifically linked to long-term hypersensitivity of microglial cell function, the resident immune cells of the brain. Here, we demonstrate that helminth colonization of pregnant dams attenuated the exaggerated brain cytokine response of their offspring to bacterial infection, and that combined with post-weaning colonization of offspring with helminths (consistent with their mothers treatment) completely prevented enduring microglial sensitization and cognitive dysfunction in adulthood. Importantly, helminths had no overt impact on adaptive immune cell subsets, whereas exaggerated innate inflammatory responses in splenic macrophages were prevented. Finally, helminths altered the effect of neonatal infection on the gut microbiome; neonatal infection with Escherichia coli caused a shift from genera within the Actinobacteria and Tenericutes phyla to genera in the Bacteroidetes phylum in rats not colonized with helminths, but helminths attenuated this effect. In sum, these data point toward an inter-relatedness of various components of the biome, and suggest potential mechanisms by which this helminth might exert therapeutic benefits in the treatment of neuroinflammatory and cognitive disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Integrated Immune Experiment

NASA Technical Reports Server (NTRS)

Crucian, Brian

2009-01-01

This viewgraph presentation reviews NASA's Integrated Immune Experiment. The objectives include: 1) Address significant lack of data regarding immune status during flight; 2) Replace several recent immune studies with one comprehensive study that will include in-flight sampling; 3) Determine the in-flight status of immunity, physiological stress, viral immunity/reactivation; 4) Determine the clinical risk related to immune dysregulation for exploration class spaceflight; and 5) Determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

The protocol for a randomised controlled trial comparing intermittent and graded exercise to usual care for chronic fatigue syndrome patients.

PubMed

Broadbent, Suzanne; Coutts, Rosanne

2013-08-30

Chronic Fatigue Syndrome is a debilitating disorder with an unknown aetiology but suspected multifactorial origins. Common "triggers" include severe viral infections and emotional stress. Recent studies have also found evidence of immune dysfunction and elevated inflammatory cytokines in CFS patients, but there has been considerable variation in the outcome measures and magnitude of these studies. Currently, there is no cure for CFS but treatments include rest, specialist medical care, cognitive behavioural therapy, and graded (self-paced) exercise. To date, several studies have examined the efficacy of graded exercise with or without Cognitive Behavioural Therapy, with some success for patients. However, improvements in functional capacity have not necessarily correlated with improvements in immune function, fatigue or other symptoms. This 12-week pilot trial compares graded and intermittent exercise to normal care, measuring physiological outcomes, fatigue levels, immune function and wellness. 90 patients aged between 16 to 60 years, who meet the diagnostic criteria for CFS and have been diagnosed by their medical practitioner, will be randomly recruited into groups consisting of Intermittent exercise, Graded exercise and usual care (Control). The outcomes will be measured pre-study (Week 0) and post-study (Week 13). Primary outcomes are VO2peak, anaerobic threshold, peak power, levels of fatigue, immune cell (CD3+CD4+, CD3+CD8+, CD19+, CD 16+CD56+) concentrations and activation. Secondary outcomes include onset of secondary CFS symptoms (e.g. fever, swollen lymph nodes), wellness, mood and sleep patterns. Primary analysis will be based on intention to treat using logistic regression models to compare treatments. Quantitative data will be analysed using repeated measures ANOVA with a linear model, and Cohen's effect size. Qualitative data such as participants' responses (e.g. changes in mood and other reactions) following the exercise modalities will be read and

Exercise, inflammation, and fatigue in cancer survivors

PubMed Central

LaVoy, Emily C.P.; Fagundes, Christopher P.; Dantzer, Robert

2016-01-01

Cancer-related fatigue significantly disrupts normal functioning and quality of life for a substantial portion of cancer survivors, and may persist for years following cancer treatment. While the causes of persistent fatigue among cancer survivors are not yet fully understood, accumulating evidence suggests that several pathways, including chronic inflammation, autonomic imbalance, HPA-axis dysfunction, and/or mitochondrial damage, could contribute towards the disruption of normal neuronal function and result in the symptom of cancer-related fatigue. Exercise training interventions have been shown to be some of the more successful treatment options to address cancer-related fatigue. In this review, we discuss the literature regarding the causes of persistent fatigue in cancer survivors and the mechanisms by which exercise may relieve this symptom. There is still much work to be done until the prescription of exercise becomes standard practice for cancer survivors. With improvements in the quality of studies, evidenced-based exercise interventions will allow exercise scientists and oncologists to work together to treat cancer-related fatigue. PMID:26853557

Is there a cognitive signature for MS-related fatigue?

PubMed

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.

The human retrovirus XMRV in prostate cancer and chronic fatigue syndrome.

PubMed

Silverman, Robert H; Nguyen, Carvell; Weight, Christopher J; Klein, Eric A

2010-07-01

Xenotropic murine leukemia virus-related virus (XMRV) is an authentic, newly recognized human retrovirus first identified in prostate cancer tissues from men with a deficiency in the innate immunity gene RNASEL. At present, studies have detected XMRV at widely different rates in prostate cancer cases (0-27%) and in patients with chronic fatigue syndrome (CFS; 0-67%). Indirect or direct modes of carcinogenesis by XMRV have been suggested depending on whether the virus was found in stroma or malignant epithelium. Viral replication in the prostate might be affected by androgens, which stimulate XMRV through a transcriptional enhancer site in viral DNA. By contrast, host restriction factors, such as APOBEC3 and tetherin, inhibit virus replication. Immune dysfunction mediated by XMRV has been suggested as a possible factor in CFS. Recent studies show that some existing antiretroviral drugs suppress XMRV infections and diagnostic assays are under development. Although other retroviruses of the same genus as XMRV (gammaretroviruses) cause cancer and neurological disease in animals, whether XMRV is a cause of either prostate cancer or CFS remains unknown. Emerging science surrounding XMRV is contributing to our knowledge of retroviral infections while focusing intense interest on two major human diseases.

Fatigue-Related Gene Networks Identified in CD14+ Cells Isolated From HIV-Infected Patients—Part I: Research Findings

PubMed Central

Voss, Joachim G.; Dobra, Adrian; Morse, Caryn; Kovacs, Joseph A.; Danner, Robert L.; Munson, Peter J.; Logan, Carolea; Rangel, Zoila; Adelsberger, Joseph W.; McLaughlin, Mary; Adams, Larry D.; Raju, Raghavan; Dalakas, Marinos C.

2016-01-01

Purpose Human immunodeficiency virus (HIV)–related fatigue (HRF) is multicausal and potentially related to mitochondrial dysfunction caused by antiretroviral therapy with nucleoside reverse transcriptase inhibitors (NRTIs). Methodology The authors compared gene expression profiles of CD14+ cells of low versus high fatigued, NRTI-treated HIV patients to healthy controls (n = 5/group). The authors identified 32 genes predictive of low versus high fatigue and 33 genes predictive of healthy versus HIV infection. The authors constructed genetic networks to further elucidate the possible biological pathways in which these genes are involved. Relevance for nursing practice Genes including the actin cytoskeletal regulatory proteins Prokineticin 2 and Cofilin 2 along with mitochondrial inner membrane proteins are involved in multiple pathways and were predictors of fatigue status. Previously identified inflammatory and signaling genes were predictive of HIV status, clearly confirming our results and suggesting a possible further connection between mitochondrial function and HIV. Isolated CD14+ cells are easily accessible cells that could be used for further study of the connection between fatigue and mitochondrial function of HIV patients. Implication for Practice The findings from this pilot study take us one step closer to identifying biomarker targets for fatigue status and mitochondrial dysfunction. Specific biomarkers will be pertinent to the development of methodologies to diagnosis, monitor, and treat fatigue and mitochondrial dysfunction. PMID:23324479

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.

PubMed

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.

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

PubMed

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.

PubMed

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.

PubMed

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.

Circadian rhythm abnormalities and autonomic dysfunction in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

PubMed Central

Díez-Noguera, Antoni

2018-01-01

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients frequently show autonomic symptoms which may be associated with a hypothalamic dysfunction. This study aimed to explore circadian rhythm patterns in rest and activity and distal skin temperature (DST) and their association with self-reported outcome measures, in CFS/ME patients and healthy controls at two different times of year. Ten women who met both the 1994 CDC/Fukuda definition and 2003 Canadian criteria for CFS/ME were included in the study, along with ten healthy controls matched for age, sex and body mass index. Self-reported measures were used to assess fatigue, sleep quality, anxiety and depression, autonomic function and health-related quality of life. The ActTrust actigraph was used to record activity, DST and light intensity, with data intervals of one minute over seven consecutive days. Sleep variables were obtained through actigraphic analysis and from subjective sleep diary. The circadian variables and the spectral analysis of the rhythms were calculated. Linear regression analysis was used to evaluate the relationship between the rhythmic variables and clinical features. Recordings were taken in the same subjects in winter and summer. Results showed no differences in rhythm stability, sleep latency or number of awakenings between groups as measured with the actigraph. However, daily activity, the relative amplitude and the stability of the activity rhythm were lower in CFS/ME patients than in controls. DST was sensitive to environmental temperature and showed lower nocturnal values in CFS/ME patients than controls only in winter. A spectral analysis showed no differences in phase or amplitude of the 24h rhythm, but the power of the second harmonic (12h), revealed differences between groups (controls showed a post-lunch dip in activity and peak in DST, while CFS/ME patients did not) and correlated with clinical features. These findings suggest that circadian regulation and skin

Consideration of sleep dysfunction in rehabilitation.

PubMed

Valenza, Marie Carmen; Rodenstein, Daniel O; Fernández-de-las-Peñas, César

2011-07-01

The physiology of sleep is not completely understood but it is widely accepted that sleep is important to the human body in the recovery of metabolic and neurological processes. This paper summarizes the effects of sleep dysfunction on different systems and considers implications in the context of rehabilitation. When sleep is experimentally completely or partially curtailed important brain functions are impacted leading to psychological and neurological disturbances. Increased cortisol levels, reduction of glucose tolerance, and increased sympathetic nervous system activity have also been identified in healthy subjects under such conditions. Several studies show that 50-80% of patients with chronic pain suffer from sleep dysfunction. It has been suggested that on the one hand pain can cause sleep dysfunction and on the other hand that sleep dysfunction can aggravate pain. The physiologic mechanism behind this interaction is not completely clear; although most authors describe the relationship between pain and sleep dysfunction as aberrant processing of tactile-cutaneous sensory inputs at the meso-encephalic level and in the trigeminal nucleus both when asleep and awake. Decreased duration of sleep also increases heart rate, blood pressure and sympathetic activity magnifying the individual's response to stressful stimuli. Possible causal mechanisms for the established connection between short sleep cycles and coronary pathology include sympathetic nervous system hyperactivity, increased blood pressure increase or reduced glucose tolerance. Finally, sleep and fatigue have traditionally been linked. Fatigue can have a physical etiology but is also associated with depression. Sleep alterations are also considered an important risk factor for psychological dysfunction and also mental illness. However, despite the noted repercussions of sleep dysfunction, studies investigating interventions to improve sleep have been limited in number. Benefits of exercise programs on

Symptoms of fatigue and coping strategies in maritime pilotage.

PubMed

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].

PubMed

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.

Does Oral Coenzyme Q10 Plus NADH Supplementation Improve Fatigue and Biochemical Parameters in Chronic Fatigue Syndrome?

PubMed Central

Cordero, Mario D.; Segundo, María José; Sáez-Francàs, Naia; Calvo, Natalia; Román-Malo, Lourdes; Aliste, Luisa; Fernández de Sevilla, Tomás; Alegre, José

2015-01-01

Abstract Chronic fatigue syndrome (CFS) is a chronic and extremely debilitating illness characterized by prolonged fatigue and multiple symptoms with unknown cause, diagnostic test, or universally effective treatment. Inflammation, oxidative stress, mitochondrial dysfunction, and CoQ10 deficiency have been well documented in CFS. We conducted an 8-week, randomized, double-blind placebo-controlled trial to evaluate the benefits of oral CoQ10 (200 mg/day) plus NADH (20 mg/day) supplementation on fatigue and biochemical parameters in 73 Spanish CFS patients. This study was registered in ClinicalTrials.gov (NCT02063126). A significant improvement of fatigue showing a reduction in fatigue impact scale total score (p<0.05) was reported in treated group versus placebo. In addition, a recovery of the biochemical parameters was also reported. NAD+/NADH (p<0.001), CoQ10 (p<0.05), ATP (p<0.05), and citrate synthase (p<0.05) were significantly higher, and lipoperoxides (p<0.05) were significantly lower in blood mononuclear cells of the treated group. These observations lead to the hypothesis that the oral CoQ10 plus NADH supplementation could confer potential therapeutic benefits on fatigue and biochemical parameters in CFS. Larger sample trials are warranted to confirm these findings. Antioxid. Redox Signal. 22, 679–685. PMID:25386668

Dysfunctional beliefs, stress and sleep disturbance in fibromyalgia.

PubMed

Theadom, Alice; Cropley, Mark

2008-05-01

To explore sleep-related dysfunctional beliefs, stress levels and sleep quality in patients with fibromyalgia in comparison to healthy controls. One hundred sixty-six participants (83 patients with fibromyalgia and 83 healthy controls) completed self-report measures exploring beliefs and attitudes about sleep, perceived stress, sleep quality and levels of pain and fatigue. Relative to healthy controls, patients with fibromyalgia revealed significantly higher levels of dysfunctional beliefs and attitudes about sleep and perceived stress. High dysfunctional beliefs were significantly associated with poorer sleep quality and high perceived stress was significantly related to higher sleep disturbances and daytime dysfunction. Beliefs about sleep and perceived stress play a significant role in the sleep quality of patients with fibromyalgia. Interventions to improve sleep quality for people with fibromyalgia need to identify and address dysfunctional beliefs about sleep and incorporate stress management approaches.

A review of research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures

PubMed Central

Rossignol, D A; Frye, R E

2012-01-01

Recent studies have implicated physiological and metabolic abnormalities in autism spectrum disorders (ASD) and other psychiatric disorders, particularly immune dysregulation or inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures (‘four major areas'). The aim of this study was to determine trends in the literature on these topics with respect to ASD. A comprehensive literature search from 1971 to 2010 was performed in these four major areas in ASD with three objectives. First, publications were divided by several criteria, including whether or not they implicated an association between the physiological abnormality and ASD. A large percentage of publications implicated an association between ASD and immune dysregulation/inflammation (416 out of 437 publications, 95%), oxidative stress (all 115), mitochondrial dysfunction (145 of 153, 95%) and toxicant exposures (170 of 190, 89%). Second, the strength of evidence for publications in each area was computed using a validated scale. The strongest evidence was for immune dysregulation/inflammation and oxidative stress, followed by toxicant exposures and mitochondrial dysfunction. In all areas, at least 45% of the publications were rated as providing strong evidence for an association between the physiological abnormalities and ASD. Third, the time trends in the four major areas were compared with trends in neuroimaging, neuropathology, theory of mind and genetics (‘four comparison areas'). The number of publications per 5-year block in all eight areas was calculated in order to identify significant changes in trends. Prior to 1986, only 12 publications were identified in the four major areas and 51 in the four comparison areas (42 for genetics). For each 5-year period, the total number of publications in the eight combined areas increased progressively. Most publications (552 of 895, 62%) in the four major areas were published in the last 5 years (2006–2010). Evaluation

Identifying patterns of immune-related disease: use in disease prevention and management.

PubMed

Dietert, Rodney R; Zelikoff, Judith T

2010-05-01

Childhood susceptibility to diseases linked with immune dysfunction affects over a quarter of the pediatric population in some countries. While this alone is a significant health issue, the actual impact of immune-related diseases extends over a lifetime and involves additional secondary conditions. Some comorbidities are well known (e.g., allergic rhinitis and asthma). However, no systematic approach has been used to identify life-long patterns of immune-based disease where the primary condition arises in childhood. Such information is useful for both disease prevention and treatment approaches. Recent primary research papers as well as review articles were obtained from PubMed, Chem Abstracts, Biosis and from the personal files of the authors. Search words used were: the diseases and conditions shown Figs. 1 and 2 in conjunction with comorbid, comorbidities, pediatric, childhood, adult, immune, immune dysfunction, allergy, autoimmune, inflammatory, infectious, health risks, environment, risk factors. Childhood diseases such as asthma, type-1 diabetes, inflammatory bowel disease, respiratory infections /rhinitis, recurrent otitis media, pediatric celiac, juvenile arthritis and Kawasaki disease are examples of significant childhood health problems where immune dysfunction plays a significant role. Each of these pediatric diseases is associated with increased risk of several secondary conditions, many of which appear only later in life. To illustrate, four prototypes of immune-related disease patterns (i.e., allergy, autoimmunity, inflammation and infectious disease) are shown as tools for: 1) enhanced disease prevention; 2) improved management of immune-based pediatric diseases; and 3) better recognition of underlying pediatric immune dysfunction. Identification of immune-related disease patterns beginning in childhood provides the framework for examining the underlying immune dysfunctions that can contribute to additional diseases in later life. Many pediatric

Psychological profiles in patients with Sjögren's syndrome related to fatigue: a cluster analysis.

PubMed

van Leeuwen, Ninke; Bossema, Ercolie R; Knoop, Hans; Kruize, Aike A; Bootsma, Hendrika; Bijlsma, Johannes W J; Geenen, Rinie

2015-05-01

Fatigue is a highly prevalent and debilitating symptom in the autoimmune disease SS. Although the disease process plays a role in fatigue, psychological factors may influence fatigue and the ability to deal with its consequences. Profiles of co-occurring psychological factors may suggest potential targets for the treatment of fatigue. The aim of this study was to identify psychological profiles in patients with SS and the accompanying levels of fatigue. Three hundred patients with primary SS (mean age 57 years, 93% female) completed questionnaires on fatigue (multidimensional fatigue inventory), physical activity cognitions (TAMPA-SK), illness cognitions, cognitive regulation, emotion processing and regulation [Toronto Alexithymia Scale 20, Emotion Regulation Questionnaire (ERQ), Berkeley Expressivity Questionnaire], coping strategies (Brief COPE) and social support. Principal axis factor analysis (oblimin rotation) yielded six psychological factors: social support, negative thinking, positive thinking, emotional expressivity, avoidance and alexithymia (i.e. the inability to differentiate emotions). Using cluster analyses, these factors were grouped in four psychological profiles: functional (39%), alexithymic (27%), self-reliant (23%) and dysfunctional (11%). Irrespective of the psychological profile, the level of fatigue was substantially higher in patients than in the general population. Patients with a dysfunctional or an alexithymic profile reported more fatigue than those with a self-reliant profile. Our study in SS yielded four psychological profiles that were differentially associated with fatigue. These profiles can be used to examine determinants and prognosis of fatigue as well as the possibility of customizing cognitive behavioural interventions for chronic fatigue. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

PubMed

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.

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

PubMed

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

Central fatigue in multiple sclerosis: a review of the literature

PubMed Central

Newland, Pamela; Starkweather, Angela; Sorenson, Matthew

2016-01-01

Concept Fatigue is a major concern for patients with multiple sclerosis (MS). A clear definition of MS-related fatigue is a prerequisite for appropriate instruments for fatigue assessment. In turn, accurate assessment of fatigue in MS will enhance exploration of plausible mechanisms underlying this common and distressing symptom. Content/Objectives To provide an integrative review of the current literature on theoretical models used to study fatigue in MS, instruments used to assess fatigue and other factors that impact fatigue during the various phases of MS. Methods Data sources: PUBMED, OVID, Ovid Health Star, Ovid MEDINE, CINAHL, Health and Psychosocial Instruments (HaPI), and PsycINFO. Seventeen articles fit the inclusion criteria and were included in the review. Results Definitions of MS-related fatigue are reviewed. Several studies found a link with neurotransmitter dysfunction, circadian rhythm, and the timing of fatigue. Central fatigue in MS is associated with neurotransmitters disruptions as well as circadian rhythm disorders, but the evidence is not strong. Perceptions of fatigue or fatigability may arise as either a primary or secondary manifestation of disease. Based on findings from the literature review, a theoretical model of fatigue in MS is proposed. Conclusion Future research on MS-related fatigue may consider a longitudinal design with a carefully selected self-report instrument to advance understanding of the underlying pathological mechanisms. PMID:27146427

Longitudinal analysis of immune abnormalities in varying severities of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients.

PubMed

Hardcastle, Sharni Lee; Brenu, Ekua Weba; Johnston, Samantha; Nguyen, Thao; Huth, Teilah; Ramos, Sandra; Staines, Donald; Marshall-Gradisnik, Sonya

2015-09-14

Research has identified immunological abnormalities in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), a heterogeneous illness with an unknown cause and absence of diagnostic test. There have been no CFS/ME studies examining innate and adaptive immune cells longitudinally in patients with varying severities. This is the first study to investigate immune cells over 6 months while also examining CFS/ME patients of varying symptom severity. Participants were grouped into 18 healthy controls, 12 moderate and 12 severe CFS/ME patients and flow cytometry was used to examine cell parameters at 0 and 6 months. Over time, iNKT CD62L expression significantly increased in moderate CFS/ME patients and CD56(bright) NK receptors differed in severe CFS/ME. Naïve CD8(+)T cells, CD8(-)CD4(-) and CD56(-)CD16(-) iNKT phenotypes, γδ2T cells and effector memory subsets were significantly increased in severe CFS/ME patients at 6 months. Severe CFS/ME patients were significantly reduced in CD56(bright)CD16(dim) NKG2D, CD56(dim)CD16(-) KIR2DL2/DL3, CD94(-)CD11a(-) γδ1T cells and CD62L(+)CD11a(-) γδ1T cells at 6 months. Severe CFS/ME patients differed from controls and moderate CFS/ME patients over time and expressed significant alterations in iNKT cell phenotypes, CD8(+)T cell markers, NK cell receptors and γδT cells at 6 months. This highlights the importance of further assessing these potential immune biomarkers longitudinally in both moderate and severe CFS/ME patients.

Reversal of Refractory Ulcerative Colitis and Severe Chronic Fatigue Syndrome Symptoms Arising from Immune Disturbance in an HLADR/DQ Genetically Susceptible Individual with Multiple Biotoxin Exposures

PubMed Central

Gunn, Shelly R.; Gibson Gunn, G.; Mueller, Francis W.

2016-01-01

Patient: Male, 25 Final Diagnosis: Ulcerative colitis and chronic fatigue syndrome Symptoms: Colitis • profound fatigue • multi-joint pain • cognitive impairment • corneal keratitis Medication: — Clinical Procedure: VIP replacement therapy Specialty: Family Medicine Objective: Unusual clinical course Background: Patients with multisymptom chronic conditions, such as refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS), present diagnostic and management challenges for clinicians, as well as the opportunity to recognize and treat emerging disease entities. In the current case we report reversal of co-existing RUC and CFS symptoms arising from biotoxin exposures in a genetically susceptible individual. Case Report: A 25-year-old previously healthy male with new-onset refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS) tested negative for autoimmune disease biomarkers. However, urine mycotoxin panel testing was positive for trichothecene group and air filter testing from the patient’s water-damaged rental house identified the toxic mold Stachybotrys chartarum. HLA-DR/DQ testing revealed a multisusceptible haplotype for development of chronic inflammation, and serum chronic inflammatory response syndrome (CIRS) biomarker testing was positive for highly elevated TGF-beta and a clinically undetectable level of vasoactive intestinal peptide (VIP). Following elimination of biotoxin exposures, VIP replacement therapy, dental extractions, and implementation of a mind body intervention-relaxation response (MBI-RR) program, the patient’s symptoms resolved. He is off medications, back to work, and resuming normal exercise. Conclusions: This constellation of RUC and CFS symptoms in an HLA-DR/DQ genetically susceptible individual with biotoxin exposures is consistent with the recently described CIRS disease pathophysiology. Chronic immune disturbance (turbatio immuno) can be identified with clinically available CIRS biomarkers and

Divergent Annexin A1 expression in periphery and gut is associated with systemic immune activation and impaired gut immune response during SIV infection

PubMed Central

Sena, Angela A. S.; Glavan, Tiffany; Jiang, Guochun; Sankaran-Walters, Sumathi; Grishina, Irina; Dandekar, Satya; Goulart, Luiz R.

2016-01-01

HIV-1 disease progression is paradoxically characterized by systemic chronic immune activation and gut mucosal immune dysfunction, which is not fully defined. Annexin A1 (ANXA1), an inflammation modulator, is a potential link between systemic inflammation and gut immune dysfunction during the simian immunodeficiency virus (SIV) infection. Gene expression of ANXA1 and cytokines were assessed in therapy-naïve rhesus macaques during early and chronic stages of SIV infection and compared with SIV-negative controls. ANXA1 expression was suppressed in the gut but systemically increased during early infection. Conversely, ANXA1 expression increased in both compartments during chronic infection. ANXA1 expression in peripheral blood was positively correlated with HLA-DR+CD4+ and CD8+ T-cell frequencies, and negatively associated with the expression of pro-inflammatory cytokines and CCR5. In contrast, the gut mucosa presented an anergic cytokine profile in relation to ANXA1 expression. In vitro stimulations with ANXA1 peptide resulted in decreased inflammatory response in PBMC but increased activation of gut lymphocytes. Our findings suggest that ANXA1 signaling is dysfunctional in SIV infection, and may contribute to chronic inflammation in periphery and with immune dysfunction in the gut mucosa. Thus, ANXA1 signaling may be a novel therapeutic target for the resolution of immune dysfunction in HIV infection. PMID:27484833

Use of valganciclovir in patients with elevated antibody titers against Human Herpesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV) who were experiencing central nervous system dysfunction including long-standing fatigue.

PubMed

Kogelnik, Andreas M; Loomis, Kristin; Hoegh-Petersen, Mette; Rosso, Fernando; Hischier, Courtney; Montoya, Jose G

2006-12-01

Twelve patients with long-standing symptoms of central nervous system (CNS) dysfunction were found to have elevated antibody titres to human herpesvirus-6 (HHV-6) and Epstein-Barr virus (EBV). All patients had four or more of the following neurocognitive symptoms: impaired cognitive functioning, slowed processing speed, sleep disturbance, short-term memory deficit, fatigue and symptoms consistent with depression. We sought to determine whether elevated antibodies to EBV and HHV-6 indicated chronic viral activation in patients with CNS dysfunction and if their symptoms could be improved by suppressing viral activity with oral valganciclovir. Patients with high IgG antibody titers against HHV-6 and EBV who were suffering from central nervous system dysfunction and debilitating fatigue for more than one year (median 3 years, range 1-8 years) were treated with 6 months of valganciclovir in an open label study. Nine out of 12 (75%) patients experienced near resolution of their symptoms, allowing them all to return to the workforce or full time activites. In the nine patients with a symptomatic response to treatment, EBV VCA IgG titers dropped from 1:2560 to 1:640 (p = 0.008) and HHV-6 IgG titers dropped from a median value of 1:1280 to 1:320 (p = 0.271). Clinically significant hematological toxicity or serious adverse events were not observed among the 12 patients. These preliminary clinical and laboratory observations merit additional studies to establish whether this clinical response is mediated by an antiviral effect of the drug, indirectly via immunomodulation or by placebo effect.

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

PubMed

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.

Interferon-alpha, immune activation and immune dysfunction in treated HIV infection

PubMed Central

Cha, Lilian; Berry, Cassandra M; Nolan, David; Castley, Allison; Fernandez, Sonia; French, Martyn A

2014-01-01

Type I interferons (IFNs) exert anti-viral effects through the induction of numerous IFN-stimulated genes and an immunomodulatory effect on innate and adaptive immune responses. This is beneficial in controlling virus infections but prolonged IFN-α activity in persistent virus infections, such as HIV infection, may contribute to immune activation and have a detrimental effect on the function of monocytes and T and B lymphocytes. Activation of monocytes, associated with increased IFN-α activity, contributes to atherosclerotic vascular disease, brain disease and other ‘age-related diseases' in HIV patients treated with long-term antiretroviral therapy (ART). In HIV patients receiving ART, the anti-viral effects of IFN-α therapy have the potential to contribute to eradication of HIV infection while IFN-α inhibitor therapy is under investigation for the treatment of immune activation. The management of HIV patients receiving ART will be improved by understanding more about the opposing effects of IFN-α on HIV infection and disease and by developing methods to assess IFN-α activity in clinical practice. PMID:25505958

Chronic Lung Allograft Dysfunction: A Systematic Review of Mechanisms.

PubMed

Royer, Pierre-Joseph; Olivera-Botello, Gustavo; Koutsokera, Angela; Aubert, John-David; Bernasconi, Eric; Tissot, Adrien; Pison, Christophe; Nicod, Laurent; Boissel, Jean-Pierre; Magnan, Antoine

2016-09-01

Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. Chronic lung allograft dysfunction manifests as bronchiolitis obliterans syndrome or the recently described restrictive allograft syndrome. Although numerous risk factors have been identified so far, the physiopathological mechanisms of CLAD remain poorly understood. We investigate here the immune mechanisms involved in the development of CLAD after lung transplantation. We explore the innate or adaptive immune reactions induced by the allograft itself or by the environment and how they lead to allograft dysfunction. Because current literature suggests bronchiolitis obliterans syndrome and restrictive allograft syndrome as 2 distinct entities, we focus on the specific factors behind one or the other syndromes. Chronic lung allograft dysfunction is a multifactorial disease that remains irreversible and unpredictable so far. We thus finally discuss the potential of systems-biology approach to predict its occurrence and to better understand its underlying mechanisms.

Muscle fatigue in fibromyalgia is in the brain, not in the muscles: a case-control study of perceived versus objective muscle fatigue.

PubMed

Bandak, Elisabeth; Amris, Kirstine; Bliddal, Henning; Danneskiold-Samsøe, Bente; Henriksen, Marius

2013-06-01

To investigate relationships between perceived and objectively measured muscle fatigue during exhausting muscle contractions in women with fibromyalgia (FM) compared with healthy controls (HC). Women with FM and HC completed an isometric muscle exhaustion task at 90° shoulder abduction. Surface electromyographic (EMG) activity in the deltoid muscle was recorded together with self-reported level of muscle fatigue. 25 participants with FM and 23 HC were included. Average time to exhaustion was 254 s shorter in participants with FM than in HC. Participants with FM did not exhibit the same level of objective signs of muscle fatigue, seen as fewer changes in the EMG activity, as the HC during the exhaustion task. The task did not provoke pain in the HC, while participants with FM reported a doubling of pain. Women with FM had shorter exhaustion times and showed fewer objective signs of muscle fatigue during an exhausting isometric shoulder abduction compared with younger HC. This indicates that perceived muscle fatigue may be of central origin and supports the notion of central nervous dysfunction as basic pathological changes in FM.

Brain-Immune Interactions as the Basis of Gulf War Illness: Consortium Development

DTIC Science & Technology

2012-12-01

advancements regarding the role of glia in chronic pain processing (Watkins et al., 2007; Watkins et al., 2009), axonal transport deficits in...cytokine signaling) Behavioral Effects (fatigue, pain , cognitive problems) Astrocyte Activation (cytokine signaling) mutually exclusive and once...K. Sullivan, Ph.D. 12 characterized by persistent pain , cognitive dysfunction, and fatigue

Gender differences in chronic fatigue syndrome.

PubMed

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.

Drosophila type IV collagen mutation associates with immune system activation and intestinal dysfunction.

PubMed

Kiss, Márton; Kiss, András A; Radics, Monika; Popovics, Nikoletta; Hermesz, Edit; Csiszár, Katalin; Mink, Mátyás

2016-01-01

The basal lamina (BM) contains numerous components with a predominance of type IV collagens. Clinical manifestations associated with mutations of the human COL4A1 gene include perinatal cerebral hemorrhage and porencephaly, hereditary angiopathy, nephropathy, aneurysms and muscle cramps (HANAC), ocular dysgenesis, myopathy, Walker–Warburg syndrome and systemic tissue degeneration. In Drosophila, the phenotype associated with dominant temperature sensitive mutations of col4a1 include severe myopathy resulting from massive degradation of striated muscle fibers, and in the gut, degeneration of circular visceral muscle cells and epithelial cells following detachment from the BM. In order to determine the consequences of altered BMfunctions due to aberrant COL4A1 protein, we have carried out a series of tests using Drosophila DTS-L3 mutants from our allelic series of col4a1 mutations with confirmed degeneration of various cell types and lowest survival rate among the col4a1 mutant lines at restrictive temperature. Results demonstrated epithelial cell degeneration in the gut, shortened gut, enlarged midgut with multiple diverticulae, intestinal dysfunction and shortened life span. Midgut immunohistochemistry analyses confirmed altered expression and distribution of BM components integrin PSI and PSII alpha subunits, laminin gamma 1, and COL4A1 both in larvae and adults. Global gene expression analysis revealed activation of the effector AMP genes of the primary innate immune system including Metchnikowin, Diptericin, Diptericin B, and edin that preceded morphological changes. Attacin::GFP midgut expression pattern further supported these changes. An increase in ROS production and changes in gut bacterial flora were also noted and may have further enhanced an immune response. The phenotypic features of Drosophila col4a1 mutants confirmed an essential role for type IV collagen in maintaining epithelial integrity, gut morphology and intestinal function and suggest that

Losartan treatment attenuates tumor-induced myocardial dysfunction

PubMed Central

Stevens, Sarah CW; Velten, Markus; Youtz, Dane J.; Clark, Yvonne; Jing, Runfeng; Reiser, Peter J.; Bicer, Sabahattin; Devine, Raymond; McCarthy, Donna O.; Wold, Loren E.

2015-01-01

Fatigue and muscle wasting are common symptoms experienced by cancer patients. Data from animal models demonstrate that angiotensin is involved in tumor-induced muscle wasting, and that tumor growth can independently affect myocardial function, which could contribute to fatigue in cancer patients. In clinical studies, inhibitors of angiotensin converting enzyme (ACE) can prevent the development of chemotherapy-induced cardiovascular dysfunction, suggesting a mechanistic role for the renin-angiotensin-aldosterone system (RAAS). In the present study, we investigated whether an angiotensin (AT)1-receptor antagonist could prevent the development of tumor-associated myocardial dysfunction. Methods and Results: Colon26 adenocarcinoma (c26) cells were implanted into female CD2F1 mice at 8 weeks of age. Simultaneously, mice were administered Losartan (10 mg/kg) daily via their drinking water. In vivo echocardiography, blood pressure, in vitro cardiomyocyte function, cell proliferation assays, and measures of systemic inflammation and myocardial protein degradation were performed 19 days following tumor cell injection. Losartan treatment prevented tumor-induced loss of muscle mass and in vitro c26 cell proliferation, decreased tumor weight, and attenuated myocardial expression of interleukin-6. Furthermore, Losartan treatment mitigated tumor-associated alterations in calcium signaling in cardiomyocytes, which was associated with improved myocyte contraction velocity, systolic function, and blood pressures in the hearts of tumor-bearing mice. Conclusions: These data suggest that Losartan may mitigate tumor-induced myocardial dysfunction and inflammation. PMID:25988231

Losartan treatment attenuates tumor-induced myocardial dysfunction.

PubMed

Stevens, Sarah C W; Velten, Markus; Youtz, Dane J; Clark, Yvonne; Jing, Runfeng; Reiser, Peter J; Bicer, Sabahattin; Devine, Raymond D; McCarthy, Donna O; Wold, Loren E

2015-08-01

Fatigue and muscle wasting are common symptoms experienced by cancer patients. Data from animal models demonstrate that angiotensin is involved in tumor-induced muscle wasting, and that tumor growth can independently affect myocardial function, which could contribute to fatigue in cancer patients. In clinical studies, inhibitors of angiotensin converting enzyme (ACE) can prevent the development of chemotherapy-induced cardiovascular dysfunction, suggesting a mechanistic role for the renin-angiotensin-aldosterone system (RAAS). In the present study, we investigated whether an angiotensin (AT) 1-receptor antagonist could prevent the development of tumor-associated myocardial dysfunction. Colon26 adenocarcinoma (c26) cells were implanted into female CD2F1 mice at 8weeks of age. Simultaneously, mice were administered Losartan (10mg/kg) daily via their drinking water. In vivo echocardiography, blood pressure, in vitro cardiomyocyte function, cell proliferation assays, and measures of systemic inflammation and myocardial protein degradation were performed 19days following tumor cell injection. Losartan treatment prevented tumor-induced loss of muscle mass and in vitro c26 cell proliferation, decreased tumor weight, and attenuated myocardial expression of interleukin-6. Furthermore, Losartan treatment mitigated tumor-associated alterations in calcium signaling in cardiomyocytes, which was associated with improved myocyte contraction velocity, systolic function, and blood pressures in the hearts of tumor-bearing mice. These data suggest that Losartan may mitigate tumor-induced myocardial dysfunction and inflammation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Investigating unexplained fatigue in general practice with a particular focus on CFS/ME.

PubMed

Bansal, Amolak S

2016-07-19

Unexplained fatigue is not infrequent in the community. It presents a number of challenges to the primary care physician and particularly if the clinical examination and routine investigations are normal. However, while fatigue is a feature of many common illnesses, it is the main problem in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). This is a poorly understood condition that is accompanied by several additional symptoms which suggest a subtle multisystem dysfunction. Not infrequently it is complicated by sleep disturbance and alterations in attention, memory and mood.Specialised services for the diagnosis and management of CFS/ME are markedly deficient in the UK and indeed in virtually all countries around the world. However, unexplained fatigue and CFS/ME may be confidently diagnosed on the basis of specific clinical criteria combined with the normality of routine blood tests. The latter include those that assess inflammation, autoimmunity, endocrine dysfunction and gluten sensitivity. Early diagnosis and intervention in general practice will do much to reduce patient anxiety, encourage improvement and prevent expensive unnecessary investigations.There is presently an on-going debate as to the precise criteria that best confirms CFS/ME to the exclusion of other medical and psychiatric/psychological causes of chronic fatigue. There is also some disagreement as to best means of investigating and managing this very challenging condition. Uncertainty here can contribute to patient stress which in some individuals can perpetuate and aggravate symptoms. A simple clinical scoring system and a short list of routine investigations should help discriminate CFS/ME from other causes of continued fatigue.

Pathophysiology and Immune Dysfunction in Endometriosis

PubMed Central

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.

PubMed

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.

Characterization and implications of thyroid dysfunction induced by immune checkpoint inhibitors in real-life clinical practice: a long-term prospective study from a referral institution.

PubMed

Guaraldi, F; La Selva, R; Samà, M T; D'Angelo, V; Gori, D; Fava, P; Fierro, M T; Savoia, P; Arvat, E

2018-05-01

Autoimmune diseases are typically associated with immune checkpoints blockade. This study aims at assessing, in real-life clinical practice, the prevalence and impact of thyroid disorders induced by immune checkpoint inhibitors. 52 patients (30 F; age 61 ± 13 years) with advanced melanoma treated with ipilimumab (3 mg/kg i.v./3 weeks; 4 doses) were included. For disease progression, 29 (16 F) of them received nivolumab (3 mg/kg i.v./2 weeks) or pembrolizumab (2 mg/kg i.v./3 weeks). Thyroid function and autoimmunity were assessed before, after 6 weeks, at the end of ipilimumab, as well as before and every 3 months during nivolumab/pembrolizumab treatment. During ipilimumab, 7 (4 F) patients developed thyroid dysfunction (4 thyroiditis, 1 associated with hypothyroidism; 2 thyrotoxicosis in a previously euthyroid multinodular goiter; 1 hypothyroidism worsened). During PD1 inhibitors, 7 patients (3 F) developed hypothyroidism with severe manifestations in 6 of them; 3 patients suffered from euthyroid autoimmune thyroiditis from baseline, one after ipilimumab; 2 patients developed after transient thyrotoxicosis. Mean follow-up after anti-CTLA4 inhibitors treatment was 36 ± 28 months. Thyroid disorders occurred 45.1 ± 20.8 and 151 ± 67 days after the initiation of CTLA4 and PD1 inhibitors, respectively. Autoimmune disorders and BRAF mutation were associated with a better clinical response to CTLA4 followed by PD1 treatment. Immune checkpoint blockade is burdened by a high incidence of autoimmune thyroid dysfunction, which is often severe. Therefore, early and careful monitoring and, eventually, treatment are crucial to prevent the negative impact of thyroid dysfunction on the clinical outcome.

Metabolic abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a mini-review.

PubMed

Tomas, Cara; Newton, Julia

2018-04-17

Chronic fatigue syndrome (CFS), commonly known as myalgic encephalomyelitis (ME), is a debilitating disease of unknown etiology. CFS/ME is a heterogeneous disease associated with a myriad of symptoms but with severe, prolonged fatigue as the core symptom associated with the disease. There are currently no known biomarkers for the disease, largely due to the lack of knowledge surrounding the eitopathogenesis of CFS/ME. Numerous studies have been conducted in an attempt to identify potential biomarkers for the disease. This mini-review offers a brief summary of current research into the identification of metabolic abnormalities in CFS/ME which may represent potential biomarkers for the disease. The progress of research into key areas including immune dysregulation, mitochondrial dysfunction, 5'-adenosine monophosphate-activated protein kinase activation, skeletal muscle cell acidosis, and metabolomics are presented here. Studies outlined in this mini-review show many potential causes for the pathogenesis of CFS/ME and identify many potential metabolic biomarkers for the disease from the aforementioned research areas. The future of CFS/ME research should focus on building on the potential biomarkers for the disease using multi-disciplinary techniques at multiple research sites in order to produce robust data sets. Whether the metabolic changes identified in this mini-review occur as a cause or a consequence of the disease must also be established. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Hypothalamic-Pituitary-Adrenal Hypofunction in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) as a Consequence of Activated Immune-Inflammatory and Oxidative and Nitrosative Pathways.

PubMed

Morris, Gerwyn; Anderson, George; Maes, Michael

2017-11-01

There is evidence that immune-inflammatory and oxidative and nitrosative stress (O&NS) pathways play a role in the pathophysiology of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). There is also evidence that these neuroimmune diseases are accompanied by hypothalamic-pituitary-adrenal (HPA) axis hypoactivity as indicated by lowered baseline glucocorticoid levels. This paper aims to review the bidirectional communications between immune-inflammatory and O&NS pathways and HPA axis hypoactivity in ME/CFS, considering two possibilities: (a) Activation of immune-inflammatory pathways is secondary to HPA axis hypofunction via attenuated negative feedback mechanisms, or (b) chronic activated immune-inflammatory and O&NS pathways play a causative role in HPA axis hypoactivity. Electronic databases, i.e., PUBMED, Scopus, and Google Scholar, were used as sources for this narrative review by using keywords CFS, ME, cortisol, ACTH, CRH, HPA axis, glucocorticoid receptor, cytokines, immune, immunity, inflammation, and O&NS. Findings show that activation of immune-inflammatory and O&NS pathways in ME/CFS are probably not secondary to HPA axis hypoactivity and that activation of these pathways may underpin HPA axis hypofunction in ME/CFS. Mechanistic explanations comprise increased levels of tumor necrosis factor-α, T regulatory responses with elevated levels of interleukin-10 and transforming growth factor-β, elevated levels of nitric oxide, and viral/bacterial-mediated mechanisms. HPA axis hypoactivity in ME/CFS is most likely a consequence and not a cause of a wide variety of activated immune-inflammatory and O&NS pathways in that illness.

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

PubMed Central

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

The fatigue experience for women with human immunodeficiency virus.

PubMed

Lee, K A; Portillo, C J; Miramontes, H

1999-01-01

To examine fatigue as a symptom experienced by women with human immunodeficiency virus (HIV). A convenience sample of 100 women with HIV. Independent sample t-tests were used to test for mean differences in fatigue related to variables in the women's sociocultural and home environment (ethnicity, employment, marital status, and parenting). Pearson product moment correlations were used to examine significant relationships between fatigue and physiologic variables (age, CD4 cell count, and sleep). Lower CD4 cell counts were related to more daytime sleep, higher evening fatigue, and higher morning fatigue. Morning fatigue was related to duration of wake episodes during the night, napping, and perception of sleep disturbance during the past week. The number of awakenings during the first night predicted the severity of fatigue the next evening. To understand the fatigue experienced by women with HIV, researchers and clinicians must focus on the relative contributions of sociocultural, home, and physiologic environments within which these women live. Additional research is ongoing to identify the strategies these women use to manage daily activities such that gender-relevant and culturally relevant interventions for alleviating fatigue can be tested in women with a variety of chronic illnesses, including HIV and acquired immune deficiency syndrome.

The Environment-Immune Route to Chronic Disease

EPA Science Inventory

Specific environmental factors including chemicals, drugs, microbes and both physical and psychological factors can affect the immune system producing dysfunction and, ultimately, an increased risk ofchronic disease. Several different types of immune alterations can result from e...

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

PubMed

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

PubMed Central

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

2015-01-01

Objectives 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. Methods 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). Results 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. Conclusions 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

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

PubMed

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 <.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

DTIC Science & Technology

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

38 CFR 4.88a - Chronic fatigue syndrome.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Chronic fatigue syndrome. 4.88a Section 4.88a Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings Infectious Diseases, Immune Disorders and Nutritional...

BP180 dysfunction triggers spontaneous skin inflammation in mice.

PubMed

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.

PubMed

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

Phagocyte dysfunction, tissue aging and degeneration

PubMed Central

2013-01-01

Immunologically-silent phagocytosis of apoptotic cells is critical to maintaining tissue homeostasis and innate immune balance. Aged phagocytes reduce their functional activity, leading to accumulation of unphagocytosed debris, chronic sterile inflammation and exacerbation of tissue aging and damage. Macrophage dysfunction plays an important role in immunosenescence. Microglial dysfunction has been linked to age-dependent neurodegenerations. Retinal pigment epithelial (RPE) cell dysfunction has been implicated in the pathogenesis of age-related macular degeneration (AMD). Despite several reports on the characterization of aged phagocytes, the role of phagocyte dysfunction in tissue aging and degeneration is yet to be fully appreciated. Lack of knowledge of molecular mechanisms by which aging reduces phagocyte function has hindered our capability to exploit the therapeutic potentials of phagocytosis for prevention or delay of tissue degeneration. This review summarizes our current knowledge of phagocyte dysfunction in aged tissues and discusses possible links to age-related diseases. We highlight the challenges to decipher the molecular mechanisms, present new research approaches and envisage future strategies to prevent phagocyte dysfunction, tissue aging and degeneration. PMID:23748186

Phagocyte dysfunction, tissue aging and degeneration.

PubMed

Li, Wei

2013-09-01

Immunologically-silent phagocytosis of apoptotic cells is critical to maintaining tissue homeostasis and innate immune balance. Aged phagocytes reduce their functional activity, leading to accumulation of unphagocytosed debris, chronic sterile inflammation and exacerbation of tissue aging and damage. Macrophage dysfunction plays an important role in immunosenescence. Microglial dysfunction has been linked to age-dependent neurodegenerations. Retinal pigment epithelial (RPE) cell dysfunction has been implicated in the pathogenesis of age-related macular degeneration (AMD). Despite several reports on the characterization of aged phagocytes, the role of phagocyte dysfunction in tissue aging and degeneration is yet to be fully appreciated. Lack of knowledge of molecular mechanisms by which aging reduces phagocyte function has hindered our capability to exploit the therapeutic potentials of phagocytosis for prevention or delay of tissue degeneration. This review summarizes our current knowledge of phagocyte dysfunction in aged tissues and discusses possible links to age-related diseases. We highlight the challenges to decipher the molecular mechanisms, present new research approaches and envisage future strategies to prevent phagocyte dysfunction, tissue aging and degeneration. Copyright © 2013 Elsevier B.V. All rights reserved.

Psychological distress, iron deficiency, active disease and female gender are independent risk factors for fatigue in patients with ulcerative colitis

PubMed Central

Jonefjäll, Börje; Simrén, Magnus; Lasson, Anders; Öhman, Lena; Strid, Hans

2017-01-01

Background Patients with ulcerative colitis often report fatigue. Objectives To investigate prevalence of and risk factors for fatigue in patients with ulcerative colitis with active disease and during deep remission. Methods In this cross-sectional study, disease activity was evaluated with endoscopy and calprotectin, and patients were classified as having active disease (n = 133) or being in deep remission (n = 155). Blood samples were analysed to assess anaemia, iron deficiency and systemic immune activity. Patients completed questionnaires to assess fatigue, psychological distress, gastrointestinal symptoms and quality of life. Results The prevalence of high fatigue (general fatigue ≥ 13, Multidimensional Fatigue Inventory) was 40% in the full study population. Among patients with high fatigue, female gender and iron deficiency were more prevalent, and these patients had more severe disease activity and reported higher levels of anxiety, depression and decreased quality of life compared with patients with no/mild fatigue. A logistic regression analysis identified probable psychiatric disorder (odds ratio (OR) (confidence interval) 6.1 (3.1–12.2)), iron deficiency (OR 2.5 (1.2–5.1)), active disease (OR 2.2 (1.2–3.9)) and female gender (OR 2.1 (1.1–3.7)) as independent risk factors for high fatigue. Similar results were found concerning psychological distress, gender and quality of life, but immune markers did not differ in patients in deep remission with high vs. no/mild fatigue. Conclusions Probable psychiatric disorder, iron deficiency, active disease and female gender are independent risk factors for high fatigue in patients with ulcerative colitis. Low-grade immune activity does not seem to be the cause of fatigue among patients in deep remission. PMID:29435325

Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin.

PubMed

Maes, Michael; Twisk, Frank N M; Kubera, Marta; Ringel, Karl

2012-02-01

There is evidence that inflammatory pathways and cell-mediated immunity (CMI) play an important role in the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Activation of inflammatory and CMI pathways, including increased levels of cytokines, is known to induce fatigue and somatic symptoms. Given the broad spectrum inflammatory state in ME/CFS, the aim of this study was to examine whether inflammatory and CMI biomarkers are increased in individuals with ME/CFS. In this study we therefore measured plasma interleukin-(IL)1, tumor necrosis factor (TNF)α, and PMN-elastase, and serum neopterin and lysozyme in 107 patients with ME/CFS, 37 patients with chronic fatigue (CF), and 20 normal controls. The severity of ME/CFS was measured with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale. Serum IL-1, TNFα, neopterin and lysozyme are significantly higher in patients with ME/CFS than in controls and CF patients. Plasma PMN-elastase is significantly higher in patients with ME/CFS than in controls and CF patients and higher in the latter than in controls. Increased IL-1 and TNFα are significantly correlated with fatigue, sadness, autonomic symptoms, and a flu-like malaise; neopterin is correlated with fatigue, autonomic symptoms, and a flu-like malaise; and increased PMN-elastase is correlated with concentration difficulties, failing memory and a subjective experience of infection. The findings show that ME/CFS is characterized by low-grade inflammation and activation of CMI. The results suggest that characteristic symptoms of ME/CFS, such as fatigue, autonomic symptoms and a flu-like malaise, may be caused by inflammatory mediators, e.g. IL-1 and TNFα. Copyright © 2011 Elsevier B.V. All rights reserved.

Soluble TNFα Signaling within the Spinal Cord Contributes to the Development of Autonomic Dysreflexia and Ensuing Vascular and Immune Dysfunction after Spinal Cord Injury.

PubMed

Mironets, Eugene; Osei-Owusu, Patrick; Bracchi-Ricard, Valerie; Fischer, Roman; Owens, Elizabeth A; Ricard, Jerome; Wu, Di; Saltos, Tatiana; Collyer, Eileen; Hou, Shaoping; Bethea, John R; Tom, Veronica J

2018-04-25

Cardiovascular disease and susceptibility to infection are leading causes of morbidity and mortality for individuals with spinal cord injury (SCI). A major contributor to these is autonomic dysreflexia (AD), an amplified reaction of the autonomic nervous system (hallmarked by severe hypertension) in response to sensory stimuli below the injury. Maladaptive plasticity of the spinal sympathetic reflex circuit below the SCI results in AD intensification over time. Mechanisms underlying this maladaptive plasticity are poorly understood, restricting the identification of treatments. Thus, no preventative treatments are currently available. Neuroinflammation has been implicated in other pathologies associated with hyperexcitable neural circuits. Specifically, the soluble form of TNFα (sTNFα) is known to play a role in neuroplasticity. We hypothesize that persistent expression of sTNFα in spinal cord underlies AD exacerbation. To test this, we intrathecally administered XPro1595, a biologic that renders sTNFα nonfunctional, after complete, high-level SCI in female rats. This dramatically attenuated the intensification of colorectal distension-induced and naturally occurring AD events. This improvement is mediated via decreased sprouting of nociceptive primary afferents and activation of the spinal sympathetic reflex circuit. We also examined peripheral vascular function using ex vivo pressurized arterial preparations and immune function via flow cytometric analysis of splenocytes. Diminishing AD via pharmacological inhibition of sTNFα mitigated ensuing vascular hypersensitivity and immune dysfunction. This is the first demonstration that neuroinflammation-induced sTNFα is critical for altering the spinal sympathetic reflex circuit, elucidating a novel mechanism for AD. Importantly, we identify the first potential pharmacological, prophylactic treatment for this life-threatening syndrome. SIGNIFICANCE STATEMENT Autonomic dysreflexia (AD), a disorder that develops

Chronic fatigue syndrome: an update focusing on phenomenology and pathophysiology.

PubMed

Cho, Hyong Jin; Skowera, Anna; Cleare, Anthony; Wessely, Simon

2006-01-01

Chronic fatigue syndrome is a controversial condition especially concerning its clinical definition and aetiopathogenesis. Most recent research progress has been made in phenomenology and pathophysiology and we focused our review on these two areas. The phenomenology research supports the notion of a discrete fatigue syndrome which can be distinguished from depression and anxiety. The current case definition, however, may need an improvement based on empirical data. Recent advances in understanding the pathophysiology of chronic fatigue syndrome continue to demonstrate the involvement of the central nervous system. Hyperserotonergic state and hypoactivity of the hypothalamic-pituitary-adrenal axis constitute other findings, but the question of whether these alterations are a cause or consequence of chronic fatigue syndrome still remains unanswered. Immune system involvement in the pathogenesis seems certain but the findings on the specific mechanisms are still inconsistent. Genetic studies provide some evidence of the syndrome being a partly genetic condition, but environmental effects seem to be still predominant and identification of specific genes is still at a very early stage. The recent findings suggest that further research is needed in improving the current case definition; investigating overlaps and boundaries among various functional somatic syndromes; answering the question of whether the pathophysiologic findings are a cause or consequence; and elucidating the involvement of the central nervous system, immune system and genetic factors.

Cytosolic nucleic acid sensors and innate immune regulation.

PubMed

Ori, Daisuke; Murase, Motoya; Kawai, Taro

2017-03-04

During viral and bacterial infections, pathogen-derived cytosolic nucleic acids are recognized by the intracellular RNA sensors retinoic acid-inducible gene I and melanoma-differentiated gene 5 and intracellular DNA sensors, including cyclic-di-GMP-AMP synthase, absent in melanoma 2, interferon (IFN)-gamma inducible protein 16, polymerase III, and so on. Binding of intracellular nucleic acids to these sensors activates downstream signaling cascades, resulting in the production of type I IFNs and pro-inflammatory cytokines to induce appropriate systematic immune responses. While these sensors also recognize endogenous nucleic acids and activate immune responses, they can discriminate between self- and non-self-nucleic acids. However, dysfunction of these sensors or failure of regulatory mechanisms causes aberrant activation of immune response and autoimmune disorders. In this review, we focus on how intracellular immune sensors recognize exogenous nucleic acids and activate the innate immune system, and furthermore, how autoimmune diseases result from dysfunction of these sensors.

Genomic deletion of GIT2 induces a premature age-related thymic dysfunction and systemic immune system disruption

PubMed Central

Siddiqui, Sana; Lustig, Ana; Carter, Arnell; Sankar, Mathavi; Daimon, Caitlin M.; Premont, Richard T.; Etienne, Harmonie; van Gastel, Jaana; Azmi, Abdelkrim; Janssens, Jonathan; Becker, Kevin G.; Zhang, Yongqing; Wood, William; Lehrmann, Elin; Martin, James G.; Martin, Bronwen; Taub, Dennis D.; Maudsley, Stuart

2017-01-01

Recent research has proposed that GIT2 (G protein-coupled receptor kinase interacting protein 2) acts as an integrator of the aging process through regulation of ‘neurometabolic’ integrity. One of the commonly accepted hallmarks of the aging process is thymic involution. At a relatively young age, 12 months old, GIT2−/− mice present a prematurely distorted thymic structure and dysfunction compared to age-matched 12 month-old wild-type control (C57BL/6) mice. Disruption of thymic structure in GIT2−/− (GIT2KO) mice was associated with a significant reduction in the expression of the cortical thymic marker, Troma-I (cytokeratin 8). Double positive (CD4+CD8+) and single positive CD4+ T cells were also markedly reduced in 12 month-old GIT2KO mice compared to age-matched control wild-type mice. Coincident with this premature thymic disruption in GIT2KO mice was the unique generation of a novel cervical ‘organ’, i.e. ‘parathymic lobes’. These novel organs did not exhibit classical peripheral lymph node-like characteristics but expressed high levels of T cell progenitors that were reflexively reduced in GIT2KO thymi. Using signaling pathway analysis of GIT2KO thymus and parathymic lobe transcriptomic data we found that the molecular signaling functions lost in the dysfunctional GIT2KO thymus were selectively reinstated in the novel parathymic lobe – suggestive of a compensatory effect for the premature thymic disruption. Broader inspection of high-dimensionality transcriptomic data from GIT2KO lymph nodes, spleen, thymus and parathymic lobes revealed a systemic alteration of multiple proteins (Dbp, Tef, Per1, Per2, Fbxl3, Ddit4, Sin3a) involved in the multidimensional control of cell cycle clock regulation, cell senescence, cellular metabolism and DNA damage. Altered cell clock regulation across both immune and non-immune tissues therefore may be responsible for the premature ‘aging’ phenotype of GIT2KO mice. PMID:28260693

A Chronic Fatigue Syndrome (CFS) severity score based on case designation criteria.

PubMed

Baraniuk, James N; Adewuyi, Oluwatoyin; Merck, Samantha Jean; Ali, Mushtaq; Ravindran, Murugan K; Timbol, Christian R; Rayhan, Rakib; Zheng, Yin; Le, Uyenphuong; Esteitie, Rania; Petrie, Kristina N

2013-01-01

Chronic Fatigue Syndrome case designation criteria are scored as physicians' subjective, nominal interpretations of patient fatigue, pain (headaches, myalgia, arthralgia, sore throat and lymph nodes), cognitive dysfunction, sleep and exertional exhaustion. Subjects self-reported symptoms using an anchored ordinal scale of 0 (no symptom), 1 (trivial complaints), 2 (mild), 3 (moderate), and 4 (severe). Fatigue of 3 or 4 distinguished "Fatigued" from "Not Fatigued" subjects. The sum of the 8(Sum8) ancillary criteria was tested as a proxy for fatigue. All subjects had history and physical examinations to exclude medical fatigue, and ensure categorization as healthy or CFS subjects. Fatigued subjects were divided into CFS with ≥4 symptoms or Chronic Idiopathic Fatigue (CIF) with ≤3 symptoms. ROC of Sum8 for CFS and Not Fatigued subjects generated a threshold of 14 (specificity=0.934; sensitivity=0.928). CFS (n=256) and CIF (n=55) criteria were refined to include Sum8≥14 and ≤13, respectively. Not Fatigued subjects had highly skewed Sum8 responses. Healthy Controls (HC; n=269) were defined by fatigue≤2 and Sum8≤13. Those with Sum8≥14 were defined as CFS-Like With Insufficient Fatigue Syndrome (CFSLWIFS; n=20). Sum8 and Fatigue were highly correlated (R(2)=0.977; Cronbach's alpha=0.924) indicating an intimate relationship between symptom constructs. Cluster analysis suggested 4 clades each in CFS and HC. Translational utility was inferred from the clustering of proteomics from cerebrospinal fluid. Plotting Fatigue severity versus Sum8 produced an internally consistent classifying system. This is a necessary step for translating symptom profiles into fatigue phenotypes and their pathophysiological mechanisms.

Altered resting brain connectivity in persistent cancer related fatigue.

PubMed

Hampson, Johnson P; Zick, Suzanna M; Khabir, Tohfa; Wright, Benjamin D; Harris, Richard E

2015-01-01

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 fatigue. As

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

PubMed

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.

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

PubMed

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.

PubMed

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.

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

PubMed Central

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

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

PubMed

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

2014-12-01

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. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cancer pain, fatigue, distress, and insomnia in cancer patients.

PubMed

Theobald, Dale E

2004-01-01

Insomnia is common among cancer patients, occurring in approximately 30% to 50% of the cancer population. The interactions between cancer pain, insomnia, fatigue, and depression/anxiety are complex, warranting treatment plans that focus not only on the relief of specific symptoms to improve quality of life but also on the impact of treatment on other related symptoms. Pain is one of the most common symptoms experienced by cancer patients and is one of the primary factors that precipitate insomnia in this population. Fatigue is also commonly reported by cancer patients, with a prevalence of nearly 80% in some tumor types. Cancer-related fatigue occurs most often after surgery, chemotherapy, radiotherapy, or immunotherapy and has been reported by cancer patients to be the major obstacle to normal functioning and a good quality of life. Insomnia in cancer patients often occurs in association with psychological disorders such as depression or anxiety. Sleep disturbances are associated with aberrant patterns of cortisol secretion, such as those found in insomnia, which are known to significantly depress the immune system, particularly the cells of the immune system responsible for mounting a defense against tumors. Evidence suggests that management of insomnia through a combination of pharmacologic and nonpharmacologic means can have a positive impact not only on insomnia but also on related symptoms and, consequently, on overall health and quality of life. Although the treatment of insomnia in cancer patients can improve cancer-related fatigue, immune functioning, and overall quality of life, insomnia in the context of cancer is still undertreated. Physicians should use hypnotic agents appropriately and be aware of the reduced potential for producing tolerance and dependence with the nonbenzodiazepine hypnotic agents. The management of insomnia in cancer patients should include a global treatment plan designed to address not only the underlying sleep disturbance but

Portable Immune-Assessment System

NASA Technical Reports Server (NTRS)

Pierson, Duane L.; Stowe, Raymond P.; Mishra, Saroj K.

1995-01-01

Portable immune-assessment system developed for use in rapidly identifying infections or contaminated environment. System combines few specific fluorescent reagents for identifying immune-cell dysfunction, toxic substances, buildup of microbial antigens or microbial growth, and potential identification of pathogenic microorganisms using fluorescent microplate reader linked to laptop computer. By using few specific dyes for cell metabolism, DNA/RNA conjugation, specific enzyme activity, or cell constituents, one makes immediate, onsite determination of person's health or of contamination of environment.

Impaired interferon signaling is a common immune defect in human cancer

PubMed Central

Critchley-Thorne, Rebecca J.; Simons, Diana L.; Yan, Ning; Miyahira, Andrea K.; Dirbas, Frederick M.; Johnson, Denise L.; Swetter, Susan M.; Carlson, Robert W.; Fisher, George A.; Koong, Albert; Holmes, Susan; Lee, Peter P.

2009-01-01

Immune dysfunction develops in patients with many cancer types and may contribute to tumor progression and failure of immunotherapy. Mechanisms underlying cancer-associated immune dysfunction are not fully understood. Efficient IFN signaling is critical to lymphocyte function; animals rendered deficient in IFN signaling develop cancer at higher rates. We hypothesized that altered IFN signaling may be a key mechanism of immune dysfunction common to cancer. To address this, we assessed the functional responses to IFN in peripheral blood lymphocytes from patients with 3 major cancers: breast cancer, melanoma, and gastrointestinal cancer. Type-I IFN (IFN-α)-induced signaling was reduced in T cells and B cells from all 3 cancer-patient groups compared to healthy controls. Type-II IFN (IFN-γ)-induced signaling was reduced in B cells from all 3 cancer patient groups, but not in T cells or natural killer cells. Impaired-IFN signaling was equally evident in stage II, III, and IV breast cancer patients, and downstream functional defects in T cell activation were identified. Taken together, these findings indicate that defects in lymphocyte IFN signaling arise in patients with breast cancer, melanoma, and gastrointestinal cancer, and these defects may represent a common cancer-associated mechanism of immune dysfunction. PMID:19451644

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

PubMed

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.

Altered resting brain connectivity in persistent cancer related fatigue

PubMed Central

Hampson, Johnson P.; Zick, Suzanna M.; Khabir, Tohfa; Wright, Benjamin D.; Harris, Richard E.

2015-01-01

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 fatigue. As

A Chronic Fatigue Syndrome (CFS) severity score based on case designation criteria

PubMed Central

Baraniuk, James N; Adewuyi, Oluwatoyin; Merck, Samantha Jean; Ali, Mushtaq; Ravindran, Murugan K; Timbol, Christian R; Rayhan, Rakib; Zheng, Yin; Le, Uyenphuong; Esteitie, Rania; Petrie, Kristina N

2013-01-01

Background: Chronic Fatigue Syndrome case designation criteria are scored as physicians’ subjective, nominal interpretations of patient fatigue, pain (headaches, myalgia, arthralgia, sore throat and lymph nodes), cognitive dysfunction, sleep and exertional exhaustion. Methods: Subjects self-reported symptoms using an anchored ordinal scale of 0 (no symptom), 1 (trivial complaints), 2 (mild), 3 (moderate), and 4 (severe). Fatigue of 3 or 4 distinguished “Fatigued” from “Not Fatigued” subjects. The sum of the 8(Sum8) ancillary criteria was tested as a proxy for fatigue. All subjects had history and physical examinations to exclude medical fatigue, and ensure categorization as healthy or CFS subjects. Results: Fatigued subjects were divided into CFS with ≥4 symptoms or Chronic Idiopathic Fatigue (CIF) with ≤3 symptoms. ROC of Sum8 for CFS and Not Fatigued subjects generated a threshold of 14 (specificity=0.934; sensitivity=0.928). CFS (n=256) and CIF (n=55) criteria were refined to include Sum8≥14 and ≤13, respectively. Not Fatigued subjects had highly skewed Sum8 responses. Healthy Controls (HC; n=269) were defined by fatigue≤2 and Sum8≤13. Those with Sum8≥14 were defined as CFS–Like With Insufficient Fatigue Syndrome (CFSLWIFS; n=20). Sum8 and Fatigue were highly correlated (R2=0.977; Cronbach’s alpha=0.924) indicating an intimate relationship between symptom constructs. Cluster analysis suggested 4 clades each in CFS and HC. Translational utility was inferred from the clustering of proteomics from cerebrospinal fluid. Conclusions: Plotting Fatigue severity versus Sum8 produced an internally consistent classifying system. This is a necessary step for translating symptom profiles into fatigue phenotypes and their pathophysiological mechanisms. PMID:23390566

Long-term pain, fatigue, and impairment in neuralgic amyotrophy.

PubMed

van Alfen, Nens; van der Werf, Sieberen P; van Engelen, Baziel G

2009-03-01

Recently, it has become clear that neuralgic amyotrophy (NA; idiopathic and hereditary brachial plexus neuropathy) has a less optimistic prognosis than usually assumed. To optimize treatment and management of these patients, one needs to know the residual symptoms and impairments they suffer. Therefore, the objective of this study was to describe the prevalence of pain, psychologic symptoms, fatigue, functional status, and quality of life in patients with NA. Neurology outpatient department of an academic teaching hospital. NA patients (N=89) were studied, and clinical details were recorded. Self-report data were on average collected 2 years after the onset of the last NA episode. Pain was assessed with the McGill Pain Questionnaire, fatigue with the Checklist Individual Strength, and psychologic distress with the Symptom Checklist 90. Functional status and handicap were assessed with the modified Rankin Scale and Medical Outcomes Study 36-Item Short-Form Health Survey. Pain was usually localized in the right shoulder and upper arm, matching the clinical predilection site for paresis in NA. About a quarter to a third of the patients reported significant long-term pain and fatigue, and half to two thirds still experienced impairments in daily life. Over one third of the individual patients suffered from severe fatigue. The group did not fulfill the criteria of chronic fatigue or major psychologic distress. There was no correlation of pain or fatigue with the level of residual paresis on a Medical Research Council scale, but patients with a comorbid condition fared worse than patients without. A significant number of NA patients suffer from persistent pain and fatigue, leading to impairment. Symptoms were not correlated with psychologic distress. This makes it likely that they are caused by residual shoulder or arm dysfunction but not as part of a chronic pain or fatigue syndrome in these patients.

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

PubMed Central

Zhong, Hong; Ma, Minjuan

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. PMID:29484304

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

PubMed

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 p<0.05). The MCF at the 15th and 20th intensity dependent fatigue stimuli of taut bands were significantly lower than those at the 1st and 5th stimuli (all p<0.01). The MCF in the frequency dependent fatigue test was significantly higher and the stimulus frequency that induced MCF was significantly lower for taut bands than for non-taut bands (both p<0.01). The present study demonstrates that the muscle taut band itself was more excitable to electrical stimulation and significantly less fatigue resistant than normal muscle fibres.

Scapular kinematic and shoulder muscle activity alterations after serratus anterior muscle fatigue.

PubMed

Umehara, Jun; Kusano, Ken; Nakamura, Masatoshi; Morishita, Katsuyuki; Nishishita, Satoru; Tanaka, Hiroki; Shimizu, Itsuroh; Ichihashi, Noriaki

2018-02-23

Although the serratus anterior muscle has an important role in scapular movement, no study to date has investigated the effect of serratus anterior fatigue on scapular kinematics and shoulder muscle activity. The purpose of this study was to clarify the effect of serratus anterior fatigue on scapular movement and shoulder muscle activity. The study participants were 16 healthy men. Electrical muscle stimulation was used to fatigue the serratus anterior muscle. Shoulder muscle strength and endurance, scapular movement, and muscle activity were measured before and after the fatigue task. The muscle activity of the serratus anterior, upper and lower trapezius, anterior and middle deltoid, and infraspinatus muscles was recorded, and the median power frequency of these muscles was calculated to examine the degree of muscle fatigue. The muscle endurance and median power frequency of the serratus anterior muscle decreased after the fatigue tasks, whereas the muscle activities of the serratus anterior, upper trapezius, and infraspinatus muscles increased. External rotation of the scapula at the shoulder elevated position increased after the fatigue task. Selective serratus anterior fatigue due to electric muscle stimulation decreased the serratus anterior endurance at the flexed shoulder position. Furthermore, the muscle activities of the serratus anterior, upper trapezius, and infraspinatus increased and the scapular external rotation was greater after serratus anterior fatigue. These results suggest that the rotator cuff and scapular muscle compensated to avoid the increase in internal rotation of the scapula caused by the dysfunction of the serratus anterior muscle. Copyright © 2018 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

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

PubMed

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.

Modified Mediterranean Diet for Enrichment of Short Chain Fatty Acids: Potential Adjunctive Therapeutic to Target Immune and Metabolic Dysfunction in Schizophrenia?

PubMed Central

Joseph, Jamie; Depp, Colin; Shih, Pei-an B.; Cadenhead, Kristen S.; Schmid-Schönbein, Geert

2017-01-01

Growing interest in gut and digestive processes and their potential link to brain and peripheral based inflammation or biobehavioral phenotypes has led to an increasing number of basic and translational scientific reports focused on the role of gut microbiota within the context of neuropsychiatric disorders. However, the effect of dietary modification on specific gut metabolites, in association with immune, metabolic, and psychopathological functioning in schizophrenia spectrum disorders has not been well characterized. The short chain fatty acids (SCFA) acetate, butyrate, and propionate, major metabolites derived from fermentation of dietary fibers by gut microbes, interact with multiple immune and metabolic pathways. The specific pathways that SCFA are thought to target, are dysregulated in cardiovascular disease, type II diabetes, and systemic inflammation. Most notably, these disorders are consistently linked to an attenuated lifespan in schizophrenia. Although, unhealthy dietary intake patterns and increased prevalence of immune and metabolic dysfunction has been observed in people with schizophrenia; dietary interventions have not been well utilized to target immune or metabolic illness. Prior schizophrenia patient trials primarily focused on the effects of gluten free diets. Findings from these studies indicate that a diet avoiding gluten benefits a limited subset of patients, individuals with celiac disease or non-celiac gluten sensitivity. Therefore, alternative dietary and nutritional modifications such as high-fiber, Mediterranean style, diets that enrich the production of SCFA, while being associated with a minimal likelihood of adverse events, may improve immune and cardiovascular outcomes linked to premature mortality in schizophrenia. With a growing literature demonstrating that SCFA can cross the blood brain barrier and target key inflammatory and metabolic pathways, this article highlights enriching dietary intake for SCFA as a potential adjunctive

Muscle Dysfunction in Androgen Deprivation: Role of Ryanodine Receptor

DTIC Science & Technology

2016-11-01

undergoing ORX have reduced muscle specific force due to calcium leak through RyR1, which is caused by high levels of TGFβ released from the bone during... leak could be causing long-term effects, such as decreased muscle mass, body weight and forelimb grip strength. 15. SUBJECT TERMS Prostate Cancer...calcium leak and contractile dysfunction in chronic muscle fatigue, heart failure and muscular dystrophy (13-16). RyR1 is the skeletal muscle

Index markers of chronic fatigue syndrome with dysfunction of TCA and urea cycles

PubMed Central

Yamano, Emi; Sugimoto, Masahiro; Hirayama, Akiyoshi; Kume, Satoshi; Yamato, Masanori; Jin, Guanghua; Tajima, Seiki; Goda, Nobuhito; Iwai, Kazuhiro; Fukuda, Sanae; Yamaguti, Kouzi; Kuratsune, Hirohiko; Soga, Tomoyoshi; Watanabe, Yasuyoshi; Kataoka, Yosky

2016-01-01

Chronic fatigue syndrome (CFS) is a persistent and unexplained pathological state characterized by exertional and severely debilitating fatigue, with/without infectious or neuropsychiatric symptoms, lasting at least 6 consecutive months. Its pathogenesis remains incompletely understood. Here, we performed comprehensive metabolomic analyses of 133 plasma samples obtained from CFS patients and healthy controls to establish an objective diagnosis of CFS. CFS patients exhibited significant differences in intermediate metabolite concentrations in the tricarboxylic acid (TCA) and urea cycles. The combination of ornithine/citrulline and pyruvate/isocitrate ratios discriminated CFS patients from healthy controls, yielding area under the receiver operating characteristic curve values of 0.801 (95% confidential interval [CI]: 0.711–0.890, P < 0.0001) and 0.750 (95% CI: 0.584–0.916, P = 0.0069) for training (n = 93) and validation (n = 40) datasets, respectively. These findings provide compelling evidence that a clinical diagnostic tool could be developed for CFS based on the ratios of metabolites in plasma. PMID:27725700

Inflammatory responses to psychological stress in fatigued breast cancer survivors: relationship to glucocorticoids.

PubMed

Bower, Julienne E; Ganz, Patricia A; Aziz, Najib; Olmstead, Richard; Irwin, Michael R; Cole, Steve W

2007-03-01

Fatigue is a common problem following cancer treatment and our previous studies suggest that a chronic inflammatory process might contribute to cancer-related fatigue. However, immune responses to challenge have not yet been evaluated among individuals with cancer-related fatigue, and it is not known what mechanisms drive increased levels of inflammatory markers in fatigued cancer survivors. We have previously reported that fatigued breast cancer survivors show a blunted cortisol response to an experimental psychological stressor. In this report, we focus on inflammatory responses to this stressor and their relationship to circulating glucocorticoids and cellular sensitivity to glucocorticoid inhibition. Relative to non-fatigued control survivors, participants experiencing persistent fatigue showed significantly greater increases in LPS-stimulated production of IL-1beta and IL-6 following the stressor (Group x Time interaction: p<.05). Fatigued participants did not show any difference in cellular sensitivity to cortisol inhibition of cytokine production, but they did show significantly less salivary cortisol increase in the aftermath of the stressor. Moreover, blunted cortisol responses were associated with significantly increased production of IL-6 in response to LPS stimulation (p<.05). These data provide further evidence of enhanced inflammatory processes in fatigued breast cancer survivors and suggest that these processes may stem in part from decreased glucocorticoid response to stress.

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

NASA Astrophysics Data System (ADS)

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.

Thyroid Dysfunction from Antineoplastic Agents

PubMed Central

Larsen, P. Reed; Marqusee, Ellen

2011-01-01

Unlike cytotoxic agents that indiscriminately affect rapidly dividing cells, newer antineoplastic agents such as targeted therapies and immunotherapies are associated with thyroid dysfunction. These include tyrosine kinase inhibitors, bexarotene, radioiodine-based cancer therapies, denileukin diftitox, alemtuzumab, interferon-α, interleukin-2, ipilimumab, tremelimumab, thalidomide, and lenalidomide. Primary hypothyroidism is the most common side effect, although thyrotoxicosis and effects on thyroid-stimulating hormone secretion and thyroid hormone metabolism have also been described. Most agents cause thyroid dysfunction in 20%–50% of patients, although some have even higher rates. Despite this, physicians may overlook drug-induced thyroid dysfunction because of the complexity of the clinical picture in the cancer patient. Symptoms of hypothyroidism, such as fatigue, weakness, depression, memory loss, cold intolerance, and cardiovascular effects, may be incorrectly attributed to the primary disease or to the antineoplastic agent. Underdiagnosis of thyroid dysfunction can have important consequences for cancer patient management. At a minimum, the symptoms will adversely affect the patient’s quality of life. Alternatively, such symptoms can lead to dose reductions of potentially life-saving therapies. Hypothyroidism can also alter the kinetics and clearance of medications, which may lead to undesirable side effects. Thyrotoxicosis can be mistaken for sepsis or a nonendocrinologic drug side effect. In some patients, thyroid disease may indicate a higher likelihood of tumor response to the agent. Both hypothyroidism and thyrotoxicosis are easily diagnosed with inexpensive and specific tests. In many patients, particularly those with hypothyroidism, the treatment is straightforward. We therefore recommend routine testing for thyroid abnormalities in patients receiving these antineoplastic agents. PMID:22010182

Fatigue, Creep-Fatigue, and Thermomechanical Fatigue Life Testing of Alloys

NASA Technical Reports Server (NTRS)

Halford, Gary R.; Lerch, Bradley A.; McGaw, Michael A.

2000-01-01

The fatigue crack initiation resistance of an alloy is determined by conducting a series of tests over a range of values of stress amplitude or strain range. The observed number of cycles to failure is plotted against the stress amplitude or strain range to obtain a fatigue curve. The fatigue properties quoted for an alloy are typically the constants used in the equation(s) that describe the fatigue curve. Fatigue lives of interest may be as low as 10(exp 2) or higher than 10(exp 9) cycles. Because of the enormous scatter associated with fatigue, dozens of tests may be needed to confidently establish a fatigue curve, and the cost may run into several thousands of dollars. To further establish the effects on fatigue life of the test temperature, environment, alloy condition, mean stress effects, creep-fatigue effects, thermomechanical cycling, etc. requires an extraordinarily large and usually very costly test matrix. The total effort required to establish the fatigue resistance of an alloy should not be taken lightly. Fatigue crack initiation tests are conducted on relatively small and presumed to be initially crack-free, samples of an alloy that are intended to be representative of the alloy's metallurgical and physical condition. Generally, samples are smooth and have uniformly polished surfaces within the test section. Some may have intentionally machined notches of well-controlled geometry, but the surface at the root of the notch is usually not polished. The purpose of polishing is to attain a reproducible surface finish. This is to eliminate surface finish as an uncontrolled variable. Representative test specimen geometries will be discussed later. Test specimens are cyclically loaded until macroscopically observable cracks initiate and eventually grow to failure. Normally, the fatigue failure life of a specimen is defined as the number of cycles to separation of the specimen into two pieces. Alternative definitions are becoming more common, particularly for

Increased nuclear factor-κB and loss of p53 are key mechanisms in Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS).

PubMed

Morris, Gerwyn; Maes, Michael

2012-11-01

Fukuda's criteria are adequate to make a distinction between Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS) and chronic fatigue (CF), but ME/CFS patients should be subdivided into those with (termed ME) and without (termed CFS) post exertional malaise [Maes et al. 2012]. ME/CFS is considered to be a neuro-immune disease. ME/CFS is characterized by activated immuno-inflammatory pathways, including increased levels of pro-inflammatory cytokines, nuclear factor κB (NF-κB) and aberrations in mitochondrial functions, including lowered ATP. These processes may explain typical symptoms of ME/CFS, e.g. fatigue, malaise, hyperalgesia, and neurologic and autonomic symptoms. Here we hypothesize that increased NF-κB together with a loss of p53 are key phenomena in ME/CFS that further explain ME/CFS symptoms, such as fatigue and neurocognitive dysfunction, and explain ME symptoms, such as post-exertional malaise following mental and physical activities. Inactivation of p53 impairs aerobic mitochondrial functions and causes greater dependence on anaerobic glycolysis, elevates lactate levels, reduces mitochondrial density in skeletal muscle and reduces endurance during physical exercise. Lowered p53 and increased NF-κB are associated with elevated reactive oxygen species. Increased NF-κB induces the production of pro-inflammatory cytokines, which increase glycolysis and further compromise mitochondrial functions. All these factors together may contribute to mitochondrial exhaustion and indicate that the demand for extra ATP upon the commencement of increased activity cannot be met. In conditions of chronic inflammation and oxidative stress, high NF-κB and low p53 may conspire to promote neuron and glial cell survival at a price of severely compromised metabolic brain function. Future research should examine p53 signaling in ME/CFS. Copyright © 2012. Published by Elsevier Ltd.

The Immune System’s Role in Sepsis Progression, Resolution and Long-Term Outcome

PubMed Central

Delano, Matthew J.; Ward, Peter A.

2016-01-01

SUMMARY Sepsis occurs when an infection exceeds local tissue containment and induces a series of dysregulated physiologic responses that result in organ dysfunction. A subset of patients with sepsis progress to septic shock, defined by profound circulatory, cellular, and metabolic abnormalities, and associated with a greater mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the complex interplay between the initial inflammatory and later anti-inflammatory responses. With advances in intensive care medicine and goal-directed interventions, early 30-day sepsis mortality has diminished, only to steadily escalate long after “recovery” from acute events. Since so many sepsis survivors succumb later to persistent, recurrent, nosocomial and secondary infections, many investigators have turned their attention to the long-term sepsis-induced alterations in cellular immune function. Sepsis clearly alters the innate and adaptive immune responses for sustained periods of time after clinical recovery, with immune suppression, chronic inflammation, and persistence of bacterial representing such alterations. Understanding that sepsis-associated immune cell defects correlate with long-term mortality, more investigations have centered on the potential for immune modulatory therapy to improve long term patient outcomes. These efforts are focused on more clearly defining and effectively reversing the persistent immune cell dysfunction associated with long-term sepsis mortality. PMID:27782333

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

PubMed

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

PubMed Central

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 (p<0.01). People with fibromyalgia performed equivalently on measures of physical performance and cognitive performance on the physical and cognitive fatigue 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

NASA Astrophysics Data System (ADS)

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.

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

PubMed

Vernon, Suzanne D; Whistler, Toni; Cameron, Barbara; Hickie, Ian B; Reeves, William C; Lloyd, Andrew

2006-01-31

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. 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. 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. These preliminary data provide insights into alterations in gene transcripts associated with the varied clinical outcomes from acute infectious mononucleosis.

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.

PubMed

Naclerio, Fernando; Larumbe-Zabala, Eneko; Cooper, Robert; Allgrove, Judith; Earnest, Conrad P

2015-01-01

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.

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

PubMed Central

Naclerio, Fernando; Larumbe-Zabala, Eneko; Cooper, Robert; Allgrove, Judith; Earnest, Conrad P.

2015-01-01

We investigated the effects of ingesting a multi-ingredient (53g carbohydrate, 14.5g whey protein, 5g glutamine, 1.5g 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), 1h and 24h 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 24h while Interleukin-6 and myoglobin increased both immediately after and at 1h compared with baseline (P<0.05) for all three conditions. However, Myoglobin (P<0.05) was lower 1h 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±1.5 109/L vs. 4.9±1.8 109/L, P = 0.016) and a reduced (P<0.05) monocytes count (0.36±0.09 109/L) compared to both multi-ingredient (0.42±0.09 109/L) and placebo (0.42±0.12 109/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. PMID:25915424

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

PubMed

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.

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

PubMed

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 < .001). A more advanced albumin-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 < .001). In this large, multi-center retrospective study, the albumin-bilirubin grade highlights the interplay between liver reserve and immune dysfunction as prognostic determinants in HIV-associated HCC. © 2017 John Wiley & Sons Ltd.

T-cell homeostasis in breast cancer survivors with persistent fatigue.

PubMed

Bower, Julienne E; Ganz, Patricia A; Aziz, Najib; Fahey, John L; Cole, Steve W

2003-08-06

Approximately 30% of women successfully treated for breast cancer suffer persistent fatigue of unknown origin. Recent studies linking inflammatory processes to central nervous system-mediated fatigue led us to examine cellular immune system status in 20 fatigued breast cancer survivors and 19 matched non-fatigued breast cancer survivors. Fatigued survivors, compared with non-fatigued survivors, had statistically significantly increased numbers of circulating T lymphocytes (mean 31% increase, 95% confidence interval [CI] = 6% to 56%; P =.015 by two-sided analysis of variance [ANOVA]), with pronounced elevation in the numbers of CD4+ T lymphocytes (mean 41% increase, 95% CI = 15% to 68%; P =.003 by two-sided ANOVA) and CD56+ effector T lymphocytes (mean 52% increase, 95% CI = 4% to 99%; P =.027 by two-sided ANOVA). These changes were independent of patient demographic and treatment characteristics. Absolute numbers of B cells, natural killer cells, granulocytes, and monocytes were not altered. The increased numbers of circulating T cells correlated with elevations in the level of serum interleukin 1 receptor antagonist (for CD3+ cells, r =.56 and P =.001; for CD3+/CD4+ cells, r =.68 and P<.001, by Spearman rank correlation). Results of this study suggest that persistent fatigue in breast cancer survivors might be associated with a chronic inflammatory process involving the T-cell compartment. These results require confirmation in a larger study that is specifically designed to address this hypothesis.

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

PubMed

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.

Polysaccharide of radix pseudostellariae improves chronic fatigue syndrome induced by poly I:C in mice.

PubMed

Sheng, Rong; Xu, Xianxiang; Tang, Qin; Bian, Difei; Li, Ying; Qian, Cheng; He, Xin; Gao, Xinghua; Pan, Rong; Wang, Chong; Luo, Yubin; Xia, Yufeng; Dai, Yue

2011-01-01

Radix Pseudostellariae is used as a tonic drug in traditional Chinese medicine with immunomodulating and anti-fatigue activities, and the polysaccharide is considered as the main active component. The purpose of this study is to examine the effect of the polysaccharide isolated from Radix Pseudostellariae (PRP) on mouse chronic fatigue syndrome (CFS) induced by intraperitoneal injection of polyriboinosinic:polyribocytidylic acid (poly I:C), a double-stranded synthetic RNA. It has shown that the fatigue symptom of mice lasted at least 1 week as evaluated by forced swimming time. PRP (100, 200, 400 mg kg(-1)), orally administered 3 days before poly I:C injection, showed dose-dependent anti-fatigue effects. In addition, poly I:C led to evident alternations in neuroendocrine and immune systems of mice, such as reduced spontaneous activity and learning ability, declined serum level of corticosterone, increased weight indexes and T lymphocyte numbers in thymuses and spleens, and increased CD4(+)/CD8(+) ratio but decreased proliferation ability of T lymphocytes in spleens. PRP alleviated the abnormalities caused by poly I:C, and restored the function of hosts to normal conditions. The findings suggest that PRP is beneficial to CFS, and the underlying mechanisms of action involve neuroendocrine and immune systems.

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

PubMed Central

Vernon, Suzanne D; Whistler, Toni; Cameron, Barbara; Hickie, Ian B; Reeves, William C; Lloyd, Andrew

2006-01-01

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. PMID:16448567

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

PubMed

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.

The role of cytokines in cancer-related fatigue.

PubMed

Kurzrock, R

2001-09-15

Fatigue is prominent in cancer patients and probably multifactorial in origin. Factors contributing to fatigue include anemia, weight loss, fever, pain, medication, and infection. In cancer patients, many of these factors are influenced by a frequently disrupted balance between endogenous cytokine levels and their natural antagonists. Indeed, cancer cells and the immune system appear to overexpress a range of cytokines in patients with malignancies. Some of these cytokines act as autocrine or paracrine growth factors for the neoplastic tissue while simultaneously causing secondary symptoms related to fatigue. For instance, cancer-associated anemia may be due to a blunted erythropoietin response and/or cytokines (interleukin-1 [IL-1], IL-6, tumor necrosis factor-alpha [TNF-alpha]), which suppress erythropoiesis. Cancerous cachexia, a wasting syndrome and a hallmark of cancer, can be attributed to loss of appetite or enhanced energy expenditure. Several different interleukins, as well as TNF, interferon-gamma, and leukemia inhibitory factor, act as cachectins in animal models. Similarly, fever and night sweats are influenced by pyrogenic cytokines. Recently, molecules that function as cytokine antagonists have been identified. These molecules may be exploitable in combating the components of cancer-related fatigue, and may inhibit tumor growth as well. Copyright 2001 American Cancer Society.

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

PubMed

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.

Non-celiac gluten sensitivity triggers gut dysbiosis, neuroinflammation, gut-brain axis dysfunction, and vulnerability for dementia.

PubMed

Daulatzai, Mak Adam

2015-01-01

The non-celiac gluten sensitivity (NCGS) is a chronic functional gastrointestinal disorder which is very common world wide. The human gut harbors microbiota which has a wide variety of microbial organisms; they are mainly symbiotic and important for well being. However, "dysbiosis" - i.e. an alteration in normal commensal gut microbiome with an increase in pathogenic microbes, impacts homeostasis/health. Dysbiosis in NCGS causes gut inflammation, diarrhea, constipation, visceral hypersensitivity, abdominal pain, dysfunctional metabolic state, and peripheral immune and neuro-immune communication. Thus, immune-mediated gut and extra-gut dysfunctions, due to gluten sensitivity with comorbid diarrhea, may last for decades. A significant proportion of NCGS patients may chronically consume alcohol, non-steroidal anti-inflammatory drugs, and fatty diet, as well as suffer from various comorbid disorders. The above pathophysiological substrate and dysbiosis are underpinned by dysfunctional bidirectional "Gut-Brain Axis" pathway. Pathogenic gut microbiota is known to upregulate gut- and systemic inflammation (due to lipopolysaccharide from pathogenic bacteria and synthesis of pro-inflammatory cytokines); they enhance energy harvest, cause obesity, insulin resistance, and dysfunctional vago-vagal gut-brain axis. Conceivably, the above cascade of pathology may promote various pathophysiological mechanisms, neuroinflammation, and cognitive dysfunction. Hence, dysbiosis, gut inflammation, and chronic dyshomeostasis are of great clinical relevance. It is argued here that we need to be aware of NCGS and its chronic pathophysiological impact. Therapeutic measures including probiotics, vagus nerve stimulation, antioxidants, alpha 7 nicotinic receptor agonists, and corticotropin-releasing factor receptor 1 antagonist may ameliorate neuroinflammation and oxidative stress in NCGS; they may therefore, prevent cognitive dysfunction and vulnerability to Alzheimer's disease.

Commensal-innate immune miscommunication in IBD pathogenesis.

PubMed

Cario, Elke

2012-01-01

Commensal microbiota plays a key role in the health and disease of the host. The innate immune system comprises an essential functional component of the intestinal mucosal barrier, maintaining hyporesponsiveness to omnipresent harmless commensals in the lumen, but rapidly recognizing and combating invading bacteria through diverse antimicrobial mechanisms. Interactions between commensals and innate immune cells are constant, multidimensional and entirely context-dependent. Environment, genetics and host defense differentially modulate commensal-innate immune effects and functions in the intestinal mucosa. In IBD, dysbiosis, mucus layer disruption, impairment in bacterial clearance, intestinal epithelial cell barrier dysfunction and/or immune cell deregulation may lead to commensal-innate immune miscommunication, which critically drives mucosal inflammation and associated cancer. Copyright © 2012 S. Karger AG, Basel.

Reversal in fatigued athletes of a defect in interferon gamma secretion after administration of Lactobacillus acidophilus.

PubMed

Clancy, R L; Gleeson, M; Cox, A; Callister, R; Dorrington, M; D'Este, C; Pang, G; Pyne, D; Fricker, P; Henriksson, A

2006-04-01

Fatigue and impaired performance in athletes is well recognised and has been loosely linked to "overtraining". Reduced concentration of IgA in the saliva and increased shedding of Epstein Barr virus (EBV) have been associated with intense training in elite athletes. To determine whether athletes presenting with fatigue and impaired performance had an immune defect relevant to defective containment of EBV infection, and whether a probiotic preparation (Lactobacillus acidophilus) shown to enhance mucosal immunity in animal models could reverse any detected abnormality. The fatigued athletes had clinical characteristics consistent with re-activation of EBV infection and significantly (p = 0.02) less secretion of interferon (IFN) gamma from blood CD4 positive T cells. After one month of daily capsules containing 2 x 10(10) colony forming units of L acidophilus, secretion of IFNgamma from T cells had increased significantly (p = 0.01) to levels found in healthy control athletes. A significant (p = 0.03) increase in salivary IFNgamma concentrations in healthy control athletes after the one month course of L acidophilus demonstrated in man the capacity for this probiotic to enhance the mucosal IFNgamma concentration. This is the first evidence of a T cell defect in fatigued athletes, and of its reversal following probiotic therapy.

Auto-immune hepatitis following delivery.

PubMed

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.

Immune Abnormalities in Autism Spectrum Disorder-Could They Hold Promise for Causative Treatment?

PubMed

Gładysz, Dominika; Krzywdzińska, Amanda; Hozyasz, Kamil K

2018-01-06

Autism spectrum disorders (ASD) are characterized by impairments in language and communication development, social behavior, and the occurrence of stereotypic patterns of behavior and interests. Despite substantial speculation about causes of ASD, its exact etiology remains unknown. Recent studies highlight a link between immune dysfunction and behavioral traits. Various immune anomalies, including humoral and cellular immunity along with abnormalities at the molecular level, have been reported. There is evidence of altered immune function both in cerebrospinal fluid and peripheral blood. Several studies hypothesize a role for neuroinflammation in ASD and are supported by brain tissue and cerebrospinal fluid analysis, as well as evidence of microglial activation. It has been shown that immune abnormalities occur in a substantial number of individuals with ASD. Identifying subgroups with immune system dysregulation and linking specific cellular immunophenotypes to different symptoms would be key to defining a group of patients with immune abnormalities as a major etiology underlying behavioral symptoms. These determinations would provide the opportunity to investigate causative treatments for a defined patient group that may specifically benefit from such an approach. This review summarizes recent insights into immune system dysfunction in individuals with ASD and discusses the potential implications for future therapies.

[Integrated Chinese and Western medical treatment on postoperative fatigue syndrome in patients with gastric cancer].

PubMed

Dong, Qian-Tong; Zhang, Xiao-Dong; Yu, Zhen

2010-10-01

To evaluate the effect of the combined use of Shenmai Injection (SMI) and enteral nutrition on postoperative fatigue syndrome (POFS) in patients with gastric cancer (GC). Fifty-eight GC patients were randomized into the parenteral nutrition group (PNG, 19 cases), enteral nutrition group (ENG, 19 cases) and combined treatment group (CTG, 20 cases). The post-operative recovery in patients was observed; patients' conditions of fatigue, mood and sleep were evaluated respectively by visual analogue scale of fatigue, profile of mood states (POMS) and Pittsburgh sleep quality index (PSQI). Meanwhile, nutritional variables, such as serum contents of total protein, albumin, pre-albumin, were measured at different time points: before operation (d0) and the 1st, 5th, and 9th day (d1, d5 and d9) after operation. Immune variables such as subsets of lymphocytes (CD3, CD4, CD8), serum immunoglobulins (IgG, IgM, IgA) were also determined. Conditions of recovery, POMS and PSQI were better and the postoperative fatigue reduced more significantly in CTG than those in the other two groups (P < 0.05). On d9, levels of pre-albumin, CD3, CD4, CD4/CD8 in CTG were significantly higher than those in the PNG and ENG (P < 0.05), meantime, levels of albumin and IgA were higher in CTG than those in PNG (P < 0.05). Combined treatment of SMI and enteral nutrition can regulate mood and sleep to some extents, and reduce the postoperative fatigue through improving nutritional status and immune function, thus speeding up the recovery of patients.

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

PubMed

Chaldakov, George Nikov; Fiore, Marco; Ghenev, Peter I; Beltowski, Jerzy; Ranćić, Gorana; Tunçel, Neşe; Aloe, Luigi

2014-01-01

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 (PAAT), we recently designated tunica adiposa (in brief, adiposa like intima, media, and adventitia). Today, atherosclerosis is considered 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. PAAT 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 vascular 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.

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

PubMed Central

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

2016-01-01

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. PMID:27927801

Ebola VP40 in Exosomes Can Cause Immune Cell Dysfunction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pleet, Michelle L.; Mathiesen, Allison; DeMarino, Catherine

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, wemore » 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. In addition, 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

Ebola VP40 in Exosomes Can Cause Immune Cell Dysfunction

DOE PAGES

Pleet, Michelle L.; Mathiesen, Allison; DeMarino, Catherine; ...

2016-11-07

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, wemore » 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. In addition, 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

Ebola VP40 in Exosomes Can Cause Immune Cell Dysfunction.

PubMed

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

Fatigue

MedlinePlus

... 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

PubMed Central

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. PMID:29109730

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

PubMed

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.

Severe fatigue after treatment of ductal carcinoma in situ: A comparison with age-matched breast cancer survivors and healthy controls.

PubMed

Abrahams, H J G; Smits, L; Lugt, M de; Roos, W K de; Kamm, Y; Heins, M J; Verhagen, C A H H V M; Gielissen, M F M; Knoop, H

2017-02-01

Severe fatigue after treatment of ductal carcinoma in situ (DCIS) has not been studied before. The current study examined (i) the prevalence of severe fatigue in DCIS patients versus breast cancer survivors (BCS) and healthy controls (HC), (ii) quality of life and functioning of severely versus non-severely fatigued DCIS patients and BCS, and (iii) the association of fatigue with psychosocial and behavioral factors in DCIS patients. 89 patients treated for DCIS were matched on age and gender to 67 BCS and 178 HC (ratio 1:1:2). Fatigue was measured with the Fatigue Severity subscale of the Checklist Individual Strength. 23% of DCIS patients, 25% of BCS, and 6% of HC were severely fatigued (DCIS versus HC: p < 0.001). Severely fatigued DCIS patients had a lower quality of life and were more impaired in all domains of functioning than non-severely fatigued DCIS patients. Sleep problems, dysfunctional cognitions regarding fatigue, avoidance of activities, all-or-nothing behavior, perceived lack of social support, DCIS-related coping problems, and fear of future cancer occurrence were related to fatigue. The prevalence of severe fatigue in DCIS patients was similar to BCS, but higher than in HC. Severely fatigued DCIS patients had a lower quality of life and more functional impairments. The psychosocial and behavioral fatigue-related factors in DCIS patients are known to perpetuate fatigue in BCS. These factors can be targeted in interventions for cancer-related fatigue. Our findings suggest that the same treatment elements might be applicable to severely fatigued DCIS patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Relationship of Mitochondrial Enzymes to Fatigue Intensity in Men With Prostate Cancer Receiving External Beam Radiation Therapy

PubMed Central

Filler, Kristin; Lyon, Debra; McCain, Nancy; Bennett, James; Fernández-Martínez, Juan Luis; deAndrés-Galiana, Enrique Juan; Elswick, R. K.; Lukkahatai, Nada; Saligan, Leorey

2015-01-01

Purpose: Mitochondrial dysfunction is a plausible biological mechanism for cancer-related fatigue. Specific aims of this study were to (1) describe the levels of mitochondrial oxidative phosphorylation complex (MOPC) enzymes, fatigue, and health-related quality of life (HRQOL) before and at completion of external beam radiation therapy (EBRT) in men with nonmetastatic prostate cancer (PC); (2) examine relationships over time among levels of MOPC enzymes, fatigue, and HRQOL; and (3) compare levels of MOPC enzymes in men with clinically significant and nonsignificant fatigue intensification during EBRT. Methods: Fatigue was measured by the revised Piper Fatigue Scale and the Functional Assessment of Cancer Therapy–Fatigue subscale (FACT-F). MOPC enzymes (Complexes I–V) and mitochondrial antioxidant superoxide dismutase 2 were measured in peripheral blood using enzyme-linked immunosorbent assay at baseline and completion of EBRT. Participants were categorized into high or low fatigue (HF vs. LF) intensification groups based on amount of change in FACT-F scores during EBRT. Results: Fatigue reported by the 22 participants with PC significantly worsened and HRQOL significantly declined from baseline to EBRT completion. The HF group comprised 12 men with clinically significant change in fatigue (HF) during EBRT. Although no significant changes were observed in MOPC enzymes from baseline to EBRT completion, there were important differences in the patterns in the levels of MOPC enzymes between HF and LF groups. Conclusion: Distinct patterns of changes in the absorbance of MOPC enzymes delineated fatigue intensification among participants. Further investigation using a larger sample is warranted. PMID:26584846

Cancer cachexia decreases specific force and accelerates fatigue in limb muscle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roberts, B.M.; Frye, G.S.; Ahn, B.

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 havemore » 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

Immunity, ageing and cancer

PubMed Central

Derhovanessian, Evelyna; Solana, Rafael; Larbi, Anis; Pawelec, Graham

2008-01-01

Compromised immunity contributes to the decreased ability of the elderly to control infectious disease and to their generally poor response to vaccination. It is controversial as to how far this phenomenon contributes to the well-known age-associated increase in the occurrence of many cancers in the elderly. However, should the immune system be important in controlling cancer, for which there is a great deal of evidence, it is logical to propose that dysfunctional immunity in the elderly would contribute to compromised immunosurveillance and increased cancer occurrence. The chronological age at which immunosenescence becomes clinically important is known to be influenced by many factors, including the pathogen load to which individuals are exposed throughout life. It is proposed here that the cancer antigen load may have a similar effect on "immune exhaustion" and that pathogen load and tumor load may act additively to accelerate immunosenescence. Understanding how and why immune responsiveness changes in humans as they age is essential for developing strategies to prevent or restore dysregulated immunity and assure healthy longevity, clearly possible only if cancer is avoided. Here, we provide an overview of the impact of age on human immune competence, emphasizing T-cell-dependent adaptive immunity, which is the most sensitive to ageing. This knowledge will pave the way for rational interventions to maintain or restore appropriate immune function not only in the elderly but also in the cancer patient. PMID:18816370

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

PubMed

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 < .001, 95% CI [.34, .86]) and GSES (B = .31, p < .01, 95% CI [.07, .55]) were both significantly associated with PSQI. There was a significant interaction between SRBQ and DBAS (B = .25, p < .05, 95% CI [.04, .47]) such that the 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.

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

PubMed

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.

PubMed

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.

Graded versus Intermittent Exercise Effects on Lymphocytes in Chronic Fatigue Syndrome.

PubMed

Broadbent, Suzanne; Coutts, Rosanne

2016-09-01

There is increasing evidence of immune system dysfunction in chronic fatigue syndrome (CFS), but little is known of the regular exercise effects on immune cell parameters. This pilot study investigated the effects of graded and intermittent exercise on CD4 lymphocyte subset counts and activation compared with usual care. Twenty-four CFS patients (50.2 ± 10 yr) were randomized to graded exercise (GE), intermittent exercise (IE), or usual care (UC) groups; 18 sedentary non-CFS participants (50.6 ± 10 yr) were controls (CTL) for blood and immunological comparisons. Outcome measures were pre- and postintervention flow cytometric analyses of circulating lymphocyte subset cell counts; expression of CD3, CD4, CD25, and CD134; full blood counts; and V˙O2peak. Preintervention, CD3 cell counts, and expression of CD4, CD25, CD134, and CD4CD25CD134 were significantly lower in GE, IE, and UC compared with CTL (P < 0.05). Total lymphocyte concentration was significantly lower in GE and IE groups compared with CTL. There were significant postintervention increases in i) expression of CD4 and CD4CD25CD134 for GE and IE, but CD25 and CD134 for IE only; ii) circulating counts of CD3 and CD4 for GE, and CD3, CD4, CD8, CD3CD4CD8, CD3CD16CD56, CD19, and CD45 for IE; iii) neutrophil concentration for GE; and iv) V˙O2peak and elapsed test time for IE and GE, V˙Epeak for IE. Twelve weeks of GE and IE training significantly improved CD4 lymphocyte activation and aerobic capacity without exacerbating CFS symptoms. IE may be a more effective exercise modality with regard to enhanced CD4 activation in CFS patients.

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

PubMed

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.

Immune Regulation during Chronic Visceral Leishmaniasis

PubMed Central

Faleiro, Rebecca J.; Kumar, Rajiv; Hafner, Louise M.; Engwerda, Christian R.

2014-01-01

Visceral leishmaniasis is a chronic parasitic disease associated with severe immune dysfunction. Treatment options are limited to relatively toxic drugs, and there is no vaccine for humans available. Hence, there is an urgent need to better understand immune responses following infection with Leishmania species by studying animal models of disease and clinical samples from patients. Here, we review recent discoveries in these areas and highlight shortcomings in our knowledge that need to be addressed if better treatment options are to be developed and effective vaccines designed. PMID:25010815

Detection of Urine Metabolites in a Rat Model of Chronic Fatigue Syndrome before and after Exercise

PubMed Central

Shao, Changzhuan; Ren, Yiming; Wang, Zinan; Kang, Chenzhe

2017-01-01

Purpose. The aim of the present study was to elucidate the metabolic mechanisms associated with chronic fatigue syndrome (CFS) via an analysis of urine metabolites prior to and following exercise in a rat model. Methods. A rat model of CFS was established using restraint-stress, forced exercise, and crowded and noisy environments over a period of 4 weeks. Behavioral experiments were conducted in order to evaluate the model. Urine metabolites were analyzed via gas chromatography-mass spectrometry (GC-MS) in combination with multivariate statistical analysis before and after exercise. Results. A total of 20 metabolites were detected in CFS rats before and after exercise. Three metabolic pathways (TCA cycle; alanine, aspartate, and glutamate metabolism; steroid hormone biosynthesis) were significantly impacted before and after exercise, while sphingolipid metabolism alone exhibited significant alterations after exercise only. Conclusion. In addition to metabolic disturbances involving some energy substances, alterations in steroid hormone biosynthesis and sphingolipid metabolism were detected in CFS rats. Sphingosine and 21-hydroxypregnenolone may be key biomarkers of CFS, potentially offering evidence in support of immune dysfunction and hypothalamic-pituitary-adrenal (HPA) axis hypoactivity in patients with CFS. PMID:28421200

The Role of the Immune System in Autism Spectrum Disorder

PubMed Central

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. PMID:27534269

A Systematic Review of the Association between Immunogenomic Markers and Cancer-Related Fatigue

PubMed Central

Saligan, LN; Kim, HS

2012-01-01

Fatigue, which is one of the most commonly reported symptoms in cancer, can negatively impact the functional status and the health-related quality of life of individuals. This paper systematically reviews 34 studies to determine patterns of associations between immunogenomic markers and levels of cancer-related fatigue (CRF). Findings from the longitudinal studies revealed that elevated fatigue symptoms especially of women with early stages of breast cancer were associated with high levels of neutrophil/monocyte, IL-1ra, and IL-6 during radiation therapy; high levels of CD4+, IL-1β, and IL-6 with stressing stimuli; high levels of IL-1β during chemotherapy; low NK cell levels after chemotherapy; and presence of homozygous IL-6 and TNF alleles. In the cross-sectional studies, associations between levels of fatigue and immune/inflammatory markers were not consistently found, especially when covariates such as BMI, ethnicity, menopausal status, and educational level were controlled in the statistical analyses. However, a number of genomic markers were observed to be elevated mostly in fatigued breast cancer survivors in the cross-sectional studies. Gaps in knowledge and recommendations for future research are discussed. PMID:22595751

A systematic review of the association between immunogenomic markers and cancer-related fatigue.

PubMed

Saligan, L N; Kim, H S

2012-08-01

Fatigue, which is one of the most commonly reported symptoms in cancer, can negatively impact the functional status and the health-related quality of life of individuals. This paper systematically reviews 34 studies to determine patterns of associations between immunogenomic markers and levels of cancer-related fatigue (CRF). Findings from the longitudinal studies revealed that elevated fatigue symptoms especially of women with early stages of breast cancer were associated with high levels of neutrophil/monocyte, IL-1ra, and IL-6 during radiation therapy; high levels of CD4+, IL-1β, and IL-6 with stressing stimuli; high levels of IL-1β during chemotherapy; low NK cell levels after chemotherapy; and presence of homozygous IL-6 and TNF alleles. In the cross-sectional studies, associations between levels of fatigue and immune/inflammatory markers were not consistently found, especially when covariates such as BMI, ethnicity, menopausal status, and educational level were controlled in the statistical analyses. However, a number of genomic markers were observed to be elevated mostly in fatigued breast cancer survivors in the cross-sectional studies. Gaps in knowledge and recommendations for future research are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

Bithermal fatigue: A simplified alternative to thermomechanical fatigue

NASA Technical Reports Server (NTRS)

Verrilli, Michael J.

1988-01-01

A bithermal fatigue test technique was proposed as a simplified alternative to the thermomechanical fatigue test. Both the thermomechanical cycle and the bithermal technique can be used to study nonisothermal fatigue behavior. The difference between the two cycles is that in a conventional thermomechanical fatigue cycle the temperature is continuously varied concurrently with the applied mechanical strains, but in the bithermal fatigue cycle the specimen is held at zero load during the temperature excursions and all the loads are applied at the two extreme temperatures of the cycle. Experimentally, the bithermal fatigue test technique offers advantages such as ease in synchronizing the temperature and mechanical strain waveforms, in minimizing temperature gradients in the specimen gauge length, and in reducing and interpreting thermal fatigue such as the influence of alternate high and low temperatures on the cyclic stress-strain response characteristics, the effects of thermal state, and the possibility of introducing high- and low-temperature deformation mechanisms within the same cycle. The bithermal technique was used to study nonisothermal fatigue behavior of alloys such as single-crystal PWA 1480, single-crystal Rene N4, cast B1900+Hf, and wrought Haynes 188.

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

PubMed Central

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

Adipose tissue immunity and cancer

PubMed Central

Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Frühbeck, Gema

2013-01-01

Inflammation and altered immune response are important components of obesity and contribute greatly to the promotion of obesity-related metabolic complications, especially cancer development. Adipose tissue expansion is associated with increased infiltration of various types of immune cells from both the innate and adaptive immune systems. Thus, adipocytes and infiltrating immune cells secrete pro-inflammatory adipokines and cytokines providing a microenvironment favorable for tumor growth. Accumulation of B and T cells in adipose tissue precedes macrophage infiltration causing a chronic low-grade inflammation. Phenotypic switching toward M1 macrophages and Th1 T cells constitutes an important mechanism described in the obese state correlating with increased tumor growth risk. Other possible synergic mechanisms causing a dysfunctional adipose tissue include fatty acid-induced inflammation, oxidative stress, endoplasmic reticulum stress, and hypoxia. Recent investigations have started to unravel the intricacy of the cross-talk between tumor cell/immune cell/adipocyte. In this sense, future therapies should take into account the combination of anti-inflammatory approaches that target the tumor microenvironment with more sophisticated and selective anti-tumoral drugs. PMID:24106481

How Does Optimism Suppress Immunity? Evaluation of Three Affective Pathways

PubMed Central

Segerstrom, Suzanne C.

2005-01-01

Studies have linked optimism to poorer immunity during difficult stressors. In the present report, when first-year law students (N = 46) relocated to attend law school, reducing conflict among curricular and extracurricular goals, optimism predicted larger delayed type hypersensitivity responses, indicating more robust in vivo cellular immunity. However, when students did not relocate, increasing goal conflict, optimism predicted smaller responses. Although this effect has been attributed to negative affect when difficult stressors violate optimistic expectancies, distress did not mediate optimism’s effects on immunity. Alternative affective mediators related to engagement – engaged affect and fatigue – likewise failed to mediate optimism’s effects, although all three types of affect independently influenced in vivo immunity. Alternative pathways include effort or self-regulatory depletion. PMID:17014284

Unravelling thyroid dysfunction in rheumatoid arthritis: History matters.

PubMed

Anoop, Joseph; Geetha, Francis; Jyothi, Idiculla; Rekha, Pradeep; Shobha, Vineeta

2018-03-01

Autoimmune thyroid disease (AITD) frequently coexists with other systemic autoimmune conditions such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Due to the overlapping and nonspecific nature of symptoms, it is difficult to clinically uncover thyroidal illnesses in RA patients. This study was conducted to estimate the prevalence of thyroid dysfunction including the presence of anti-thyroid peroxidase (antiTPO) autoantibodies in patients with RA and to analyze symptomatology of thyroid dysfunction in patients diagnosed with RA. This cross-sectional, prospective study was conducted on 100 patients with RA, attending the Rheumatology Outpatient Department at St John's Medical College and Hospital, Bangalore, India. Twenty-two patients had biochemical evidence of thyroid dysfunction, hypothyroidism being the commonest (15/22 patients). Although fatigue and hair loss were the most common symptoms, only weight gain and cold intolerance were found to be statistically significant (P < 0.05) predictors of hypothyroidism and 32 patients were antiTPO positive. It was observed that equal numbers of patients developed hypothyroidism after diagnosis of RA and vice versa. History taking at the bedside to elicit symptoms, especially weight gain and cold intolerance, is quintessential to ensure timely diagnosis of hypothyroidism. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Parallels in Immunometabolic Adipose Tissue Dysfunction with Ageing and Obesity

PubMed Central

Trim, William; Turner, James E.; Thompson, Dylan

2018-01-01

Ageing, like obesity, is often associated with alterations in metabolic and inflammatory processes resulting in morbidity from diseases characterised by poor metabolic control, insulin insensitivity, and inflammation. Ageing populations also exhibit a decline in immune competence referred to as immunosenescence, which contributes to, or might be driven by chronic, low-grade inflammation termed “inflammageing”. In recent years, animal and human studies have started to uncover a role for immune cells within the stromal fraction of adipose tissue in driving the health complications that come with obesity, but relatively little work has been conducted in the context of immunometabolic adipose function in ageing. It is now clear that aberrant immune function within adipose tissue in obesity—including an accumulation of pro-inflammatory immune cell populations—plays a major role in the development of systemic chronic, low-grade inflammation, and limiting the function of adipocytes leading to an impaired fat handling capacity. As a consequence, these changes increase the chance of multiorgan dysfunction and disease onset. Considering the important role of the immune system in obesity-associated metabolic and inflammatory diseases, it is critically important to further understand the interplay between immunological processes and adipose tissue function, establishing whether this interaction contributes to age-associated immunometabolic dysfunction and inflammation. Therefore, the aim of this article is to summarise how the interaction between adipose tissue and the immune system changes with ageing, likely contributing to the age-associated increase in inflammatory activity and loss of metabolic control. To understand the potential mechanisms involved, parallels will be drawn to the current knowledge derived from investigations in obesity. We also highlight gaps in research and propose potential future directions based on the current evidence. PMID:29479350

Low cycle fatigue

NASA Technical Reports Server (NTRS)

Solomon, H. D. (Editor); Kaisand, L. R. (Editor); Halford, G. R. (Editor); Leis, B. N. (Editor)

1988-01-01

The papers contained in this volume focus on various aspects of low cycle fatigue, including cyclic deformation, crack propagation, high-temperature low cycle fatigue, microstructural defects, multiaxial and variable amplitude loading, and life prediction. Papers are presented on the low cycle fatigue of some aluminum alloys, prediction of crack growth under creep-fatigue loading conditions, high-temperature low cycle fatigue behavior and lifetime prediction of a nickel-base ODS alloy, and an integrated approach to creep-fatigue life prediction. Other topics discussed include thermal fatigue testing of coated monocrystalline superalloys, low cycle fatigue of Al-Mg-Si alloys, and the effect of superimposed stresses at high frequency on low cycle fatigue.

Mitochondrial dysfunction in a family with psychosis and chronic fatigue syndrome.

PubMed

Torrell, Helena; Alonso, Yolanda; Garrabou, Glòria; Mulet, David; Catalán, Marc; Valiente-Pallejà, Alba; Carreño-Gago, Lidia; García-Arumí, Elena; Montaña, Elena; Vilella, Elisabet; Martorell, Lourdes

2017-05-01

Mitochondrial impairment is hypothesized to be involved in chronic fatigue syndrome (CFS) and schizophrenia. We performed a clinical, genetic and functional mitochondrial study in a family consisting of a female presenting schizophrenia in addition to CFS symptoms and her mother and older sister, both presenting with CFS. The three family members showed higher blood lactate levels, higher mitochondrial mass, lower mtDNA content and overall lower mitochondrial enzymatic activities and lower oxygen consumption capacities than healthy women. This family presented mtDNA depletion; however, no mutation was identified neither in the mtDNA nor in the nuclear genes related with mtDNA depletion, even though C16179A and T16519A variants should be further studied. Copyright © 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Increased Incidence of Fatigue in Patients with Primary Immunodeficiency Disorders: Prevalence and Associations Within the US Immunodeficiency Network Registry.

PubMed

Hajjar, Joud; Guffey, Danielle; Minard, Charles G; Orange, Jordan S

2017-02-01

Patients with primary immunodeficiency (PID) often report fatigue, yet this symptom has not been studied in PID. Fatigue affects 6-7.5% of healthy adults. The goal of this study is to estimate the prevalence of fatigue in patients with PID and investigate its associated factors. We analyzed 2537 PID patients registered in USIDNET to determine responses to the field "fatigue" in the core registry form. Demographics, immune phenotypes, and comorbid conditions were compared between fatigued and non-fatigued patients to identify relevant associations and potential drivers. A focused analysis was performed for patients with predominantly antibody deficiency disorders (PADs). Fatigue was reported in 25.9% (95% CI 23.7-28.3) of PAD patients, compared to 6.4% (95% CI 4.9-8.2) of non-PAD. Patients with common variable immunodeficiency (CVID) had the highest prevalence of fatigue (p < 0.001) among all PID diagnoses. Other factors that were associated with a higher rate of fatigue among PAD patients included female sex, higher BMI, depression, bronchiectasis, and autoimmunity. Additionally, fatigued PAD patients had lower absolute lymphocyte, CD3, CD4, and CD8 counts compared to non-fatigued patients. Our findings suggest that fatigue is overrepresented in PAD patients. Prospective studies to estimate prevalence, risk factors, and fatigue etiology in PID are warranted, so therapeutic interventions can be considered.

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

PubMed

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.

Molecular Signatures of Peripheral Blood Mononuclear Cells during Chronic Interferon-alpha Treatment: Relationship with Depression and Fatigue

PubMed Central

Felger, Jennifer C.; Cole, Steve W.; Pace, Thaddeus W. W.; Hu, Fang; Woolwine, Bobbi J.; Doho, Gregory H.; Raison, Charles L.; Miller, Andrew H.

2012-01-01

Background Interferon (IFN)-alpha treatment for infectious disease and cancer causes high rates of depression and fatigue, and has been used to investigate the impact of inflammatory cytokines on brain and behavior. However, little is known about the transcriptional impact of chronic IFN-alpha on immune cells in vivo and its relationship to IFN-alpha-induced behavioral changes. Methods Genome-wide transcriptional profiling was performed on peripheral blood mononuclear cells from 21 patients with chronic hepatitis C either awaiting IFN-alpha therapy (n=10) or at 12 weeks of IFN-alpha treatment (n=11). Results Significance analysis of microarray data identified 252 up-regulated and 116 down-regulated gene transcripts. Of up-regulated genes, 2'-5'-oligoadenylate synthetase 2 (OAS2), a gene linked to chronic fatigue syndrome (CFS), was the only gene that was differentially expressed in patients with IFN-alpha-induced depression/fatigue, and correlated with depression and fatigue scores at 12 weeks (r=0.80, p=0.003 and r=0.70, p=0.017, respectively). Promoter-based bioinformatic analyses linked IFN-alpha-related transcriptional alterations to transcription factors involved in myeloid differentiation, IFN-alpha signaling, AP1 and CREB/ATF pathways, which were derived primarily from monocytes and plasmacytoid dendritic cells. IFN-alpha-treated patients with high depression/fatigue scores demonstrated up-regulation of genes bearing promoter motifs for transcription factors involved in myeloid differentiation, IFN-alpha and AP1 signaling, and reduced prevalence of motifs for CREB/ATF, which has been implicated in major depression. Conclusions Depression and fatigue during chronic IFN-alpha administration were associated with alterations in the expression (OAS2) and transcriptional control (CREB/ATF) of genes linked to behavioral disorders including CFS and major depression, further supporting an immune contribution to these diseases. PMID:22152193

Fatigue is not associated with impaired function of regulatory T cells in untreated patients with multiple sclerosis.

PubMed

Yaldizli, Ozguer; Kumar, Manoj; Vago, Susanne; Kreuzfelder, Erich; Limmroth, Volker; Putzki, Norman

2009-01-01

The pathophysiology of multiple sclerosis (MS)-associated fatigue is poorly understood. Immunological mechanisms may play a role. Alterations in immunological profile indicate a chronic immune activation in MS patients with fatigue. T-regulatory (Treg) cells seem to play a key role in coordinating autoimmune mechanisms in MS. This is the first study investigating the relationship between Treg cell function and fatigue in MS patients. In this cross-sectional in vitro, ex vivo study, we isolated peripheral blood mononuclear cells (PBMCs) from 20 MS patients with fatigue, determined lymphocyte subsets by flow cytometry and suppressive function of Treg cells in PBMC cultures with antigen stimulation. Forkhead box protein 3 expression was evaluated by PCR. Results were compared with 20 MS patients without fatigue and with 19 healthy controls. Leukocytes and lymphocyte subsets including Treg cell frequency did not differ in patients with and without fatigue. Co-culturing of Treg cells with CD4+CD25- cells did not lead to a significant suppression of myelin basic protein- and pokeweed mitogen-induced proliferation in MS patients in contrast to healthy controls. There were no statistical differences between MS patients with and without fatigue regarding this suppression activity. Fatigue seems not to be associated with impaired function of Treg cells in untreated MS patients.

Increased Incidence of Fatigue in Patients with Primary Immunodeficiency Disorders: Prevalence and Associations Within the US Immunodeficiency Network Registry

PubMed Central

Guffey, Danielle; Minard, Charles G.; Orange, Jordan S.

2017-01-01

Introduction Patients with primary immunodeficiency (PID) often report fatigue, yet this symptom has not been studied in PID. Fatigue affects 6–7.5% of healthy adults. The goal of this study is to estimate the prevalence of fatigue in patients with PID and investigate its associated factors. Methods We analyzed 2537 PID patients registered in USIDNET to determine responses to the field “fatigue” in the core registry form. Demographics, immune phenotypes, and comorbid conditions were compared between fatigued and non-fatigued patients to identify relevant associations and potential drivers. A focused analysis was performed for patients with predominantly antibody deficiency disorders (PADs). Results Fatigue was reported in 25.9%(95% CI 23.7–28.3) of PAD patients, compared to 6.4% (95% CI 4.9–8.2) of non-PAD. Patients with common variable immunodeficiency (CVID) had the highest prevalence of fatigue (p < 0.001) among all PID diagnoses. Other factors that were associated with a higher rate of fatigue among PAD patients included female sex, higher BMI, depression, bronchiectasis, and autoimmunity. Additionally, fatigued PAD patients had lower absolute lymphocyte, CD3, CD4, and CD8 counts compared to non-fatigued patients. Conclusion Our findings suggest that fatigue is overrepresented in PAD patients. Prospective studies to estimate prevalence, risk factors, and fatigue etiology in PID are warranted, so therapeutic interventions can be considered. PMID:28124237

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

NASA Technical Reports Server (NTRS)

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

NASA Technical Reports Server (NTRS)

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.

Learning and cognitive fatigue trajectories in multiple sclerosis defined using a burst measurement design.

PubMed

Holtzer, Roee; Foley, Frederick; D'Orio, Vanessa; Spat, Jessica; Shuman, Melissa; Wang, Cuiling

2013-10-01

Compromised learning and cognitive fatigue are critical clinical features in multiple sclerosis. This study was designed to determine the effect of repeated exposures within and across study visits on performance measures of learning and cognitive fatigue in relapsing-remitting multiple sclerosis (RRMS). Thirty patients with RRMS and 30 controls were recruited. Using a burst measurement design (i.e. repeated assessments within and across study visits) the oral version of the Symbol Digit Modalities Test (SDMT) was administered three times during the baseline and two consecutive monthly follow-up visits for a total of nine test administrations. Learning was assessed within and across study visits whereas cognitive fatigue was assessed during the course of each test administration that was divided into three 30-second intervals. Linear mixed-effect models revealed compromised learning within (95% CI: 2.6355 to 3.9867) and across (95% CI: 1.3250 to 3.1861) visits and worse cognitive fatigue (95% CI: -2.1761 to -0.1720) in patients with RRMS compared with controls. Among patients with RRMS, worse self-rated cognitive dysfunction predicted poor learning within (95% CI: -0.1112 to -0.0020) and across (95% CI: -0.0724 to -0.0106) visits. Burst design is optimal to study learning and cognitive fatigue. This methodology, using the SDMT or other time-efficient tests as outcome measures, can be successfully implemented in longitudinal studies and clinical trials.

Fatigue During and After Breast Cancer Therapy-A Prospective Study.

PubMed

Reinertsen, Kristin V; Engebraaten, Olav; Loge, Jon H; Cvancarova, Milada; Naume, Bjørn; Wist, Erik; Edvardsen, Hege; Wille, Elisabeth; Bjøro, Trine; Kiserud, Cecilie E

2017-03-01

Chronic fatigue (CF) in breast cancer (BC) survivors is multifactorial and may be caused by immune activation triggered by BC or its treatment. In the Neoadjuvant Avastin in Breast Cancer study, BC patients received neoadjuvant chemotherapy (FEC100→taxane) ± bevacizumab, a monoclonal antibody with fatigue as a potential side effect. To examine fatigue levels and prevalence of CF before and during chemotherapy and at follow-up, and their associations with C-reactive protein (CRP) and clinical variables. Eighty-four HER2-negative patients with cT2-4N0-3M0 BC responded to questionnaires and had CRP measured before treatment (T0), after FEC100 (T1), after taxanes before surgery (T2), and at two-year follow-up (T3). The prevalence of CF increased from 8% at T0 to 36% at T3, P < 0.0001. Fatigue levels peaked during chemotherapy from 12.0 at T0 to 20.0 at T2, and declined to 16.7 at T3, P < 0.001. Women with CF at T3 had higher fatigue levels at T0, T2, and T3 than those without CF (P ≤ 0.01). Psychological distress (P = 0.03) and pain (P = 0.04) at T3 were associated with CF at T3. Only psychological distress remained a significant predictor in multivariate analysis. CRP increased from T0 to T1 (P < 0.01) and declined to baseline values at T3, but changes were not associated with bevacizumab treatment. No association was found between bevacizumab or CRP, and fatigue levels or CF. Neither bevacizumab treatment nor low-grade systemic inflammation as measured by CRP was associated with the increased fatigue levels and raised prevalence of CF, observed during and after BC therapy. Increased fatigue levels at baseline and psychological distress at T3 were associated with CF at T3. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

The biology of cancer-related fatigue: a review of the literature.

PubMed

Saligan, Leorey N; Olson, Karin; Filler, Kristin; Larkin, David; Cramp, Fiona; Yennurajalingam, Sriram; Sriram, Yennu; Escalante, Carmen P; del Giglio, Auro; Kober, Kord M; Kamath, Jayesh; Palesh, Oxana; Mustian, Karen

2015-08-01

Understanding the etiology of cancer-related fatigue (CRF) is critical to identify targets to develop therapies to reduce CRF burden. The goal of this systematic review was to expand on the initial work by the National Cancer Institute CRF Working Group to understand the state of the science related to the biology of CRF and, specifically, to evaluate studies that examined the relationships between biomarkers and CRF and to develop an etiologic model of CRF to guide researchers on pathways to explore or therapeutic targets to investigate. This review was completed by the Multinational Association of Supportive Care in Cancer Fatigue Study Group-Biomarker Working Group. The initial search used three terms (biomarkers, fatigue, cancer), which yielded 11,129 articles. After removing duplicates, 9145 articles remained. Titles were assessed for the keywords "cancer" and "fatigue" resulting in 3811 articles. Articles published before 2010 and those with samples <50 were excluded, leaving 75 articles for full-text review. Of the 75 articles, 28 were further excluded for not investigating the associations of biomarkers and CRF. Of the 47 articles reviewed, 25 were cross-sectional and 22 were longitudinal studies. More than half (about 70 %) were published recently (2010-2013). Almost half (45 %) enrolled breast cancer participants. The majority of studies assessed fatigue using self-report questionnaires, and only two studies used clinical parameters to measure fatigue. The findings from this review suggest that CRF is linked to immune/inflammatory, metabolic, neuroendocrine, and genetic biomarkers. We also identified gaps in knowledge and made recommendations for future research.

Adrenal Fatigue

MedlinePlus

... unlikely to cover the costs. What is the theory behind adrenal fatigue? Supporters of adrenal fatigue believe ... by producing hormones like cortisol. According to the theory of adrenal fatigue, when people are faced with ...

Dietary nucleotides prevent decrease in cellular immunity in ground-based microgravity analog

NASA Technical Reports Server (NTRS)

Yamauchi, Keiko; Hales, Nathan W.; Robinson, Sandra M.; Niehoff, Michael L.; Ramesh, Vani; Pellis, Neal R.; Kulkarni, Anil D.

2002-01-01

Microgravity and stress of spaceflights result in immune dysfunction. The role of nutrition, especially nucleotide supplementation, has become an area of intensive research and significant interest in immunomodulation for maintenance of cellular immune responses. The studies presented here evaluate the plausibility of administering nucleotides to obviate immune dysfunction in an Earth-based in vivo analog of microgravity as studied in anti-orthostatic tail suspension (AOS) of mice. Mice were divided into three housing groups: group, isolation, and AOS. Mice were fed either control chow diet (CD), or RNA-, adenine-, or uracil-supplemented CD for the 1-wk duration of the experiments. In AOS mice, supplemental nucleotides significantly increased in vivo lymph node proliferation and ex vivo lymphoproliferation response to alloantigen and mitogens, respectively, and interleukin-2 and interferon-gamma production. A lower corticosterone level was observed in uracil-supplemented CD compared with CD. These results suggest that exogenous nucleotide supplementation, especially uracil, of normal diet is beneficial in the maintenance and restoration of the immune response during the microgravity analog conditions.

Biomarkers of Fatigue: Ranking Mental Fatigue Susceptibility

DTIC Science & Technology

2010-12-10

expected declines in performance during the 36-hour, 15-minute period of sleep deprivation without caffeine. The simple change from baseline results...rankings for fatigue resistance were then determined via a percent- change rule similar to that used in Chaiken, Harville, Harrison, Fischer, Fisher...and Whitmore (2008). This rule ranks subjects on percent change of cognitive performance from a baseline performance (before fatigue) to a fatigue

Fatigue crack tip deformation and fatigue crack propagation

NASA Technical Reports Server (NTRS)

Kang, T. S.; Liu, H. W.

1972-01-01

The effects of stress ratio, prestress cycling and plate thickness on the fatigue crack propagation rate are studied on 2024-T351 aluminum alloy. Fatigue crack propagation rate increases with the plate thickness and the stress ratio. Prestress cycling below the static yield strength has no noticeable effect on the fatigue crack propagation rate. However, prestress cycling above the static yield strength causes the material to strain harden and increases the fatigue crack propagation rate. Crack tip deformation is used to study the fatigue crack propagation. The crack tip strains and the crack opening displacements were measured from moire fringe patterns. The moire fringe patterns were obtained by a double exposure technique, using a very high density master grille (13,400 lines per inch).

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

PubMed

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 <.001. These factors were significantly positively correlated among CFS/ME patients (β=.36, p <.001), but not the 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.

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

PubMed Central

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’s<.001. These factors were significantly positively correlated among CFS/ME patients (β=.36, p<.001), but not the fatigued 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

Fatigue in industry.

PubMed Central

Grandjean, E

1979-01-01

Physical fatigue is a painful phenomenon which is localised in overstressed muscles. Mental fatigue is a diffuse sensation of weariness; it is a functional state, one of several intermediate conditions between the two extremes of alarm and sleep. A neurophysiological model of fatigue, involving an activating and inhibitory system has been developed. Fatigue in industrial practice has clinical symptoms: psychic instability, fits of depression and increased liability to illness. Indicators of fatigue are work of performance, subjective feelings of fatigue, electroencephalography, flicker-fusion frequency and various psychomotor and mental tests. Several field studies do, to some extent, confirm the above-mentioned concept of fatigue. PMID:40999

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

PubMed

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.

Poststroke Fatigue: Who Is at Risk for an Increase in Fatigue?

PubMed Central

van Eijsden, Hanna Maria; van de Port, Ingrid Gerrie Lambert; Visser-Meily, Johanna Maria August; Kwakkel, Gert

2012-01-01

Background. Several studies have examined determinants related to post-stroke fatigue. However, it is unclear which determinants can predict an increase in poststroke fatigue over time. Aim. This prospective cohort study aimed to identify determinants which predict an increase in post-stroke fatigue. Methods. A total of 250 patients with stroke were examined at inpatient rehabilitation discharge (T0) and 24 weeks later (T1). Fatigue was measured using the Fatigue Severity Scale (FSS). An increase in post-stroke fatigue was defined as an increase in the FSS score beyond the 95% limits of the standard error of measurement of the FSS (i.e., 1.41 points) between T0 and T1. Candidate determinants included personal factors, stroke characteristics, physical, cognitive, and emotional functions, and activities and participation and were assessed at T0. Factors predicting an increase in fatigue were identified using forward multivariate logistic regression analysis. Results. The only independent predictor of an increase in post-stroke fatigue was FSS (OR 0.50; 0.38–0.64, P < 0.001). The model including FSS at baseline correctly predicted 7.9% of the patients who showed increased fatigue at T1. Conclusion. The prognostic model to predict an increase in fatigue after stroke has limited predictive value, but baseline fatigue is the most important independent predictor. Overall, fatigue levels remained stable over time. PMID:22028989

Assessing fatigue in inflammatory bowel disease: comparison of three fatigue scales.

PubMed

Norton, C; Czuber-Dochan, W; Bassett, P; Berliner, S; Bredin, F; Darvell, M; Forbes, A; Gay, M; Ream, E; Terry, H

2015-07-01

Fatigue is commonly reported by patients with inflammatory bowel disease (IBD), both in quiescent and active disease. Few fatigue scales have been tested in IBD. To assess three fatigue assessment scales in IBD and to determine correlates of fatigue. Potential participants (n = 2131) were randomly selected from an IBD organisation's members' database; 605 volunteered and were posted three fatigue scales: Inflammatory Bowel Disease Fatigue scale, Multidimensional Fatigue Inventory and Multidimensional Assessment Fatigue scale and questionnaires assessing anxiety, depression, quality of life (QoL) and IBD activity. The questionnaires were tested for stability over time with another group (n = 70) of invited participants. Internal consistency was measured by Cronbach's alpha and test-retest reliability by the intraclass correlation coefficient (ICC). Four hundred and sixty-five of 605 (77%) questionnaires were returned; of 70 invited, 48/70 returned test (68.6%) and 41/70 (58.6%) returned retest. The three scales are highly correlated (P < 0.001). Test-retest suggests reasonable agreement with ICC values between 0.65 and 0.84. Lower age, female gender, IBD diagnosis, anxiety, depression and QoL were associated with fatigue (P < 0.001) on univariable analysis. However, on multivariable analysis only depression and low QoL were consistently associated with fatigue, while female gender was associated on most scales. IBD diagnosis, age and other factors were not consistently associated with severity or impact of fatigue once other variables were controlled for. All three fatigue scales are likely to measure IBD fatigue adequately. Responsiveness to change has not been tested. Depression, poorer QoL and probably female gender are the major associations of fatigue in IBD. © 2015 John Wiley & Sons Ltd.

miR-29b and miR-198 overexpression in CD8+ T cells of renal cell carcinoma patients down-modulates JAK3 and MCL-1 leading to immune dysfunction.

PubMed

Gigante, Margherita; Pontrelli, Paola; Herr, Wolfgang; Gigante, Maddalena; D'Avenia, Morena; Zaza, Gianluigi; Cavalcanti, Elisabetta; Accetturo, Matteo; Lucarelli, Giuseppe; Carrieri, Giuseppe; Battaglia, Michele; Storkus, Walter J; Gesualdo, Loreto; Ranieri, Elena

2016-04-11

Mammalian microRNAs (miR) regulate the expression of genes relevant for the development of adaptive and innate immunity against cancer. Since T cell dysfunction has previously been reported in patients with renal cell carcinoma (RCC; clear cell type), we aimed to analyze these immune cells for genetic and protein differences when compared to normal donor T cells freshly after isolation and 35 days after in vitro stimulation (IVS) with HLA-matched RCC tumor cells. We investigated gene expression profiles of tumor-reactive CD8(+) T cells obtained from RCC patient and compared with their HLA-matched healthy sibling donors using a microarray approach. In addition, miRNAs analysis was performed in a validation cohort of peripheral blood CD8(+) T cells from 25 RCC patients compared to 15 healthy volunteers. We observed that CD8(+) T cells from RCC patients expressed reduced levels of anti-apoptotic and proliferation-associated gene products when compared with normal donor T cells both pre- and post-IVS. In particular, JAK3 and MCL-1 were down-regulated in patient CD8(+) T cells versus their normal counterparts, likely due to defective suppressor activity of miR-29b and miR-198 in RCC CD8(+) T cells. Indeed, specific inhibition of miR-29b or miR-198 in peripheral blood mononuclear cells (PBMCs) isolated from RCC patients, resulted in the up-regulation of JAK3 and MCL-1 proteins and significant improvement of cell survival in vitro. Our results suggest that miR-29b and miR-198 dysregulation in RCC patient CD8(+) T cells is associated with dysfunctional immunity and foreshadow the development of miR-targeted therapeutics to correct such T cell defects in vivo.

Regulation of immunity and inflammation by hypoxia in immunological niches.

PubMed

Taylor, Cormac T; Colgan, Sean P

2017-12-01

Immunological niches are focal sites of immune activity that can have varying microenvironmental features. Hypoxia is a feature of physiological and pathological immunological niches. The impact of hypoxia on immunity and inflammation can vary depending on the microenvironment and immune processes occurring in a given niche. In physiological immunological niches, such as the bone marrow, lymphoid tissue, placenta and intestinal mucosa, physiological hypoxia controls innate and adaptive immunity by modulating immune cell proliferation, development and effector function, largely via transcriptional changes driven by hypoxia-inducible factor (HIF). By contrast, in pathological immunological niches, such as tumours and chronically inflamed, infected or ischaemic tissues, pathological hypoxia can drive tissue dysfunction and disease development through immune cell dysregulation. Here, we differentiate between the effects of physiological and pathological hypoxia on immune cells and the consequences for immunity and inflammation in different immunological niches. Furthermore, we discuss the possibility of targeting hypoxia-sensitive pathways in immune cells for the treatment of inflammatory disease.

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

PubMed

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.

Investigations Concerning Cavitation and Frost Fatigue in Clonal 84K Poplar Using High-Resolution Cavitron Measurements1[OPEN

PubMed Central

Feng, Feng; Ding, Fei; Tyree, Melvin T.

2015-01-01

Both drought and freezing-thawing of stems induce a loss of hydraulic conductivity (percentage loss of conductivity [PLC]) in woody plants. Drought-induced PLC is often accompanied by physical damage to pit membranes, causing a shift in vulnerability curves (cavitation fatigue). Hence, if cavitated stems are flushed to remove embolisms, the next vulnerability curve is different (shifted to lower tensions). The 84K poplar (Populus alba × Populus glandulosa) clone has small vessels that should be immune from frost-induced PLC, but results demonstrated that freezing-thawing in combination with tension synergistically increased PLC. Frost fatigue has already been defined, which is similar to cavitation fatigue but induced by freezing. Frost fatigue caused a transition from a single to a dual Weibull curve, but drought-fatigued stems had single Weibull curves shifted to lower tensions. Studying the combined impact of tension plus freezing on fatigue provided evidence that the mechanism of frost fatigue may be the extra water tension induced by freezing or thawing while spinning stems in a centrifuge rather than direct ice damage. A hypothesis is advanced that tension is enhanced as ice crystals grow or melt during the freeze or thaw event, respectively, causing a nearly identical fatigue event to that induced by drought. PMID:25786827

[Thyroid dysfunction in adults infected by human immunodeficiency virus].

PubMed

Abelleira, Erika; De Cross, Graciela A; Pitoia, Fabián

2014-01-01

Patients infected with human immunodeficiency virus (HIV) have a higher prevalence of thyroid dysfunction when compared with the general population. The most frequently observed manifestations are euthyroid sick syndrome, Graves' disease and subclinical hypothyroidism. The relationship between the use of highly active antiretroviral therapy and the increased prevalence of thyroid dysfunction has been demonstrated in several series of patients. Grave's disease is recognized as a consequence of immune restitution syndrome. Besides, several studies have suggested an association between hypothyroidism and the use of nucleoside reverse transcriptase inhibitors, particularly stavudine and non-nucleoside reverse transcriptase inhibitors such as efavirenz. Further studies could provide additional evidence of the need for routine assessment of thyroid function in HIV-infected patients.

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

PubMed

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

PubMed Central

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

2013-01-01

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. PMID:23732397

The innate immune response during urinary tract infection and pyelonephritis.

PubMed

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.

Microstructural evaluation of cumulative fatigue damage below the fatigue limit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fukuoka, C.; Nakagawa, Y.G.

1996-05-01

The objective of this work is to evaluate the microstructural changes induced near and below the fatigue limit in a pressure vessel steel plate, SA508. Dislocation cell to cell misorientation differences, {theta}, which increase with fatigue damage accumulation, are measured by the Selected Area Diffraction (SAD) method. The misorientation difference, {theta}, of the sample failed just above the fatigue limit is about 4.0 degrees on the average, which is about the same as that for the failure conditions of low cycle fatigue at higher stresses. The {theta} value increases even below the fatigue limit, but it does not increase atmore » stresses which are lower than 50% of the fatigue limit.« less

Fatigue in the Presence of Corrosion (Fatigue sous corrosion)

DTIC Science & Technology

1999-03-01

Fatigue Crack Growth Propagation of Aluminum Lithium cycle managers to safely delay repairs to a more appropriate Alloys " described the effect of... effects of service corrosion on fatigue lab tests with 2024 -T3, because 7178 life , if any, can be established in this was not available. However, we did not... life and the fatigue crack growth behavior of the cases where a structural member is the 2024 alloy was studied as well. stressed or fatigued

Studies of Cell-Mediated Immunity Against Immune Disorders Using Synthetic Peptides and Rotating Bioreactor System

NASA Technical Reports Server (NTRS)

Sastry, Jagannadha K.

1998-01-01

We conducted a series of experiments using mouse immune-precursor cells, and observed that bioreactor culturing results in the loss of antigen-specific cytotoxic T lymphocyte (CTL) function. The reason for the abrogation of CTL function is microgravity conditions in the bioreactor, but not the antigen per se or its MHC restriction. Similarly, we observed that allostimulation of human PBMC in the bioreactor, but not in the T flask, resulted in the blunting of both allo-CTL function and the NK activity, indicating that the microgravity-associated functional defects are not unique to the mouse system. These results provide further confirmation to the microgravity-associated immune dysfunction, and constitute ground-based confirmatory data for those related to space-travel.

Predictors and Trajectories of Morning Fatigue Are Distinct from Evening Fatigue

PubMed Central

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

Rituximab is Ineffective for Treatment of Fatigue in Primary Biliary Cholangitis: A phase-2 Randomised Controlled Trial.

PubMed

Khanna, Amardeep; Jopson, Laura; Howel, Denise; Bryant, Andrew; Blamire, Andrew; Newton, Julia L; Jones, David E

2018-05-23

Primary Biliary Cholangitis (PBC) is a chronic cholestatic liver disease. Half of patients experience debilitating fatigue which is currently untreatable. Previous studies have shown muscle bioenergetic abnormalities in PBC, including increased muscle acidosis with exercise linked to the anti-mitochondrial antibody (AMA) diagnostic of the disease, and reduced anaerobic threshold. In this study we addressed the hypothesis that fatigue in PBC is driven by muscle bioenergetic abnormality related to AMA, and that AMA reduction with B-cell depletion therapy will improve fatigue. In our single-centred Phase II randomised controlled trial (RCT) 57 participants aged ≥18 years with PBC and moderate or severe fatigue were randomized to receive 2 doses of either rituximab (1000mg) or saline (placebo). The primary outcome measure was fatigue severity assessed using the PBC-40 fatigue domain at 3 months. Secondary outcomes measures included patient-reported outcomes, immunological and bioenergetics disease parameters. Experimental outcomes included biochemical markers of disease severity. Improvement in fatigue score at 3 months was seen in both arms, with no significant difference (adjusted mean difference -0.9 95%CI -4.6 to 3.1). Little difference was observed in other patient reported outcomes or physical activity. Significant anaerobic threshold improvement was seen in the Rituximab group only but this was not associated with fatigue improvement. No treatment-emergent SAEs were seen. Rituximab was safe over the 12 month study period but showed no evidence of effectiveness for the treatment of fatigue in PBC. Anaerobic threshold improvement was seen; potentially linking AMA with muscle bioenergetics dysfunction, however, this was not related to improvement in fatigue. Rituximab had some evidence of a beneficial effect on alkaline phosphatase levels in this largely UDCA-responding, early disease stage cohort. This article is protected by copyright. All rights reserved. �

HIV-associated fatigue in the era of highly active antiretroviral therapy: novel biological mechanisms?

PubMed

Payne, B A I; Hateley, C L; Ong, E L C; Premchand, N; Schmid, M L; Schwab, U; Newton, J L; Price, D A

2013-04-01

The aim of the study was to determine the prevalence and risk factors for HIV-associated fatigue in the era of highly active antiretroviral therapy (HAART). A cross-sectional survey of 100 stable HIV-infected out-patients was carried out. Severity of fatigue was measured using the Fatigue Impact Scale (FIS). Symptoms of orthostatic intolerance (dysautonomia) were evaluated using the Orthostatic Grading Scale (OGS). Data for HIV-infected patients were compared with those for 166 uninfected controls and 74 patients with chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (encephalopathy) (ME). Ninety-one per cent of HIV-infected patients were on HAART and 78% had suppressed plasma HIV viral load (≤ 40 HIV-1 RNA copies/mL). Fifty-one per cent of HIV-infected patients reported excessive symptomatic fatigue (FIS ≥ 40), and 28% reported severe fatigue symptoms (FIS ≥ 80). The mean FIS score among HIV-infected patients was 50.8 [standard deviation (SD) 41.9] compared with 13.0 (SD 17.6) in uninfected control subjects, and 92.9 (SD 29.0) in CFS patients (P < 0.001 for comparison of HIV-infected patients and uninfected controls). Among HIV-infected patients, fatigue severity was not significantly associated with current or nadir CD4 lymphocyte count, HIV plasma viral load, or whether on HAART. Prior dideoxynucleoside analogue (d-drug) exposure (P = 0.016) and the presence of clinical lipodystrophy syndrome (P = 0.011) were associated with fatigue. Additionally, fatigue severity correlated strongly with symptomatic orthostatic intolerance (r = 0.65; P < 0.001). Fatigue is very common and often severe in HIV-infected out-patients, despite viral suppression and good immune function. In a subgroup of patients, prior d-drug exposure may contribute to fatigue, suggesting a metabolic basis. Dysautonomia may also drive fatigue associated with HIV infection, as in other chronic diseases, and CFS/ME, and should be further evaluated with the potential for a shared

Exertion fatigue and chronic fatigue are two distinct constructs in people post-stroke.

PubMed

Tseng, Benjamin Y; Billinger, Sandra A; Gajewski, Byron J; Kluding, Patricia M

2010-12-01

Post-stroke fatigue is a common and neglected issue despite the fact that it impacts daily functions, quality of life, and has been linked with a higher mortality rate because of its association with a sedentary lifestyle. The purpose of this study was to identify the contributing factors of exertion fatigue and chronic fatigue in people post-stroke. Twenty-one post-stroke people (12 males, 9 females; 59.5 ± 10.3 years of age; time after stroke 4.1 ± 3.5 years) participated in the study. The response variables included exertion fatigue and chronic fatigue. Participants underwent a standardized fatigue-inducing exercise on a recumbent stepper. Exertion fatigue level was assessed at rest and immediately after exercise using the Visual Analog Fatigue Scale. Chronic fatigue was measured by the Fatigue Severity Scale. The explanatory variables included aerobic fitness, motor control, and depressive symptoms measured by peak oxygen uptake, Fugl-Meyer motor score, and the Geriatric Depression Scale, respectively. Using forward stepwise regression, we found that peak oxygen uptake was an independent predictor of exertion fatigue (P = 0.006), whereas depression was an independent predictor of chronic fatigue (P = 0.002). Exertion fatigue and chronic fatigue are 2 distinct fatigue constructs, as identified by 2 different contributing factors.

The mediating role of emotional symptomatology between anticipatory fatigue and the perception of fatigue.

PubMed

Rodríguez Testal, Juan F; Fuentes Márquez, Sandra; Senín Calderón, Cristina; Carrasco, Miguel A

2016-05-01

Clinical research stresses the importance of cognitive variables for predisposition, onset, and especially, perpetuation of perceived fatigue. The aim was to analyze the mediating effects of emotional symptomatology (somatic, depressive and anxiety) between anticipatory fatigue and perception of physical and cognitive fatigue. The sample was composed of 317 participants (29% from a clinical population) aged 18 to 76. Anticipatory fatigue and perception of fatigue were measured by fatigue scales. Emotional symptoms were assessed by the General Health Questionnaire, GHQ-28.  Results : Depressive symptomatology mediated the relationship between anticipatory fatigue and cognitive fatigue in both groups, and also somatic symptoms/somatization in patients. The indirect effect of physical fatigue was observed only in the clinical group, with depressive symptoms partially mediating the anticipatory fatigue and cognitive fatigue relationship. Anticipatory fatigue has a partial indirect effect on total physical fatigue, and full indirect effect on cognitive fatigue, mediated by depressive and somatic symptoms. Anticipatory fatigue is a relevant cognitive factor in the design of psychological intervention for improvement of cognitive and physical fatigue.

Increased brain white matter axial diffusivity associated with fatigue, pain and hyperalgesia in Gulf War illness.

PubMed

Rayhan, Rakib U; Stevens, Benson W; Timbol, Christian R; Adewuyi, Oluwatoyin; Walitt, Brian; VanMeter, John W; Baraniuk, James N

2013-01-01

Gulf War exposures in 1990 and 1991 have caused 25% to 30% of deployed personnel to develop a syndrome of chronic fatigue, pain, hyperalgesia, cognitive and affective dysfunction. Gulf War veterans (n = 31) and sedentary veteran and civilian controls (n = 20) completed fMRI scans for diffusion tensor imaging. A combination of dolorimetry, subjective reports of pain and fatigue were correlated to white matter diffusivity properties to identify tracts associated with symptom constructs. Gulf War Illness subjects had significantly correlated fatigue, pain, hyperalgesia, and increased axial diffusivity in the right inferior fronto-occipital fasciculus. ROC generated thresholds and subsequent binary regression analysis predicted CMI classification based upon axial diffusivity in the right inferior fronto-occipital fasciculus. These correlates were absent for controls in dichotomous regression analysis. The right inferior fronto-occipital fasciculus may be a potential biomarker for Gulf War Illness. This tract links cortical regions involved in fatigue, pain, emotional and reward processing, and the right ventral attention network in cognition. The axonal neuropathological mechanism(s) explaining increased axial diffusivity may account for the most prominent symptoms of Gulf War Illness.

Intracellular iron overload leading to DNA damage of lymphocytes and immune dysfunction in thalassemia major patients.

PubMed

Shaw, Jyoti; Chakraborty, Ayan; Nag, Arijit; Chattopadyay, Arnab; Dasgupta, Anjan K; Bhattacharyya, Maitreyee

2017-11-01

To investigate the cause and effects of intracellular iron overload in lymphocytes of thalassemia major patients. Sixty-six thalassemia major patients having iron overload and 10 age-matched controls were chosen for the study. Blood sample was collected, and serum ferritin, oxidative stress; lymphocyte DNA damage were examined, and infective episodes were also counted. Case-control analysis revealed significant oxidative stress, iron overload, DNA damage, and rate of infections in thalassemia cases as compared to controls. For cases, oxidative stress (ROS) and iron overload (serum ferritin) showed good correlation with R 2  = 0.934 and correlation between DNA damage and ROS gave R 2  = 0.961. We also demonstrated that intracellular iron overload in thalassemia caused oxidative damage of lymphocyte DNA as exhibited by DNA damage assay. The inference is further confirmed by partial inhibition of such damage by chelation of iron and the concurrent lowering of the ROS level in the presence of chelator deferasirox. Therefore, intracellular iron overload caused DNA fragmentation, which may ultimately hamper lymphocyte function, and this may contribute to immune dysfunction and increased susceptibility to infections in thalassemia patients as indicated by the good correlation (R 2  = 0.91) between lymphocyte DNA damage and rate of infection found in this study. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Validation of Procedures for Monitoring Crewmember Immune Function SDBI-1900, SMO-015 - Integrated Immune

NASA Technical Reports Server (NTRS)

Crucian, Brian; Stowe, Raymond; Mehta, Satish; Uchakin, Peter; Nehlsen-Cannarella, Sandra; Morukov, Boris; Pierson, Duane; Sams, Clarence

2007-01-01

There is ample evidence to suggest that space flight leads to immune system dysregulation. This may be a result of microgravity, confinement, physiological stress, radiation, environment or other mission-associated factors. The clinical risk from prolonged immune dysregulation during space flight are not yet determined, but may include increased incidence of infection, allergy, hypersensitivity, hematological malignancy or altered wound healing. Each of the clinical events resulting from immune dysfunction has the potential to impact mission critical objectives during exploration-class missions. To date, precious little in-flight immune data has been generated to assess this phenomenon. The majority of recent flight immune studies have been post-flight assessments, which may not accurately reflect the in-flight condition. There are no procedures currently in place to monitor immune function or its effect on crew health. The objective of this Supplemental Medical Objective (SMO) is to develop and validate an immune monitoring strategy consistent with operational flight requirements and constraints. This SMO will assess the clinical risks resulting from the adverse effects of space flight on the human immune system and will validate a flight-compatible immune monitoring strategy. Characterization of the clinical risk and the development of a monitoring strategy are necessary prerequisite activities prior to validating countermeasures. This study will determine, to the best level allowed by current technology, the in-flight status of crewmembers immune system. Pre-flight, in-flight and post-flight assessments of immune status, immune function, viral reactivation and physiological stress will be performed. The in-flight samples will allow a distinction between legitimate in-flight alterations and the physiological stresses of landing and readaptation which are believed to alter landing day assessments. The overall status of the immune system during flight (activation

Integrated Immunomodulatory Mechanisms through which Long-Chain n-3 Polyunsaturated Fatty Acids Attenuate Obese Adipose Tissue Dysfunction

PubMed Central

Liddle, Danyelle M.; Wellings, Hannah R.; Power, Krista A.; Robinson, Lindsay E.; Monk, Jennifer M.

2017-01-01

Obesity is a global health concern with rising prevalence that increases the risk of developing other chronic diseases. A causal link connecting overnutrition, the development of obesity and obesity-associated co-morbidities is visceral adipose tissue (AT) dysfunction, characterized by changes in the cellularity of various immune cell populations, altered production of inflammatory adipokines that sustain a chronic state of low-grade inflammation and, ultimately, dysregulated AT metabolic function. Therefore, dietary intervention strategies aimed to halt the progression of obese AT dysfunction through any of the aforementioned processes represent an important active area of research. In this connection, fish oil-derived dietary long-chain n-3 polyunsaturated fatty acids (PUFA) in the form of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been demonstrated to attenuate obese AT dysfunction through multiple mechanisms, ultimately affecting AT immune cellularity and function, adipokine production, and metabolic signaling pathways, all of which will be discussed herein. PMID:29186929

X-Linked Syndrome of Polyendocrinopathy, Immune Dysfunction, and Diarrhea Maps to Xp11.23-Xq13.3

PubMed Central

Bennett, Craig L.; Yoshioka, Ritsuko; Kiyosawa, Hidenori; Barker, David F.; Fain, Pamela R.; Shigeoka, Ann O.; Chance, Phillip F.

2000-01-01

Summary We describe genetic analysis of a large pedigree with an X-linked syndrome of polyendocrinopathy, immune dysfunction, and diarrhea (XPID), which frequently results in death during infancy or childhood. Linkage analysis mapped the XPID gene to a 17-cM interval defined by markers DXS8083 and DXS8107 on the X chromosome, at Xp11.23-Xq13.3. The maximum LOD score was 3.99 (recombination fraction0) at DXS1235. Because this interval also harbors the gene for Wiskott-Aldrich syndrome (WAS), we investigated mutations in the WASP gene, as the molecular basis of XPID. Northern blot analysis detected the same relative amount and the same-sized WASP message in patients with XPID and in a control. Analysis of the WASP coding sequence, an alternate promoter, and an untranslated upstream first exon was carried out, and no mutations were found in patients with XPID. A C→T transition within the alternate translation start site cosegregated with the XPID phenotype in this family; however, the same transition site was detected in a normal control male. We conclude that XPID maps to Xp11.23-Xq13.3 and that mutations of WASP are not associated with XPID. PMID:10677306

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

PubMed

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.

PubMed

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.

Fatigue - Multiple Languages

MedlinePlus

... a new window. Arabic (العربية) Expand Section Fatigue - English PDF Fatigue - العربية (Arabic) PDF American Cancer Society ... Chinese, Traditional (Cantonese dialect) (繁體中文) Expand Section Fatigue - English PDF Fatigue - 繁體中文 (Chinese, Traditional (Cantonese dialect)) PDF ...

Exercise therapy for fatigue in multiple sclerosis.

PubMed

Heine, Martin; van de Port, Ingrid; Rietberg, Marc B; van Wegen, Erwin E H; Kwakkel, Gert

2015-09-11

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system affecting an estimated 1.3 million people worldwide. It is characterised by a variety of disabling symptoms of which excessive fatigue is the most frequent. Fatigue is often reported as the most invalidating symptom in people with MS. Various mechanisms directly and indirectly related to the disease and physical inactivity have been proposed to contribute to the degree of fatigue. Exercise therapy can induce physiological and psychological changes that may counter these mechanisms and reduce fatigue in MS. To determine the effectiveness and safety of exercise therapy compared to a no-exercise control condition or another intervention on fatigue, measured with self-reported questionnaires, of people with MS. We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Trials Specialised Register, which, among other sources, contains trials from: the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 10), MEDLINE (from 1966 to October 2014), EMBASE (from 1974 to October 2014), CINAHL (from 1981 to October 2014), LILACS (from 1982 to October 2014), PEDro (from 1999 to October 2014), and Clinical trials registries (October 2014). Two review authors independently screened the reference lists of identified trials and related reviews. We included randomized controlled trials (RCTs) evaluating the efficacy of exercise therapy compared to no exercise therapy or other interventions for adults with MS that included subjective fatigue as an outcome. In these trials, fatigue should have been measured using questionnaires that primarily assessed fatigue or sub-scales of questionnaires that measured fatigue or sub-scales of questionnaires not primarily designed for the assessment of fatigue but explicitly used as such. Two review authors independently selected the articles, extracted data, and determined methodological quality of the included

Local activation of p53 in the tumor microenvironment overcomes immune suppression and enhances antitumor immunity

PubMed Central

Guo, Gang; Yu, Miao; Xiao, Wei; Celis, Esteban; Cui, Yan

2017-01-01

Mutations in tumor suppressor p53 remain a vital mechanism of tumor escape from apoptosis and senescence. Emerging evidence suggests that p53 dysfunction also fuels inflammation and supports tumor immune evasion, thereby serving as an immunological driver of tumorigenesis. Therefore, targeting p53 in the tumor microenvironment (TME) also represents an immunologically desirable strategy for reversing immunosuppression and enhancing antitumor immunity. Using a pharmacological p53 activator nutlin-3a, we show that local p53 activation in TME comprising overt tumor infiltrating leukocytes (TILeus) induces systemic antitumor immunity and tumor regression, but not in TME with scarce TILeus, such as B16 melanoma. Maneuvers that recruit leukocytes to TME, such as TLR3 ligand in B16 tumors, greatly enhanced nutlin-induced antitumor immunity and tumor control. Mechanistically, nutlin-3a-induced antitumor immunity was contingent on two non-redundant but immunologically synergistic p53-dependent processes: reversal of immunosuppression in TME and induction of tumor immunogenic cell death (ICD), leading to activation and expansion of polyfunctional CD8 CTLs and tumor regression. Our study demonstrates that unlike conventional tumoricidal therapies, which rely on effective p53 targeting in each tumor cell and often associate with systemic toxicity, this immune-based strategy requires only limited local p53 activation to alter the immune landscape of TME and subsequently amplify immune response to systemic antitumor immunity. Hence, targeting the p53 pathway in TME can be exploited to reverse immunosuppression and augment therapeutic benefits beyond tumoricidal effects to harness tumor-specific, durable, and systemic antitumor immunity with minimal toxicity. PMID:28280037

Central nervous system abnormalities in fibromyalgia and chronic fatigue syndrome: new concepts in treatment.

PubMed

Gur, Ali; Oktayoglu, Pelin

2008-01-01

Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are poorly understood disorders that share similar demographic and clinical characteristics. The etiology and pathophysiology of these diseases remain unclear. Because of the similarities between both disorders it was suggested that they share a common pathophysiological mechanisms, namely, central nervous system (CNS) dysfunction. Current hypotheses center on atypical sensory processing in the CNS and dysfunction of skeletal muscle nociception and the hypothalamic-pituitary-adrenal (HPA) axis. Researches suggest that the (CNS) is primarily involved in both disorders in regard to the pain, fatigue and sleep disturbances. Many patients experience difficulty with concentration and memory and many others have mood disturbance, including depression and anxiety. Although fibromyalgia is common and associated with substantial morbidity and disability, there are no US Food and Drug Administration (FDA)-approved treatments except pregabalin. Recent pharmacological treatment studies about fibromyalgia have focused on selective serotonin and norepinephrine (NE) reuptake inhibitors, which enhance serotonin and NE neurotransmission in the descending pain pathways and lack many of the adverse side effects associated with tricyclic medications. CFS is a descriptive term used to define a recognisable pattern of symptoms that cannot be attributed to any alternative condition. The symptoms are currently believed to be the result of disturbed brain function. To date, no pharmacological agent has been reliably shown to be effective treatment for CFS. Management strategies are therefore primarily directed at relief of symptoms and minimising impediments to recovery. This chapter presents data demonstrating CFS, abnormal pain processing and autonomic nervous system (ANS) dysfunction in FM and CFS and concludes by reviewing the new concepts in treatments in CFS and FM.

Endocrine dysfunction in sepsis: a beneficial or deleterious host response?

PubMed Central

Gheorghiţă, Valeriu; Barbu, Alina Elena; Gheorghiu, Monica Livia; Căruntu, Florin Alexandru

2015-01-01

Sepsis is a systemic, deleterious inflammatory host response triggered by an infective agent leading to severe sepsis, septic shock and multi-organ failure. The host response to infection involves a complex, organized and coherent interaction between immune, autonomic, neuroendocrine and behavioral systems. Recent data have confirmed that disturbances of the autonomic nervous and neuroendocrine systems could contribute to sepsis-induced organ dysfunction. Through this review, we aimed to summarize the current knowledge about the endocrine dysfunction as response to sepsis, specifically addressed to vasopressin, copeptin, cortisol, insulin and leptin. We searched the following readily accessible, clinically relevant databases: PubMed, UpToDate, BioMed Central. The immune system could be regarded as a “diffuse sensory organ” that signals the presence of pathogens to the brain through different pathways, such as the vagus nerve, endothelial activation/dysfunction, cytokines and neurotoxic mediators and the circumventricular organs, especially the neurohypophysis. The hormonal profile changes substantially as a consequence of inflammatory mediators and microorganism products leading to inappropriately low levels of vasopressin, sick euthyroid syndrome, reduced adrenal responsiveness to ACTH, insulin resistance, hyperglycemia as well as hyperleptinemia. In conclusion, clinical diagnosis of this “pan-endocrine illness” is frequently challenging due to the many limiting factors. The most important benefits of endocrine markers in the management of sepsis may be reflected by their potential to be used as biomarkers in different scoring systems to estimate the severity of the disease and the risk of death. PMID:25763364

Pathogenic Correlates of Simian Immunodeficiency Virus-Associated B Cell Dysfunction.

PubMed

Brocca-Cofano, Egidio; Kuhrt, David; Siewe, Basile; Xu, Cuiling; Haret-Richter, George S; Craigo, Jodi; Labranche, Celia; Montefiori, David C; Landay, Alan; Apetrei, Cristian; Pandrea, Ivona

2017-12-01

We compared and contrasted pathogenic (in pig-tailed macaques [PTMs]) and nonpathogenic (in African green monkeys [AGMs]) SIVsab infections to assess the significance of the B cell dysfunction observed in simian (SIV) and human immunodeficiency virus (HIV) infections. We report that the loss of B cells is specifically associated with the pathogenic SIV infection, while in the natural hosts, in which SIV is nonpathogenic, B cells rapidly increase in both lymph nodes (LNs) and intestine. SIV-associated B cell dysfunction associated with the pathogenic SIV infection is characterized by loss of naive B cells, loss of resting memory B cells due to their redistribution to the gut, increases of the activated B cells and circulating tissue-like memory B cells, and expansion of the B regulatory cells (Bregs). While circulating B cells are virtually restored to preinfection levels during the chronic pathogenic SIV infection, restoration is mainly due to an expansion of the "exhausted," virus-specific B cells, i.e., activated memory cells and tissue-like memory B cells. Despite of the B cell dysfunction, SIV-specific antibody (Ab) production was higher in the PTMs than in AGMs, with the caveat that rapid disease progression in PTMs was strongly associated with lack of anti-SIV Ab. Neutralization titers and the avidity and maturation of immune responses did not differ between pathogenic and nonpathogenic infections, with the exception of the conformational epitope recognition, which evolved from low to high conformations in the natural host. The patterns of humoral immune responses in the natural host are therefore more similar to those observed in HIV-infected subjects, suggesting that natural hosts may be more appropriate for modeling the immunization strategies aimed at preventing HIV disease progression. The numerous differences between the pathogenic and nonpathogenic infections with regard to dynamics of the memory B cell subsets point to their role in the pathogenesis

Gastric motor dysfunctions in Parkinson's disease: Current pre-clinical evidence.

PubMed

Pellegrini, Carolina; Antonioli, Luca; Colucci, Rocchina; Ballabeni, Vigilio; Barocelli, Elisabetta; Bernardini, Nunzia; Blandizzi, Corrado; Fornai, Matteo

2015-12-01

Parkinson's disease (PD) is associated with several non-motor symptoms, such as behavioral changes, urinary dysfunction, sleep disorders, fatigue and, above all, gastrointestinal (GI) dysfunction, including gastric dysmotility, constipation and anorectal dysfunction. Delayed gastric emptying, progressing to gastroparesis, is reported in up to 100% of patients with PD, and it occurs at all stages of the disease with severe consequences to the patient's quality of life. The presence of α-synuclein (α-syn) aggregates in myenteric neurons throughout the digestive tract, as well as morpho-functional alterations of the enteric nervous system (ENS), have been documented in PD. In particular, gastric dysmotility in PD has been associated with an impairment of the brain-gut axis, involving the efferent fibers of the vagal pathway projecting directly to the gastric myenteric plexus. The present review intends to provide an integrated overview of available knowledge on the possible role played by the ENS, considered as a semi-autonomous nervous network, in the pathophysiology of gastric dysmotility in PD. Particular attention has been paid review how translational evidence in humans and studies in pre-clinical models are allowing a better understanding of the functional, neurochemical and molecular alterations likely underlying gastric motor abnormalities occurring in PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Crosstalk between cancer and the neuro-immune system.

PubMed

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.

PubMed

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.

The Representation of Inflammatory Signals in the Brain – A Model for Subjective Fatigue in Multiple Sclerosis

PubMed Central

Hanken, Katrin; Eling, Paul; Hildebrandt, Helmut

2014-01-01

In multiple sclerosis (MS) patients, fatigue is rated as one of the most common and disabling symptoms. However, the pathophysiology underlying this fatigue is not yet clear. Several lines of evidence suggest that immunological factors, such as elevated levels of pro-inflammatory cytokines, may contribute to subjective fatigue in MS patients. Pro-inflammatory cytokines represent primary mediators of immune-to-brain-communication, modulating changes in the neurophysiology of the central nervous system. Recently, we proposed a model arguing that fatigue in MS patients is a subjective feeling, which is related to inflammation. Moreover, it implies that fatigue can be measured behaviorally only by applying specific cognitive tasks related to alertness and vigilance. In the present review, we focus on the subjective feeling of MS-related fatigue. We examine the hypothesis that the subjective feeling of MS-related fatigue may be a variant of inflammation-induced sickness behavior, resulting from cytokine-mediated activity changes within brain areas involved in interoception and homeostasis including the insula, the anterior cingulate, and the hypothalamus. We first present studies demonstrating a relationship between pro-inflammatory cytokines and subjective fatigue in healthy individuals, in people with inflammatory disorders, and particularly in MS patients. Subsequently, we discuss studies analyzing the impact of anti-inflammatory treatment on fatigue. In the next part of this review, we present studies on the transmission and neural representation of inflammatory signals, with a special focus on possible neural concomitants of inflammation-induced fatigue. We also present two of our studies on the relationship between local gray and white matter atrophy and fatigue in MS patients. Finally, we discuss some implications of our findings and future perspectives. PMID:25566171

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

PubMed Central

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.

PubMed

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.

Role of Microglia Disturbances and Immune-Related Marker Abnormalities in Cortical Circuitry Dysfunction in Schizophrenia

PubMed Central

Volk, David W.

2017-01-01

Studies of genetics, serum cytokines, and autoimmune illnesses suggest that immune-related abnormalities are involved in the disease process of schizophrenia. Furthermore, direct evidence of cortical immune activation, including markedly elevated levels of many immune-related markers, have been reported in the prefrontal cortex in multiple cohorts of schizophrenia subjects. Within the prefrontal cortex in schizophrenia, deficits in the basilar dendritic spines of layer 3 pyramidal neurons and disturbances in inhibitory inputs to pyramidal neurons have also been commonly reported. Interestingly, microglia, the resident immune-related cells of the brain, also regulate excitatory and inhibitory input to pyramidal neurons. Consequently, in this review, we describe the cytological and molecular evidence of immune activation that has been reported in the brains of individuals with schizophrenia and the potential links between these immune-related disturbances with previously reported disturbances in pyramidal and inhibitory neurons in the disorder. Finally, we discuss the role that activated microglia may play in connecting these observations and as potential therapeutic treatment targets in schizophrenia. PMID:28007586

The Immune System and Developmental Programming of Brain and Behavior

PubMed Central

Bilbo, Staci D.; Schwarz, Jaclyn M.

2012-01-01

The brain, endocrine, and immune systems are inextricably linked. Immune molecules have a powerful impact on neuroendocrine function, including hormone-behavior interactions, during health as well as sickness. Similarly, alterations in hormones, such as during stress, can powerfully impact immune function or reactivity. These functional shifts are evolved, adaptive responses that organize changes in behavior and mobilize immune resources, but can also lead to pathology or exacerbate disease if prolonged or exaggerated. The developing brain in particular is exquisitely sensitive to both endogenous and exogenous signals, and increasing evidence suggests the immune system has a critical role in brain development and associated behavioral outcomes for the life of the individual. Indeed, there are associations between many neuropsychiatric disorders and immune dysfunction, with a distinct etiology in neurodevelopment. The goal of this review is to describe the important role of the immune system during brain development, and to discuss some of the many ways in which immune activation during early brain development can affect the later-life outcomes of neural function, immune function, mood and cognition. PMID:22982535

Side Effects: Fatigue

Cancer.gov

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.

Myoelectrical Manifestation of Fatigue Less Prominent in Patients with Cancer Related Fatigue

PubMed Central

Kisiel-Sajewicz, Katarzyna; Siemionow, Vlodek; Seyidova-Khoshknabi, Dilara; Davis, Mellar P.; Wyant, Alexandria; Ranganathan, Vinoth K.; Walsh, Declan; Yan, Jin H.; Hou, Juliet; Yue, Guang H.

2013-01-01

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. PMID:24391800

[Immunopathogenesis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)].

PubMed

Yamamura, Takashi; Ono, Hirohiko; Sato, Wakiro

2018-01-01

A recent study on the pathogenesis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has revealed an elevation of inflammatory and anti-inflammatory cytokines in the sera and cerebrospinal fluids of the patients and presence of autoantibodies in subgroups of ME/CFS patients. Furthermore, investigator-initiated clinical trials have proved the efficacy of anti-CD20 antibody (rituximab), that eliminate B cells, in the treatment of ME/CFS. Based on these findings, we hypothesize that immune abnormalities, such as enhanced autoimmune responses, may play an essential role in the neuroinflammatory pathogenesis of ME/CFS.

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

PubMed Central

Fife, Terry D.; Robb, Michael J. A.; Steenerson, Kristen K.; Saha, Kamala C.

2018-01-01

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. PMID:29867750

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

PubMed

Fife, Terry D; Robb, Michael J A; Steenerson, Kristen K; Saha, Kamala C

2018-01-01

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.

Cardiorespiratory and neuromuscular deconditioning in fatigued and non-fatigued breast cancer survivors.

PubMed

Neil, Sarah E; Klika, Riggs J; Garland, S Jayne; McKenzie, Donald C; Campbell, Kristin L

2013-03-01

Fatigue is one of the most commonly reported side effects during treatment for breast cancer and can persist following treatment completion. Cancer-related fatigue after treatment is multifactorial in nature, and one hypothesized mechanism is cardiorespiratory and neuromuscular deconditioning. The purpose of this study was to compare cardiorespiratory and neuromuscular function in breast cancer survivors who had completed treatment and met the specified criteria for cancer-related fatigue and a control group of breast cancer survivors without fatigue. Participants in the fatigue (n = 16) and control group (n = 11) performed a maximal exercise test on a cycle ergometer for determination of peak power, power at lactate threshold, and VO(2) peak. Neuromuscular fatigue was induced with a sustained submaximal contraction of the right quadriceps. Central fatigue (failure of voluntary activation) was evaluated using twitch interpolation, and peripheral fatigue was measured with an electrically evoked twitch. Power at lactate threshold was lower in the fatigue group (p = 0.05). There were no differences between groups for power at lactate threshold as percentage of peak power (p = 0.10) or absolute or relative VO(2) peak (p = 0.08 and 0.33, respectively). When adjusted for age, the fatigue group had a lower power at lactate threshold (p = 0.02) and absolute VO(2) peak (p = 0.03). There were no differences between groups in change in any neuromuscular parameters after the muscle-fatiguing protocol. Findings support the hypothesis that cardiorespiratory deconditioning may play a role in the development and persistence of cancer-related fatigue following treatment. Future research into the use of exercise training to reduce cardiorespiratory deconditioning as a treatment for cancer-related fatigue is warranted to confirm these preliminary findings.

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

PubMed

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

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

NASA Astrophysics Data System (ADS)

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

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

PubMed

Brenu, Ekua W; van Driel, Mieke L; Staines, Don R; Ashton, Kevin J; Ramos, Sandra B; Keane, James; Klimas, Nancy G; Marshall-Gradisnik, Sonya M

2011-05-28

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. 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 (CD56(bright) and CD56(dim)) and regulatory T cells expressing FoxP3 transcription factor. 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 CD56(bright) 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. Our study found immunological abnormalities which may serve as biomarkers in CFS/ME patients with potential for an application as a diagnostic tool.

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

PubMed Central

2011-01-01

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. PMID:21619669

Reduced Electromyographic Fatigue Threshold after Performing a Cognitive Fatiguing Task.

PubMed

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.

PubMed

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

Prevalence and Predictors of Thyroid Dysfunction in Patients with HIV Infection and Acquired Immunodeficiency Syndrome: An Indian Perspective.

PubMed

Sharma, Neera; Sharma, Lokesh Kumar; Dutta, Deep; Gadpayle, Adesh Kisanji; Anand, Atul; Gaurav, Kumar; Mukherjee, Sabyasachi; Bansal, Rahul

2015-01-01

Background. Predictors of thyroid dysfunction in HIV are not well determined. This study aimed to determine the prevalence and predictors of thyroid dysfunction in HIV infected Indians. Methods. Consecutive HIV patients, 18-70 years of age, without any severe comorbid state, having at least 1-year follow-up at the antiretroviral therapy clinic, underwent clinical assessment and hormone assays. Results. From initially screened 527 patients, 359 patients (61.44 ± 39.42 months' disease duration), having good immune function [CD4 count >200 cell/mm(3): 90.25%; highly active antiretroviral therapy (HAART): 88.58%], were analyzed. Subclinical hypothyroidism (ScH) was the commonest thyroid dysfunction (14.76%) followed by sick euthyroid syndrome (SES) (5.29%) and isolated low TSH (3.1%). Anti-TPO antibody (TPOAb) was positive in 3.90%. Baseline CD4 count had inverse correlation with TPOAb after adjusting for age and body mass index. Stepwise linear regression revealed baseline CD4 count, TPOAb, and tuberculosis to be best predictors of ScH after adjusting for age, weight, duration of HIV, and history of opportunistic fungal and viral infections. Conclusion. Burden of thyroid dysfunction in chronic HIV infection with stable immune function is lower compared to pre-HAART era. Thyroid dysfunction is primarily of nonautoimmune origin, predominantly ScH. Severe immunodeficiency at disease onset, TPOAb positivity, and tuberculosis were best predictors of ScH.

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

PubMed

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.

Evaluating Fatigue in Operational Settings: The NASA Ames Fatigue Countermeasures Program

NASA Technical Reports Server (NTRS)

Rosekind, Mark R.; Gregory, Kevin; Miller, Donna; Webbon, Lissa; Oyung, Ray

1996-01-01

In response to a 1980 Congressional request, NASA Ames initiated a program to examine fatigue in flight operations. The Program objectives are to examine fatigue, sleep loss, and circadian disruption in flight operations, determine the effects of these factors on flight crew performance, and the development of fatigue countermeasures. The NASA Ames Fatigue Countermeasures Program conducts controlled laboratory experiments, full-mission flight simulations, and field studies. A range of subjective, behavioral, performance, physiological, and environmental measures are used depending on study objectives. The Program has developed substantial expertise in gathering data during actual flight operations and in other work settings. This has required the development of ambulatory and other measures that can be carried throughout the world and used at 41,000 feet in aircraft cockpits. The NASA Ames Fatigue Countermeasures Program has examined fatigue in shorthaul, longhaul, overnight cargo, and helicopter operations. A recent study of planned cockpit rest periods demonstrated the effectiveness of a brief inflight nap to improve pilot performance and alertness. This study involved inflight reaction time/vigilance performance testing and EEG/EOG measures of physiological alertness. The NASA Ames Fatigue Countermeasures Program has applied scientific findings to the development of education and training materials on fatigue countermeasures, input to federal regulatory activities on pilot flight, duty, and rest requirements, and support of National Transportation Safety Board accident investigations. Current activities are examining fatigue in nonaugmented longhaul flights, regional/commuter flight operations, corporate/business aviation, and psychophysiological variables related to performance.

Consolidation of fatigue and fatigue-crack-propagation data for design use

NASA Technical Reports Server (NTRS)

Rice, R. C.; Davies, K. B.; Jaske, C. E.; Feddersen, C. E.

1975-01-01

Analytical methods developed for consolidation of fatigue and fatigue-crack-propagation data for use in design of metallic aerospace structural components are evaluated. A comprehensive file of data on 2024 and 7075 aluminums, Ti-6Al-4V alloy, and 300M steel was established by obtaining information from both published literature and reports furnished by aerospace companies. Analyses are restricted to information obtained from constant-amplitude load or strain cycling of specimens in air at room temperature. Both fatigue and fatigue-crack-propagation data are analyzed on a statistical basis using a least-squares regression approach. For fatigue, an equivalent strain parameter is used to account for mean stress or stress ratio effects and is treated as the independent variable; cyclic fatigue life is considered to be the dependent variable. An effective stress-intensity factor is used to account for the effect of load ratio on fatigue-crack-propagation and treated as the independent variable. In this latter case, crack-growth rate is considered to be the dependent variable. A two term power function is used to relate equivalent strain to fatigue life, and an arc-hyperbolic-tangent function is used to relate effective stress intensity to crack-growth rate.

Immune system gene dysregulation in autism and schizophrenia.

PubMed

Michel, Maximilian; Schmidt, Martin J; Mirnics, Karoly

2012-10-01

Gene*environment interactions play critical roles in the emergence of autism and schizophrenia pathophysiology. In both disorders, recent genetic association studies have provided evidence for disease-linked variation in immune system genes and postmortem gene expression studies have shown extensive chronic immune abnormalities in brains of diseased subjects. Furthermore, peripheral biomarker studies revealed that both innate and adaptive immune systems are dysregulated. In both disorders symptoms of the disease correlate with the immune system dysfunction; yet, in autism this process appears to be chronic and sustained, while in schizophrenia it is exacerbated during acute episodes. Furthermore, since immune abnormalities endure into adulthood and anti-inflammatory agents appear to be beneficial, it is likely that these immune changes actively contribute to disease symptoms. Modeling these changes in animals provided further evidence that prenatal maternal immune activation alters neurodevelopment and leads to behavioral changes that are relevant for autism and schizophrenia. The converging evidence strongly argues that neurodevelopmental immune insults and genetic background critically interact and result in increased risk for either autism or schizophrenia. Further research in these areas may improve prenatal health screening in genetically at-risk families and may also lead to new preventive and/or therapeutic strategies. Copyright © 2012 Wiley Periodicals, Inc.

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

PubMed

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

PubMed Central

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

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

PubMed

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.

Low-cycle thermal fatigue

NASA Technical Reports Server (NTRS)

Halford, G. R.

1986-01-01

A state-of-the-art review is presented of the field of thermal fatigue. Following a brief historical review, the concept is developed that thermal fatigue can be viewed as processes of unbalanced deformation and cracking. The unbalances refer to dissimilar mechanisms occurring in opposing halves of thermal fatigue loading and unloading cycles. Extensive data summaries are presented and results are interpreted in terms of the unbalanced processes involved. Both crack initiation and crack propagation results are summarized. Testing techniques are reviewed, and considerable discussion is given to a technique for thermal fatigue simulation, known as the bithermal fatigue test. Attention is given to the use of isothermal life prediction methods for the prediction of thermal fatigue lives. Shortcomings of isothermally-based life prediction methods are pointed out. Several examples of analyses and thermal fatigue life predictions of high technology structural components are presented. Finally, numerous dos and don'ts relative to design against thermal fatigue are presented.

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

PubMed

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.

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

PubMed

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 < 0.001). Quantitative sensory testing demonstrated heat and mechanical hyperalgesia in CFS subjects. Our findings provide indirect evidence for significant contributions of peripheral tissues to the increased exercise-related 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.

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

PubMed

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 < 0.05). The change was statistically significant when compared to the control group (p < 0.05). Qigong exercise may be used as an alternative and complementary therapy or rehabilitative program for chronic fatigue and chronic fatigue syndrome.

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

PubMed Central

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

Regulatory immune cells in regulation of intestinal inflammatory response to microbiota.

PubMed

Sun, M; He, C; Cong, Y; Liu, Z

2015-09-01

The intestinal lumen harbors nearly 100 trillion commensal bacteria that exert crucial function for health. An elaborate balance between immune responses and tolerance to intestinal microbiota is required to maintain intestinal homeostasis. This process depends on diverse regulatory mechanisms, including both innate and adaptive immunity. Dysregulation of the homeostasis between intestinal immune systems and microbiota has been shown to be associated with the development of inflammatory bowel diseases (IBD) in genetically susceptible populations. In this review, we discuss the recent progress reported in studies of distinct types of regulatory immune cells in the gut, including intestinal intraepithelial lymphocytes, Foxp3(+) regulatory T cells, regulatory B cells, alternatively activated macrophages, dendritic cells, and innate lymphoid cells, and how dysfunction of this immune regulatory system contributes to intestinal diseases such as IBD. Moreover, we discuss the manipulation of these regulatory immune cells as a potential therapeutic method for management of intestinal inflammatory disorders.

HLA Immune Function Genes in Autism

PubMed Central

Torres, Anthony R.; Westover, Jonna B.; Rosenspire, Allen J.

2012-01-01

The human leukocyte antigen (HLA) genes on chromosome 6 are instrumental in many innate and adaptive immune responses. The HLA genes/haplotypes can also be involved in immune dysfunction and autoimmune diseases. It is now becoming apparent that many of the non-antigen-presenting HLA genes make significant contributions to autoimmune diseases. Interestingly, it has been reported that autism subjects often have associations with HLA genes/haplotypes, suggesting an underlying dysregulation of the immune system mediated by HLA genes. Genetic studies have only succeeded in identifying autism-causing genes in a small number of subjects suggesting that the genome has not been adequately interrogated. Close examination of the HLA region in autism has been relatively ignored, largely due to extraordinary genetic complexity. It is our proposition that genetic polymorphisms in the HLA region, especially in the non-antigen-presenting regions, may be important in the etiology of autism in certain subjects. PMID:22928105

Aging and Immune Function: Molecular Mechanisms to Interventions

PubMed Central

Ponnappan, Subramaniam

2011-01-01

Abstract The immune system of an organism is an essential component of the defense mechanism aimed at combating pathogenic stress. Age-associated immune dysfunction, also dubbed “immune senescence,” manifests as increased susceptibility to infections, increased onset and progression of autoimmune diseases, and onset of neoplasia. Over the years, extensive research has generated consensus in terms of the phenotypic and functional defects within the immune system in various organisms, including humans. Indeed, age-associated alterations such as thymic involution, T cell repertoire skewing, decreased ability to activate naïve T cells and to generate robust memory responses, have been shown to have a causative role in immune decline. Further, understanding the molecular mechanisms underlying the generation of proteotoxic stress, DNA damage response, modulation of ubiquitin proteasome pathway, and regulation of transcription factor NFκB activation, in immune decline, have paved the way to delineating signaling pathways that cross-talk and impact immune senescence. Given the role of the immune system in combating infections, its effectiveness with age may well be a marker of health and a predictor of longevity. It is therefore believed that a better understanding of the mechanisms underlying immune senescence will lead to an effective interventional strategy aimed at improving the health span of individuals. Antioxid. Redox Signal. 14, 1551–1585. PMID:20812785

The emerging role of autoimmunity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/cfs).

PubMed

Morris, Gerwyn; Berk, Michael; Galecki, Piotr; Maes, Michael

2014-04-01

The World Health Organization classifies myalgic encephalomyelitis/chronic fatigue syndrome (ME/cfs) as a nervous system disease. Together with other diseases under the G93 heading, ME/cfs shares a triad of abnormalities involving elevated oxidative and nitrosative stress (O&NS), activation of immuno-inflammatory pathways, and mitochondrial dysfunctions with depleted levels of adenosine triphosphate (ATP) synthesis. There is also abundant evidence that many patients with ME/cfs (up to around 60 %) may suffer from autoimmune responses. A wide range of reported abnormalities in ME/cfs are highly pertinent to the generation of autoimmunity. Here we review the potential sources of autoimmunity which are observed in people with ME/cfs. The increased levels of pro-inflammatory cytokines, e.g., interleukin-1 and tumor necrosis factor-α, and increased levels of nuclear factor-κB predispose to an autoimmune environment. Many cytokine abnormalities conspire to produce a predominance of effector B cells and autoreactive T cells. The common observation of reduced natural killer cell function in ME/cfs is a source of disrupted homeostasis and prolonged effector T cell survival. B cells may be pathogenic by playing a role in autoimmunity independent of their ability to produce antibodies. The chronic or recurrent viral infections seen in many patients with ME/cfs can induce autoimmunity by mechanisms involving molecular mimicry and bystander activation. Increased bacterial translocation, as observed in ME/cfs, is known to induce chronic inflammation and autoimmunity. Low ATP production and mitochondrial dysfunction is a source of autoimmunity by inhibiting apoptosis and stimulating necrotic cell death. Self-epitopes may be damaged by exposure to prolonged O&NS, altering their immunogenic profile and become a target for the host's immune system. Nitric oxide may induce many faces of autoimmunity stemming from elevated mitochondrial membrane hyperpolarization and blockade of the

Innate immune reconstitution with suppression of HIV-1.

PubMed

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.

Innate immune reconstitution with suppression of HIV-1

PubMed Central

Scully, Eileen P.; Garcia-Beltran, Wilfredo; Palmer, Christine D.; Musante, Chelsey; Rosenberg, Eric; Allen, Todd M.; Bosch, Ronald J.

2016-01-01

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. PMID:27158667

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

PubMed

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.

Fatigue-Arrestor Bolts

NASA Technical Reports Server (NTRS)

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.

Modafinil treatment for fatigue in HIV/AIDS: a randomized placebo-controlled study.

PubMed

Rabkin, Judith G; McElhiney, Martin C; Rabkin, Richard; McGrath, Patrick J

2010-06-01

To evaluate the efficacy and safety of modafinil in the treatment of fatigue in patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and to assess effect on depressive symptoms. Patients who were HIV+ and had clinically significant fatigue (according to the Fatigue Severity Scale [FSS]) were included in a 4-week randomized, placebo-controlled, double-blind trial. This was followed by an additional 8 weeks of open-label treatment for modafinil responders and 12 weeks for placebo nonresponders. The primary outcome measure for fatigue and depression was the Clinical Global Impressions-Improvement scale, supplemented by the FSS, Hamilton Depression Rating Scale, and Beck Depression Inventory. Safety was assessed with assays of CD4 cell count and HIV ribonucleic acid (RNA) viral load. Visits were weekly for 4 weeks, then biweekly, with a follow-up visit at 6 months. Maximum trial dose of modafinil was 200 mg/d. Data for this study were collected between December 2004 and December 2008. 115 patients were randomly assigned. In intention-to-treat analyses, fatigue response rate to modafinil was 73% and to placebo, 28%. Attrition was 9%. Modafinil did not have an effect on mood alone in the absence of improved energy. At week 4, CD4 cell counts did not change significantly; HIV RNA viral load showed a trend decline for patients taking modafinil but not for those taking placebo. At 6 months, those still taking modafinil had more energy and fewer depressive symptoms than patients who were not taking modafinil, and only those still taking modafinil showed a significant decline from baseline in their HIV RNA viral load. Modafinil appears to be effective and well tolerated in treating fatigue in HIV+ patients. Consideration of its use is warranted considering the high prevalence of fatigue in the HIV community, its minimal side effects, and overall patient acceptance. clinicaltrials.gov Identifier: NCT00118378. 2010 Physicians Postgraduate

Fatigue With Systolic Heart Failure

PubMed Central

Fink, Anne M.; Sullivan, Shawna L.; Zerwic, Julie J.; Piano, Mariann R.

2010-01-01

Background and Research Objective Fatigue is one of the most prevalent symptoms in persons with systolic heart failure (HF). There remains insufficient information about the physiological and psychosocial underpinnings of fatigue in HF. The specific aims of this study were to (1) determine the psychometric properties of 2 fatigue questionnaires in patients with HF, (2) compare fatigue in patients with HF to published scores of healthy adults and patients with cancer undergoing treatment, and (3) identify the physiological (eg, hemoglobin, B-type natriuretic peptide, body mass index, and ejection fraction) and psychosocial (eg, depressed mood) correlates of fatigue in HF. Subjects and Methods A convenience sample of 87 HF outpatients was recruited from 2 urban medical centers. Patients completed the Fatigue Symptom Inventory, Profile of Mood States, and Short Form-36 Health Survey. Results and Conclusions Patients with HF and patients with cancer reported similar levels of fatigue, and both patient groups reported significantly more fatigue than did healthy adults. Physical functioning and hemoglobin categories explained 30% of the variance in Fatigue Symptom Inventory-Interference Scale scores, whereas depressed mood and physical functioning explained 47% of the variance in Profile of Mood States Fatigue subscale scores. Patients with HF experienced substantial fatigue that is comparable with cancer-related fatigue. Low physical functioning, depressed mood, and low hemoglobin level were associated with HF-related fatigue. PMID:19707101

Fatigue and gynecologic cancer.

PubMed

Olt, George J

2003-02-01

Fatigue is common in women with gynecologic cancers and is thought to be multifactorial. Anemia, cachexia, pain, and depression are frequently associated with cancer and treatment-related fatigue and should be evaluated and treated. The National Comprehensive Cancer Network Fatigue Practice Guidelines are helpful in the assessment and treatment of women with gynecologic cancer-related fatigue.

Regulatory immune cells in regulation of intestinal inflammatory response to microbiota

PubMed Central

Cong, Y; Liu, Z

2015-01-01

The intestinal lumen harbors nearly 100 trillion commensal bacteria that exert crucial function for health. An elaborate balance between immune responses and tolerance to intestinal microbiota is required to maintain intestinal homeostasis. This process depends on diverse regulatory mechanisms, including both innate and adaptive immunity. Dysregulation of the homeostasis between intestinal immune systems and microbiota has been shown to be associated with the development of inflammatory bowel diseases (IBD) in genetically susceptible populations. In this review, we discuss the recent progress reported in studies of distinct types of regulatory immune cells in the gut, including intestinal intraepithelial lymphocytes, Foxp3+ regulatory T cells, regulatory B cells, alternatively activated macrophages, dendritic cells, and innate lymphoid cells, and how dysfunction of this immune regulatory system contributes to intestinal diseases such as IBD. Moreover, we discuss the manipulation of these regulatory immune cells as a potential therapeutic method for management of intestinal inflammatory disorders. PMID:26080708

Reduced Cardiac Vagal Modulation Impacts on Cognitive Performance in Chronic Fatigue Syndrome

PubMed Central

Beaumont, Alison; Burton, Alexander R.; Lemon, Jim; Bennett, Barbara K.; Lloyd, Andrew; Vollmer-Conna, Uté

2012-01-01

Background Cognitive difficulties and autonomic dysfunction have been reported separately in patients with chronic fatigue syndrome (CFS). A role for heart rate variability (HRV) in cognitive flexibility has been demonstrated in healthy individuals, but this relationship has not as yet been examined in CFS. The objective of this study was to examine the relationship between HRV and cognitive performance in patients with CFS. Methods Participants were 30 patients with CFS and 40 healthy controls; the groups were matched for age, sex, education, body mass index, and hours of moderate exercise/week. Questionnaires were used to obtain relevant medical and demographic information, and assess current symptoms and functional impairment. Electrocardiograms, perceived fatigue/effort and performance data were recorded during cognitive tasks. Between–group differences in autonomic reactivity and associations with cognitive performance were analysed. Results Patients with CFS showed no deficits in performance accuracy, but were significantly slower than healthy controls. CFS was further characterized by low and unresponsive HRV; greater heart rate (HR) reactivity and prolonged HR-recovery after cognitive challenge. Fatigue levels, perceived effort and distress did not affect cognitive performance. HRV was consistently associated with performance indices and significantly predicted variance in cognitive outcomes. Conclusions These findings reveal for the first time an association between reduced cardiac vagal tone and cognitive impairment in CFS and confirm previous reports of diminished vagal activity. PMID:23166694

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

PubMed

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.

PubMed

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.

Developmental origins of inflammatory and immune diseases

PubMed Central

Chen, Ting; Liu, Han-xiao; Yan, Hui-yi; Wu, Dong-mei; Ping, Jie

2016-01-01

Epidemiological and experimental animal studies show that suboptimal environments in fetal and neonatal life exert a profound influence on physiological function and risk of diseases in adult life. The concepts of the ‘developmental programming’ and Developmental Origins of Health and Diseases (DOHaD) have become well accepted and have been applied across almost all fields of medicine. Adverse intrauterine environments may have programming effects on the crucial functions of the immune system during critical periods of fetal development, which can permanently alter the immune function of offspring. Immune dysfunction may in turn lead offspring to be susceptible to inflammatory and immune diseases in adulthood. These facts suggest that inflammatory and immune disorders might have developmental origins. In recent years, inflammatory and immune disorders have become a growing health problem worldwide. However, there is no systematic report in the literature on the developmental origins of inflammatory and immune diseases and the potential mechanisms involved. Here, we review the impacts of adverse intrauterine environments on the immune function in offspring. This review shows the results from human and different animal species and highlights the underlying mechanisms, including damaged development of cells in the thymus, helper T cell 1/helper T cell 2 balance disturbance, abnormal epigenetic modification, effects of maternal glucocorticoid overexposure on fetal lymphocytes and effects of the fetal hypothalamic–pituitary–adrenal axis on the immune system. Although the phenomena have already been clearly implicated in epidemiologic and experimental studies, new studies investigating the mechanisms of these effects may provide new avenues for exploiting these pathways for disease prevention. PMID:27226490

The Effect of Fatigue and Fatigue Intensity on Exercise Tolerance in Moderate COPD.

PubMed

Al-Shair, Khaled; Kolsum, Umme; Singh, Dave; Vestbo, Jørgen

2016-12-01

Fatigue is one of the most disabling symptoms in COPD, but little is known about the impact of fatigue on functional disability. We explored the impact of fatigue and fatigue intensity on exercise tolerance after adjusting for other factors using multivariate analysis and compared it to that of dyspnoea. A total of 119 patients with mainly moderate-severe stable COPD (38 % women, mean age 66 years) were enrolled. We used the Medical Research Council dyspnoea scores (MRC), Manchester COPD fatigue scale (MCFS) and its three dimensions, Borg scales for fatigue and dyspnoea, six-minute walk distance (6MWD), St George's Respiratory Questionnaire, the BODE index, and the Centre for Epidemiological Study on Depression scale (CES-D), and we measured spirometry, blood gases, systemic inflammatory markers and fat-free mass index (FFMI). Fatigue measured using the MCFS was associated with 6MWD and explained 22 % of the variability in 6MWD (p < 0.001). Fatigue remained associated with 6MWD after adjusting for MRC dyspnoea, FFMI and FEV 1 , FVC, PaO 2 , PaCO 2 , CES-D, TNF-alpha, smoking status, age and gender. We found that 33, 50 and 23 % of patients reported an increase by 2 scores on Borg scales for fatigue, dyspnoea or both at the end of the 6MWT. Fatigue scores (both before and after the 6MWT) were negatively correlated with 6MWD after adjusting for FEV 1 , FFMI, CES-D score and age (p = 0.007 and 0.001, respectively). In moderate stable COPD, fatigue may be a central driver of functional disability, to the same extent as dyspnoea.

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

PubMed

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.

Classifying Patients with Chronic Pelvic Pain into Levels of Biopsychosocial Dysfunction Using Latent Class Modeling of Patient Reported Outcome Measures

PubMed Central

Fenton, Bradford W.; Grey, Scott F.; Tossone, Krystel; McCarroll, Michele; Von Gruenigen, Vivian E.

2015-01-01

Chronic pelvic pain affects multiple aspects of a patient's physical, social, and emotional functioning. Latent class analysis (LCA) of Patient Reported Outcome Measures Information System (PROMIS) domains has the potential to improve clinical insight into these patients' pain. Based on the 11 PROMIS domains applied to n=613 patients referred for evaluation in a chronic pelvic pain specialty center, exploratory factor analysis (EFA) was used to identify unidimensional superdomains. Latent profile analysis (LPA) was performed to identify the number of homogeneous classes present and to further define the pain classification system. The EFA combined the 11 PROMIS domains into four unidimensional superdomains of biopsychosocial dysfunction: Pain, Negative Affect, Fatigue, and Social Function. Based on multiple fit criteria, a latent class model revealed four distinct classes of CPP: No dysfunction (3.2%); Low Dysfunction (17.8%); Moderate Dysfunction (53.2%); and High Dysfunction (25.8%). This study is the first description of a novel approach to the complex disease process such as chronic pelvic pain and was validated by demographic, medical, and psychosocial variables. In addition to an essentially normal class, three classes of increasing biopsychosocial dysfunction were identified. The LCA approach has the potential for application to other complex multifactorial disease processes. PMID:26355825

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

PubMed

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].

PubMed

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.

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

PubMed

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.

Investigation into Fretting Fatigue Under Cyclic Contact Load and in Conjunction with Plain Fatigue of Titanium Alloy

DTIC Science & Technology

2008-03-01

by plain fatigue and the process kept alternating or finishing all fretting fatigue cycles first followed by plain fatigue...fatigue and the process kept alternating or finishing all fretting fatigue cycles first followed by plain fatigue. 127  6.2.2. Phase Difference...component’s life. Figure 1.2 illustrates the process of combination of fretting fatigue and plain fatigue, by using three parts. The first part of this figure

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

PubMed

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

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

PubMed Central

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

2012-01-01

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 (Kv1.1V408A/+). Here, we investigated the neuromuscular transmission of Kv1.1V408A/+ ataxic mice and their susceptibility to physiologically relevant stressors. By using in vivo preparations of lateral gastrocnemius (LG) nerve–muscle from Kv1.1+/+ and Kv1.1V408A/+ 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 Ca2 + signals that occurred abnormally only in preparations dissected from Kv1.1V408A/+ 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 Ca2 + 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 fatigue or

Low cycle fatigue and creep-fatigue behavior of Ni-based alloy 230 at 850 C

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Xiang; Yang, Zhiqing; Sokolov, Mikhail A

Strain-controlled low cycle fatigue (LCF) and creep-fatigue testing of Ni-based alloy 230 were carried out at 850 C. The material creep-fatigue life decreased compared with its low cycle fatigue life at the same total strain range. Longer hold time at peak tensile strain further reduced the material creep-fatigue life. Based on the electron backscatter diffraction, a novel material deformation characterization method was applied, which revealed that in low cycle fatigue testing as the total strain range increased, the deformation was segregated to grain boundaries since the test temperature was higher than the material equicohesive temperature and grain boundaries became weakermore » regions compared with grains. Creep-fatigue tests enhanced the localized deformation, resulting in material interior intergranular cracking, and accelerated material damage. Precipitation in alloy 230 helped slip dispersion, favorable for fatigue property, but grain boundary cellular precipitates formed after material exposure to the elevated temperature had a deleterious effect on the material low cycle fatigue and creep-fatigue property.« less

Ubiquinol reduces muscle wasting but not fatigue in tumor-bearing mice.

PubMed

Clark, Yvonne Y; Wold, Loren E; Szalacha, Laura A; McCarthy, Donna O

2015-05-01

Fatigue is the most common and distressing symptom reported by cancer patients during and after treatment. Tumor growth increases oxidative stress and cytokine production, which causes skeletal muscle wasting and cardiac dysfunction. The purpose of this study was to determine whether treatment with the antioxidant ubiquinol improves muscle mass, cardiac function, and behavioral measures of fatigue in tumor-bearing mice. Adult female mice were inoculated with colon26 tumor cells. Half the control and tumor-bearing mice were administered ubiquinol (500 mg/kg/day) in their drinking water. Voluntary wheel running (i.e., voluntary running activity [VRA]) and grip strength were measured at Days 0, 8, 14, and 17 of tumor growth. Cardiac function was measured using echocardiography on Day 18 or 19. Biomarkers of inflammation, protein degradation, and oxidative stress were measured in serum and heart and gastrocnemius tissue. VRA and grip strength progressively declined in tumor-bearing mice. Muscle mass and myocardial diastolic function were decreased, and expression of proinflammatory cytokines was increased in serum and muscle and heart tissue on Day 19 of tumor growth. Oxidative stress was present only in the heart, while biomarkers of protein degradation were increased only in the gastrocnemius muscle. Ubiquinol increased muscle mass in the tumor-bearing and control animals but had no effect on the expression of biomarkers of inflammation, protein degradation, or oxidative stress or on behavioral measures of fatigue. © The Author(s) 2014.

Herpes zoster-associated voiding dysfunction in hematopoietic malignancy patients.

PubMed

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.

Gender differences in fatigue: biopsychosocial factors relating to fatigue in men and women.

PubMed

Bensing, J M; Hulsman, R L; Schreurs, K M

1999-10-01

Fatigue is a common problem, which is found more frequently among women than men. To date, neither the etiology of fatigue nor the factors that explain the gender difference in its incidence are still fully understood. In a sample of men (n = 4,681) and women (n = 4,698) (age range, 15-64 years) in the Dutch National Survey of Morbidity and Interventions in General Practice, the gender differences in the underlying biological, psychological, and social factors of fatigue were analyzed. Both general and gender-specific factors were recognized. Men and women who experience complaints of fatigue appeared to be younger and more highly educated. They had more acute health complaints and more psychosocial problems and also showed a lower level of perceived health. Among women, only gender-specific biological complaints and psychosocial problems were related to fatigue. In addition, relevant sociodemographic variables included taking care of young children and being employed. Among men, fatigue was particularly related to having handicaps and severe chronic complaints. Taking care of young children did not make a difference in the male sample. Fatigue can only be adequately understood in a multicausal model with biomedical and psychosocial factors. Complaints of fatigue are too often ignored in general practice. By adopting a patient-centered style of communication, physicians can acquire a more complete picture of the patients' fatigue.

Dysfunctions of the Iga system: a common link between intestinal and renal diseases

PubMed Central

Papista, Christina; Berthelot, Laureline; Monteiro, Renato C

2011-01-01

Immunoglobulin A (Iga)-isotype antibodies play an important role in immunity owing to their structure, glycosylation, localization and receptor interactions. Dysfunctions in this system can lead to multiple types of pathology. This review describes the characteristics of Iga and discusses the involvement of abnormalities in the Iga system on the development of celiac disease and Iga nephropathy. PMID:21278767

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

PubMed

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.

Review of Corrosion Fatigue.

DTIC Science & Technology

1981-11-16

other is not always well defined. 3.0 CORROSIM FATIGUE VARIABLES AND THEIR EFFECTS Corrosion fatigue behavior is pverned, y Ir of variables- environmental...on near threshold fatigue crack growth behavior is primarily a function of environmental reaction in this steel . 3.2 Mechanical Effects Among the...Gallagher""’ and Pao studied the corrosion fatigue behavior of 4340 steel at various * Ifrequencies in distilled water and water vapor, respectively

Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy

PubMed Central

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

Creep-Fatigue Interaction Testing

NASA Technical Reports Server (NTRS)

Halford, Gary R.

2001-01-01

Fatigue fives in metals are nominally time independent below 0.5 T(sub Melt). At higher temperatures, fatigue lives are altered due to time-dependent, thermally activated creep. Conversely, creep rates are altered by super. imposed fatigue loading. Creep and fatigue generally interact synergistically to reduce material lifetime. Their interaction, therefore, is of importance to structural durability of high-temperature structures such as nuclear reactors, reusable rocket engines, gas turbine engines, terrestrial steam turbines, pressure vessel and piping components, casting dies, molds for plastics, and pollution control devices. Safety and lifecycle costs force designers to quantify these interactions. Analytical and experimental approaches to creep-fatigue began in the era following World War II. In this article experimental and life prediction approaches are reviewed for assessing creep-fatigue interactions of metallic materials. Mechanistic models are also discussed briefly.

Effect of aromatherapy via inhalation on the sleep quality and fatigue level in people undergoing hemodialysis.

PubMed

Muz, Gamze; Taşcı, Sultan

2017-10-01

The most common problems in hemodialysis patients are sleep disorders and fatigue. This randomized-controlled experimental study was conducted to determine the effect of aromatherapy applied by inhalation on sleep quality and fatigue level in hemodialysis patients. The study was completed in five hemodialysis centers settled in two provinces with 27 intervention group patients and 35 controls, being totally 62 patients, recruited with simple randomization. Ethical approval, informed consent from the individuals and institutional permission were obtained. Data were collected with a questionnaire form and Visual Analogue Scale (VAS) for fatigue, Piper fatigue scale, Pittsburgh Sleep Quality Index (PSQI), and follow-up forms for the patient and the researcher. Aromatherapy inhalation (sweet orange and lavender oil) was performed before going to bed every day for one month to the intervention group patients. No other application has been made to the control group patients except for standard hemodialysis treatment. All of the forms were performed at baseline and at follow-up at the end of the four weeks (baseline and last follow-up), VAS and Piper fatigue scale were performed during follow-ups at the end of every week (the first, second and third follow-ups). Data were statistically analyzed with Independent Samples t-test, one way analysis of variance, Pearson correlation analysis, chi-square test, Friedman and Mann Whitney U tests and Bonferroni test. p<0.05 was set as statistically significant in comparisons. Mean total and sub-dimension scores of VAS, Piper fatigue scale and PSQI (except for daytime sleepiness dysfunction sub-dimension) of the intervention and control groups at baseline were not significantly different (p>0.05). It was found that mean total and sub-dimension scores of VAS, Piper fatigue scale and PSQI of the intervention group significantly decreased in other follow-ups compared to the control group (p<0.05). Consequently, it was determined that

Fatigue Assessment: Subjective Peer-to-Peer Fatigue Scoring (Reprint)

DTIC Science & Technology

2013-10-01

impor- tant role of fatigue in aviation safety and fl ight perfor- mance, the compelling tasks of predicting dangerous fatigued states and quantifying ... risk and associated per- formance defi cits have been immoderately diffi cult. This is particularly true for an individual functioning within the

Chronic Systemic Immune Dysfunction in African-Americans with Small Vessel-Type Ischemic Stroke.

PubMed

Brown, Candice M; Bushnell, Cheryl D; Samsa, Gregory P; Goldstein, Larry B; Colton, Carol A

2015-12-01

The incidence of small vessel-type (lacunar) ischemic strokes is greater in African-Americans compared to whites. The chronic inflammatory changes that result from lacunar stroke are poorly understood. To elucidate these changes, we measured serum inflammatory and thrombotic biomarkers in African-Americans at least 6 weeks post-stroke compared to control individuals. Cases were African-Americans with lacunar stroke (n = 30), and controls were age-matched African-Americans with no history of stroke or other major neurologic disease (n = 37). Blood was obtained >6 weeks post-stroke and was analyzed for inflammatory biomarkers. Freshly isolated peripheral blood mononuclear cells were stimulated with lipopolysaccharide (LPS) to assess immune responsiveness in a subset of cases (n = 5) and controls (n = 4). After adjustment for covariates, the pro-inflammatory biomarkers, soluble vascular cadherin adhesion molecule-1 (sVCAM-1) and thrombin anti-thrombin (TAT), were independently associated with lacunar stroke. Immune responsiveness to LPS challenge was abnormal in cases compared to controls. African-Americans with lacunar stroke had elevated blood levels of VCAM-1 and TAT and an abnormal response to acute immune challenge >6 weeks post-stroke, suggesting a chronically compromised systemic inflammatory response.

Ultrasonic Evaluation of Fatigue Damage

NASA Astrophysics Data System (ADS)

Bayer, P.; Singher, L.; Notea, A.

2004-02-01

Despite the fact that most engineers and designers are aware of fatigue, many severe breakdowns of industrial plant and machinery still occur due to fatigue. In effect, it's been estimated that fatigue causes at least 80% of the failures in modern engineering components. From an operational point of view, the detection of fatigue damage, preferably at a very early stage, is a critically important consideration in order to prevent possible catastrophic equipment failure and associated losses. This paper describes the investigation involving the use of ultrasonic waves as a potential tool for early detection of fatigue damage. The parameters investigated were the ultrasonic wave velocities (longitudinal and transverse waves) and attenuation coefficient before fatigue damage and after progressive stages of fatigue. Although comparatively small uncertainties were observed, the feasibility of utilizing the velocity of ultrasonic waves as a fatigue monitor was barely substantiated within actual research conditions. However, careful measurements of the ultrasonic attenuation parameter had demonstrated its potential to provide an early assessment of damage during fatigue.

Fatigue life prediction in bending from axial fatigue information

NASA Technical Reports Server (NTRS)

Manson, S. S.; Muralidharan, U.

1982-01-01

Bending fatigue in the low cyclic life range differs from axial fatigue due to the plastic flow which alters the linear stress-strain relation normally used to determine the nominal stresses. An approach is presented to take into account the plastic flow in calculating nominal bending stress (S sub bending) based on true surface stress. These functions are derived in closed form for rectangular and circular cross sections. The nominal bending stress and the axial fatigue stress are plotted as a function of life (N sub S) and these curves are shown for several materials of engineering interest.

Dysfunctional brain-bone marrow communication: a paradigm shift in the pathophysiology of hypertension.

PubMed

Santisteban, Monica M; Zubcevic, Jasenka; Baekey, David M; Raizada, Mohan K

2013-08-01

It is widely accepted that the pathophysiology of hypertension involves autonomic nervous system dysfunction, as well as a multitude of immune responses. However, the close interplay of these systems in the development and establishment of high blood pressure and its associated pathophysiology remains elusive and is the subject of extensive investigation. It has been proposed that an imbalance of the neuro-immune systems is a result of an enhancement of the "proinflammatory sympathetic" arm in conjunction with dampening of the "anti-inflammatory parasympathetic" arm of the autonomic nervous system. In addition to the neuronal modulation of the immune system, it is proposed that key inflammatory responses are relayed back to the central nervous system and alter the neuronal communication to the periphery. The overall objective of this review is to critically discuss recent advances in the understanding of autonomic immune modulation, and propose a unifying hypothesis underlying the mechanisms leading to the development and maintenance of hypertension, with particular emphasis on the bone marrow, as it is a crucial meeting point for neural, immune, and vascular networks.

Dysfunctional brain-bone marrow communication: A paradigm shift in the pathophysiology of hypertension

PubMed Central

Santisteban, Monica M.; Zubcevic, Jasenka; Baekey, David M.; Raizada, Mohan K.

2013-01-01

It is widely accepted that the pathophysiology of hypertension involves autonomic nervous system dysfunction, as well as a multitude of immune responses. However, the close interplay of these systems in the development and establishment of high blood pressure and its associated pathophysiology remains elusive and is the subject of extensive investigation. It has been proposed that an imbalance of the neuro-immune systems is a result of an enhancement of the “pro-inflammatory sympathetic” arm in conjunction with dampening of the “anti-inflammatory parasympathetic” arm of the autonomic nervous system. In addition to the neuronal modulation of the immune system, it is proposed that key inflammatory responses are relayed back to the central nervous system and alter the neuronal communication to the periphery. The overall objective of this review is to critically discuss recent advances in the understanding of autonomic immune modulation, and propose a unifying hypothesis underlying the mechanisms leading to the development and maintenance of hypertension, with particular emphasis on the bone marrow, as it is a crucial meeting point for neural, immune, and vascular networks. PMID:23715920

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

PubMed Central

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

NASA Astrophysics Data System (ADS)

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.

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

NASA Astrophysics Data System (ADS)

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.

Sleep quality in fibromyalgia and rheumatoid arthritis: associations with pain, fatigue, depression, and disease activity.

PubMed

Ulus, Y; Akyol, Y; Tander, B; Durmus, D; Bilgici, A; Kuru, O

2011-01-01

The aim of this study was to compare the sleep quality in patients with rheumatoid arthritis (RA) and fibromyalgia syndrome (FMS); and to evaluate the relationship between sleep quality and pain, fatigue, depression, and disease activity in patients with RA and FMS. Forty RA, 40 FMS and 40 healthy controls were enrolled in the study. Disease activity and disease duration were reported in patients. Pain by visual analogue scale (VAS), fatigue by Multidimensional Assesment of Fatigue (MAF), depression by Beck Depression Index (BDI), and sleep quality by Pittsburgh Sleep Quality Index (PSQI) were gathered in all participants. All participants were aged between 20 and 65 years, with a mean age of 42.97±10.75 years. There was no significant difference with respect to demographic characteristics among the three study groups. Patients reported more depression than controls, but BDI scores were similar in FMS and RA patients. VAS pain scores and MAF scores were significantly different in the three groups (p<0.001). FMS and RA patients had poor sleep quality (p<0.001). FMS patients had daytime dysfunction due to sleep disorder and had worse habitual sleep efficiency than RA patients (p<0.05). In patients, positive correlations were found between PSQI and clinic assessment variables except disease duration. FMS and RA may have poor sleep quality when compared to subjects without rheumatologic disorders. The quality of sleep can be impaired by pain, fatigue, depression, and disease activity in such patients.

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

PubMed

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].

PubMed

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.

Hydraulic Fatigue-Testing Machine

NASA Technical Reports Server (NTRS)

Hodo, James D.; Moore, Dennis R.; Morris, Thomas F.; Tiller, Newton G.

1987-01-01

Fatigue-testing machine applies fluctuating tension to number of specimens at same time. When sample breaks, machine continues to test remaining specimens. Series of tensile tests needed to determine fatigue properties of materials performed more rapidly than in conventional fatigue-testing machine.

Decision fatigue: A conceptual analysis.

PubMed

Pignatiello, Grant A; Martin, Richard J; Hickman, Ronald L

2018-03-01

Decision fatigue is an applicable concept to healthcare psychology. Due to a lack of conceptual clarity, we present a concept analysis of decision fatigue. A search of the term "decision fatigue" was conducted across seven research databases, which yielded 17 relevant articles. The authors identified three antecedent themes (decisional, self-regulatory, and situational) and three attributional themes (behavioral, cognitive, and physiological) of decision fatigue. However, the extant literature failed to adequately describe consequences of decision fatigue. This concept analysis provides needed conceptual clarity for decision fatigue, a concept possessing relevance to nursing and allied health sciences.

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.

PubMed

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.

Handgrip fatiguing exercise can provide objective assessment of cancer-related fatigue: a pilot study.

PubMed

Veni, T; Boyas, S; Beaune, B; Bourgeois, H; Rahmani, A; Landry, S; Bochereau, A; Durand, S; Morel, B

2018-06-24

As a subjective symptom, cancer-related fatigue is assessed via patient-reported outcomes. Due to the inherent bias of such evaluation, screening and treatment for cancer-related fatigue remains suboptimal. The purpose is to evaluate whether objective cancer patients' hand muscle mechanical parameters (maximal force, critical force, force variability) extracted from a fatiguing handgrip exercise may be correlated to the different dimensions (physical, emotional, and cognitive) of cancer-related fatigue. Fourteen women with advanced breast cancer, still under or having previously received chemotherapy within the preceding 3 months, and 11 healthy women participated to the present study. Cancer-related fatigue was first assessed through the EORTC QLQ-30 and its fatigue module. Fatigability was then measured during 60 maximal repeated handgrip contractions. The maximum force, critical force (asymptote of the force-time evolution), and force variability (root mean square of the successive differences) were extracted. Multiple regression models were performed to investigate the influence of the force parameters on cancer-related fatigue's dimensions. The multiple linear regression analysis evidenced that physical fatigue was best explained by maximum force and critical force (r = 0.81; p = 0.029). The emotional fatigue was best explained by maximum force, critical force, and force variability (r = 0.83; p = 0.008). The cognitive fatigue was best explained by critical force and force variability (r = 0.62; p = 0.035). The handgrip maximal force, critical force, and force variability may offer objective measures of the different dimensions of cancer-related fatigue and could provide a complementary approach to the patient reported outcomes.

Physical activity in ovarian cancer survivors: associations with fatigue, sleep, and psychosocial functioning.

PubMed

Stevinson, Clare; Steed, Helen; Faught, Wylam; Tonkin, Katia; Vallance, Jeffrey K; Ladha, Aliya B; Schepansky, Alexandra; Capstick, Valerie; Courneya, Kerry S

2009-01-01

Physical activity has been associated with better health-related outcomes in several cancer survivor groups but very few data exist for women with ovarian cancer. The purpose of this study was to investigate the associations between physical activity and health-related outcomes in ovarian cancer survivors and to examine any dose-response relationship. A cross-sectional postal survey of ovarian cancer survivors on and off treatment identified through the Alberta Cancer Registry was performed. Participants completed self-report measures of physical activity, cancer-related fatigue, peripheral neuropathy, depression, anxiety, and happiness, as well as demographic and medical variables. A total of 359 ovarian cancer survivors participated (51.4% response rate) of whom 31.1% were meeting the public health physical activity guidelines of the Centers for Disease Control and Prevention. Those meeting guidelines reported significantly lower fatigue than those not meeting guidelines (mean difference, 7.1; 95% confidence interval, 5.5-8.8; d = 0.87; P < 0.001). Meeting guidelines was also significantly inversely associated with peripheral neuropathy, depression, anxiety, sleep latency, use of sleep medication, and daytime dysfunction and was positively associated with happiness, sleep quality, and sleep efficiency. There was no evidence of a dose-response relationship beyond meeting or not meeting the guidelines for any variables. Ovarian cancer survivors who were meeting physical activity guidelines reported more favorable outcomes of fatigue, peripheral neuropathy, sleep, and psychosocial functioning.

Elevated temperature biaxial fatigue

NASA Technical Reports Server (NTRS)

Jordan, E. H.

1985-01-01

A 3 year experimental program for studying elevated temperature biaxial fatigue of a nickel based alloy Hastelloy-X has been completed. A new high temperature fatigue test facility with unique capabilities has been developed. Effort was directed toward understanding multiaxial fatigue and correlating the experimental data to the existing theories of fatigue failure. The difficult task of predicting fatigue lives for nonproportional loading was used as an ultimate test for various life prediction methods being considered. The primary means of reaching improved understanding were through several critical nonproportional loading experiments. The direction of cracking observed on failed specimens was also recorded and used to guide the development of the theory. Cyclic deformation responses were permanently recorded digitally during each test. It was discovered that the cracking mode switched from primarily cracking on the maximum shear planes at room temperature to cracking on the maximum normal strain planes at 649 C. In contrast to some other metals, loading path in nonproportional loading had little effect on fatigue lives. Strain rate had a small effect on fatigue lives at 649 C. Of the various correlating parameters the modified plastic work and octahedral shear stress were the most successful.

Translating Fatigue to Human Performance.

PubMed

Enoka, Roger M; Duchateau, Jacques

2016-11-01

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 effect 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. On the basis of 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 affect real-world performance.

A chronic fatigue syndrome – related proteome in human cerebrospinal fluid

PubMed Central

Baraniuk, James N; Casado, Begona; Maibach, Hilda; Clauw, Daniel J; Pannell, Lewis K; Hess S, Sonja

2005-01-01

Background Chronic Fatigue Syndrome (CFS), Persian Gulf War Illness (PGI), and fibromyalgia are overlapping symptom complexes without objective markers or known pathophysiology. Neurological dysfunction is common. We assessed cerebrospinal fluid to find proteins that were differentially expressed in this CFS-spectrum of illnesses compared to control subjects. Methods Cerebrospinal fluid specimens from 10 CFS, 10 PGI, and 10 control subjects (50 μl/subject) were pooled into one sample per group (cohort 1). Cohort 2 of 12 control and 9 CFS subjects had their fluids (200 μl/subject) assessed individually. After trypsin digestion, peptides were analyzed by capillary chromatography, quadrupole-time-of-flight mass spectrometry, peptide sequencing, bioinformatic protein identification, and statistical analysis. Results Pooled CFS and PGI samples shared 20 proteins that were not detectable in the pooled control sample (cohort 1 CFS-related proteome). Multilogistic regression analysis (GLM) of cohort 2 detected 10 proteins that were shared by CFS individuals and the cohort 1 CFS-related proteome, but were not detected in control samples. Detection of ≥1 of a select set of 5 CFS-related proteins predicted CFS status with 80% concordance (logistic model). The proteins were α-1-macroglobulin, amyloid precursor-like protein 1, keratin 16, orosomucoid 2 and pigment epithelium-derived factor. Overall, 62 of 115 proteins were newly described. Conclusion This pilot study detected an identical set of central nervous system, innate immune and amyloidogenic proteins in cerebrospinal fluids from two independent cohorts of subjects with overlapping CFS, PGI and fibromyalgia. Although syndrome names and definitions were different, the proteome and presumed pathological mechanism(s) may be shared. PMID:16321154

Ascending caudal medullary catecholamine pathways drive sickness-induced deficits in exploratory behavior: brain substrates for fatigue?

PubMed

Gaykema, Ronald P A; Goehler, Lisa E

2011-03-01

Immune challenges can lead to marked behavioral changes, including fatigue, reduced social interest, anorexia, and somnolence, but the precise neuronal mechanisms that underlie sickness behavior remain elusive. Part of the neurocircuitry influencing behavior associated with illness likely includes viscerosensory nuclei located in the caudal brainstem, based on findings that inactivation of the dorsal vagal complex (DVC) can prevent social withdrawal. These brainstem nuclei contribute multiple neuronal projections that target different components of autonomic and stress-related neurocircuitry. In particular, catecholaminergic neurons in the ventrolateral medulla (VLM) and DVC target the hypothalamus and drive neuroendocrine responses to immune challenge, but their particular role in sickness behavior is not known. To test whether this catecholamine pathway also mediates sickness behavior, we compared effects of DVC inactivation with targeted lesion of the catecholamine pathway on exploratory behavior, which provides an index of motivation and fatigue, and associated patterns of brain activation assessed by immunohistochemical detection of c-Fos protein. LPS treatment dramatically reduced exploratory behavior, and produced a pattern of increased c-Fos expression in brain regions associated with stress and autonomic adjustments paraventricular hypothalamus (PVN), bed nucleus of the stria terminalis (BST), central amygdala (CEA), whereas activation was reduced in regions involved in exploratory behavior (hippocampus, dorsal striatum, ventral tuberomammillary nucleus, and ventral tegmental area). Both DVC inactivation and catecholamine lesion prevented reductions in exploratory behavior and completely blocked the inhibitory LPS effects on c-Fos expression in the behavior-associated regions. In contrast, LPS-induced activation in the CEA and BST was inhibited by DVC inactivation but not by catecholamine lesion. The findings support the idea that parallel pathways from

High levels of type 2 cytokine-producing cells in chronic fatigue syndrome.

PubMed

Skowera, A; Cleare, A; Blair, D; Bevis, L; Wessely, S C; Peakman, M

2004-02-01

The aetiology of chronic fatigue syndrome (CFS) is not known. However, it has been suggested that CFS may be associated with underlying immune activation resulting in a Th2-type response. We measured intracellular production of interferon (IFN)-gamma and interleukin (IL)-2; type 1 cytokines), IL-4 (type 2) and IL-10 (regulatory) by both polyclonally stimulated and non-stimulated CD4 and CD8 lymphocytes from patients with CFS and control subjects by flow cytometry. After polyclonal activation we found evidence of a significant bias towards Th2- and Tc2-type immune responses in CFS compared to controls. In contrast, levels of IFN-gamma, IL-2 and IL-10-producing cells were similar in both study groups. Non-stimulated cultures revealed significantly higher levels of T cells producing IFN-gamma or IL-4 in CFS patients. Concluding, we show evidence for an effector memory cell bias towards type 2 responsiveness in patients with CFS, as well as ongoing type 0 immune activation in unstimulated cultures of peripheral blood cells.

High levels of type 2 cytokine-producing cells in chronic fatigue syndrome

PubMed Central

SKOWERA, A; CLEARE, A; BLAIR, D; BEVIS, L; WESSELY, S C; PEAKMAN, M

2004-01-01

The aetiology of chronic fatigue syndrome (CFS) is not known. However, it has been suggested that CFS may be associated with underlying immune activation resulting in a Th2-type response. We measured intracellular production of interferon (IFN)-γ and interleukin (IL)-2; type 1 cytokines), IL-4 (type 2) and IL-10 (regulatory) by both polyclonally stimulated and non-stimulated CD4 and CD8 lymphocytes from patients with CFS and control subjects by flow cytometry. After polyclonal activation we found evidence of a significant bias towards Th2- and Tc2-type immune responses in CFS compared to controls. In contrast, levels of IFN-γ, IL-2 and IL-10-producing cells were similar in both study groups. Non-stimulated cultures revealed significantly higher levels of T cells producing IFN-γ or IL-4 in CFS patients. Concluding, we show evidence for an effector memory cell bias towards type 2 responsiveness in patients with CFS, as well as ongoing type 0 immune activation in unstimulated cultures of peripheral blood cells. PMID:14738459

Inflammation-induced lymphangiogenesis and lymphatic dysfunction

PubMed Central

Liao, Shan; von der Weid, Pierre-Yves

2014-01-01

The lymphatic system is intimately linked to tissue fluid homeostasis and immune cell trafficking. These functions are paramount in the establishment and development of an inflammatory response. In the past decade, an increasing number of reports has revealed that marked changes, such as lymphangiogenesis and lymphatic contractile dysfunction occur in both vascular and nodal parts of the lymphatic system during inflammation, as well as other disease processes. This review provides a critical update on the role of the lymphatic system in disease process such as chronic inflammation and cancer and examines the changes in lymphatic functions the diseases cause and the influence these changes have on the progression of the diseases. PMID:24449090

Transcriptome Network Analysis Reveals Aging-Related Mitochondrial and Proteasomal Dysfunction and Immune Activation in Human Thyroid

PubMed Central

Cho, Byuri Angela; Yoo, Seong-Keun; Song, Young Shin; Kim, Su-jin; Lee, Kyu Eun; Shong, Minho

2018-01-01

Background: Elucidating aging-related transcriptomic changes in human organs is necessary to understand the aging physiology and mechanisms, but little is known regarding the thyroid gland. We investigated aging-related transcriptomic alterations in the human thyroid gland and characterized the related molecular functions. Methods: Publicly available RNA sequencing data of 322 thyroid tissue samples from the Genotype-Tissue Expression project were analyzed. In addition, our own 64 RNA sequencing data of normal thyroid tissue samples were used as a validation set. To comprehensively evaluate the associations between aging and transcriptomic changes, we performed a weighted gene coexpression network analysis and pathway enrichment analysis. The thyroid differentiation score was then used for further analysis, defining the correlations between thyroid differentiation and aging. Results: The most significant aging-related transcriptomic change in thyroid was the downregulation of genes related to the mitochondrial and proteasomal functions (p = 3 × 10−6). Moreover, genes that are associated with immune processes were significantly upregulated with age (p = 3 × 10−4), and all of them overlapped with the upregulated genes in the thyroid glands affected by lymphocytic thyroiditis. Furthermore, these aging-related changes were not significantly different according to sex, but in terms of the thyroid differentiation, females were more susceptible to aging-related changes (p for trend = 0.03). Conclusions: Aging-related transcriptomic changes in the thyroid gland were associated with mitochondrial and proteasomal dysfunction, loss of differentiation, and activation of autoimmune processes. Our results provide clues to better understanding the age-related decline in thyroid function and higher susceptibility to autoimmune thyroid disease. PMID:29652618

Fatigue Experiences Among OCD Outpatients.

PubMed

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.

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

PubMed Central

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

Crack tip field and fatigue crack growth in general yielding and low cycle fatigue

NASA Technical Reports Server (NTRS)

Minzhong, Z.; Liu, H. W.

1984-01-01

Fatigue life consists of crack nucleation and crack propagation periods. Fatigue crack nucleation period is shorter relative to the propagation period at higher stresses. Crack nucleation period of low cycle fatigue might even be shortened by material and fabrication defects and by environmental attack. In these cases, fatigue life is largely crack propagation period. The characteristic crack tip field was studied by the finite element method, and the crack tip field is related to the far field parameters: the deformation work density, and the product of applied stress and applied strain. The cyclic carck growth rates in specimens in general yielding as measured by Solomon are analyzed in terms of J-integral. A generalized crack behavior in terms of delta is developed. The relations between J and the far field parameters and the relation for the general cyclic crack growth behavior are used to analyze fatigue lives of specimens under general-yielding cyclic-load. Fatigue life is related to the applied stress and strain ranges, the deformation work density, crack nucleus size, fracture toughness, fatigue crack growth threshold, Young's modulus, and the cyclic yield stress and strain. The fatigue lives of two aluminum alloys correlate well with the deformation work density as depicted by the derived theory. The general relation is reduced to Coffin-Manson low cycle fatigue law in the high strain region.

Driver fatigue: electroencephalography and psychological assessment.

PubMed

Lal, Saroj K L; Craig, Ashley

2002-05-01

Fatigue has major implications for transportation system safety; therefore, investigating the psychophysiological links to fatigue could enhance our understanding and management of fatigue in the transport industry. This study examined the psychophysiological changes that occurred during a driver simulator task in 35 randomly selected subjects. Results showed that significant electroencephalographic changes occur during fatigue. Delta and theta activity were found to increase significantly during fatigue. Heart rate was significantly lower after the driving task. Blink rate also changed during the fatigue task. Increased trait anxiety, tension-anxiety, fatigue-inertia and reduced vigor-activity were shown to be associated with neurophysiological indicators of fatigue such as increased delta and theta activity. The results are discussed in light of directions for future studies and for the development of a fatigue countermeasure device.

Elevated temperature biaxial fatigue

NASA Technical Reports Server (NTRS)

Jordan, E. H.

1984-01-01

A three year experimental program for studying elevated temperature biaxial fatigue of a nickel based alloy Hastelloy-X has been completed. A new high temperature fatigue test facility with unique capabilities has been developed. Effort was directed toward understanding multiaxial fatigue and correlating the experimental data to the existing theories of fatigue failure. The difficult task of predicting fatigue lives for non-proportional loading was used as an ultimate test for various life prediction methods being considered. The primary means of reaching improved undertanding were through several critical non-proportional loading experiments. It was discovered that the cracking mode switched from primarily cracking on the maximum shear planes at room temperature to cracking on the maximum normal strain planes at 649 C.

[Endothelial dysfunction and nonspecific immune reactions in development and progression of osteoarthrosis in women engaged into manual work].

PubMed

Maliutina, N N; Nevzorova, M S

2015-01-01

The article considers mechanisms of development and progression of osteoarthrosis as an occupationally conditioned disease in women of manual work. Women working in physical overstrain conditions are under occupational risk with dysfunction of many body systems. The authors set a hypothesis on association of endothelial dysfunction markers dysbalance and structural remodelling of cartilage matrix as a proof of degenerative changes.

Factors associated with intern fatigue.

PubMed

Friesen, Lindsay D; Vidyarthi, Arpana R; Baron, Robert B; Katz, Patricia P

2008-12-01

Prior data suggest that fatigue adversely affects patient safety and resident well-being. ACGME duty hour limitations were intended, in part, to reduce resident fatigue, but the factors that affect intern fatigue are unknown. To identify factors associated with intern fatigue following implementation of duty hour limitations. Cross-sectional confidential survey of validated questions related to fatigue, sleep, and stress, as well as author-developed teamwork questions. Interns in cognitive specialties at the University of California, San Francisco. Univariate statistics characterized the distribution of responses. Pearson correlations elucidated bivariate relationships between fatigue and other variables. Multivariate linear regression models identified factors independently associated with fatigue, sleep, and stress. Of 111 eligible interns, 66 responded (59%). In a regression analysis including gender, hours worked in the previous week, sleep quality, perceived stress, and teamwork, only poorer quality of sleep and greater perceived stress were significantly associated with fatigue (p < 0.001 and p = 0.02, respectively). To identify factors that may affect sleep, specifically duty hours and stress, a secondary model was constructed. Only greater perceived stress was significantly associated with diminished sleep quality (p = 0.04), and only poorer teamwork was significantly associated with perceived stress (p < 0.001). Working >80 h was not significantly associated with perceived stress, quality of sleep, or fatigue. Simply decreasing the number of duty hours may be insufficient to reduce intern fatigue. Residency programs may need to incorporate programmatic changes to reduce stress, improve sleep quality, and foster teamwork in order to decrease intern fatigue and its deleterious consequences.

Fatigue: an overview.

PubMed

Rosenthal, Thomas C; Majeroni, Barbara A; Pretorius, Richard; Malik, Khalid

2008-11-15

Fatigue, a common presenting symptom in primary care, negatively impacts work performance, family life, and social relationships. The differential diagnosis of fatigue includes lifestyle issues, physical conditions, mental disorders, and treatment side effects. Fatigue can be classified as secondary to other medical conditions, physiologic, or chronic. The history and physical examination should focus on identifying common secondary causes (e.g., medications, anemia, pregnancy) and life-threatening problems, such as cancer. Results of laboratory studies affect management in only 5 percent of patients, and if initial results are normal, repeat testing is generally not indicated. Treatment of all types of fatigue should include a structured plan for regular physical activity that consists of stretching and aerobic exercise, such as walking. Caffeine and modafinil may be useful for episodic situations requiring alertness. Short naps are proven performance enhancers. Selective serotonin reuptake inhibitors, such as fluoxetine, paroxetine, or sertraline, may improve energy in patients with depression. Patients with chronic fatigue may respond to cognitive behavior therapy. Scheduling regular follow-up visits, rather than sporadic urgent appointments, is recommended for effective long-term management.

The brain and immune system prompt energy shortage in chronic inflammation and ageing.

PubMed

Straub, Rainer H

2017-12-01

Sequelae frequently seen in patients with chronic inflammatory diseases, such as fatigue, depressed mood, sleep alterations, loss of appetite, muscle wasting, cachectic obesity, bone loss and hypertension, can be the result of energy shortages caused by an overactive immune system. These sequelae can also be found in patients with chronic inflammatory diseases that are in remission and in ageing individuals, despite the immune system being less active in these situations. This Perspectives article proposes a new way of understanding situations of chronic inflammation (such as rheumatic diseases) and ageing based on the principles of evolutionary medicine, energy regulation and neuroendocrine-immune crosstalk. A conceptual framework is provided to enable physicians and scientists to better understand the signs and symptoms of chronic inflammatory diseases and long-term disease consequences resulting from physical and mental inactivity.

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.

PubMed

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.

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

PubMed

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.

Fracture mechanics and corrosion fatigue.

NASA Technical Reports Server (NTRS)

Mcevily, A. J.; Wei, R. P.

1972-01-01

Review of the current state-of-the-art in fracture mechanics, particularly in relation to the study of problems in environment-enhanced fatigue crack growth. The usefulness of this approach in developing understanding of the mechanisms for environmental embrittlement and its engineering utility are discussed. After a brief review of the evolution of the fracture mechanics approach and the study of environmental effects on the fatigue behavior of materials, a study is made of the response of materials to fatigue and corrosion fatigue, the modeling of the mechanisms of the fatigue process is considered, and the application of knowledge of fatigue crack growth to the prediction of the high cycle life of unnotched specimens is illustrated.

Innate Immunity and Saliva in Candida albicans–mediated Oral Diseases

PubMed Central

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

Pathological Type-2 Immune Response, Enhanced Tumor Growth, and Glucose Intolerance in Retnlβ (RELMβ) Null Mice: A Model of Intestinal Immune System Dysfunction in Disease Susceptibility.

PubMed

Wernstedt Asterholm, Ingrid; Kim-Muller, Ja Young; Rutkowski, Joseph M; Crewe, Clair; Tao, Caroline; Scherer, Philipp E

2016-09-01

Resistin, and its closely related homologs, the resistin-like molecules (RELMs) have been implicated in metabolic dysregulation, inflammation, and cancer. Specifically, RELMβ, expressed predominantly in the goblet cells in the colon, is released both apically and basolaterally, and is hence found in both the intestinal lumen in the mucosal layer as well as in the circulation. RELMβ has been linked to both the pathogenesis of colon cancer and type 2 diabetes. RELMβ plays a complex role in immune system regulation, and the impact of loss of function of RELMβ on colon cancer and metabolic regulation has not been fully elucidated. We therefore tested whether Retnlβ (mouse ortholog of human RETNLβ) null mice have an enhanced or reduced susceptibility for colon cancer as well as metabolic dysfunction. We found that the lack of RELMβ leads to increased colonic expression of T helper cell type-2 cytokines and IL-17, associated with a reduced ability to maintain intestinal homeostasis. This defect leads to an enhanced susceptibility to the development of inflammation, colorectal cancer, and glucose intolerance. In conclusion, the phenotype of the Retnlβ null mice unravels new aspects of inflammation-mediated diseases and strengthens the notion that a proper intestinal barrier function is essential to sustain a healthy phenotype. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Translating Fatigue to Human Performance

PubMed Central

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

Factors Associated with Intern Fatigue

PubMed Central

Vidyarthi, Arpana R.; Baron, Robert B.; Katz, Patricia P.

2008-01-01

ABSTRACT BACKGROUND Prior data suggest that fatigue adversely affects patient safety and resident well-being. ACGME duty hour limitations were intended, in part, to reduce resident fatigue, but the factors that affect intern fatigue are unknown. OBJECTIVE To identify factors associated with intern fatigue following implementation of duty hour limitations. DESIGN Cross-sectional confidential survey of validated questions related to fatigue, sleep, and stress, as well as author-developed teamwork questions. SUBJECTS Interns in cognitive specialties at the University of California, San Francisco. MEASUREMENTS Univariate statistics characterized the distribution of responses. Pearson correlations elucidated bivariate relationships between fatigue and other variables. Multivariate linear regression models identified factors independently associated with fatigue, sleep, and stress. RESULTS Of 111 eligible interns, 66 responded (59%). In a regression analysis including gender, hours worked in the previous week, sleep quality, perceived stress, and teamwork, only poorer quality of sleep and greater perceived stress were significantly associated with fatigue (p < 0.001 and p = 0.02, respectively). To identify factors that may affect sleep, specifically duty hours and stress, a secondary model was constructed. Only greater perceived stress was significantly associated with diminished sleep quality (p = 0.04), and only poorer teamwork was significantly associated with perceived stress (p < 0.001). Working >80 h was not significantly associated with perceived stress, quality of sleep, or fatigue. CONCLUSIONS Simply decreasing the number of duty hours may be insufficient to reduce intern fatigue. Residency programs may need to incorporate programmatic changes to reduce stress, improve sleep quality, and foster teamwork in order to decrease intern fatigue and its deleterious consequences. PMID:18807096

The frequency of the chronic fatigue syndrome in patients with symptoms of persistent fatigue.

PubMed

Manu, P; Lane, T J; Matthews, D A

1988-10-01

To determine the frequency of the chronic fatigue syndrome among patients with symptoms of fatigue. Prospective, cohort study. Referral clinic, based in a primary care general internal medicine faculty practice of a university medical center. Consecutive sample of 135 patients (53 men, 82 women) with 6 months or more of debilitating fatigue. All patients had a complete history taken, had a physical examination and a comprehensive battery of blood tests, and were given the Diagnostic Interview Schedule of the National Institute of Mental Health, a highly-structured 260-item instrument designed to enable accurate psychiatric diagnoses. Other diagnostic studies (for example, sleep studies and electroencephalography) were ordered if necessary for individual patients. Six of the one hundred thirty-five patients met criteria for chronic fatigue syndrome (95% CI, 0 to 10). Ninety-one (67%) patients (CI, 56 to 78) had clinically active psychiatric disorders and 4 (3%) patients (CI, 0 to 8) had medical disorders that were considered a major cause of their fatigue. Thirty-four (25%) patients (CI, 14 to 36) had insufficient symptoms or objective findings of the chronic fatigue syndrome. The chronic fatigue syndrome is rare among patients with symptoms of persistent fatigue. Most of these patients have psychiatric disorders.

The Immune System’s Role in the Biology of Autism

PubMed Central

Goines, Paula; Van de Water, Judy

2010-01-01

PURPOSE OF REVIEW The following is a review of the most recent research concerning the potential role of immune system dysfunction in autism. This body of literature has expanded dramatically over the past few years as researchers continue to identify immune anomalies in individuals with autism. RECENT FINDINGS The most exciting of these recent findings is the discovery of autoantibodies targeting brain proteins in both children with autism and their mothers. In particular, circulating maternal autoantibodies directed towards fetal brain proteins are highly specific for autism. This finding has great potential as a biomarker for disease risk, and may provide an avenue for future therapeutics and prevention. Additionally, data concerning the cellular immune system in children with autism suggest there may be a defect in signaling pathways that are shared by the immune and central nervous systems. While studies to explore this hypothesis are ongoing, there is great interest in the commonalities between the neural and immune systems and their extensive interactions. SUMMARY In summary, there is exciting research regarding the role of the immune system in autism spectrum disorders that may have profound implications for diagnosis and treatment of this devastating disease. PMID:20160651

Nutritional strategies to optimize dairy cattle immunity.

PubMed

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.

Toll-like receptor 2 deficiency increases resistance to Pseudomonas aeruginosa pneumonia in the setting of sepsis-induced immune dysfunction.

PubMed

Pène, Frédéric; Grimaldi, David; Zuber, Benjamin; Sauneuf, Bertrand; Rousseau, Christophe; El Hachem, Carole; Martin, Clémence; Belaïdouni, Nadia; Balloy, Viviane; Mira, Jean-Paul; Chiche, Jean-Daniel

2012-09-15

Sepsis is characterized by a dysregulated inflammatory response followed by immunosuppression that favors the development of secondary infections. Toll-like receptors (TLRs) are major regulators of the host's response to infections. How variability in TLR signaling may impact the development of sepsis-induced immune dysfunction has not been established. We sought to establish the role of TLR2, TLR4, and TLR5 in postseptic mice with Pseudomonas aeruginosa pneumonia. We used an experimental model of sublethal polymicrobial sepsis induced by cecal ligation and puncture (CLP). Wild-type, tlr2(-/-), tlr4(-/-), tlr5(-/-), tlr2 4(-/-) mice that underwent CLP were secondarily subjected to P. aeruginosa pulmonary infection. Postseptic wild-type and tlr4(-/-) and tlr5(-/-) mice displayed high susceptibility to P. aeruginosa pneumonia. In contrast, TLR2-deficient mice, either tlr2(-/-)or tlr2 4(-/-), that underwent CLP were resistant to the secondary pulmonary infection. As compared to wild-type mice, tlr2(-/-) mice displayed improvement in bacterial clearance, decreased bacteremic dissemination, and attenuated lung damage. Furthermore, tlr2(-/-) mice exhibited a pulmonary proinflammatory cytokine balance, with increased production of tumor necrosis factor α and decreased release of interleukin 10. In a model of secondary P. aeruginosa pneumonia in postseptic mice, TLR2 deficiency improves survival by promoting efficient bacterial clearance and restoring a proinflammatory cytokine balance in the lung.

Immune Cells Link Obesity-associated Type 2 Diabetes and Periodontitis

PubMed Central

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

Countermeasure for space flight effects on immune system: nutritional nucleotides

NASA Technical Reports Server (NTRS)

Kulkarni, A. D.; Yamauchi, K.; Sundaresan, A.; Ramesh, G. T.; Pellis, N. R.

2005-01-01

Microgravity and its environment have adverse effects on the immune system. Abnormal immune responses observed in microgravity may pose serious consequences, especially for the recent directions of NASA for long-term space missions to Moon, Mars and deep Space exploration. The study of space flight immunology is limited due to relative inaccessibility, difficulty of performing experiments in space, and inadequate provisions in this area in the United States and Russian space programs (Taylor 1993). Microgravity and stress experienced during space flights results in immune system aberration (Taylor 1993). In ground-based mouse models for some of the microgravity effects on the human body, hindlimb unloading (HU) has been reported to cause abnormal cell proliferation and cytokine production (Armstrong et al., 1993, Chapes et al. 1993). In this report, we document that a nutritional nucleotide supplementation as studied in ground-based microgravity analogs, has potential to serve as a countermeasure for the immune dysfunction observed in space travel.

Effects of a One-to-One Fatigue Management Course for People With Chronic Conditions and Fatigue.

PubMed

Van Heest, Katy N L; Mogush, Ashley R; Mathiowetz, Virgil G

We assessed the impact of a one-to-one fatigue management course on participants' fatigue, self-efficacy, quality of life, and energy conservation behaviors. This observational study used a one-group, pretest-posttest, follow-up design. Forty-nine people with chronic conditions and fatigue participated in the one-to-one fatigue management course in outpatient and community-based settings. The Functional Assessment of Chronic Illness Therapy-Fatigue Scale was used to measure fatigue; the Functional Assessment of Cancer Therapy-General measured quality of life; and the Self-Efficacy for Performing Energy Conservation Strategies Assessment was used to measure self-efficacy. Participants showed significant reductions in fatigue and significant increases in self-efficacy and quality of life at posttest. These beneficial effects were maintained at follow-up. The Social Well-Being subscale was the only measure on which outcomes did not change significantly. The one-to-one fatigue management course is a beneficial intervention for people with chronic conditions and fatigue. Copyright © 2017 by the American Occupational Therapy Association, Inc.

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

PubMed

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

Fatigue-induced early onset of anticipatory postural adjustments in non-fatigued muscles: support for a centrally mediated adaptation.

PubMed

Strang, Adam J; Berg, William P; Hieronymus, Mathias

2009-08-01

Muscle fatigue has been shown to result in early onset of anticipatory postural adjustments (APAs) relative to those produced in a non-fatigued state. This adaptation is thought to reflect an attempt to preserve postural stability during a focal movement performed in a fatigued state. It remains unclear, however, whether this adaptation is of central (e.g., central nervous system motor command) or peripheral (e.g., muscle contractile properties), origin. One way to confirm that this adaptation is centrally driven is to identify fatigued-induced early APA onsets in non-fatigued muscles. In this study, APAs were obtained using a rapid bilateral reaching maneuver and recorded via surface electromyography before and after conditions of rest (n = 25) or fatigue (n = 25). Fatigue was generated using isokinetic exercise of the right leg. Results showed that fatigue-induced early APA onsets occurred in fatigued and non-fatigued muscles, confirming that fatigue-induced early APA onset is a centrally mediated adaptation.

Influence of diabetes mellitus on immunity to human tuberculosis.

PubMed

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.

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

PubMed

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 < 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

The Boeing 747 fatigue integrity program

NASA Technical Reports Server (NTRS)

Spencer, M. M.

1972-01-01

The fatigue integrity program which was established to insure economic operations and to provide foundation data for inspection and maintenance is discussed. Significant features of the 747 fatigue integrity program are: (1) fatigue analyses which are continually updated to reflect design changes, fatigue test results, and static and flight load survey measurements; (2) material selection and detail design by using initial fatigue analyses, service experience, and testing; and (3) fatigue testing to check detail design quality and to verify the analyses, culminated by the test of a structurally complete airframe. Fatigue stress analyses were performed with the aid of experimental as well as analytical procedures. Extensive application was made of the stress severity factor, developed at Boeing, for evaluating peak stresses in complex joints. A frame of reference was established by families of structural fatigue performance curves (S-N curves) encompassing the range of materials and fatigue qualities anticipated for the 747 airplane design.

Developmental origins of inflammatory and immune diseases.

PubMed

Chen, Ting; Liu, Han-Xiao; Yan, Hui-Yi; Wu, Dong-Mei; Ping, Jie

2016-08-01

Epidemiological and experimental animal studies show that suboptimal environments in fetal and neonatal life exert a profound influence on physiological function and risk of diseases in adult life. The concepts of the 'developmental programming' and Developmental Origins of Health and Diseases (DOHaD) have become well accepted and have been applied across almost all fields of medicine. Adverse intrauterine environments may have programming effects on the crucial functions of the immune system during critical periods of fetal development, which can permanently alter the immune function of offspring. Immune dysfunction may in turn lead offspring to be susceptible to inflammatory and immune diseases in adulthood. These facts suggest that inflammatory and immune disorders might have developmental origins. In recent years, inflammatory and immune disorders have become a growing health problem worldwide. However, there is no systematic report in the literature on the developmental origins of inflammatory and immune diseases and the potential mechanisms involved. Here, we review the impacts of adverse intrauterine environments on the immune function in offspring. This review shows the results from human and different animal species and highlights the underlying mechanisms, including damaged development of cells in the thymus, helper T cell 1/helper T cell 2 balance disturbance, abnormal epigenetic modification, effects of maternal glucocorticoid overexposure on fetal lymphocytes and effects of the fetal hypothalamic-pituitary-adrenal axis on the immune system. Although the phenomena have already been clearly implicated in epidemiologic and experimental studies, new studies investigating the mechanisms of these effects may provide new avenues for exploiting these pathways for disease prevention. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email

HIV and neurocognitive dysfunction.

PubMed

Spudich, Serena

2013-09-01

The spectrum of HIV-associated neurocognitive disorder (HAND) has been dramatically altered in the setting of widely available effective antiretroviral therapy (ART). Once culminating in dementia in many individuals infected with HIV, HAND now typically manifests as more subtle, though still morbid, forms of cognitive impairment in persons surviving long-term with treated HIV infection. Despite the substantial improvement in severity of this disorder, the fact that neurologic injury persists despite ART remains a challenge to the community of patients, providers and investigators aiming to optimize quality of life for those living with HIV. Cognitive dysfunction in treated HIV may reflect early irreversible CNS injury accrued before ART is typically initiated, ongoing low-level CNS infection and progressive injury in the setting of ART, or comborbidities including effects of treatment which may confound the beneficial reduction in viral replication and immune activation effected by ART.

Fatigue crack growth and low cycle fatigue of two nickel base superalloys

NASA Technical Reports Server (NTRS)

Stoloff, N. S.; Duquette, D. J.; Choe, S. J.; Golwalkar, S.

1983-01-01

The fatigue crack growth and low cycle fatigue behavior of two P/M superalloys, Rene 95 and Astroloy, in the hot isostatically pressed (HIP) condition, was determined. Test variables included frequency, temperature, environment, and hold times at peak tensile loads (or strains). Crack initiation sites were identified in both alloys. Crack growth rates were shown to increase in argon with decreasing frequency or with the imposition of hold times. This behavior was attributed to the effect of oxygen in the argon. Auger analyses were performed on oxide films formed in argon. Low cycle fatigue lives also were degraded by tensile hold, contrary to previous reports in the literature. The role of environment in low cycle fatigue behavior is discussed.

Muscle fatigue effects can be anticipated to reproduce a movement kinematics learned without fatigue.

PubMed

Monjo, Florian; Forestier, Nicolas

2016-12-17

Muscle fatigue modifies the gain between motor command magnitude and the mechanical muscular response. In other words, post-fatigue, central drives to the muscles must increase to maintain a particular submaximum mechanical output. In this study, we tested the hypothesis that this modified gain can be predicted by the central nervous system (CNS) during discrete ballistic movements. In two separate experiments, subjects were required to perform shoulder flexions in standing and sitting positions at submaximum target peak accelerations. They were assisted with visual feedback informing them on their performance after each trial. Shoulder flexions were performed before and after fatiguing protocols of the focal muscles. Acceleration signals, focal and postural muscle electromyograms (EMGs) were recorded. The results demonstrated that participants were able to reach with precision the target acceleration during the first movements post-fatigue at the cost of significant increase in focal motor command magnitude. Decreased variance of peak accelerations associated with increased focal command variability was observed post-fatigue. During the standing experiment, postural muscle EMGs revealed that anticipatory postural adjustments (APAs) scaled to focal movement acceleration post-fatigue. All these results support that fatigue effects are taken into account during movement planning. Indeed, given that no feedback could enable participants to adjust acceleration during movement, this capacity to anticipate fatigue effects is the exclusive result of feedforward processes. To account for this prediction capacity, we discuss the role of fatigue-related modifications in sensory inputs from the working muscles. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Physical fitness and physical activity in fatigued and non-fatigued inflammatory bowel disease patients.

PubMed

Vogelaar, Lauran; van den Berg-Emons, Rita; Bussmann, Hans; Rozenberg, Robert; Timman, Reinier; van der Woude, Christien J

2015-01-01

To assess physical fitness and physical activity in inflammatory bowel disease (IBD) patients and whether fatigue is associated with impaired physical fitness and impaired physical activity. Ten patients with quiescent IBD and fatigue (fatigue group [FG]) based on the Checklist Individual Strength-Fatigue score of ≥35 were matched for age (±5 years) and sex with a non-fatigue group (NFG) with IBD. Physical fitness was measured with a cyclo-ergometric-based maximal exercise test, a submaximal 6-min walk test, and a dynamometer test to quantify the isokinetic muscle strength of the knee extensors and flexors. Level of physical activity was measured with an accelerometer-based activity monitor. The patients in both groups did not differ in regard to medication use, clinical characteristics, and body composition. However, medium-to-large effect sizes for impaired physical fitness (both cardiorespiratory fitness and muscle strength) and physical activity were seen between the patients in the FG and the NFG. Especially, intensity of physical activity was significantly lower in the FG patients compared with the NFG patients (effect size: 1.02; p = 0.037). Similar results were seen when outcomes of the FG and NFG were compared with reference values of the normal population. Fatigued IBD patients show an impaired physical fitness and physical activity compared with non-fatigued IBD patients. This gives directions for a physical component in fatigue in IBD patients. Therefore, these new insights into fatigue indicate that these patients might benefit from an exercise program to improve physical fitness and physical activity.

Temporomandibular dysfunction

PubMed

Lomas, Jonathan; Gurgenci, Taylan; Jackson, Christopher; Campbell, Duncan

2018-04-01

Orofacial pain is a common presentation in the primary healthcare setting and temporomandibular dysfunction represents one of the major causes. Its aetiology is multifactorial, caused by both masticatory muscle dysfunction and derangement within the temporomandibular joint. The aim of this article is to provide an overview of temporomandibular dysfunction, its management and referral considerations for general practioners. Temporomandibular joint dysfunction affects a large number of adults. Conservative management involving non-pharmacological and pharmacological therapies is effective in the majority of cases.

Fatigue and fatigability in neurologic illnesses

PubMed Central

Krupp, Lauren B.; Enoka, Roger M.

2013-01-01

Fatigue is commonly reported in many neurologic illnesses, including multiple sclerosis, Parkinson disease, myasthenia gravis, traumatic brain injury, and stroke. Fatigue contributes substantially to decrements in quality of life and disability in these illnesses. Despite the clear impact of fatigue as a disabling symptom, our understanding of fatigue pathophysiology is limited and current treatment options rarely lead to meaningful improvements in fatigue. Progress continues to be hampered by issues related to terminology and assessment. In this article, we propose a unified taxonomy and a novel assessment approach to addressing distinct aspects of fatigue and fatigability in clinical and research settings. This taxonomy is based on our current knowledge of the pathophysiology and phenomenology of fatigue and fatigability. Application of our approach indicates that the assessment and reporting of fatigue can be clarified and improved by utilizing this taxonomy and creating measures to address distinct aspects of fatigue and fatigability. We review the strengths and weaknesses of several common measures of fatigue and suggest, based on our model, that many research questions may be better addressed by using multiple measures. We also provide examples of how to apply and validate the taxonomy and suggest directions for future research. PMID:23339207

Effects of Astragalus Polysaccharides on Dysfunction of Mitochondrial Dynamics Induced by Oxidative Stress.

PubMed

Huang, Yan-Feng; Lu, Lu; Zhu, Da-Jian; Wang, Ming; Yin, Yi; Chen, De-Xiu; Wei, Lian-Bo

2016-01-01

This paper studied the chronic fatigue induced by excessive exercise and the restoration effects of Astragalus polysaccharides (APS) on mitochondria. In vivo, we found that excessive exercise could cause oxidative stress statue which led to morphological and functional changes of mitochondria. The changes, including imbalance between mitochondria fusion-fission processes, activation of mitophagy, and decrease of PGC-1α expression, could be restored by APS. We further confirmed in vitro, and what is more, we found that APS may ameliorate mitochondrial dysfunction through Sirt1 pathway. Based on the results, we may figure out part of the molecular mechanism of mitochondrial amelioration by APS.

Evaluation of Giga-cycle Fatigue Properties of Austenitic Stainless Steels Using Ultrasonic Fatigue Test

NASA Astrophysics Data System (ADS)

Takahashi, Kyouhei; Ogawa, Takeshi

Ultrasonic fatigue tests have been performed in austenitic stainless steel, SUS316NG, in order to investigate giga-cycle fatigue strength of pre-strained materials, i.e. 5, 10 and 20% tensile pre-strains and -20% compressive pre-strain. The pre-strains were applied before specimen machining. The austenitic stainless steels are known to exhibit remarkable self-heating during the fatigue experiment. Therefore, heat radiation method was established by setting fatigue specimens in a low temperature chamber at about -100°C. The self-heating was controlled by intermittent loading condition, which enabled us to maintain the test section of the specimens at about room temperature. The results revealed that the fatigue strength increased with increasing pre-strain levels. Fish-eye fracture was observed for -20% pre-strained specimen fractured at 4.11×107 cycles, while the other specimens exhibited ordinary fatigue fracture surface originated from stage I facet on the specimen surface. The increase in fatigue limit was predicted by Vickers hardness, HV, which depended on the size of indented region. The prediction was successful using HV values obtained by the size of the indented region similar to those of the stage I facets.

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

PubMed Central

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

2015-01-01

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. PMID:25979947

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

PubMed

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.

Fatigue in osteoarthritis: a qualitative study

PubMed Central

Power, J Denise; Badley, Elizabeth M; French, Melissa R; Wall, Angela J; Hawker, Gillian A

2008-01-01

Background Fatigue is recognized as a disabling symptom in many chronic conditions including rheumatic disorders such as rheumatoid arthritis (RA) and lupus. Fatigue in osteoarthritis (OA) is not routinely evaluated and has only been considered in a very limited number of studies. To date, these studies have focused primarily on patients with OA under rheumatological care, which represent the minority of people living with OA. The purpose of this study was to increase our understanding of the fatigue experience in community dwelling people with OA. Methods In 2004, 8 focus groups were conducted with 28 men and 18 women (mean age 72.3) with symptomatic hip or knee OA recruited from a population-based cohort. Participants completed a self-administered questionnaire, which included demographics, measures of OA severity (WOMAC), depression (CES-D) and fatigue (FACIT). Sessions were audio taped and transcribed verbatim. Two researchers independently reviewed the transcripts to identify themes. Findings were compared and consensus reached. Results Mean pain, disability, depression and fatigue scores were 8.7/20, 27.8/68, 15.4/60, and 30.9/52, respectively. Participants described their fatigue as exhaustion, being tired and "coming up against a brick wall". Participants generally perceived fatigue as different from sleepiness and distinguished physical from mental fatigue. Factors believed to increase fatigue included OA pain and pain medications, aging, various types of weather and poor sleep. Mental health was identified as both affecting fatigue and being affected by fatigue. Participants described fatigue as impacting physical function, and their ability to participate in social activities and to do household chores. Rest, exercise, and avoiding or getting assistance with activities were cited as ways of coping. Participants generally did not discuss their fatigue with anyone except their spouses. Conclusion Participants with OA described experiencing notable amounts

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

PubMed

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.

PubMed

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.

The Prevalence of Compassion Fatigue among Veterinary Students in Australia and the Associated Psychological Factors.

PubMed

McArthur, Michelle L; Andrews, Jena R; Brand, Conor; Hazel, Susan J

Compassion fatigue, compassion satisfaction, and other characteristics such as mindfulness and mental health stigma have not been investigated in veterinary students. The aims of this study were twofold: first to determine the prevalence of compassion, satisfaction, burnout, and secondary traumatic stress among Australian veterinary students and second to investigate the association between these factors and self-stigma, coping, empathy, and mindfulness. A cross-sectional online survey consisting of demographic questions and four validated psychological measures sampled 828 students, with a response rate of 31% (255/828). We obtained a usable sample of completed surveys from 193 of 828 (23%) veterinary students from six of the seven Australian veterinary schools. Bivariate correlations and multiple regression analyses were used to examine associations between the psychological predictors and the outcome variables. Approximately 30% of veterinary students were at high risk of burnout, 24% were at high risk of secondary traumatic stress, and 21% reported low compassion satisfaction. High empathic concern, low personal distress, female gender, and employment history at a veterinary clinic were associated with high compassion satisfaction. High dysfunctional coping, low nonjudgmental and acting-with-awareness mindfulness, and lack of previous employment at a veterinary clinic were associated with high burnout. High dysfunctional coping, low acting-with-awareness mindfulness, high self-stigma, and high personal distress were associated with high secondary traumatic stress. As a result of these findings, certain emotional characteristics can be identified as targets for intervention to minimize the frequency and potentially negative impact of compassion fatigue and burnout in veterinary students.

Compassion fatigue in nurses.

PubMed

Yoder, Elizabeth A

2010-11-01

Compassion fatigue, trigger situations, and coping strategies were investigated in hospital and home care nurses. The Professional Quality of Life Scale measured compassion fatigue, compassion satisfaction, and burnout. Narrative questions elicited trigger situations and coping strategies. Compassion fatigue scores were significantly different between nurses who worked 8- or 12-hour shifts. Fifteen percent of the participants had scores indicating risk of the compassion fatigue. There were significant differences in compassion satisfaction, depending on the unit worked and time as a nurse. The most common category of trigger situations was caring for the patient. Work-related and personal coping strategies were identified. Copyright © 2010 Elsevier Inc. All rights reserved.

Fatigue Fractures

PubMed Central

Morris, James M.

1968-01-01

Fatigue (or stress) fracture of bone in military recruits has been recognized for many years. Most often it is a metatarsal bone that is involved but the tarsal bones, calcaneus, tibia, fibula, femur, and pelvis are occasionally affected. Reports of such fractures in the ribs, ulna and vertebral bodies may be found in the literature. In recent years, there has been increasing awareness of the occurrence of fatigue fractures in the civilian population. Weekend sportsmen, athletes in an early phase of training, and persons engaged in unaccustomed, repetitive, vigorous activity are potential victims of such a fracture. The signs and symptoms, roentgenographic findings, treatment and etiology of fatigue fractures are dealt with in this presentation. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6. PMID:5652745

Innate immune activation in neurodegenerative disease.

PubMed

Heneka, Michael T; Kummer, Markus P; Latz, Eicke

2014-07-01

The triggering of innate immune mechanisms is emerging as a crucial component of major neurodegenerative diseases. Microglia and other cell types in the brain can be activated in response to misfolded proteins or aberrantly localized nucleic acids. This diverts microglia from their physiological and beneficial functions, and leads to their sustained release of pro-inflammatory mediators. In this Review, we discuss how the activation of innate immune signalling pathways - in particular, the NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome - by aberrant host proteins may be a common step in the development of diverse neurodegenerative disorders. During chronic activation of microglia, the sustained exposure of neurons to pro-inflammatory mediators can cause neuronal dysfunction and contribute to cell death. As chronic neuroinflammation is observed at relatively early stages of neurodegenerative disease, targeting the mechanisms that drive this process may be useful for diagnostic and therapeutic purposes.

Muscle Deoxygenation Causes Muscle Fatigue

NASA Technical Reports Server (NTRS)

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.