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Sample records for fatigue immune dysfunction

  1. Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome

    SciTech Connect

    DeFreitas, E.; Hilliard, B.; Cheney, P.R.; Bell, D.S.; Kiggundu, E.; Sankey, D.; Wroblewska, Z.; Palladino, M.; Woodward, J.P.; Koprowski, H. )

    1991-04-01

    Chronic fatigue immune dysfunction syndrome (CFIDS) is a recently recognized illness characterized by debilitating fatigue as well as immunological and neurological abnormalities. Once thought to be caused by Epstein-Barr virus, it is now thought to have a different but unknown etiology. The authors evaluted 30 adult and pediatric CFIDS patients from six eastern states for the presence of human T-lymphotropic virus (HTLV) types I and II by Western immunoblotting, polymerase chain reaction, and in situ hybridization of blood samples. The majority of patients were positive for HTLV antibodies by Western blotting and for HTLV-II gag sequences by polymerase chain reaction and in situ hybridization. Twenty nonexposure healthy controls were negative in all assays. These data support an association between an HTLV-II-like virus and CFIDS.

  2. Understanding Muscle Dysfunction in Chronic Fatigue Syndrome.

    PubMed

    Rutherford, Gina; Manning, Philip; Newton, Julia L

    2016-01-01

    Introduction. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a debilitating disorder of unknown aetiology, characterised by severe disabling fatigue in the absence of alternative diagnosis. Historically, there has been a tendency to draw psychological explanations for the origin of fatigue; however, this model is at odds with findings that fatigue and accompanying symptoms may be explained by central and peripheral pathophysiological mechanisms, including effects of the immune, oxidative, mitochondrial, and neuronal pathways. For example, patient descriptions of their fatigue regularly cite difficulty in maintaining muscle activity due to perceived lack of energy. This narrative review examined the literature for evidence of biochemical dysfunction in CFS/ME at the skeletal muscle level. Methods. Literature was examined following searches of PUB MED, MEDLINE, and Google Scholar, using key words such as CFS/ME, immune, autoimmune, mitochondria, muscle, and acidosis. Results. Studies show evidence for skeletal muscle biochemical abnormality in CFS/ME patients, particularly in relation to bioenergetic dysfunction. Discussion. Bioenergetic muscle dysfunction is evident in CFS/ME, with a tendency towards an overutilisation of the lactate dehydrogenase pathway following low-level exercise, in addition to slowed acid clearance after exercise. Potentially, these abnormalities may lead to the perception of severe fatigue in CFS/ME.

  3. Understanding Muscle Dysfunction in Chronic Fatigue Syndrome

    PubMed Central

    Rutherford, Gina; Manning, Philip; Newton, Julia L.

    2016-01-01

    Introduction. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a debilitating disorder of unknown aetiology, characterised by severe disabling fatigue in the absence of alternative diagnosis. Historically, there has been a tendency to draw psychological explanations for the origin of fatigue; however, this model is at odds with findings that fatigue and accompanying symptoms may be explained by central and peripheral pathophysiological mechanisms, including effects of the immune, oxidative, mitochondrial, and neuronal pathways. For example, patient descriptions of their fatigue regularly cite difficulty in maintaining muscle activity due to perceived lack of energy. This narrative review examined the literature for evidence of biochemical dysfunction in CFS/ME at the skeletal muscle level. Methods. Literature was examined following searches of PUB MED, MEDLINE, and Google Scholar, using key words such as CFS/ME, immune, autoimmune, mitochondria, muscle, and acidosis. Results. Studies show evidence for skeletal muscle biochemical abnormality in CFS/ME patients, particularly in relation to bioenergetic dysfunction. Discussion. Bioenergetic muscle dysfunction is evident in CFS/ME, with a tendency towards an overutilisation of the lactate dehydrogenase pathway following low-level exercise, in addition to slowed acid clearance after exercise. Potentially, these abnormalities may lead to the perception of severe fatigue in CFS/ME. PMID:26998359

  4. Effects of Nutritional Supplementation on Fatigue, and Autonomic and Immune Dysfunction in Patients with End-Stage Renal Disease: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial

    PubMed Central

    Fukuda, Sanae; Koyama, Hidenori; Kondo, Kazuhiro; Fujii, Hisako; Hirayama, Yoshinobu; Tabata, Tsutomu; Okamura, Mikio; Yamakawa, Tomoyuki; Okada, Shigeki; Hirata, Sumio; Kiyama, Hiroshi; Kajimoto, Osami; Watanabe, Yasuyoshi; Inaba, Masaaki; Nishizawa, Yoshiki

    2015-01-01

    Background Fatigue is a predictor of cardiovascular events in patients with end-stage renal disease (ESRD) undergoing hemodialysis treatment. We hypothesized that multinutritional support would improve quality of life, fatigue symptoms, and potential quantitative measures including endocrine, immune and autonomic functions in patients with ESRD undergoing hemodialysis. Methods Two hundred and two hemodialysis patients were randomly assigned to receive active treatment (containing vitamin B1, vitamin B2, niacin, vitamin B6, vitamin B12, folic acid, vitamin C, carnitine, coenzyme Q10, naïve galacto-oligosaccharide, and zinc) or placebo after each dialysis session for 12 weeks. The patients and attending physicians were blinded to the treatment, and 172 patients (86 in each group) completed the study. Fatigue was evaluated via fatigue questionnaire at 0, 4, and 12 weeks. To assess human herpes virus (HHV) 6 and 7 reactivation, numbers of viral DNA copies were determined in saliva by polymerase chain reaction at weeks 0 and 12. Autonomic function was determined via measurement of beat-to-beat variation by using acceleration plethysmography. Results Clinical characteristics, changes in fatigue, quality of life score, endocrine functions, and laboratory data did not differ significantly between the two groups. Several parameters of heart rate variability significantly increased after nutritional treatment compared to placebo. Nutritional drink for 12 weeks significantly suppressed HHV7 DNA copy numbers. Similarly, HHV6 DNA copy numbers tended to be decreased by treatment but without reaching statistical significance. Conclusions Nutritional supplementation may modulate immune and autonomic dysfunction in ESRD patients undergoing hemodialysis. PMID:25746727

  5. Chronic fatigue syndrome and mitochondrial dysfunction

    PubMed Central

    Myhill, Sarah; Booth, Norman E.; McLaren-Howard, John

    2009-01-01

    This study aims to improve the health of patients suffering from chronic fatigue syndrome (CFS) by interventions based on the biochemistry of the illness, specifically the function of mitochondria in producing ATP (adenosine triphosphate), the energy currency for all body functions, and recycling ADP (adenosine diphosphate) to replenish the ATP supply as needed. Patients attending a private medical practice specializing in CFS were diagnosed using the Centers for Disease Control criteria. In consultation with each patient, an integer on the Bell Ability Scale was assigned, and a blood sample was taken for the “ATP profile” test, designed for CFS and other fatigue conditions. Each test produced 5 numerical factors which describe the availability of ATP in neutrophils, the fraction complexed with magnesium, the efficiency of oxidative phosphorylation, and the transfer efficiencies of ADP into the mitochondria and ATP into the cytosol where the energy is used. With the consent of each of 71 patients and 53 normal, healthy controls the 5 factors have been collated and compared with the Bell Ability Scale. The individual numerical factors show that patients have different combinations of biochemical lesions. When the factors are combined, a remarkable correlation is observed between the degree of mitochondrial dysfunction and the severity of illness (P<0.001). Only 1 of the 71 patients overlaps the normal region. The “ATP profile” test is a powerful diagnostic tool and can differentiate patients who have fatigue and other symptoms as a result of energy wastage by stress and psychological factors from those who have insufficient energy due to cellular respiration dysfunction. The individual factors indicate which remedial actions, in the form of dietary supplements, drugs and detoxification, are most likely to be of benefit, and what further tests should be carried out. PMID:19436827

  6. The effect of fatigue and fibromyalgia on sexual dysfunction in women with chronic fatigue syndrome.

    PubMed

    Blazquez, Alicia; Ruiz, Eva; Aliste, Luisa; García-Quintana, Ana; Alegre, José

    2015-01-01

    Sexual dysfunction in patients with chronic fatigue syndrome is attracting growing interest but, to date, few studies have analyzed it. For this reason, the authors evaluated sexual dysfunction in women with chronic fatigue syndrome (using the Golombok Rust Inventory of Sexual Satisfaction) and explore correlations with fatigue and other symptoms. Sexual dysfunction was greater in patients with chronic fatigue syndrome (n = 615) with a higher number of cognitive, neurological, and neurovegetative symptoms, concomitant fibromyalgia, Sjögren's syndrome, or myofascial pain syndrome, and more intense fatigue (p <.05).

  7. Tumor-induced immune dysfunction.

    PubMed

    Kiessling, R; Wasserman, K; Horiguchi, S; Kono, K; Sjöberg, J; Pisa, P; Petersson, M

    1999-10-01

    Immune system-based approaches for the treatment of malignant disease over the past decades have often focused on cytolytic effector cells such as cytotoxic T lymphocytes (CTL), and natural killer (NK) cells. It has also been demonstrated that tumor-bearing mice can be cured using a wide variety of approaches, some of which involve cytokine-mediated enhancement of CTL and NK cell activity. However, the apparent success in mice stands in contrast to the current situation in the clinic, wherein only a minority of patients have thus far benefited from CTL- or NK cell-based antitumor approaches. The underlying causes of tumor-associated immune suppression of CTL and NK cell activity are discussed, and features of interest shared with HIV infection, leprosy, and rheumatoid arthritis are also be mentioned. Remarkable and very recent observations have shed more light upon the causes of dysfunctional alterations in CTL and NK cells often associated with these diseases, that in turn have suggested new immunotherapeutic approaches for cancer and infectious disease. PMID:10501847

  8. The Neuro-Immune Pathophysiology of Central and Peripheral Fatigue in Systemic Immune-Inflammatory and Neuro-Immune Diseases.

    PubMed

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

    2016-03-01

    Many patients with systemic immune-inflammatory and neuro-inflammatory disorders, including depression, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's disease, cancer, cardiovascular disorder, Parkinson's disease, multiple sclerosis, stroke, and chronic fatigue syndrome/myalgic encephalomyelitis, endure pathological levels of fatigue. The aim of this narrative review is to delineate the wide array of pathways that may underpin the incapacitating fatigue occurring in systemic and neuro-inflammatory disorders. A wide array of immune, inflammatory, oxidative and nitrosative stress (O&NS), bioenergetic, and neurophysiological abnormalities are involved in the etiopathology of these disease states and may underpin the incapacitating fatigue that accompanies these disorders. This range of abnormalities comprises: increased levels of pro-inflammatory cytokines, e.g., interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF) α and interferon (IFN) α; O&NS-induced muscle fatigue; activation of the Toll-Like Receptor Cycle through pathogen-associated (PAMPs) and damage-associated (DAMPs) molecular patterns, including heat shock proteins; altered glutaminergic and dopaminergic neurotransmission; mitochondrial dysfunctions; and O&NS-induced defects in the sodium-potassium pump. Fatigue is also associated with altered activities in specific brain regions and muscle pathology, such as reductions in maximum voluntary muscle force, downregulation of the mitochondrial biogenesis master gene peroxisome proliferator-activated receptor gamma coactivator 1-alpha, a shift to glycolysis and buildup of toxic metabolites within myocytes. As such, both mental and physical fatigue, which frequently accompany immune-inflammatory and neuro-inflammatory disorders, are the consequence of interactions between multiple systemic and central pathways.

  9. Skin Immunization Obviates Alcohol-Related Immune Dysfunction.

    PubMed

    Brand, Rhonda M; Stottlemyer, John Mark; Cline, Rachel A; Donahue, Cara; Behari, Jaideep; Falo, Louis D

    2015-01-01

    Alcoholics suffer from immune dysfunction that can impede vaccine efficacy. If ethanol (EtOH)-induced immune impairment is in part a result of direct exposure of immune cells to EtOH, then reduced levels of exposure could result in less immune dysfunction. As alcohol ingestion results in lower alcohol levels in skin than blood, we hypothesized that the skin immune network may be relatively preserved, enabling skin-targeted immunizations to obviate the immune inhibitory effects of alcohol consumption on conventional vaccines. We employed the two most common chronic EtOH mouse feeding models, the liver-damaging Lieber-DeCarli (LD) and liver-sparing Meadows-Cook (MC) diets, to examine the roles of EtOH and/or EtOH-induced liver dysfunction on alcohol related immunosuppression. Pair-fed mice were immunized against the model antigen ovalbumin (OVA) by DNA immunization or against flu by administering the protein-based influenza vaccine either systemically (IV, IM), directly to liver (hydrodynamic), or cutaneously (biolistic, ID). We measured resulting tissue EtOH levels, liver stress, regulatory T cell (Treg), and myeloid-derived suppressor cell (MDSC) populations. We compared immune responsiveness by measuring delayed-type hypersensitivity (DTH), antigen-specific cytotoxic T lymphocyte (CTL), and antibody induction as a function of delivery route and feeding model. We found that, as expected, and independent of the feeding model, EtOH ingestion inhibits DTH, CTL lysis, and antigen-specific total IgG induced by traditional systemic vaccines. On the other hand, skin-targeted vaccines were equally immunogenic in alcohol-exposed and non-exposed subjects, suggesting that cutaneous immunization may result in more efficacious vaccination in alcohol-ingesting subjects. PMID:26561838

  10. Immune dysfunction in acute alcoholic hepatitis

    PubMed Central

    Dhanda, Ashwin D; Collins, Peter L

    2015-01-01

    Acute alcoholic hepatitis (AAH) is a serious complication of alcohol misuse and has high short term mortality. It is a clinical syndrome characterised by jaundice and coagulopathy in a patient with a history of recent heavy alcohol use and is associated with profound immune dysfunction with a primed but ineffective immune response against pathogens. Here, we review the current knowledge of the pathogenesis and immune defects of AAH and identify areas requiring further study. Alcohol activates the immune system primarily through the disruption of gut tight junction integrity allowing the escape of pathogen-associated molecular particles (PAMPs) into the portal venous system. PAMPs stimulate cells expressing toll-like receptors (mainly myeloid derived cells) and initiate a network of intercellular signalling by secretion of many soluble mediators including cytokines and chemokines. The latter coordinates the infiltration of neutrophils, monocytes and T cells and results in hepatic stellate cell activation, cellular damage and hepatocyte death by necrosis or apoptosis. On the converse of this immune activation is the growing evidence of impaired microbial defence. Neutrophils have reduced phagocytic capacity and oxidative burst and there is recent evidence that T cell exhaustion plays a role in this. PMID:26576079

  11. 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.

  12. Monitoring of the Immune Dysfunction in Cancer Patients.

    PubMed

    Santegoets, Saskia J A M; Welters, Marij J P; van der Burg, Sjoerd H

    2016-01-01

    Immunotherapy shows promising clinical results in patients with different types of cancer, but its full potential is not reached due to immune dysfunction as a result of several suppressive mechanisms that play a role in cancer development and progression. Monitoring of immune dysfunction is a prerequisite for the development of strategies aiming to alleviate cancer-induced immune suppression. At this point, the level at which immune dysfunction occurs has to be established, the underlying mechanism(s) need to be known, as well as the techniques to assess this. While it is relatively easy to measure general signs of immune suppression, it turns out that accurate monitoring of the frequency and function of immune-suppressive cells is still difficult. A lack of truly specific markers, the phenotypic complexity among suppressive cells of the same lineage, but potentially with different functions and functional assays that may not cover every mechanistic aspect of immune suppression are among the reasons complicating proper assessments. Technical innovations in flow and mass cytometry will allow for more complete sets of markers to precisely determine phenotype and associated function. There is, however, a clear need for functional assays that recapitulate more of the mechanisms employed to suppress the immune system. PMID:27598210

  13. Monitoring of the Immune Dysfunction in Cancer Patients

    PubMed Central

    Santegoets, Saskia J. A. M.; Welters, Marij J. P.; van der Burg, Sjoerd H.

    2016-01-01

    Immunotherapy shows promising clinical results in patients with different types of cancer, but its full potential is not reached due to immune dysfunction as a result of several suppressive mechanisms that play a role in cancer development and progression. Monitoring of immune dysfunction is a prerequisite for the development of strategies aiming to alleviate cancer-induced immune suppression. At this point, the level at which immune dysfunction occurs has to be established, the underlying mechanism(s) need to be known, as well as the techniques to assess this. While it is relatively easy to measure general signs of immune suppression, it turns out that accurate monitoring of the frequency and function of immune-suppressive cells is still difficult. A lack of truly specific markers, the phenotypic complexity among suppressive cells of the same lineage, but potentially with different functions and functional assays that may not cover every mechanistic aspect of immune suppression are among the reasons complicating proper assessments. Technical innovations in flow and mass cytometry will allow for more complete sets of markers to precisely determine phenotype and associated function. There is, however, a clear need for functional assays that recapitulate more of the mechanisms employed to suppress the immune system. PMID:27598210

  14. Monitoring of the Immune Dysfunction in Cancer Patients.

    PubMed

    Santegoets, Saskia J A M; Welters, Marij J P; van der Burg, Sjoerd H

    2016-09-02

    Immunotherapy shows promising clinical results in patients with different types of cancer, but its full potential is not reached due to immune dysfunction as a result of several suppressive mechanisms that play a role in cancer development and progression. Monitoring of immune dysfunction is a prerequisite for the development of strategies aiming to alleviate cancer-induced immune suppression. At this point, the level at which immune dysfunction occurs has to be established, the underlying mechanism(s) need to be known, as well as the techniques to assess this. While it is relatively easy to measure general signs of immune suppression, it turns out that accurate monitoring of the frequency and function of immune-suppressive cells is still difficult. A lack of truly specific markers, the phenotypic complexity among suppressive cells of the same lineage, but potentially with different functions and functional assays that may not cover every mechanistic aspect of immune suppression are among the reasons complicating proper assessments. Technical innovations in flow and mass cytometry will allow for more complete sets of markers to precisely determine phenotype and associated function. There is, however, a clear need for functional assays that recapitulate more of the mechanisms employed to suppress the immune system.

  15. Immune activation during cerebellar dysfunction following Plasmodium falciparum malaria.

    PubMed

    de Silva, H J; Hoang, P; Dalton, H; de Silva, N R; Jewell, D P; Peiris, J B

    1992-01-01

    Evidence for immune activation was investigated in 12 patients with a rare syndrome of self-limiting, delayed onset cerebellar dysfunction following an attack of falciparum malaria which occurred 18-26 d previously. Concentrations of tumour necrosis factor, interleukin 6 and interleukin 2 were all significantly higher in serum samples of patients during cerebellar ataxia than in recovery sera and in the sera of 8 patients who did not develop delayed cerebellar dysfunction following an attack of falciparum malaria. Cytokine concentrations in the cerebrospinal fluid were also significantly higher in ataxic patients than in controls. These findings suggest that immunological mechanisms may play a role in delayed cerebellar dysfunction following falciparum malaria.

  16. Epigenetic Dysfunction in Turner Syndrome Immune Cells.

    PubMed

    Thrasher, Bradly J; Hong, Lee Kyung; Whitmire, Jason K; Su, Maureen A

    2016-05-01

    Turner syndrome (TS) is a chromosomal condition associated with partial or complete absence of the X chromosome that involves characteristic findings in multiple organ systems. In addition to well-known clinical characteristics such as short stature and gonadal failure, TS is also associated with T cell immune alterations and chronic otitis media, suggestive of a possible immune deficiency. Recently, ubiquitously transcribed tetratricopeptide repeat on the X chromosome (UTX), a histone H3 lysine 27 (H3K27) demethylase, has been identified as a downregulated gene in TS immune cells. Importantly, UTX is an X-linked gene that escapes X-chromosome inactivation and thus is haploinsufficient in TS. Mice with T cell-specific UTX deficiency have impaired clearance of chronic viral infection due to decreased frequencies of T follicular helper (Tfh) cells, which are critical for B cell antibody generation. In parallel, TS patients have decreased Tfh frequencies in peripheral blood. Together, these findings suggest that haploinsufficiency of the X-linked UTX gene in TS T cells underlies an immune deficit, which may manifest as increased predisposition to chronic otitis media.

  17. 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.

  18. 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

  19. 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. PMID:26247027

  20. The role of neutrophils in immune dysfunction during severe inflammation.

    PubMed

    Leliefeld, Pieter H C; Wessels, Catharina M; Leenen, Luke P H; Koenderman, Leo; Pillay, Janesh

    2016-01-01

    Critically ill post-surgical, post-trauma and/or septic patients are characterised by severe inflammation. This immune response consists of both a pro- and an anti-inflammatory component. The pro-inflammatory component contributes to (multiple) organ failure whereas occurrence of immune paralysis predisposes to infections. Strikingly, infectious complications arise in these patients despite the presence of a clear neutrophilia. We propose that dysfunction of neutrophils potentially increases the susceptibility to infections or can result in the inability to clear existing infections. Under homeostatic conditions these effector cells of the innate immune system circulate in a quiescent state and serve as the first line of defence against invading pathogens. In severe inflammation, however, neutrophils are rapidly activated, which affects their functional capacities, such as chemotaxis, phagocytosis, intra-cellular killing, NETosis, and their capacity to modulate adaptive immunity. This review provides an overview of the current understanding of neutrophil dysfunction in severe inflammation. We will discuss the possible mechanisms of downregulation of anti-microbial function, suppression of adaptive immunity by neutrophils and the contribution of neutrophil subsets to immune paralysis. PMID:27005275

  1. 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.

  2. Aspects of Immune Dysfunction in End-stage Renal Disease

    PubMed Central

    Kato, Sawako; Chmielewski, Michal; Honda, Hirokazu; Pecoits-Filho, Roberto; Matsuo, Seiichi; Yuzawa, Yukio; Tranaeus, Anders; Stenvinkel, Peter; Lindholm, Bengt

    2008-01-01

    End-stage renal disease (ESRD) is associated with significantly increased morbidity and mortality resulting from cardiovascular disease (CVD) and infections, accounting for 50% and 20%, respectively, of the total mortality in ESRD patients. It is possible that these two complications are linked to alterations in the immune system in ESRD, as uremia is associated with a state of immune dysfunction characterized by immunodepression that contributes to the high prevalence of infections among these patients, as well as by immunoactivation resulting in inflammation that may contribute to CVD. This review describes disorders of the innate and adaptive immune systems in ESRD, underlining the specific role of ESRD-associated disturbances of Toll-like receptors. Finally, based on the emerging links between the alterations of immune system, CVD, and infections in ESRD patients, it emphasizes the potential role of the immune dysfunction in ESRD as an underlying cause for the high mortality in this patient population and the need for more studies in this area. PMID:18701615

  3. Immune dysfunction in autism: a pathway to treatment.

    PubMed

    Careaga, Milo; Van de Water, Judy; Ashwood, Paul

    2010-07-01

    Autism is a complex and clinically heterogeneous disorder with a spectrum of symptoms. Clinicians, schools, and service agencies worldwide have reported a dramatic increase in the number of children identified with autism. Despite expanding research, the etiology and underlying biological processes of autism remain poorly understood, and the relative contribution from genetic, epigenetic, and environmental factors remains unclear. Although autism affects primarily brain function (especially affect, social functioning, and cognition), it is unknown to what extent other organs and systems are disrupted. Published findings have identified widespread changes in the immune systems of children with autism, at both systemic and cellular levels. Brain specimens from autism subjects exhibit signs of active, ongoing inflammation, as well as alterations in gene pathways associated with immune signaling and immune function. Moreover, many genetic studies have indicated a link between autism and genes that are relevant to both the nervous system and the immune system. Alterations in these pathways can affect function in both systems. Together, these reports suggest that autism may in fact be a systemic disorder with connections to abnormal immune responses. Such immune system dysfunction may represent novel targets for treatment. A better understanding of the involvement of the immune response in autism, and of how early brain development is altered, may have important therapeutic implications.

  4. Muscle fatigue in the temporal and masseter muscles in patients with temporomandibular dysfunction.

    PubMed

    Woźniak, Krzysztof; Lipski, Mariusz; Lichota, Damian; Szyszka-Sommerfeld, Liliana

    2015-01-01

    The aim of this study is to evaluate muscle fatigue in the temporal and masseter muscles in patients with temporomandibular dysfunction (TMD). Two hundred volunteers aged 19.3 to 27.8 years (mean 21.50, SD 0.97) participated in this study. Electromyographical (EMG) recordings were performed using a DAB-Bluetooth Instrument (Zebris Medical GmbH, Germany). Muscle fatigue was evaluated on the basis of a maximum effort test. The test was performed during a 10-second maximum isometric contraction (MVC) of the jaws. An analysis of changes in the mean power frequency of the two pairs of temporal and masseter muscles (MPF%) revealed significant differences in the groups of patients with varying degrees of temporomandibular disorders according to Di (P < 0.0000). The study showed an increase in the muscle fatigue of the temporal and masseter muscles correlated with the intensity of temporomandibular dysfunction symptoms in patients. The use of surface electromyography in assessing muscle fatigue is an excellent diagnostic tool for identifying patients with temporomandibular dysfunction.

  5. The effects of low-intensity laser irradiation on the fatigue induced by dysfunction of mitochondria

    NASA Astrophysics Data System (ADS)

    Xu, Xiao-Yang; Liu, Timon C.; Duan, Rui; Liu, Xiao-Guang

    2003-12-01

    Exercise-induced fatigue has long been an important field in sports medicine. The electron leak of mitochondrial respiratory chain during the ATP synthesis integrated with proton leak and O-.2 can decrease the efficiency of ATP synthesis in mitochondria. And the exercise-induced fatigue occur followed by the decrease of performance. If the dysfunction of mitochondria can be avoided, the fatigue during the exercise may be delayed and the performance may be enhanced. Indeed there are some kind of materials can partially prevent the decrease of ATP synthesis efficiency in mitochondria. But the side effects and safety of these materials is still needed to be studied. Low intensity laser can improve the mitochondria function. It is reasonable to consider that low intensity laser therapy may become the new and more effective way to delay or elimination the fatigue induced by dysfunction of mitochondria. Because the effect of laser irradiation may not be controlled exactly when study in vivo, we use electrical stimulation of C2C12 muscle cells in culture to define the effect of low intensity laser on the dysfunction of mitochondria, and to define the optimal laser intensity to prevent the decrease of ATP synthesis efficiency. Our study use the C2C12 muscle cells in culture to define some of the mechanisms involved in the contractile-induced changes of mitochondrial function firstly in sports medicine and may suggest a useful study way to other researchers. We also give a new way to delay or eliminating the fatigue induced by dysfunction of mitochondria without side effect.

  6. Oxidative and Nitrosative Stress and Immune-Inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

    PubMed Central

    Morris, Gerwyn; Maes, Michael

    2014-01-01

    Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) has been classified as a disease of the central nervous system by the WHO since 1969. Many patients carrying this diagnosis do demonstrate an almost bewildering array of biological abnormalities particularly the presence of oxidative and nitrosative stress (O&NS) and a chronically activated innate immune system. The proposal made herein is that once generated chronically activated O&NS and immune-inflammatory pathways conspire to generate a multitude of self-sustaining and self-amplifying pathological processes which are associated with the onset of ME/CFS. Sources of continuous activation of O&NS and immune-inflammatory pathways in ME/CFS are chronic, intermittent and opportunistic infections, bacterial translocation, autoimmune responses, mitochondrial dysfunctions, activation of the Toll-Like Receptor Radical Cycle, and decreased antioxidant levels. Consequences of chronically activated O&NS and immune-inflammatory pathways in ME/CFS are brain disorders, including neuroinflammation and brain hypometabolism / hypoperfusion, toxic effects of nitric oxide and peroxynitrite, lipid peroxidation and oxidative damage to DNA, secondary autoimmune responses directed against disrupted lipid membrane components and proteins, mitochondrial dysfunctions with a disruption of energy metabolism (e.g. compromised ATP production) and dysfunctional intracellular signaling pathways. The interplay between all of these factors leads to self-amplifying feed forward loops causing a chronic state of activated O&NS, immune-inflammatory and autoimmune pathways which may sustain the disease. PMID:24669210

  7. Cognitive Dysfunction in Chronic Fatigue Syndrome: a Review of Recent Evidence.

    PubMed

    Cvejic, Erin; Birch, Rachael C; Vollmer-Conna, Uté

    2016-05-01

    Cognitive difficulties represent a common and debilitating feature of the enigmatic chronic fatigue syndrome (CFS). These difficulties manifest as self-reported problems with attention, memory, and concentration and present objectively as slowed information processing speed particularly on complex tasks requiring sustained attention. The mechanisms underlying cognitive dysfunction remain to be established; however, alterations in autonomic nervous system activity and cerebral blood flow have been proposed as possibilities. Heterogeneity in the experience of cognitive impairment, as well as differences in the methods utilised to quantify dysfunction, may contribute to the difficulties in establishing plausible biological underpinnings. The development of a brief neurocognitive battery specifically tailored to CFS and adoption by the international research community would be beneficial in establishing a profile of cognitive dysfunction. This could also provide better insights into the underlying biological mechanisms of cognitive dysfunction in CFS and enhance the development of targeted treatments. PMID:27032787

  8. A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome.

    PubMed

    Morris, Gerwyn; Maes, Michael

    2013-12-01

    This paper proposes a neuro-immune model for Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS). A wide range of immunological and neurological abnormalities have been reported in people suffering from ME/CFS. They include abnormalities in proinflammatory cytokines, raised production of nuclear factor-κB, mitochondrial dysfunctions, autoimmune responses, autonomic disturbances and brain pathology. Raised levels of oxidative and nitrosative stress (O&NS), together with reduced levels of antioxidants are indicative of an immuno-inflammatory pathology. A number of different pathogens have been reported either as triggering or maintaining factors. Our model proposes that initial infection and immune activation caused by a number of possible pathogens leads to a state of chronic peripheral immune activation driven by activated O&NS pathways that lead to progressive damage of self epitopes even when the initial infection has been cleared. Subsequent activation of autoreactive T cells conspiring with O&NS pathways cause further damage and provoke chronic activation of immuno-inflammatory pathways. The subsequent upregulation of proinflammatory compounds may activate microglia via the vagus nerve. Elevated proinflammatory cytokines together with raised O&NS conspire to produce mitochondrial damage. The subsequent ATP deficit together with inflammation and O&NS are responsible for the landmark symptoms of ME/CFS, including post-exertional malaise. Raised levels of O&NS subsequently cause progressive elevation of autoimmune activity facilitated by molecular mimicry, bystander activation or epitope spreading. These processes provoke central nervous system (CNS) activation in an attempt to restore immune homeostatsis. This model proposes that the antagonistic activities of the CNS response to peripheral inflammation, O&NS and chronic immune activation are responsible for the remitting-relapsing nature of ME/CFS. Leads for future research are suggested based on this

  9. Multiple sclerosis and fatigue: A review on the contribution of inflammation and immune-mediated neurodegeneration.

    PubMed

    Patejdl, Robert; Penner, Iris K; Noack, Thomas K; Zettl, Uwe K

    2016-03-01

    Multiple sclerosis (MS) is an immune mediated disease of the central nervous system (CNS) and the leading cause of non-traumatic disability among young and middle-aged adults in the western world. One of its most prevalent and debilitating symptoms is fatigue. Despite the general acceptance of the idea of an immune pathogenesis of MS itself, the role of autoimmunity in the course of MS-fatigue is a matter of debate. Both immune-related processes (acute inflammation, chronic inflammation, immune-mediated neurodegeneration, immune-mediated alterations of endocrine functions related to fatigue) and presumably non-immune-mediated disturbances and factors (sleep disturbances, depression, cognitive alterations, chronic infections, adverse effects of medications) contribute to the clinical picture. Data from in vitro and animal experiments has provided evidence for a role of cytokines as IL-1 and TNF-alpha. This association could not be verified directly in blood samples from humans whereas whole blood stimulation protocols gave some indirect evidence for a role of cytokines in MS-fatigue. MRI being able to detect acute and chronic immune mediated damage to the CNS could depict that global atrophy of gray or white matter does not correlate with fatigue. Rather, distinctive clusters of lesions and atrophy at different locations, mostly bifrontal or in subcortical structures, correlate specifically with fatigue. Regardless of the difficulties in pinpointing the immunogenesis of MS-fatigue, an important role of autoimmunity is strongly supported by an indirect route: A growing amount of data shows that the highly effective immunotherapeutics which have been introduced to MS-treatment over the last years effectively and sustainably stabilize and ameliorate fatigue in parallel to their dampening effects on the neuroinflammatory process. This review summarizes the existing data on the relation between inflammation, patterns of CNS-lesions and the effects of immunotherapeutics

  10. Cardiovascular Complications of HIV-Associated Immune Dysfunction

    PubMed Central

    Zaaqoq, Akram M.; Khasawneh, Faisal A.; Smalligan, Roger D.

    2015-01-01

    Prolonged survival in HIV infection is accompanied by an increased frequency of non-HIV-related comorbidities. It is suggested that cardiovascular diseases (CVD) occur earlier among HIV-positive patients compared with HIV-negative patients, and at a higher rate. Several factors have been proposed which can be categorized into traditional and nontraditional risk factors. Immune dysfunction is a nontraditional risk factor that contributes significantly to cardiovascular pathology. Markers of inflammation are elevated in HIV-infected patients, and elevations in markers such as high-sensitivity C-reactive protein, D-dimer, and interleukin-6 (IL-6) have been associated with increased risk for cardiovascular disease. However, the data currently suggest the most practical advice is to start antiretroviral therapy early and to manage traditional risk factors for CVD aggressively. A better understanding of the mechanisms of CVD in this population and further efforts to modify chronic inflammation remain an important research area. PMID:25648075

  11. 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, ...

  12. Placenta Peptide Can Protect Mitochondrial Dysfunction through Inhibiting ROS and TNF-α Generation, by Maintaining Mitochondrial Dynamic Network and by Increasing IL-6 Level during Chronic Fatigue

    PubMed Central

    Muluye, Rekik A.; Bian, Yuhong; Wang, Li; Alemu, Paulos N.; Cui, Huantian; Peng, Xiaofei; Li, Shanshan

    2016-01-01

    Background: Level of fatigue is related to the metabolic energy available to tissues and cells, mainly through mitochondrial respiration, as well fatigue is the most common symptom of poorly functioning mitochondria. Hence, dysfunction of these organelles may be the cause of the fatigue seen in Chronic fatigue (CF). Placenta has been used for treatment of fatigue and various disease, moreover peptides has known protect mitochondrial viability, and alleviate fatigue. These properties of placenta and peptides may link with its effect on mitochondria; therefore, it is highly important to investigate the effectiveness of placenta peptide on fatigue and mitochondrial dysfunction. Methods: After administration of sheep placenta peptide (SPP) for 1 month, mice’s were forced to swim till exhaustion for 90 min to induce chronic fatigue. Electron microscopic examination of skeletal muscle mitochondrial structure, tissue Malondialdehyde (MDA), mitochondrial SOD and serum inflammatory cytokines level were investigated in order to determine the potential effect of SPP on mitochondria during CF. Rat skeletal muscle (L6 cell) were also treated with different concentration of SPP to determine the effect of SPP on cell viability using Thiazoyl blue tetrazolium assay. Results: Our finding revealed that forced swimming induced fatigue model can cause mitochondrial damage through Reactive oxygen species (ROS) mediated lipid peroxidation and Tumor Necrosis factor alpha (TNF-α) elevation. Whereas SPP protected fatigue induced mitochondrial dysfunction through preventing ROS and TNF-α generation, by maintaining mitochondrial dynamic network and by increasing serum IL-6 level. Conclusion: SPP can protect damage in mitochondrial components which will allow proper functioning of mitochondria that will in turn inhibit progression of chronic fatigue. Therefore, SPP may represent a novel therapeutic advantage for preventing mitochondrial dysfunction in patients with chronic fatigue. PMID

  13. Immune-Mediated Vascular Injury and Dysfunction in Transplant Arteriosclerosis

    PubMed Central

    von Rossum, Anna; Laher, Ismail; Choy, Jonathan C.

    2015-01-01

    Solid organ transplantation is the only treatment for end-stage organ failure but this life-saving procedure is limited by immune-mediated rejection of most grafts. Blood vessels within transplanted organs are targeted by the immune system and the resultant vascular damage is a main contributor to acute and chronic graft failure. The vasculature is a unique tissue with specific immunological properties. This review discusses the interactions of the immune system with blood vessels in transplanted organs and how these interactions lead to the development of transplant arteriosclerosis, a leading cause of heart transplant failure. PMID:25628623

  14. 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.

  15. Pathogenesis of endometriosis: natural immunity dysfunction or autoimmune disease?

    PubMed

    Matarese, Giuseppe; De Placido, Giuseppe; Nikas, Yorgos; Alviggi, Carlo

    2003-05-01

    Endometriosis is a chronic inflammatory disease, characterized by implantation and growth of endometrial tissue outside the uterine cavity. This disabling condition is considered one of the most frequent diseases in gynecology, affecting 15-20% of women in their reproductive life. Pelvic endometriosis, the most common form of the disease, is associated with increased secretion of pro-inflammatory cytokines, neo-angiogenesis, intrinsic anomalies of the refluxed endometrium and impaired function of cell-mediated natural immunity. Recently, endometriosis has also been considered to be an autoimmune disease, owing to the presence of autoantibodies, the association with other autoimmune diseases and recurrent immune-mediated abortion. These findings are in apparent contradiction with the reduced cell-mediated natural immunity observed during the disease. In this review, we focus on the multiple processes underlying the complex pathogenesis of endometriosis, with particular emphasis on the role played by the immune system with the induction of autoimmunity. PMID:12763528

  16. The measurement of stress-related immune dysfunction in psychoneuroimmunology.

    PubMed

    Vedhara, K; Fox, J D; Wang, E C

    1999-05-01

    In recent years there has been a dramatic increase in research dedicated to the psycho-behavioural modulation of immune function, i.e. the field of Psychoneuroimmunology (PNI). This has led, necessarily, to the use of several in vitro and in vivo techniques in attempts to delineate the relationship between these two phenomena. However, since the field's inception, considerable uncertainty has existed over the significance of the immune outcomes detected and this has been compounded by the equivocal nature of some of the published data. A great deal of this uncertainty could, however, be overcome if a clearer understanding was achieved on the advantages and limitations conferred by the manifold immune assays described in the literature. This would, in turn, encourage their more appropriate use within PNI. Hence, in this review we describe the rationale behind, and offer an evaluation of, some of the more frequently used in vitro and in vivo immunological and virological techniques. We hope that a clear understanding of the rationale behind such assays and their inherent advantages and limitations will inform the discussion of the significance of stress-related immune impairment.

  17. Immune dysfunction in patients with diabetes mellitus (DM).

    PubMed

    Geerlings, S E; Hoepelman, A I

    1999-12-01

    Patients with diabetes mellitus (DM) have infections more often than those without DM. The course of the infections is also more complicated in this patient group. One of the possible causes of this increased prevalence of infections is defects in immunity. Besides some decreased cellular responses in vitro, no disturbances in adaptive immunity in diabetic patients have been described. Different disturbances (low complement factor 4, decreased cytokine response after stimulation) in humoral innate immunity have been described in diabetic patients. However, the clinical relevance of these findings is not clear. Concerning cellular innate immunity most studies show decreased functions (chemotaxis, phagocytosis, killing) of diabetic polymorphonuclear cells and diabetic monocytes/macrophages compared to cells of controls. In general, a better regulation of the DM leads to an improvement of these cellular functions. Furthermore, some microorganisms become more virulent in a high glucose environment. Another mechanism which can lead to the increased prevalence of infections in diabetic patients is an increased adherence of microorganisms to diabetic compared to nondiabetic cells. This has been described for Candida albicans. Possibly the carbohydrate composition of the receptor plays a role in this phenomenon.

  18. The Relationship between Renal Dysfunction and Abnormalities of the Immune System in Patients with Decompensated Cirrhosis.

    PubMed

    Kakazu, Eiji; Kondo, Yasuteru; Shimosegawa, Tooru

    2012-01-01

    In patients with advanced cirrhosis, not only hepatocellular carcinoma but also bacterial infections, such as spontaneous bacterial peritonitis (SBP) or pneumonia, are frequent clinical complications in such immune-compromised patients. These pathologies often progress to renal dysfunction, especially hepatorenal syndrome (HRS). The central pathology of HRS is splanchnic arterial vasodilation and hyperpermeability followed by bacterial translocation (BT). BT induces a severe inflammatory response in the peritoneal lymphoid tissue, with the activation of the immune systems and the long-lasting production of vasoactive mediators that can impair the circulatory function and cause renal failure. Recent studies report that the plasma amino acid imbalance appeared to be related to an abnormality of the immune system in patients with decompensated cirrhosis. This paper can provide a new approach for future studies of the pathology in cirrhotic patients with renal dysfunction. PMID:23326675

  19. The Relationship between Renal Dysfunction and Abnormalities of the Immune System in Patients with Decompensated Cirrhosis

    PubMed Central

    Kakazu, Eiji; Kondo, Yasuteru; Shimosegawa, Tooru

    2012-01-01

    In patients with advanced cirrhosis, not only hepatocellular carcinoma but also bacterial infections, such as spontaneous bacterial peritonitis (SBP) or pneumonia, are frequent clinical complications in such immune-compromised patients. These pathologies often progress to renal dysfunction, especially hepatorenal syndrome (HRS). The central pathology of HRS is splanchnic arterial vasodilation and hyperpermeability followed by bacterial translocation (BT). BT induces a severe inflammatory response in the peritoneal lymphoid tissue, with the activation of the immune systems and the long-lasting production of vasoactive mediators that can impair the circulatory function and cause renal failure. Recent studies report that the plasma amino acid imbalance appeared to be related to an abnormality of the immune system in patients with decompensated cirrhosis. This paper can provide a new approach for future studies of the pathology in cirrhotic patients with renal dysfunction. PMID:23326675

  20. Fatigue

    MedlinePlus

    Bennett RM. Fibromyalgia, chronic fatigue syndrome, and myofascial pain. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 274. Thames TA, Karrh ...

  1. Mitoprotective dietary approaches for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Caloric restriction, fasting, and ketogenic diets.

    PubMed

    Craig, Courtney

    2015-11-01

    Myalgic Encephalomyelitis/Chronic Fatigue Syndrome is an idiopathic illness characterized by debilitating fatigue and neuro-immune abnormalities. A growing body of evidence proposes mitochondrial dysfunction as a central perpetrator of the illness due to activation of immune-inflammatory pathways that burden the mitochondria. Under a model of mitochondrial dysfunction, this paper explores dietary strategies that are mitoprotective. Studied for decades, the cellular mechanisms of ketogenic diets, fasting, and caloric restriction now reveal mitochondria-specific mechanisms which could play a role in symptom reduction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Future research should examine the physiological effects of these dietary strategies in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

  2. Stress Mediators and Immune Dysfunction in Patients with Acute Cerebrovascular Diseases

    PubMed Central

    Liesz, Arthur; Rüger, Holger; Purrucker, Jan; Zorn, Markus; Dalpke, Alexander; Möhlenbruch, Markus; Englert, Stefan; Nawroth, Peter P.; Veltkamp, Roland

    2013-01-01

    Background Post-stroke immune depression contributes to the development of infections which are major complications after stroke. Previous experimental and clinical studies suggested that humoral stress mediators induce immune dysfunction. However, prospective clinical studies testing this concept are missing and no data exists for other cerebrovascular diseases including intracerebral hemorrhage (ICH) and TIA. Methods We performed a prospective clinical study investigating 166 patients with TIA, ischemic and hemorrhagic stroke. We measured a broad panel of stress mediators, leukocyte subpopulations, cytokines and infection markers from hospital admission to day 7 and on follow-up after 2–3 months. Multivariate regression analyses detected independent predictors of immune dysfunction and bacterial infections. ROC curves were used to test the diagnostic value of these parameters. Results Only severe ischemic strokes and ICH increased some catecholamine metabolites, ACTH and cortisol levels. Immunodysfunction was eminent already on hospital admission after large brain lesions with lymphocytopenia as a key feature. None of the stress mediators was an independent predictor of lymphocytopenia or infections. However, lymphocytopenia on hospital admission was detected as an independent explanatory variable of later infections. NIHSSS and lymphocytopenia on admission were excellent predictors of infection. Conclusions Our results question the present pathophysiological concept of stress-hormone mediated immunodysfunction after stroke. Early lymphocytopenia was identified as an early independent predictor of post-stroke infections. Absence of lymphocytopenia may serve as a negative predictive marker for stratification for early antibiotic treatment. PMID:24069356

  3. Prevention effects of Schisandra polysaccharide on radiation-induced immune system dysfunction.

    PubMed

    Zhao, Lian-Mei; Jia, Yun-Long; Ma, Ming; Duan, Yu-Qing; Liu, Li-Hua

    2015-05-01

    In this study, we investigate the efficacy of SP (Schisandra polysaccharide) in prevention of radiation-induced immune dysfunction and discussed the underlying mechanisms with a Bal/bc mouse model. The data demonstrated that SP could reverse the decreases in the number of white blood cells and lymphocytes in peripheral blood. In addition, the immunoglobulin G (IgG) and complement C3 in blood serum were all decreased after radiation and SP could restore this radiation disorder. Furthermore, SP could reverse the deregulation of CD3(+)CD4(+) and CD3(+)CD8(+) T cell subsets in peripheral blood and thymus of mice after radiotherapy. We also performed terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) and Immunohistochemistry (IHC) to investigate the apoptosis and underlying mechanisms of SP in thymus. Data showed that radiation-induced apoptosis of thymocytes could be reversed by SP through inducing upregulation of Bcl-2 expression and downregulation of Fas and Bax levels. Furthermore, SP has no any side-effects on immunity of normal mice. In conclusion, our results indicated that SP could effectively prevent immune injury during radiotherapy by protecting the immune system. This valuable information should be of assistance in choosing a rational design for therapeutic interventions of prevention immune system damage in the radiation treatment.

  4. Effector, Memory, and Dysfunctional CD8+ T Cell Fates in the Antitumor Immune Response

    PubMed Central

    2016-01-01

    The adaptive immune system plays a pivotal role in the host's ability to mount an effective, antigen-specific immune response against tumors. CD8+ tumor-infiltrating lymphocytes (TILs) mediate tumor rejection through recognition of tumor antigens and direct killing of transformed cells. In growing tumors, TILs are often functionally impaired as a result of interaction with, or signals from, transformed cells and the tumor microenvironment. These interactions and signals can lead to transcriptional, functional, and phenotypic changes in TILs that diminish the host's ability to eradicate the tumor. In addition to effector and memory CD8+ T cells, populations described as exhausted, anergic, senescent, and regulatory CD8+ T cells have been observed in clinical and basic studies of antitumor immune responses. In the context of antitumor immunity, these CD8+ T cell subsets remain poorly characterized in terms of fate-specific biomarkers and transcription factor profiles. Here we discuss the current characterization of CD8+ T cell fates in antitumor immune responses and discuss recent insights into how signals in the tumor microenvironment influence TIL transcriptional networks to promote CD8+ T cell dysfunction. PMID:27314056

  5. 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

  6. Is there a potential immune dysfunction with anabolic androgenic steroid use?: A review.

    PubMed

    Brenu, E W; McNaughton, L; Marshall-Gradisnik, S M

    2011-05-01

    Anabolic androgenic steroids (AAS) are artificial substances, acting through androgen receptors and were primarily developed for the treatment of hypogonadism, tumors, hypercalcemia, hypercalcuria and other chronic diseases. The discovery, in the early 1930s that these substances may have other benefits related to improvement in physique and athletic performance, has encouraged extensive use of these substances by amateur and professional athletes and members of the general public. The range of AAS used can be classified as either endogenous or exogenous. When used for ergogenic or recreational purposes the dosage is more often higher than the recommended dosage, and at supraphysiological levels, AAS can cause a number of serious side effects including liver dysfunction, myocardial infarction and potentially stroke, due to its ability to increase platelet and platelet aggregation. Furthermore, these high dosages may or can affect other physiological systems including the immune system. Hence, this paper reviews the current research on the effects of a number of specific AAS in the immune system.

  7. 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

  8. Lung involvement in childhood measles: severe immune dysfunction revealed by quantitative immunohistochemistry.

    PubMed

    Moussallem, Tálib Moysés; Guedes, Fernanda; Fernandes, Elaine Raniero; Pagliari, Carla; Lancellotti, Carmen Lucia Penteado; de Andrade, Heitor Franco; Duarte, Maria Irma Seixas

    2007-08-01

    Measles, accounting for nearly 1 million deaths each year, presents intense involvement of lymphoid organs and the lungs. The immune response in situ in the lungs was determined in blocks recovered from 42 necropsies of children who died from measles determined by immune cell phenotype (CD4, CD8, CD20, CD45RO, CD68, natural killer [NK], and antigen S-100 B [S100]) and cytokine production (interferon, tumor necrosis factor, interleukin [IL]-1, IL-2, IL-4, IL-10, and IL-12). Compared with the lungs of age-paired controls, patients with measles presented severe depletion of CD4+, CD20+, CD68+, NK+, and S100+ cells in alveolus- and bronchus-associated lymphoid tissue without depletion of CD8+ cells. Most of these features were similar in both forms of measles lung involvement, Hecht giant cell, or interstitial pneumonia, but S100+ cells were depleted in bronchus-associated lymphoid tissue from patients with Hecht pneumonia, which also occurs more frequently in malnourished children. IL-10- and IL-12-producing cells were depleted in patients with measles, whereas IL-1-, interferon-, and IL-4-producing cells were more frequently seen in the alveolus of patients with measles compared with controls. Quantitative in situ immune cell phenotype and function in the lung in measles demonstrated severe immune dysfunction, with loss of key cells, such as dendritic, CD4+, and NK+ cells, and deficient cytokine production, which allows for a better comprehension of local reactions in this process.

  9. The Toll-Like Receptor Radical Cycle Pathway: A New Drug Target in Immune-Related Chronic Fatigue.

    PubMed

    Lucas, Kurt; Morris, Gerwyn; Anderson, George; Maes, Michael

    2015-01-01

    In this review we discuss that peripheral and central activation of the Toll-like receptor 2/4 (TLR2/4) Radical Cycle may underpin the pathophysiology of immune-related chronic fatigue secondary to other medical diseases and conditions. The TLR Radical Cycle plays a role in illnesses and conditions that are disproportionately commonly comorbid with secondary chronic fatigue, including a) neuroinflammatory disorders, e.g. Parkinson's disease, stroke, depression, psychological stressors, and b) systemic disorders, e.g. (auto)immune disorders, chronic obstructive pulmonary disease, ankylosing spondylitis, chronic kidney disease, inflammatory bowel disease, cardiovascular disease, incl. myocardial infarction, cancer and its treatments. Increased TLR signaling is driven by activated immuneinflammatory and oxidative and nitrosative stress pathways, pathogen derived molecular patterns, including lipopolysaccharides, and damage associated molecular patterns (DAMPs). Newly formed redox-derived DAMPs, secondary to oxidative processes, may further activate the TLR complex leading to an auto-amplifying TLR Radical feedback loop. Increased gut permeability with translocation of gram negative bacteria and LPS, which activates the TLR Radical Cycle, is another pathway that may play a role in most of the abovementioned diseases and the secondary fatigue accompanying them. It is concluded that secondary fatigue may be associated with activation of the TLR Radical Cycle pathway due to activated immune-inflammatory pathways, classical and redox-derived DAMPs and PAMPs plays a role in its pathophysiology. Such an activation of the TLR Radical Cycle pathway may also explain why the abovementioned conditions are primed for an increased expression of secondary chronic fatigue. Targeting the TLR Radical Cycle pathway may be an effective method to treat TLR-Radical Cycle-related diseases such as secondary chronic fatigue.

  10. In vitro immune toxicity of polybrominated diphenyl ethers on murine peritoneal macrophages: apoptosis and immune cell dysfunction.

    PubMed

    Lv, Qi-Yan; Wan, Bin; Guo, Liang-Hong; Zhao, Lixia; Yang, Yu

    2015-02-01

    Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants and are often detected in the environment, wildlife, and humans, presenting potential threats to ecosystem and human health. PBDEs can cause neurotoxicity, hepatotoxicity, and endocrine disruption. However, data on PBDE immunotoxicity are limited, and the toxicity mechanisms remain largely unknown. Both immune cell death and dysfunction can modulate the responses of the immune system. This study examined the toxic effects of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and decabromodiphenyl ether (BDE-209) on the immune system by using peritoneal macrophages as the model. The macrophages were exposed to PBDEs, and cell death was determined through flow cytometry and immunochemical blot. The results showed that after 24h of exposure, BDE-47 (>5 μM) and BDE-209 (>20 μM) induced cell apoptosis, increased intracellular reactive oxygen species (ROS) formation and depleted glutathione. BDE-47 was more potent than BDE-209; the cytotoxic concentrations for BDE-47 and BDE-209 were determined to be 5 μM and 20 μM, respectively, during 24h of exposure. However, pretreatment with n-acetyl-l-cysteine (ROS scavenger) partially reversed the cytotoxic effects. Further gene expression analyses on Caspase-3,-8,-9, TNFR1, and Bax revealed that both intrinsic and extrinsic apoptotic pathways were activated. More importantly, non-cytotoxic concentrations BDE-47 (<2 μM) and BDE-209 (<10 μM) could impair macrophage accessory cell function in a concentration-dependent manner, but no effects were observed on phagocytic responses. These revealed effects of PBDEs on macrophages may shed light on the toxicity mechanisms of PBDEs and suggest the necessity of evaluating cellular functionality during the risk assessment of PBDE immunotoxicity. PMID:25462306

  11. Immune Dysfunction in Children with CHARGE Syndrome: A Cross-Sectional Study

    PubMed Central

    van der Burg, Mirjam; la Bastide-van Gemert, Sacha; Hogendorf, Lianne A.; van Ravenswaaij-Arts, Conny M. A.; Schölvinck, Elisabeth H.

    2015-01-01

    CHARGE syndrome is a variable, multiple congenital malformation syndrome. Patients with CHARGE syndrome have frequent infections that are presumed to be due to anatomical anomalies of the craniofacial region and upper airway, and cranial nerve problems resulting in swallowing difficulties and aspiration. The possible contribution of immunological abnormalities to these infections has not been systematically studied even though immune deficiencies have been described in patients with 22q11.2 deletion syndrome, a condition which shares remarkable clinical overlap with CHARGE syndrome. We assessed the frequency and nature of immune dysfunction in 24 children with genetically proven CHARGE syndrome. All patients, or their parents, completed a questionnaire on infectious history. Their immune system was extensively assessed through full blood counts, immunoglobulin levels, lymphocyte subpopulations, peripheral B- and T-cell differentiation, T-receptor excision circle (TREC) analysis, T-cell function, and vaccination responses. All CHARGE patients had a history of infections (often frequent), mainly otitis media and pneumonia, leading to frequent use of antibiotics and to hospital admissions. Decreased T-cell numbers were found in 12 (50%) patients, presumably caused by insufficient thymic output since TREC amounts were also diminished in CHARGE patients. Despite normal peripheral B-cell differentiation and immunoglobulin production in all patients, 83% of patients had insufficient antibody titers to one or more early childhood vaccinations. Based on our results, we recommend immunological evaluation of CHARGE patients with recurrent infections. PMID:26544072

  12. Variable Neuroendocrine-Immune Dysfunction in Individuals with Unfavorable Outcome after Severe Traumatic Brain Injury

    PubMed Central

    Santarsieri, Martina; Kumar, Raj G.; Kochanek, Patrick M.; Berga, Sarah L.; Wagner, Amy K.

    2014-01-01

    Bidirectional communication between the immune and neuroendocrine systems is not well understood in the context of traumatic brain injury (TBI). The purpose of this study was to characterize relationships between cerebrospinal fluid (CSF) cortisol and inflammation after TBI, and to determine how these relationships differ by outcome. CSF samples were collected from 91 subjects with severe TBI during days 0–6 post-injury, analyzed for cortisol and inflammatory markers, and compared to healthy controls (n=13 cortisol, n=11 inflammatory markers). Group-based trajectory analysis (TRAJ) delineated subpopulations with similar longitudinal CSF cortisol profiles (high vs. low cortisol). Glasgow Outcome Scale (GOS) scores at 6 months served as the primary outcome measure reflecting global outcome. Inflammatory markers that displayed significant bivariate associations with both GOS and cortisol TRAJ (interleukin [IL]-6, IL-10, soluble Fas [sFas], soluble intracellular adhesion molecule [sICAM]-1, and tumor necrosis factor alpha [TNF]-α) were used to generate a cumulative inflammatory load score (ILS). Subsequent analysis revealed that cortisol TRAJ group membership mediated ILS effects on outcome (indirect effect estimate= −0.253, 95% CI (−0.481, −0.025), p=0.03). Correlational analysis between mean cortisol levels and ILS were examined separately within each cortisol TRAJ group and by outcome. Within the low cortisol TRAJ group, subjects with unfavorable 6-month outcome displayed a negative correlation between ILS and mean cortisol (r=−0.562, p=0.045). Conversely, subjects with unfavorable outcome in the high cortisol TRAJ group displayed a positive correlation between ILS and mean cortisol (r=0.391, p=0.006). Our results suggest that unfavorable outcome after TBI may result from dysfunctional neuroendocrine-immune communication wherein an adequate immune response is not mounted or, alternatively, neuroinflammation is prolonged. Importantly, the nature of

  13. Radiation-induced hemopoietic and immune dysfunction. Technical report, 16 Aug 86-31 Mar 90

    SciTech Connect

    Storb, R.; Schuening, F.

    1991-06-01

    This work was aimed at investigating radiation-induced hemopoietic and immune dysfunction in the dog model. One project was to produce monoclonal antibodies directed against canine hemopoietic precursor cells and specific for pluripotent stem cells. Antibodies obtained reacted with different myeloid and erythroid precursor cells; unfortunately, none of the antibodies were specific for pluripotent hemopoietic stem cells. Positive selections for these cells were performed using magnetic beads and an antibody against class 2-antigen. Transplantation of class 2 positive marrow cells into otherwise lethally irradiated dogs led to sustained recovery in only 1 of 5 dogs. A second project established and investigated long-term marrow cultures in the dog. Culture conditions were studied and optimized, and marrow cells were transplanted into otherwise lethally irradiated dogs to investigate stem cell survival in long-term cultures. Engraftment was observed only with short-term marrow cultures.

  14. Adult hemophagocytic lymphohistiocytosis causing multi organ dysfunction in a patient with multiple autoimmune disorders: when the immune system runs amok.

    PubMed

    Fleischmann, Robert; Böhmerle, Wolfgang; von Laffert, Maximilian; Jöhrens, Korinna; Mengel, Annerose; Hotter, Benjamin; Lindenberg, Robert; Scheibe, Franziska; Köhnlein, Martin; von Bahr Greenwood, Tatiana; Henter, Jan Inge; Meisel, Andreas

    2016-02-01

    We report a case of several autoimmune disorders eventually presenting as severe multi organ dysfunction syndrome caused by adult hemophagocytic lymphohistiocytosis (HLH). Clinical and laboratory tests might lead to fatal misinterpretation without awareness of its diagnostic evaluation, as HLH shares common features with sepsis and immune-mediated systemic inflammatory response syndromes.

  15. Immune System Dysfunction and Autoimmune Disease in Mice Lacking Emk (Par-1) Protein Kinase

    PubMed Central

    Hurov, Jonathan B.; Stappenbeck, Thaddeus S.; Zmasek, Christian M.; White, Lynn S.; Ranganath, Sheila H.; Russell, John H.; Chan, Andrew C.; Murphy, Kenneth M.; Piwnica-Worms, Helen

    2001-01-01

    Emk is a serine/threonine protein kinase implicated in regulating polarity, cell cycle progression, and microtubule dynamics. To delineate the role of Emk in development and adult tissues, mice lacking Emk were generated by targeted gene disruption. Emk−/− mice displayed growth retardation and immune cell dysfunction. Although B- and T-cell development were normal, CD4+T cells lacking Emk exhibited a marked upregulation of the memory marker CD44/pgp-1 and produced more gamma interferon and interleukin-4 on stimulation through the T-cell receptor in vitro. In addition, B-cell responses to T-cell-dependent and -independent antigen challenge were altered in vivo. As Emk−/− animals aged, they developed splenomegaly, lymphadenopathy, membranoproliferative glomerulonephritis, and lymphocytic infiltrates in the lungs, parotid glands and kidneys. Taken together, these results demonstrate that the Emk protein kinase is essential for maintaining immune system homeostasis and that loss of Emk may contribute to autoimmune disease in mammals. PMID:11287624

  16. TRESK channel as a potential target to treat T-cell mediated immune dysfunction

    SciTech Connect

    Han, Jaehee; Kang, Dawon

    2009-12-25

    In this review, we propose that TRESK background K{sup +} channel could serve as a potential therapeutic target for T-cell mediated immune dysfunction. TRESK has many immune function-related properties. TRESK is abundantly expressed in the thymus, the spleen, and human leukemic T-lymphocytes. TRESK is highly activated by Ca{sup 2+}, calcineurin, acetylcholine, and histamine which induce hypertrophy, whereas TRESK is inhibited by immunosuppressants, such as cyclosporin A and FK506. Cyclosporine A and FK506 target the binding site of nuclear factor of activated T-cells (NFAT) to inhibit calcineurin. Interestingly, TRESK possesses an NFAT-like docking site that is present at its intracellular loop. Calcineurin has been found to interact with TRESK via specific NFAT-like docking site. When the T-cell is activated, calcineurin can bind to the NFAT-docking site of TRESK. The activation of both TRESK and NFAT via Ca{sup 2+}-calcineurin-NFAT/TRESK pathway could modulate the transcription of new genes in addition to regulating several aspects of T-cell function.

  17. Form follows function: astrocyte morphology and immune dysfunction in SIV neuroAIDS.

    PubMed

    Lee, Kim M; Chiu, Kevin B; Renner, Nicole A; Sansing, Hope A; Didier, Peter J; MacLean, Andrew G

    2014-10-01

    Cortical function is disrupted in neuroinflammatory disorders, including HIV-associated neurocognitive disorders (HAND). Astrocyte dysfunction includes retraction of foot processes from the blood-brain barrier and decreased removal of neurotransmitters from synaptic clefts. Mechanisms of astrocyte activation, including innate immune function and the fine neuroanatomy of astrocytes, however, remain to be investigated. We quantified the number of glial fibrillary acidic protein (GFAP)-labeled astrocytes per square millimeter and the proportion of astrocytes immunopositive for Toll-like receptor 2 (TLR2) to examine innate immune activation in astrocytes. We also performed detailed morphometric analyses of gray and white matter astrocytes in the frontal and parietal lobes of rhesus macaques infected with simian immunodeficiency virus (SIV), both with and without encephalitis, an established model of AIDS neuropathogenesis. Protoplasmic astrocytes (gray matter) and fibrous astrocytes (deep white matter) were imaged, and morphometric features were analyzed using Neurolucida. Gray matter and white matter astrocytes showed no change in cell body size in animals infected with SIV regardless of encephalitic status. In SIV-infected macaques, both gray and white matter astrocytes had shorter, less ramified processes, resulting in decreased cell arbor compared with controls. SIV-infected macaques with encephalitis showed decreases in arbor length in white matter astrocytes and reduced complexity in gray matter astrocytes compared to controls. These results provide the first evidence that innate immune activation of astrocytes is linked to altered cortical astrocyte morphology in SIV/HIV infection. Here, we demonstrate that astrocyte remodeling is correlated with infection. Perturbed neuron-glia signaling may be a driving factor in the development of HAND.

  18. A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome

    PubMed Central

    2013-01-01

    Background Though potentially linked to the basic physiology of stress response we still have no clear understanding of Gulf War Illness (GWI), a debilitating condition presenting complex immune, endocrine and neurological symptoms. Here we compared male (n = 20) and female (n = 10) veterans with GWI separately against their healthy counterparts (n = 21 male, n = 9 female) as well as subjects with chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME) (n = 12 male, n = 10 female). Methods Subjects were assessed using a Graded eXercise Test (GXT) with blood drawn prior to exercise, at peak effort (VO2 max) and 4-hours post exercise. Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70), 13, 15, 17 and 23, IFNγ, TNFα and TNFβ in plasma samples from each phase of exercise. Linear classification models were constructed using stepwise variable selection to identify cytokine co-expression patterns characteristic of each subject group. Results Classification accuracies in excess of 80% were obtained using between 2 and 5 cytokine markers. Common to both GWI and CFS, IL-10 and IL-23 expression contributed in an illness and time-dependent manner, accompanied in male subjects by NK and Th1 markers IL-12, IL-15, IL-2 and IFNγ. In female GWI and CFS subjects IL-10 was again identified as a delineator but this time in the context of IL-17 and Th2 markers IL-4 and IL-5. Exercise response also differed between sexes: male GWI subjects presented characteristic cytokine signatures at rest but not at peak effort whereas the opposite was true for female subjects. Conclusions Though individual markers varied, results collectively supported involvement of the IL-23/Th17/IL-17 axis in the delineation of GWI and CFS in a sex-specific way. PMID:23800166

  19. Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review.

    PubMed

    Nijs, Jo; Nees, Andrea; Paul, Lorna; De Kooning, Margot; Ickmans, Kelly; Meeus, Mira; Van Oosterwijck, Jessica

    2014-01-01

    An increasing number of studies have examined how the immune system of patients with Chronic Fatigue Syndrome (CFS), or myalgic encephalomyelitis, responds to exercise. The objective of the present study was to systematically review the scientific literature addressing exercise-induced immunological changes in CFS patients compared to healthy control subjects. A systematic literature search was conducted in the PubMed and Web of science databases using different keyword combinations. We included 23 case control studies that examined whether CFS patients, compared to healthy sedentary controls, have a different immune response to exercise. The included articles were evaluated on their methodological quality. Compared to the normal response of the immune system to exercise as seen in healthy subjects, patients with CFS have a more pronounced response in the complement system (i.e. C4a split product levels), oxidative stress system (i.e. enhanced oxidative stress combined with a delayed and reduced anti-oxidant response), and an alteration in the immune cells' gene expression profile (increases in post-exercise interleukin-10 and toll-like receptor 4 gene expression), but not in circulating pro- or anti-inflammatory cytokines. Many of these immune changes relate to post-exertional malaise in CFS, a major characteristic of the illness. The literature review provides level B evidence for an altered immune response to exercise in patients with CFS.

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

    PubMed Central

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

    2015-01-01

    Objective: This study was designed to investigate the effects of acupuncturing Pishu combined with Ginsenoside Rg3 on the immune function of rats with chronic fatigue. Methods: 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. Results: 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. Conclusions: 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. PMID:26770528

  1. Immune Dysfunction Associated with Abnormal Bone Marrow-Derived Mesenchymal Stroma Cells in Senescence Accelerated Mice

    PubMed Central

    Li, Ming; Guo, Kequan; Adachi, Yasushi; Ikehara, Susumu

    2016-01-01

    Senescence accelerated mice (SAM) are a group of mice that show aging-related diseases, and SAM prone 10 (SAMP10) show spontaneous brain atrophy and defects in learning and memory. Our previous report showed that the thymus and the percentage of T lymphocytes are abnormal in the SAMP10, but it was unclear whether the bone marrow-derived mesenchymal stroma cells (BMMSCs) were abnormal, and whether they played an important role in regenerative medicine. We thus compared BMMSCs from SAMP10 and their control, SAM-resistant (SAMR1), in terms of cell cycle, oxidative stress, and the expression of PI3K and mitogen-activated protein kinase (MAPK). Our cell cycle analysis showed that cell cycle arrest occurred in the G0/G1 phase in the SAMP10. We also found increased reactive oxygen stress and decreased PI3K and MAPK on the BMMSCs. These results suggested the BMMSCs were abnormal in SAMP10, and that this might be related to the immune system dysfunction in these mice. PMID:26840301

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

    PubMed

    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.

  3. PD-1 Blockage Reverses Immune Dysfunction and Hepatitis B Viral Persistence in a Mouse Animal Model

    PubMed Central

    Tzeng, Horng-Tay; Tsai, Hwei-Fang; Liao, Hsiu-Jung; Lin, Yi-Jiun; Chen, Lieping; Chen, Pei-Jer; Hsu, Ping-Ning

    2012-01-01

    Persistent hepatitis B viral (HBV) infection results in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Recent studies in animal models of viral infection indicate that the interaction between the inhibitory receptor, programmed death (PD)-1, on lymphocytes and its ligand (PD-L1) play a critical role in T-cell exhaustion by inducing T-cell inactivation. High PD-1 expression levels by peripheral T-lymphocytes and the possibility of improving T-cell function by blocking PD-1-mediated signaling confirm the importance of this inhibitory pathway in inducing T-cell exhaustion. We studied T-cell exhaustion and the effects of PD-1 and PD-L1 blockade on intrahepatic infiltrating T-cells in our recently developed mouse model of HBV persistence. In this mouse animal model, we demonstrated that there were increased intrahepatic PD-1-expressing CD8+ and CD4+ T cells in mice with HBV persistence, but PD-1 upregulation was resolved in mice which had cleared HBV. The Intrahepatic CD8+ T-cells expressed higher levels of PD-1 and lower levels of CD127 in mice with HBV persistence. Blockade of PD-1/PD-L1 interactions increased HBcAg-specific interferon (IFN)-γ production in intrahepatic T lymphocytes. Furthermore, blocking the interaction of PD-1 with PD-L1 by an anti-PD-1 monoclonal antibody (mAb) reversed the exhausted phenotype in intrahepatic T lymphocytes and viral persistence to clearance of HBV in vivo. Our results indicated that PD-1 blockage reverses immune dysfunction and viral persistence of HBV infection in a mouse animal model, suggesting that the anti-PD-1 mAb might be a good therapeutic candidate for chronic HBV infection. PMID:22761734

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

    PubMed Central

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

    2016-01-01

    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. PMID:26819512

  5. 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.

  6. PD-L1 blockade improves immune dysfunction of spleen dendritic cells and T-cells in zymosan-induced multiple organs dysfunction syndromes.

    PubMed

    Liu, Qian; Lv, Yi; Zhao, Min; Jin, Yiduo; Lu, Jiangyang

    2015-01-01

    This research is to investigate the role of tolerant spleen dendritic cells (DC) in multiple organs dysfunction syndromes (MODS) at late stage. Tolerant DC and MODS were induced by intraperotineal injection of zymosan. The immunity of DC was determined by examining interleukin (IL)-10, IL-12, IL-2, major histocompatibility complex (MHC), CD86, programmed death (PD-1), programmed death ligand 1 (PD-L1), paired immunoglobulin-like receptor B (PIR-B) or T-cell proliferation in serum, spleen homogenate, DC culture or DC/T-cell co-culture. The PD-L1/PD-1 pathway was blocked using PD-L1 antibody. The IL-12p70 in serum, spleen homogenate and DC culture supernatant were decreased at 5 d and 12 d after zymosan injection while the IL-12p40 and IL-10 were increased. The expression of MHC, cluster of differentiation 86 (CD86), PD-1 and PD-L1 in spleen DCs were increased at early stage after zymosan injection. At 5 d and 12 d, the expression of MHC and CD86 was reduced while the expression of PD-1, PD-L1 and PIR-B was increased, accompanied with decreased proliferation of T-cell and decrease of IL-2 in spleen and serum. Application of PD-L1 antibody improved the above changes. At late stage of MODS mice induced by zymosan, the expression of co-stimulators and inhibitors in spleen DCs was imbalanced to form tolerant DCs which reduced the activation of T-cells. PD-L1 antibody improved the immune tolerance of DCs through intervening PD-1/PD-L1 pathway, and attenuated the inhibition of T-cell activities by tolerant DCs and the immune inhibition.

  7. PD-L1 blockade improves immune dysfunction of spleen dendritic cells and T-cells in zymosan-induced multiple organs dysfunction syndromes

    PubMed Central

    Liu, Qian; Lv, Yi; Zhao, Min; Jin, Yiduo; Lu, Jiangyang

    2015-01-01

    This research is to investigate the role of tolerant spleen dendritic cells (DC) in multiple organs dysfunction syndromes (MODS) at late stage. Tolerant DC and MODS were induced by intraperotineal injection of zymosan. The immunity of DC was determined by examining interleukin (IL)-10, IL-12, IL-2, major histocompatibility complex (MHC), CD86, programmed death (PD-1), programmed death ligand 1 (PD-L1), paired immunoglobulin-like receptor B (PIR-B) or T-cell proliferation in serum, spleen homogenate, DC culture or DC/T-cell co-culture. The PD-L1/PD-1 pathway was blocked using PD-L1 antibody. The IL-12p70 in serum, spleen homogenate and DC culture supernatant were decreased at 5 d and 12 d after zymosan injection while the IL-12p40 and IL-10 were increased. The expression of MHC, cluster of differentiation 86 (CD86), PD-1 and PD-L1 in spleen DCs were increased at early stage after zymosan injection. At 5 d and 12 d, the expression of MHC and CD86 was reduced while the expression of PD-1, PD-L1 and PIR-B was increased, accompanied with decreased proliferation of T-cell and decrease of IL-2 in spleen and serum. Application of PD-L1 antibody improved the above changes. At late stage of MODS mice induced by zymosan, the expression of co-stimulators and inhibitors in spleen DCs was imbalanced to form tolerant DCs which reduced the activation of T-cells. PD-L1 antibody improved the immune tolerance of DCs through intervening PD-1/PD-L1 pathway, and attenuated the inhibition of T-cell activities by tolerant DCs and the immune inhibition. PMID:25973021

  8. Evidence for Immune Response, Axonal Dysfunction and Reduced Endocytosis in the Substantia Nigra in Early Stage Parkinson’s Disease

    PubMed Central

    Dijkstra, Anke A.; Ingrassia, Angela; de Menezes, Renee X.; van Kesteren, Ronald E.; Rozemuller, Annemieke J. M.; Heutink, Peter; van de Berg, Wilma D. J.

    2015-01-01

    Subjects with incidental Lewy body disease (iLBD) may represent the premotor stage of Parkinson’s disease (PD). To elucidate molecular mechanisms underlying neuronal dysfunction and alpha-synuclein pathology in the premotor phase of PD, we investigated the transcriptome of the substantia nigra (SN) of well-characterized iLBD, PD donors and age-matched controls with Braak alpha-synuclein stage ranging from 0–6. In Braak alpha-synuclein stages 1 and 2, we observed deregulation of pathways linked to axonal degeneration, immune response and endocytosis, including axonal guidance signaling, mTOR signaling, EIF2 signaling and clathrin-mediated endocytosis in the SN. In Braak stages 3 and 4, we observed deregulation of pathways involved in protein translation and cell survival, including mTOR and EIF2 signaling. In Braak stages 5 and 6, we observed deregulation of dopaminergic signaling, axonal guidance signaling and thrombin signaling. Throughout the progression of PD pathology, we observed a deregulation of mTOR, EIF2 and regulation of eIF4 and p70S6K signaling in the SN. Our results indicate that molecular mechanisms related to axonal dysfunction, endocytosis and immune response are an early event in PD pathology, whereas mTOR and EIF2 signaling are impaired throughout disease progression. These pathways may hold the key to altering the disease progression in PD. PMID:26087293

  9. Immune-Mediated Metabolic Kynurenine Pathways Are Involved in the Postoperative Cognitive Dysfunction after Cardiopulmonary Bypass.

    PubMed

    Yi, Shuang Qiang; Yang, Mi; Duan, Kai Ming

    2015-10-01

    Postoperative cognitive dysfunction (POCD) after cardiopulmonary bypass is a serious complication that can lead to personality changes, memory loss, reduction in the ability to learn, and other central nervous system dysfunctions. In recent years, there have been improvements in measures to protect the brain during surgery, although the incidence of cognitive dysfunction after cardiac surgery remains high (33 to 83% short-term and 20 to 60% long-term cognitive dysfunction). Despite the large amount of basic and clinical research on the incidence of POCD, its exact pathogenesis and complexity are not clear. Many studies have shown that the kynurenine pathway (KP) and cognitive function in humans are closely related. Some reports also show that the imbalance of some metabolites of the KP such as kynurenic acid and quinolinic acid (QUIN), which act in dynamic equilibrium under physiologic conditions, have effects on the central nervous system and can significantly affect cognitive function. Further studies have shown that inflammatory mediators may act on key enzymes of the KP causing KP-induced disorders. Severe inflammatory reaction occurs in patients undergoing cardiopulmonary bypass, which triggers metabolic pathways that are closely related to changes in cognitive function. In this review, we summarize that inflammation-induced metabolic kynurenine (KYN) pathway disorders are likely to have an important role in incidence of POCD after CPB surgery. PMID:25893921

  10. Depletion of Bone Marrow-derived Macrophages Perturbs the Innate Immune Response to Surgery and Reduces Postoperative Memory Dysfunction

    PubMed Central

    Degos, Vincent; Vacas, Susana; Han, Zhenying; van Rooijen, Nico; Gressens, Pierre; Su, Hua; Young, William L.; Maze, Mervyn

    2013-01-01

    Background According to rodent models of postoperative cognitive decline, activation of the innate immune response following aseptic surgical trauma results in the elaboration of hippocampal proinflammatory cytokines, which are capable of disrupting long-term potentiation, the neurobiologic correlate of memory. We hypothesize that hippocampal recruitment of bone marrow-derived (BMD) macrophages plays a causal role in these processes, resulting in memory dysfunction. Methods Clodrolip injection (liposomal formulation of clodronate) prior to stabilized tibial fracture under general anesthesia was used to deplete BMD macrophages. Systemic and neuroinflammation were studied on postoperative day 1, and memory in a fear-trace conditioning paradigm was assessed on postoperative day 3. CX3CR1GFP/+ CCR2RFP/+ mice were used to identify BMD macrophages. Results Clodrolip effectively depleted splenic CCR2+ BMD macrophages. It also attenuated the surgery-induced increase of interleukin-6 in the serum and the hippocampus, and prevented hippocampal infiltration of CCR2+ cells without affecting the number of CX3CR1+ microglia. It did not alter the surgery-induced increase in hippocampal MCP-1, the recruitment signal for CCR2+ cells. Clodrolip prevented surgery-induced memory dysfunction, as evidenced by a significant increase in freezing time (29%, 95% CI: 21 to 38% vs. 48%, 95% CI: 38 to 58%, n= 20, P = 0.004), but did not affect memory in nonsurgical mice. Conclusion Depletion of BMD macrophages prevents hippocampal neuroinflammation and memory dysfunction after experimental tibial fracture. These data suggest that the hippocampal recruitment of BMD macrophages is a necessary mechanism in murine postoperative cognitive dysfunction. Interventions designed to prevent its activation and/or migration into the brain may represent a feasible preemptive strategy. PMID:23426204

  11. Immune cell dysfunctions in breast cancer patients detected through whole blood multi-parametric flow cytometry assay

    PubMed Central

    Verronèse, E.; Delgado, A.; Valladeau-Guilemond, J.; Garin, G.; Guillemaut, S.; Tredan, O.; Ray-Coquard, I.; Bachelot, T.; N'Kodia, A.; Bardin-Dit-Courageot, C.; Rigal, C.; Pérol, D.; Caux, C.; Ménétrier-Caux, C.

    2016-01-01

    ABSTRACT Monitoring functional competence of immune cell populations in clinical routine represents a major challenge. We developed a whole-blood assay to monitor functional competence of peripheral innate immune cells including NK cells, dendritic and monocyte cell subsets through their ability to produce specific cytokines after short-term stimulation, detected through intra-cytoplasmic staining and multi-parametric flow-cytometry. A PMA/ionomycin T cell activation assay complemented this analysis. Comparing cohorts of healthy women and breast cancer (BC) patients at different stages, we identified significant functional alteration of circulating immune cells during BC progression prior to initiation of treatment. Of upmost importance, as early as the localized primary tumor (PT) stage, we observed functional alterations in several innate immune populations and T cells i.e. (i) reduced TNFα production by BDCA-1+ DC and non-classical monocytes in response to Type-I IFN, (ii) a strong drop in IFNγ production by NK cells in response to either Type-I IFN or TLR7/8 ligand, and (iii) a coordinated impairment of cytokine (IL-2, IFNγ, IL-21) production by T cell subpopulations. Overall, these alterations are further accentuated according to the stage of the disease in first-line metastatic patients. Finally, whereas we did not detect functional modification of DC subsets in response to TLR7/8 ligand, we highlighted increased IL-12p40 production by monocytes specifically at first relapse (FR). Our results reinforce the importance of monitoring both innate and adaptive immunity to better evaluate dysfunctions in cancer patients and suggest that our whole-blood assay will be useful to monitor response to treatment, particularly for immunotherapeutic strategies. PMID:27141361

  12. Group I metabotropic glutamate receptor mediated dynamic immune dysfunction in children with fragile X syndrome

    PubMed Central

    2014-01-01

    Background Fragile X syndrome (FXS) is the leading cause of inheritable intellectual disability in male children, and is predominantly caused by a single gene mutation resulting in expanded trinucleotide CGG-repeats within the 5’ untranslated region of the fragile X mental retardation (FMR1) gene. Reports have suggested the presence of immune dysregulation in FXS with evidence of altered plasma cytokine levels; however, no studies have directly assessed functional cellular immune responses in children with FXS. In order to ascertain if immune dysregulation is present in children with FXS, dynamic cellular responses to immune stimulation were examined. Methods Peripheral blood mononuclear cells (PBMC) were from male children with FXS (n = 27) and from male aged-matched typically developing (TD) controls (n = 8). PBMC were cultured for 48 hours in media alone or with lipopolysaccharides (LPS; 1 μg/mL) to stimulate the innate immune response or with phytohemagglutinin (PHA; 8 μg/mL) to stimulate the adaptive T-cell response. Additionally, the group I mGluR agonist, DHPG, was added to cultures to ascertain the role of mGluR signaling in the immune response in subject with FXS. Supernatants were harvested and cytokine levels were assessed using Luminex multiplexing technology. Results Children with FXS displayed similar innate immune response following challenge with LPS alone when compared with TD controls; however, when LPS was added in the presence of a group I mGluR agonist, DHPG, increased immune response were observed in children with FXS for a number of pro-inflammatory cytokines including IL-6 (P = 0.02), and IL-12p40 (P < 0.01). Following PHA stimulation, with or without DHPG, no significant differences between subjects with FXS and TD were seen. Conclusions In unstimulated cultures, subjects with FXS did not display altered dynamic immune response to LPS or PHA alone; however, subjects with FXS showed an altered response to co

  13. Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients

    PubMed Central

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

    2015-01-01

    Immunological dysregulation is present in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), with recent studies also highlighting the importance of examining symptom severity. This research addressed this relationship between CFS/ME severity subgroups, assessing serum immunoglobulins and serum cytokines in severe and moderate CFS/ME patients. Participants included healthy controls (n= 22), moderately (n = 22) and severely (n=19) affected CFS/ME patients. The 1994 Fukuda Criteria defined CFS/ME and severity scales confirmed mobile and housebound CFS/ME patients as moderate and severe respectively. IL-1β was significantly reduced in severe compared with moderate CFS/ME patients. IL-6 was significantly decreased in moderate CFS/ME patients compared with healthy controls and severe CFS/ME patients. RANTES was significantly increased in moderate CFS/ME patients compared to severe CFS/ME patients. Serum IL-7 and IL-8 were significantly higher in the severe CFS/ME group compared with healthy controls and moderate CFS/ME patients. IFN-γ was significantly increased in severe CFS/ME patients compared with moderately affected patients. This was the first study to show cytokine variation in moderate and severe CFS/ME patients, with significant differences shown between CFS/ME symptom severity groups. This research suggests that distinguishing severity subgroups in CFS/ME research settings may allow for a more stringent analysis of the heterogeneous and otherwise inconsistent illness. PMID:26516304

  14. 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

  15. 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

  16. 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. PMID:26373290

  17. Targeting Transcriptional Regulators of CD8+ T Cell Dysfunction to Boost Anti-Tumor Immunity.

    PubMed

    Waugh, Katherine A; Leach, Sonia M; Slansky, Jill E

    2015-01-01

    Transcription is a dynamic process influenced by the cellular environment: healthy, transformed, and otherwise. Genome-wide mRNA expression profiles reflect the collective impact of pathways modulating cell function under different conditions. In this review we focus on the transcriptional pathways that control tumor infiltrating CD8+ T cell (TIL) function. Simultaneous restraint of overlapping inhibitory pathways may confer TIL resistance to multiple mechanisms of suppression traditionally referred to as exhaustion, tolerance, or anergy. Although decades of work have laid a solid foundation of altered transcriptional networks underlying various subsets of hypofunctional or "dysfunctional" CD8+ T cells, an understanding of the relevance in TIL has just begun. With recent technological advances, it is now feasible to further elucidate and utilize these pathways in immunotherapy platforms that seek to increase TIL function.

  18. Immune suppression prevents renal damage and dysfunction and reduces arterial pressure in salt-sensitive hypertension.

    PubMed

    Tian, N; Gu, J-W; Jordan, S; Rose, R A; Hughson, M D; Manning, R D

    2007-02-01

    The goal of this study was to test the hypothesis that renal infiltration of immune cells in Dahl S rats on increased dietary sodium intake contributes to the progression of renal damage, decreases in renal hemodynamics, and development of hypertension. We specifically studied whether anti-immune therapy, using mycophenolate mofetil (MMF), could help prevent increases in renal NF-kappaB activation, renal infiltration of monocytes/macrophages, renal damage, decreases in glomerular filtration rate (GFR) and renal plasma flow, and increases in arterial pressure. Seventy-four 7-to 8-wk-old Dahl S, Rapp strain rats were maintained on an 8% Na, 8% Na + MMF (20 mg.kg(-1).day(-1)), 0.3% Na, or 0.3% Na + MMF diet for 5 wk. Arterial and venous catheters were implanted at day 21. By day 35, renal NF-kappaB in 8% Na rats was 47% higher than in 0.3% Na rats and renal NF-kappaB was 41% lower in 8% Na + MMF rats compared with the 8% Na group. MMF treatment significantly decreased renal monocyte/macrophage infiltration and renal damage and increased GFR and renal plasma flow. In high-NA Dahl S rats mean arterial pressure increased to 182 +/- 5 mmHg, and MMF reduced this arterial pressure to 124 +/- 3 mmHg. In summary, in Dahl S rats on high sodium intake, treatment with MMF decreases renal NF-kappaB and renal monocyte/macrophage infiltration and improves renal function, lessens renal injury, and decreases arterial pressure. This suggests that renal infiltration of immune cells is associated with increased arterial pressure and renal damage and decreasing GFR and renal plasma flow in Dahl salt-sensitive hypertension.

  19. Immunotoxicology: environmental contamination by polybrominated biphenyls and immune dysfunction among residents of the State of Michigan

    SciTech Connect

    Bekesi, J.G.; Roboz, J.P.; Fischbein, A.; Mason, P.

    1987-01-01

    In 1973, inadvertent contamination occurred in a special farm feed supplement for lactating cows. Polybrominated biphenyls (PBBs) were used in place of magnesium oxide resulting in serious harm to farm animals, including cattle, chickens, geese, ducks. Farm families, accustomed to eating their own products, were most heavily exposed. To study the impact of PBBs, 336 adult Michigan farm residents, 117 general consumers for comparison, 75 dairy farm residents in Wisconsin, who had not eaten PBB-contaminated food, were examined, as were 79 healthy subjects in New York City. Abnormalities in the Michigan groups included hypergammaglobulinemia, exaggerated hypersensitive response to streptococci, significant decrease in absolute numbers and percentage of T and B-lymphocytes, and increased number of lymphocytes with no detectable surface markers (''null cells''). Significant reduction of in vitro immune function was noted in 20-25% of the Michigan farm residents who had eaten food containing PBB. The decreased immune function detected among the PBB-exposed farm residents tended to affect families as a unit and was independent of exposed individuals' age or sex, pointing against the possibility of genetic predisposition.

  20. Effect of Splenic Regulatory T-cell Apoptosis on the Postresuscitation Immune Dysfunction in a Porcine Model

    PubMed Central

    Gu, Wei; Zhang, Qian; Li, Chun-Sheng

    2016-01-01

    Background: Postresuscitation immune dysfunction contributes to the low survival rate after successful resuscitation, but its mechanism remains poorly understood. The purpose of this study was to investigate whether splenic regulatory T-cell (Treg) apoptosis was involved in the postresuscitation immune dysfunction. Methods: Thirty-eight pigs were randomly divided into sham-operated group (SHAM group, n = 8), 12 h post return of spontaneous circulation (ROSC) group, 24 h post-ROSC group, and 48 h post-ROSC group (n = 10 per group). A Wuzhishan miniature porcine model of 8-min ventricular fibrillation cardiac arrest (CA) was established. The apoptosis rates of Treg in the spleen were tested by flow cytometry; the expressions of forkhead/winged helix transcription factor (Foxp3) of Treg in the spleen were detected by real-time polymerase chain reaction; and the levels of interleukin-4 (IL-4), IL-10, and interferon gamma (IFN-γ) of Treg in the spleen were detected by enzyme-linked immunosorbent assay. Results: The apoptosis rates of Treg in all post-ROSC groups were significantly lower than that of SHAM group (7.7% ± 1.9%, 7.1% ± 1.8%, 6.2% ± 0.4% vs. 13.1% ± 1.6%; P < 0.05); the expression levels of Foxp3 and IL-10 were also decreased with the increase of apoptosis rates of Treg. Helper T-cells CD4+ lymphocyte subsets were significantly lower in the post-ROSC groups compared with SHAM group (29.1% ± 2.2%, 24.3% ± 2.2%, 24.1% ± 2.5% vs. 43.8% ± 4.5%; P < 0.01) at 12, 24, and 48 h after ROSC. Compared with SHAM group, the levels of IFN-γ (161.0 ± 12.9, 167.7 ± 10.5, 191.2 ± 7.7 vs. 7.6 ± 0.9 ng/L) and IL-4 (27.7 ± 6.2, 35.9 ± 3.5, 50.6 ± 6.1 vs. 13.3 ± 2.3 ng/L) and the ratio of IFN-γ/IL-4 (8.6 ± 2.3, 4.9 ± 0.4, 4.5 ± 0.9 vs. 0.8 ± 0.2) were all greatly elevated in all post-ROSC groups (P < 0.05). Conclusions: Apoptosis rate of Treg was significantly decreased after CA, and thus the proportion of Treg was increased and the inhibitory effects were

  1. Genetic, Immune, and Vasoactive Factors in the Vascular Dysfunction Associated with Hypertension in Pregnancy

    PubMed Central

    Ali, Sajjadh M. J.; Khalil, Raouf A.

    2015-01-01

    Introduction Preeclampsia (PE) is a major complication of pregnancy that could lead to maternal and fetal morbidity and mortality. The pathophysiological mechanisms of PE are not completely understood, but recent research has begun to unravel some of the potential mechanisms. Areas covered Genetic polymorphisms and altered maternal immune response may cause impaired remodeling of the spiral arteries; a potential early defect in PE. Inadequate invasion of cytotrophoblasts into the decidua leads to reduced uteroplacental perfusion pressure (RUPP) and placental ischemia/hypoxia. Placental ischemia causes the release of biologically active factors such as anti-angiogenic factors, inflammatory cytokines, reactive oxygen species, hypoxia-inducible factors, and angiotensin II receptor autoantibodies. These vasoactive factors could cause systemic vascular endotheliosis and consequent increase in vascular resistance and blood pressure, glomerular endotheliosis causing proteinuria, cerebrovascular endotheliosis causing cerebral edema, seizures and visual disturbances, and hepatic endotheliosis which may contribute to the manifestations of HELLP syndrome. PE-associated vascular endotheliosis causes a decrease in vasodilator mediators such as nitric oxide, prostacyclin and endothelium-derived hyperpolarizing factor, an increase in vasoconstrictors such as endothelin-1, angiotensin II and thromboxane A2, and enhanced mechanisms of vascular smooth muscle contraction such as intracellular Ca2+, protein kinase C and Rho-kinase. Changes in matrix metalloproteinase activity and extracellular matrix cause vascular remodeling and further vasoconstriction. Expert opinion Some of the genetic, immune and vasoactive factors involved in vascular endotheliosis could be used as biomarkers for early detection, and as potential targets for prevention and treatment of PE. PMID:26294111

  2. Protective effect of hydrogen-rich saline against radiation-induced immune dysfunction.

    PubMed

    Zhao, Sanhu; Yang, Yanyong; Liu, Wen; Xuan, Zhiqiang; Wu, Shouming; Yu, Shunfei; Mei, Ke; Huang, Yijuan; Zhang, Pei; Cai, Jianming; Ni, Jin; Zhao, Yaoxian

    2014-05-01

    Recent studies showed that hydrogen can be used as an effective radioprotective agent through scavenging free radicals. This study was undertaken to evaluate the radioprotective effects of hydrogen on immune system in mice. H(2) was dissolved in physiological saline using an apparatus produced by our department. Spleen index and histological analysis were used to evaluate the splenic structural damage. Spleen superoxide dismutase, GSH, MDA were measured to appraise the antioxidant capacity and a DCF assay for the measurement of radical oxygen species. Cell apoptosis was evaluated by an Annexin V-FITC and propidium iodide staining method as well as the apoptotic proteins such as Bcl-2, Bax, caspase-3 and c-caspase-3. CD4+ and CD8+ T cells subtypes were detected by flow cytometry with FITC-labelled antimouse CD4 and PE antimouse CD8 staining. Real-time PCR was utilized to determine the CD4+ T cell subtypes and related cytokines. Our study demonstrated that pre-treatment with H(2) could increase the spleen index and attenuate the radiation damage on splenic structure. Radical oxygen species level was also reduced by H(2) treatment. H(2) also inhibited radiation-induced apoptosis in splenocytes and down-regulated pro-apoptotic proteins in living mice. Radiation-induced imbalance of T cells was attenuated by H(2). Finally, we found that H(2) could regulate the polarization of CD4+ T cells and the level of related cytokines. This study suggests H(2) as an effective radioprotective agent on immune system by scavenging reactive oxygen species.

  3. Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) - a clinical audit.

    PubMed

    Myhill, Sarah; Booth, Norman E; McLaren-Howard, John

    2013-01-01

    We report on an audit of 138 ME/CFS patients who attended a private practice and took the ATP Profile biomedical test. The results revealed that all of these patients had measureable mitochondrial dysfunction. A basic treatment regime, based on 1) eating the evolutionary correct stone-age diet, 2) ensuring optimum hours of good quality sleep, 3) taking a standard package of nutritional supplements, and 4) getting the right balance between work and rest, was recommended for all patients. Additions to the basic regime were tailored for each patient according to the results of the ATP Profile and additional nutritional tests and clues from the clinical history. Mitochondrial function is typically impaired in two ways: substrate or co-factor deficiency, and inhibition by chemicals, exogenous or endogenous. For the former, additional nutrients are recommended where there is a deficiency, and for the latter, improvement of anti-oxidant status and selective chelation therapy or far-infrared saunas are appropriate. We show case histories of nine patients who have taken the ATP Profile on three or four occasions, and a before-and-after treatment summary of the 34 patients who have had at least two ATP Profile tests separated by some months. Finally, we summarize the results for the 30 patients who followed all aspects of the treatment regime and compare them with the 4 patients who were lax on two or more aspects of the treatment regime. All patients who followed the treatment regime improved in mitochondrial function by on average a factor of 4. PMID:23236553

  4. 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. PMID:27397737

  5. 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

  6. A new hypothesis of chronic fatigue syndrome: co-conditioning theory.

    PubMed

    Tanaka, Masaaki; Watanabe, Yasuyoshi

    2010-08-01

    Chronic fatigue syndrome is an illness characterized by a profound, disabling, and unexplained sensation of fatigue lasting at least 6 months, which severely impairs daily functioning and is accompanied by a combination of non-specific symptoms. Many potential causes of chronic fatigue syndrome have been investigated, including viral infections, immune dysfunctions, abnormal neuroendocrine responses, central nervous system abnormalities, autonomic dysfunctions, impaired exercise capacities, sleep disruptions, genetic backgrounds, psychiatric abnormalities, personality, and abnormal psychological processes. However, no etiology, specific physical signs or laboratory test abnormalities have been found. It is essential to establish a conceptual theory of chronic fatigue syndrome that can explain its pathophysiology in order to identify the clinical entity and to develop effective treatment methods. In this article, a new conceptual hypothesis about the pathophysiology of chronic fatigue syndrome, the co-conditioning theory, is presented: after repetitive overwork and/or stress, alarm signal to rest and fatigue sensation may cause in response to an unconditioned stimulus (impaired homeostasis and function) that has been paired with a conditioned stimulus (overwork and/or stress). In the future, a new treatment strategy for patients with chronic fatigue syndrome, re-co-conditioning therapy, may be developed on the basis of the co-conditioning theory. In addition, this theory will likely contribute to a better understanding of the pathophysiology of chronic fatigue syndrome.

  7. A countermeasure to ameliorate immune dysfunction in in vitro simulated microgravity environment: role of cellularnucleotide nutrition.

    PubMed

    Hales, N W; Yamauchi, K; Alicea, A; Sundaresan, A; Pellis, N R; Kulkarni, A D

    2002-04-01

    Considerable evidence suggests that space travelers are immunosuppressed, presumably by microgravity environmental stresses, putting them at risk for adverse effects, such as opportunistic infections, poor wound healing, and cancer. The purpose of this study was to examine the role and mechanisms of nucleotide (NT) supplementation as a countermeasure to obviate immunosuppression during space travel. The in vitro rotary cell culture system, a bioreactor (BIO), was used to simulate the effect of microgravity and to isolate the neuroendocrine effects inherent to in vitro models. The splenocytes from normal mice were cultured in BIO and control tissue culture (TC) flasks with and without phytohemagglutinin (PHA) for mitogen assays. The culture medium was then supplemented with various concentrations of a nucleosides-nucleotides mixture (NS + NT), inosine, and uridine. Cytokines interleukin (IL)-1beta, IL-2, IL-3, tumor necrosis factor-alpha, and interferon (IFN)-gamma were measured from the supernatant by enzyme-linked immunosorbent assay. In the PHA-stimulated cultures the cellular proliferation in the BIO was significantly decreased as compared with the TC flask cells. BIO-cultured cells in the presence of NS + NT maintained mitogen responses similar to the control TC flask cells. The maintenance of the mitogen response in BIO was observed by the supplementation of uridine and not of inosine. These results are in agreement with our earlier results from unit gravity experiments that showed that pyrimidines are more effective in pleiogenic immunoprotection to hosts. Cytokines IL-1beta, IL-2, and IFN-gamma in the BIO supernatants of cells cultured in the presence of NS + NT had a significantly higher response than the control vessel. Thus, supplemental NT, especially pyrimidines, can confer immune protection and enhance cytokine responses during space travel.

  8. Chronic fatigue syndrome. 1: Etiology and pathogenesis.

    PubMed

    Farrar, D J; Locke, S E; Kantrowitz, F G

    1995-01-01

    Chronic fatigue syndrome (CFS) is a disorder of unknown etiology characterized by debilitating fatigue and other somatic and neuropsychiatric symptoms. A range of heterogeneous clinical and laboratory findings have been reported in patients with CFS. Various theories have been proposed to explain the underlying pathophysiologic processes but none has been proved. Research findings of immunologic dysfunction and neuroendocrine changes suggest the possible dysregulation of interactions between the nervous system and the immune system. Without a clear understanding of its etiopathogenesis, CFS has no definitive treatment. Management approaches have been necessarily speculative, and they have evolved separately in a number of medical and nonmedical disciplines. The results of several controlled treatment studies have been inconclusive. An accurate case definition identifying homogeneous subtypes of CFS is needed. The integration of medical and psychologic treatment modalities and the use of both biologic and psychologic markers to evaluate treatment response will enhance future treatment strategies. PMID:7579775

  9. [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. PMID:26596115

  10. The polyhydroxylated fullerene derivative C{sub 60}(OH){sub 24} protects mice from ionizing-radiation-induced immune and mitochondrial dysfunction

    SciTech Connect

    Cai Xiaoqing; Hao Jiejie; Zhang Xiaoyong; Yu Bozhang; Ren Jinming; Luo Cheng; Li Qingnuan; Huang Qing; Shi Xianglin; Li Wenxin; Liu Jiankang

    2010-02-15

    Although the protective effect of the polyhydroxylated fullerene derivative C{sub 60}(OH){sub n} against ionizing radiation is an area of much interest, the mechanisms relating to how polyhydroxylated fullerene derivatives improve mitochondrial dysfunction remain unknown. In order to find new and effective radioprotective agents, we synthesized a new polyhydroxylated fullerene molecule with 24 hydroxyl groups of known positions on C{sub 60} and studied its protective effects in mice subjected to irradiation. Mice were pretreated with C{sub 60}(OH){sub 24} for 2 weeks (daily, 40 mg/kg i. p.), then subjected to a lethal dose of whole body gamma-irradiation (from a {sup 60}Co source). Survival was observed for 30 days after irradiation. Immune and mitochondrial dysfunction and oxidative damage were analyzed in mice with the same C{sub 60}(OH){sub 24} pretreatment and irradiation except that the animals were euthanized at day 5 after the irradiation. It was found that 2-week C{sub 60}(OH){sub 24} pretreatment effectively reduced whole body irradiation-induced mortality without apparent toxicity. C{sub 60}(OH){sub 24} pretreatment also showed significant protective effects against ionizing-radiation-induced decreases in immune and mitochondrial function and antioxidant defense in the liver and spleen. These results suggest that the polyhydroxylated fullerene derivative C{sub 60}(OH){sub 24} protects against ionizing-radiation-induced mortality, possibly by enhancing immune function, decreasing oxidative damage and improving mitochondrial function.

  11. Long-term persistence of vaccine-derived aluminum hydroxide is associated with chronic cognitive dysfunction.

    PubMed

    Couette, Maryline; Boisse, Marie-Françoise; Maison, Patrick; Brugieres, Pierre; Cesaro, Pierre; Chevalier, Xavier; Gherardi, Romain K; Bachoud-Levi, Anne-Catherine; Authier, François-Jérôme

    2009-11-01

    Macrophagic myofasciitis (MMF) is an emerging condition, characterized by specific muscle lesions assessing long-term persistence of aluminum hydroxide within macrophages at the site of previous immunization. Affected patients mainly complain of arthromyalgias, chronic fatigue, and cognitive difficulties. We designed a comprehensive battery of neuropsychological tests to prospectively delineate MMF-associated cognitive dysfunction (MACD). Compared to control patients with arthritis and chronic pain, MMF patients had pronounced and specific cognitive impairment. MACD mainly affected (i) both visual and verbal memory; (ii) executive functions, including attention, working memory, and planning; and (iii) left ear extinction at dichotic listening test. Cognitive deficits did not correlate with pain, fatigue, depression, or disease duration. Pathophysiological mechanisms underlying MACD remain to be determined. In conclusion, long-term persistence of vaccine-derived aluminum hydroxide within the body assessed by MMF is associated with cognitive dysfunction, not solely due to chronic pain, fatigue and depression.

  12. Immunization

    MedlinePlus

    ... a lot worse. Some are even life-threatening. Immunization shots, or vaccinations, are essential. They protect against things like measles, ... B, polio, tetanus, diphtheria, and pertussis (whooping cough). Immunizations are important for adults as well as children. ...

  13. Immunizations

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Immunizations KidsHealth > For Teens > Immunizations Print A A A ... That Shot? en español Las vacunas Why Are Vaccinations Important? Measles, mumps, and whooping cough may seem ...

  14. CD4:CD8 ratio as a frontier marker for clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed HIV-positive patients

    PubMed Central

    Lu, Wei; Mehraj, Vikram; Vyboh, Kishanda; Cao, Wei; Li, Taisheng; Routy, Jean-Pierre

    2015-01-01

    Introduction Absolute CD4 T cell count and plasma viral load have been established as predictors of HIV disease progression, and CD4 T cell count is used as an indicator for initiation of antiretroviral therapy. Following long-term therapy, patients generally present with significant CD4 T cell recovery contrasting with persistently elevated CD8 T cell counts, which leads to a partial restoration of CD4:CD8 ratio. This review focuses on the relevance of the CD4:CD8 ratio on clinical outcomes, immune dysfunction and HIV reservoir size in long-term treated patients. Method We conducted a comprehensive literature review of publications in English language using major electronic databases. Our search was focused on factors contributing to CD4:CD8 T cell ratio and clinical outcome in adult HIV-positive patients in the context of treated infection. Discussion Low CD4:CD8 ratio has been linked to ageing and acts as a predictor of mortality in the general population. This ratio may represent the combined effects of inflammation and immunological changes called “inflammaging.” Although the mechanisms underlying partial correction of the CD4:CD8 ratio and persistently elevated CD8 T cell count in long-term treated patients remain poorly understood, it has been recently indicated that patients with optimal CD4 T cell recovery and low CD4:CD8 ratio still harbour increased immune activation, an immune senescent phenotype and have a higher risk of non-AIDS morbidity and mortality. This review reconsiders CD4:CD8 ratio in the light of advances in the understanding of immune dysfunction and examines its pathophysiological features and implications on clinical outcome and HIV reservoir size in long-term treated HIV-positive adults. Conclusion The CD4:CD8 ratio can contribute to the immunological evaluation of treated patients in a long-term follow-up and may be applied for monitoring both immune dysfunction and viral reservoir size in immune-based clinical trials. PMID:26130226

  15. 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

  16. 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.

  17. The role of immune activation in contributing to vascular dysfunction and the pathophysiology of hypertension during preeclampsia

    PubMed Central

    LaMarca, Babbette

    2012-01-01

    Summary Alterations in vascular function contributes to hypertension as well as multi-organ dysfunction in women with preeclampsia (1,4, 11–14). Preterm preeclampsia remains a leading cause of maternal death and perinatal morbidity and most recently it has been recognized that women whom endure preeclampsia are at a greater risk for cardiovascular disease later in life. The pathophysiologic processes that underlie preeclampsia has been proposed to occur in two stages: stage 1, reduced placental perfusion, and stage 2, the maternal clinical syndrome (1,4). Placental ischemia/hypoxia is believed to result in the release of a variety of placental factors that have profound effects on blood flow and arterial pressure regulation (Figure 1) (1, 4, 10, 11). These factors include a host of molecules such as the soluble VEGF receptor-1 (sFlt-1), the angiotensin II type-1 receptor autoantibody (AT1-AA), and cytokines such as TNF-α and Interleukin 6 which in turn generate widespread dysfunction of the maternal vascular endothelium (1–11). This dysfunction results in formation of factors such as endothelin, reactive oxygen species (ROS), and augmented vascular sensitivity to angiotensin II (1–11). In addition, preeclampsia is also associated with decreased formation of vasodilators such as nitric oxide and prostacyclin (1–11). These alterations in vascular function not only lead to hypertension but multi-organ dysfunction, especially in women with early onset preeclampsia (1,4, 11–14). Therefore, identifying the connection between placental ischemia and maternal cardiovascular abnormalities is an important area of investigation (1,10,11,21). In addition, the quantitative importance of the various endothelial and humoral factors that mediate vascular dysfunction and hypertension during preeclampsia remains to be elucidated. PMID:20502423

  18. 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.

  19. Chronic fatigue syndrome: an approach combining self-management with graded exercise to avoid exacerbations.

    PubMed

    Nijs, Jo; Paul, Lorna; Wallman, Karen

    2008-04-01

    Controversy regarding the aetiology and treatment of patients with chronic fatigue syndrome continues among the medical professions. The Cochrane Collaboration advises practitioners to implement graded exercise therapy for patients with chronic fatigue syndrome using cognitive behavioural principles. Conversely, there is evidence that exercise can exacerbate symptoms in chronic fatigue syndrome, if too-vigorous exercise/activity promotes immune dysfunction, which in turn increases symptoms. When designing and implementing an exercise programme for chronic fatigue syndrome it is important to be aware of both of these seemingly opposing viewpoints in order to deliver a programme with no detrimental effects on the pathophysiology of the condition. Using evidence from both the biological and clinical sciences, this paper explains that graded exercise therapy for people with chronic fatigue syndrome can be undertaken safely with no detrimental effects on the immune system. Exercise programmes should be designed to cater for individual physical capabilities and should take into account the fluctuating nature of symptoms. In line with cognitive behaviourally and graded exercise-based strategies, self-management for people with chronic fatigue syndrome involves encouraging patients to pace their activities and respect their physical and mental limitations, with the ultimate aim of improving their everyday functioning.

  20. Examining T cells at vaccine sites of tumor-bearing hosts provides insights to dysfunctional T-cell immunity.

    PubMed

    Barr, Kristen M; Jing, Weiqing; Hallett, William H D; Gershan, Jill A; Johnson, Bryon D

    2013-01-01

    When tumor vaccines are administered as cancer immunotherapy, cellular interactions at the vaccine site are crucial to the generation of antitumor immunity. Examining interactions at the vaccine site could provide important insights to the success or failure of vaccination. Our laboratory previously showed that while administration of a cell-based vaccine to tumor-free mice leads to productive antineuroblastoma immunity, vaccination of tumor-bearing mice does not. The goal of this study was to examine immune effectors at the vaccine site to identify mechanisms responsible for the generation of ineffective antitumor immunity in tumor-bearing mice. The results of this study show that vaccine sites of tumor-bearing mice contained significantly fewer T cells than vaccine sites of tumor-free mice. Similar migration and proliferation of T cells was observed in the vaccine sites of tumor-bearing and tumor-free mice, but T cells in the sites of tumor-bearing mice were more apoptotic. T cells at the vaccine sites of both tumor-free and tumor-bearing mice had an effector-memory phenotype and expressed activation markers. Despite the activated phenotype, T cells from tumor-bearing mice elicited defective antitumor immune responses. Although T cells from vaccine sites of tumor-bearing mice were capable of producing inflammatory cytokines, the T cells from tumor-bearing mice produced lower levels of cytokines compared with T cells from the tumor-free mice. Remarkably, this defect seems to be systemic, affecting distal T cells in tumor-bearing mice. This study demonstrates that the defective vaccine-induced immune response to neuroblastoma in tumor-bearing hosts originates as a result of tumor burden, resulting in poor antitumor immunity.

  1. Fatigue in systemic lupus erythematosus

    PubMed Central

    Ahn, Grace E; Ramsey-Goldman, Rosalind

    2012-01-01

    Systemic lupus erythematosus is a chronic inflammatory autoimmune disease often characterized by fatigue, with significant effects on physical functioning and wellbeing. The definition, prevalence and factors associated with fatigue, including physical activity, obesity, sleep, depression, anxiety, mood, cognitive dysfunction, vitamin D deficiency/insufficiency, pain, effects of medications and comorbidities, as well as potential therapeutic options of fatigue in the systemic lupus erythematosus population are reviewed. Due to variability in the reliability and validity of various fatigue measures used in clinical studies, clinical trial data have been challenging to interpret. Further investigation into the relationships between these risk factors and fatigue, and improved measures of fatigue, may lead to an improvement in the management of this chronic inflammatory disease. PMID:22737181

  2. Immunization.

    ERIC Educational Resources Information Center

    Guerin, Nicole; And Others

    1986-01-01

    Contents of this double journal issue concern immunization and primary health care of children. The issue decribes vaccine storage and sterilization techniques, giving particular emphasis to the role of the cold chain, i.e., the maintenance of a specific temperature range to assure potency of vaccines as they are moved from a national storage…

  3. Urinary Dysfunction

    MedlinePlus

    ... PCF Spotlight Glossary African American Men Living with Prostate Cancer Urinary Dysfunction Side Effects Urinary Dysfunction Bowel Dysfunction ... dysfunction is normal following initial therapy for localized prostate cancer. But it’s important to realize that not all ...

  4. Dysfunction of constitutive and inducible ubiquitin-proteasome system in amyotrophic lateral sclerosis: implication for protein aggregation and immune response.

    PubMed

    Bendotti, Caterina; Marino, Marianna; Cheroni, Cristina; Fontana, Elena; Crippa, Valeria; Poletti, Angelo; De Biasi, Silvia

    2012-05-01

    The ubiquitin-proteasome system (UPS) is the major intracellular proteolytic mechanism controlling the degradation of misfolded/abnormal proteins. A common hallmark in amyotrophic lateral sclerosis (ALS) and in other neurodegenerative disorders is the accumulation of misfolded/abnormal proteins into the damaged neurons, leading to the formation of cellular inclusions that are mostly ubiquitin-positive. Although proteolysis is a complex mechanism requiring the participation of different pathways, the abundant accumulation of ubiquitinated proteins strongly suggests an important contribution of UPS to these neuropathological features. The use of cellular and animal models of ALS, particularly those expressing mutant SOD1, the gene mutation most represented in familiar ALS, has provided significant evidence for a role of UPS in protein inclusions formation and motor neuron death. This review will specifically discuss this piece of evidence and provide suggestions of potential strategies for therapeutic intervention. We will also discuss the finding that, unlike the constitutive proteasome subunits, the inducible subunits are overexpressed early during disease progression in SOD1 mice models of ALS. These subunits form the immunoproteasome and generate peptides for the major histocompatibility complex class I molecules, suggesting a role of this system in the immune responses associated with the pathological features of ALS. Since recent discoveries indicate that innate and adaptive immunity may influence the disease process, in this review we will also provide evidence of a possible connection between immune-inflammatory reactions and UPS function, in the attempt to better understand the etiopathology of ALS and to identify appropriate targets for novel treatment strategies of this devastating disease. PMID:22033150

  5. Overcoming Hypoxia-Mediated Tumor Progression: Combinatorial Approaches Targeting pH Regulation, Angiogenesis and Immune Dysfunction

    PubMed Central

    McDonald, Paul C.; Chafe, Shawn C.; Dedhar, Shoukat

    2016-01-01

    Hypoxia is an important contributor to the heterogeneity of the microenvironment of solid tumors and is a significant environmental stressor that drives adaptations which are essential for the survival and metastatic capabilities of tumor cells. Critical adaptive mechanisms include altered metabolism, pH regulation, epithelial-mesenchymal transition, angiogenesis, migration/invasion, diminished response to immune cells and resistance to chemotherapy and radiation therapy. In particular, pH regulation by hypoxic tumor cells, through the modulation of cell surface molecules such as extracellular carbonic anhydrases (CAIX and CAXII) and monocarboxylate transporters (MCT-1 and MCT-4) functions to increase cancer cell survival and enhance cell invasion while also contributing to immune evasion. Indeed, CAIX is a vital regulator of hypoxia mediated tumor progression, and targeted inhibition of its function results in reduced tumor growth, metastasis, and cancer stem cell function. However, the integrated contributions of the repertoire of hypoxia-induced effectors of pH regulation for tumor survival and invasion remain to be fully explored and exploited as therapeutic avenues. For example, the clinical use of anti-angiogenic agents has identified a conundrum whereby this treatment increases hypoxia and cancer stem cell components of tumors, and accelerates metastasis. Furthermore, hypoxia results in the infiltration of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Treg) and Tumor Associated Macrophages (TAMs), and also stimulates the expression of PD-L1 on tumor cells, which collectively suppress T-cell mediated tumor cell killing. Therefore, combinatorial targeting of angiogenesis, the immune system and pH regulation in the context of hypoxia may lead to more effective strategies for curbing tumor progression and therapeutic resistance, thereby increasing therapeutic efficacy and leading to more effective strategies for the treatment of patients with

  6. Comparison of Watermelon and Carbohydrate Beverage on Exercise-Induced Alterations in Systemic Inflammation, Immune Dysfunction, and Plasma Antioxidant Capacity

    PubMed Central

    Shanely, R. Andrew; Nieman, David C.; Perkins-Veazie, Penelope; Henson, Dru A.; Meaney, Mary P.; Knab, Amy M.; Cialdell-Kam, Lynn

    2016-01-01

    Consuming carbohydrate- and antioxidant-rich fruits during exercise as a means of supporting and enhancing both performance and health is of interest to endurance athletes. Watermelon (WM) contains carbohydrate, lycopene, l-citrulline, and l-arginine. WM may support exercise performance, augment antioxidant capacity, and act as a countermeasure to exercise-induced inflammation and innate immune changes. Trained cyclists (n = 20, 48 ± 2 years) participated in a randomized, placebo controlled, crossover study. Subjects completed two 75 km cycling time trials after either 2 weeks ingestion of 980 mL/day WM puree or no treatment. Subjects drank either WM puree containing 0.2 gm/kg carbohydrate or a 6% carbohydrate beverage every 15 min during the time trials. Blood samples were taken pre-study and pre-, post-, 1 h post-exercise. WM ingestion versus no treatment for 2-weeks increased plasma l-citrulline and l-arginine concentrations (p < 0.0125). Exercise performance did not differ between WM puree or carbohydrate beverage trials (p > 0.05), however, the rating of perceived exertion was greater during the WM trial (p > 0.05). WM puree versus carbohydrate beverage resulted in a similar pattern of increase in blood glucose, and greater increases in post-exercise plasma antioxidant capacity, l-citrulline, l-arginine, and total nitrate (all p < 0.05), but without differences in systemic markers of inflammation or innate immune function. Daily WM puree consumption fully supported the energy demands of exercise, and increased post-exercise blood levels of WM nutritional components (l-citrulline and l-arginine), antioxidant capacity, and total nitrate, but without an influence on post-exercise inflammation and changes in innate immune function. PMID:27556488

  7. Comparison of Watermelon and Carbohydrate Beverage on Exercise-Induced Alterations in Systemic Inflammation, Immune Dysfunction, and Plasma Antioxidant Capacity.

    PubMed

    Shanely, R Andrew; Nieman, David C; Perkins-Veazie, Penelope; Henson, Dru A; Meaney, Mary P; Knab, Amy M; Cialdell-Kam, Lynn

    2016-01-01

    Consuming carbohydrate- and antioxidant-rich fruits during exercise as a means of supporting and enhancing both performance and health is of interest to endurance athletes. Watermelon (WM) contains carbohydrate, lycopene, l-citrulline, and l-arginine. WM may support exercise performance, augment antioxidant capacity, and act as a countermeasure to exercise-induced inflammation and innate immune changes. Trained cyclists (n = 20, 48 ± 2 years) participated in a randomized, placebo controlled, crossover study. Subjects completed two 75 km cycling time trials after either 2 weeks ingestion of 980 mL/day WM puree or no treatment. Subjects drank either WM puree containing 0.2 gm/kg carbohydrate or a 6% carbohydrate beverage every 15 min during the time trials. Blood samples were taken pre-study and pre-, post-, 1 h post-exercise. WM ingestion versus no treatment for 2-weeks increased plasma l-citrulline and l-arginine concentrations (p < 0.0125). Exercise performance did not differ between WM puree or carbohydrate beverage trials (p > 0.05), however, the rating of perceived exertion was greater during the WM trial (p > 0.05). WM puree versus carbohydrate beverage resulted in a similar pattern of increase in blood glucose, and greater increases in post-exercise plasma antioxidant capacity, l-citrulline, l-arginine, and total nitrate (all p < 0.05), but without differences in systemic markers of inflammation or innate immune function. Daily WM puree consumption fully supported the energy demands of exercise, and increased post-exercise blood levels of WM nutritional components (l-citrulline and l-arginine), antioxidant capacity, and total nitrate, but without an influence on post-exercise inflammation and changes in innate immune function. PMID:27556488

  8. Fatigue in cholestatic liver disease—a perplexing symptom

    PubMed Central

    Kumar, D; Tandon, R

    2002-01-01

    Fatigue is an important symptom and a quality of life determinant in patients with cholestatic liver disease. The pathogenesis of fatigue is obscure, although alterations in central neurotransmission and peripheral muscle dysfunction have been incriminated. No effective treatment is available at present. The available literature on fatigue in cholestatic liver disease is reviewed. PMID:12151655

  9. ED 05-2 INTERACTION OF GUT DYSBIOSIS AND INNATE IMMUNE DYSFUNCTION IN THE DEVELOPMENT OF METABOLIC SYNDROME.

    PubMed

    Lee, Myung-Shik

    2016-09-01

    Low-grade systemic inflammation in adipose tissues or liver, is an important etiologic factor in insulin resistance. LPS is an important element causing such metabolic inflammation, and intestinal flora is considered a major source of systemic LPS. We studied changes of intestinal microbiota associated with high-fat diet (HFD) that causes insulin resistance and metabolic stress. 16S rRNA gene sequencing showed that HFD significantly decreased the abundance of a mucin-degrading bacterium Akkermansia muciniphila compared to control diet. Reduced abundance of Akkermansia in HFD-fed mice was reversed by metformin, a widely prescribed anti-diabetic medicine. Oral administration of Akkermansia to HFD-fed mice significantly enhanced insulin sensitivity and attenuated adipose tissue inflammation probably by inducing Foxp3 regulatory T cells (Tregs) in the visceral adipose tissue. We also studied Paneth cells, specialized intestinal epithelial cells that produce antimicrobial peptides (AMP) and shape gut microbial milieu. We studied whether high-fat diet (HFD) impairs the function of Paneth cells and interferes with intestinal microbial homeostasis, potentially contributing to the development of metabolic syndrome. HFD-fed mice exhibited reduced expressions of some AMP and defective antimicrobial activity, which led to loss of epithelial integrity and a significantly higher content of LPS in the liver and serum of HFD-fed mice compared to chow-fed mice. Antibiotic treatment reduced translocation of bacterial components, steatosis, and inflammation in the liver of HFD-fed mice, which in turn improved systemic glucose metabolism. HFD-fed mice were also more susceptible to dextran sodium sulfate-induced colitis, probably due to impaired Paneth cell function. Our data suggest that Paneth cell dysfunction may be one of the underlying mechanisms of glucose intolerance and inflammatory bowel disease associated with western diet. These results suggest that high-fat diet could be a

  10. Gene Expression of Mesothelioma in Vinylidene Chloride-Exposed F344/N Rats Reveals Immune Dysfunction, Tissue Damage, and Inflammation Pathways

    PubMed Central

    Blackshear, Pamela E.; Pandiri, Arun R.; Nagai, Hiroaki; Bhusari, Sachin; Hong, Lily; Ton, Thai-Vu T.; Clayton, Natasha P.; Wyde, Michael; Shockley, Keith R.; Peddada, Shyamal D.; Gerrish, Kevin E.; Sills, Robert C.; Hoenerhoff, Mark J.

    2014-01-01

    A majority (~80%) of human malignant mesotheliomas are asbestos-related. However, non-asbestos risk factors (radiation, chemicals, genetic factors) account for up to 30% of cases. A recent two-year National Toxicology Program carcinogenicity bioassay showed that male F344/N rats exposed to the industrial toxicant vinylidene chloride (VDC) resulted in a marked increase in malignant mesothelioma. Global gene expression profiles of these tumors were compared to spontaneous mesotheliomas and the F344/N rat mesothelial cell line (Fred-PE) in order to characterize the molecular features and chemical-specific profiles of mesothelioma in VDC-exposed rats. As expected, mesotheliomas from control and vinylidene chloride-exposed rats shared pathways associated with tumorigenesis, including cellular and tissue development, organismal injury, embryonic development, inflammatory response, cell cycle regulation, and cellular growth and proliferation, while mesotheliomas from vinylidene chloride-exposed rats alone showed overrepresentation of pathways associated with pro-inflammatory pathways and immune dysfunction such as the NF-kB signaling pathway, IL-8 and IL-12 signaling, interleukin responses, Fc receptor signaling, and NK and DC signaling, as well as overrepresentation of DNA damage and repair. These data suggest that a chronic, proinflammatory environment associated with VDC exposure may exacerbate disturbances in oncogene, growth factor and cell cycle regulation, resulting in an increased incidence of mesothelioma. PMID:24958746

  11. Bowel Dysfunction

    MedlinePlus

    ... PCF Spotlight Glossary African American Men Living with Prostate Cancer Bowel Dysfunction Side Effects Urinary Dysfunction Bowel Dysfunction ... rectal worse. Back to Side Effects Print | Understanding Prostate Cancer Research Faces of Prostate Cancer About PCF Take ...

  12. 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

  13. Prognosis of hormone-dependent breast cancers: implications of the presence of dysfunctional transcriptional networks activated by insulin via the immune transcription factor T-bet.

    PubMed

    McCune, Kasi; Bhat-Nakshatri, Poornima; Thorat, Mangesh A; Nephew, Kenneth P; Badve, Sunil; Nakshatri, Harikrishna

    2010-01-15

    Estrogen receptor alpha (ERalpha)-positive breast cancers that co-express transcription factors GATA-3 and FOXA1 have a favorable prognosis. These transcription factors form an autoregulatory hormonal network that influences estrogen responsiveness and sensitivity to hormonal therapy. Disruption of this network may be a mechanism whereby ERalpha-positive breast cancers become resistant to therapy. The transcription factor T-bet is a negative regulator of GATA-3 in the immune system. In this study, we report that insulin increases the expression of T-bet in breast cancer cells, which correlates with reduced expression of GATA-3, FOXA1, and the ERalpha:FOXA1:GATA-3 target gene GREB-1. The effects of insulin on GATA-3 and FOXA1 could be recapitulated through overexpression of T-bet in MCF-7 cells (MCF-7-T-bet). Chromatin immunoprecipitation assays revealed reduced ERalpha binding to GREB-1 enhancer regions in MCF-7-T-bet cells and in insulin-treated MCF-7 cells. MCF-7-T-bet cells were resistant to tamoxifen in the presence of insulin and displayed prolonged extracellular signal-regulated kinase and AKT activation in response to epidermal growth factor treatment. ERalpha-positive cells with intrinsic tamoxifen resistance as well as MCF-7 cells with acquired tamoxifen and fulvestrant resistance expressed elevated levels of T-bet and/or reduced levels of FOXA1 and GATA-3. Analysis of publicly available databases revealed ERalpha-positive/T-bet-positive breast cancers expressing lower levels of FOXA1 (P = 0.0137) and GATA-3 (P = 0.0063) compared with ERalpha-positive/T-bet-negative breast cancers. Thus, T-bet expression in primary tumors and circulating insulin levels may serve as surrogate biomarkers to identify ERalpha-positive breast cancers with a dysfunctional hormonal network, enhanced growth factor signaling, and resistance to hormonal therapy.

  14. The Structure of the Mammalian RNase H2 Complex Provides Insight into RNA.NA Hybrid Processing to Prevent Immune Dysfunction

    SciTech Connect

    Shaban, N.; Harvey, S; Perrino, F; Hollis, T

    2010-01-01

    The mammalian RNase H2 ribonuclease complex has a critical function in nucleic acid metabolism to prevent immune activation with likely roles in processing of RNA primers in Okazaki fragments during DNA replication, in removing ribonucleotides misinserted by DNA polymerases, and in eliminating RNA {center_dot} DNA hybrids during cell death. Mammalian RNase H2 is a heterotrimeric complex of the RNase H2A, RNase H2B, and RNase H2C proteins that are all required for proper function and activity. Mutations in the human RNase H2 genes cause Aicardi-Goutieres syndrome. We have determined the crystal structure of the three-protein mouse RNase H2 enzyme complex to better understand the molecular basis of RNase H2 dysfunction in human autoimmunity. The structure reveals the intimately interwoven architecture of RNase H2B and RNase H2C that interface with RNase H2A in a complex ideally suited for nucleic acid binding and hydrolysis coupled to protein-protein interaction motifs that could allow for efficient participation in multiple cellular functions. We have identified four conserved acidic residues in the active site that are necessary for activity and suggest a two-metal ion mechanism of catalysis for RNase H2. An Okazaki fragment has been modeled into the RNase H2 nucleic acid binding site providing insight into the recognition of RNA {center_dot} DNA junctions by the RNase H2. Further structural and biochemical analyses show that some RNase H2 disease-causing mutations likely result in aberrant protein-protein interactions while the RNase H2A subunit-G37S mutation appears to distort the active site accounting for the demonstrated substrate specificity modification.

  15. Influence of Pistachios on Performance and Exercise-Induced Inflammation, Oxidative Stress, Immune Dysfunction, and Metabolite Shifts in Cyclists: A Randomized, Crossover Trial

    PubMed Central

    Nieman, David C.; Scherr, Johannes; Luo, Beibei; Meaney, Mary Pat; Dréau, Didier; Sha, Wei; Dew, Dustin A.; Henson, Dru A.; Pappan, Kirk L.

    2014-01-01

    Objectives Pistachio nut ingestion (3 oz./d, two weeks) was tested for effects on exercise performance and 21-h post-exercise recovery from inflammation, oxidative stress, immune dysfunction, and metabolite shifts. Methods Using a randomized, crossover approach, cyclists (N = 19) engaged in two 75-km time trials after 2-weeks pistachio or no pistachio supplementation, with a 2-week washout period. Subjects came to the lab in an overnight fasted state, and ingested water only or 3 oz. pistachios with water before and during exercise. Blood samples were collected 45 min pre-exercise, and immediately post-, 1.5-h post-, and 21-h post-exercise, and analyzed for plasma cytokines, C-reactive protein (CRP), F2-isoprostanes (F2-IsoP), granulocyte phagocytosis (GPHAG) and oxidative burst activity (GOBA), and shifts in metabolites. Results Performance time for the 75-km time trial was 4.8% slower under pistachio conditions (2.84±0.11 and 2.71±0.07 h, respectively, P = 0.034). Significant time effects were shown for plasma cytokines, CRP, F2-IsoP, GPHAG, and GOBA, with few group differences. Metabolomics analysis revealed 423 detectable compounds of known identity, with significant interaction effects for 19 metabolites, especially raffinose, (12Z)-9,10-Dihydroxyoctadec-12-enoate (9,10-DiHOME), and sucrose. Dietary intake of raffinose was 2.19±0.15 and 0.35±0.08 mg/d during the pistachio and no pistachio periods, and metabolomics revealed that colon raffinose and sucrose translocated to the circulation during exercise due to increased gut permeability. The post-exercise increase in plasma raffinose correlated significantly with 9,10-DiHOME and other oxidative stress metabolites. Conclusions In summary, 2-weeks pistachio nut ingestion was associated with reduced 75-km cycling time trial performance and increased post-exercise plasma levels of raffinose, sucrose, and metabolites related to leukotoxic effects and oxidative stress. Trial Registration Clinical

  16. Autonomic dysfunction in multiple sclerosis.

    PubMed

    Racosta, Juan Manuel; Kimpinski, Kurt; Morrow, Sarah Anne; Kremenchutzky, Marcelo

    2015-12-01

    Autonomic dysfunction is a prevalent and significant cause of disability among patients with multiple sclerosis. Autonomic dysfunction in multiple sclerosis is usually explained by lesions within central nervous system regions responsible for autonomic regulation, but novel evidence suggests that other factors may be involved as well. Additionally, the interactions between the autonomic nervous system and the immune system have generated increased interest about the role of autonomic dysfunction in the pathogenesis of multiple sclerosis. In this paper we analyze systematically the most relevant signs and symptoms of autonomic dysfunction in MS, considering separately their potential causes and implications.

  17. Managing fatigue in the syncope unit.

    PubMed

    Newton, Julia L

    2012-12-01

    The symptom of fatigue is frequently described by patients attending the syncope unit with a wide range of conditions including vasovagal syncope and postural orthostatic tachycardia syndrome. It is possible that the presence of autonomic dysfunction provides the common pathogenetic mechanism linking neurally mediated hypotension and fatigue. Managing this debilitating symptom can often be challenging but, with a structured approach, immensely rewarding, and as a result improve how patients cope with their disease.

  18. Postpartum thyroid dysfunction.

    PubMed

    Browne-Martin, K; Emerson, C H

    1997-03-01

    Four disorders of the postpartum period are associated with thyroid dysfunction. The most common is PPT. Although recovery from thyroid dysfunction often occurs in PPT, many patients eventually develop permanent hypothyroidism. Postpartum Graves' Disease is less common than PPT, but it is not unusual. Whereas antithyroid drugs are indicated for postpartum Graves' Disease, they are not useful in PPT. Although they are rare, lymphocytic hypophysitis and postpartum pituitary infarction are important entities because they cause deficiencies of many critical hormones. The autoimmune nature of PPT, postpartum Graves' disease, and lymphocytic hypophysitis highlights the unique effects of pregnancy on the immune system.

  19. Biobehavioral Factors Mediate Exercise Effects on Fatigue in Breast Cancer Survivors

    PubMed Central

    Rogers, Laura Q; Vicari, Sandra; Trammell, Rita; Hopkins-Price, Patricia; Fogleman, Amanda; Spenner, Allison; Rao, Krishna; Courneya, Kerry S; Hoelzer, Karen S; Robbs, Randall; Verhulst, Steven

    2015-01-01

    Purpose Examine mediators of fatigue response to an exercise intervention for breast cancer survivors (BCS) in a pilot randomized controlled trial. Methods Postmenopausal BCS (n=46; ≤ Stage II), off primary treatment, and reporting fatigue and/or sleep dysfunction were randomized to a 3-month exercise intervention (160 minutes/week of moderate intensity aerobic walking, twice weekly resistance training with resistance bands) or control group. Six discussion group sessions provided behavioral support to improve adherence. Fatigue, serum cytokines, accelerometer physical activity, cardiorespiratory fitness, sleep dysfunction, and psychosocial factors were assessed at baseline and 3 months. Results Exercise intervention effect sizes for fatigue were: fatigue intensity d=0.30 (p=.34), interference d=−0.38 (p=.22), and general fatigue d=−0.49 (p=.13). Using Freedman-Schatzkin difference-in-coefficients tests, increase in fatigue intensity was significantly mediated by interleukin (IL)-6 (82%), IL-10 (94%), IL-6:IL-10 (49%), and tumor necrosis factor (TNF)-alpha:IL-10 (78%) with reduced sleep dysfunction increasing the relationship between intervention and fatigue intensity rather than mediating intervention effects (−88%). Decrease in fatigue interference was mediated by sleep dysfunction (35%) while IL-10 and pro:anti-inflammatory cytokine ratios increased the relationship between intervention and interference (−25% to −40%). The reduction in general fatigue was significantly mediated by minutes of physical activity (76%), sleep dysfunction (45%), and physical activity enjoyment (40%) with IL-10 (−40%) and IL-6:IL-10 (−11%) increasing the intervention-fatigue relationship. In the intervention group, higher baseline fatigue, anxiety, depression, and perceived exercise barriers interference predicted a greater decline in fatigue interference and/or general fatigue during the intervention. Conclusions Biobehavioral factors mediated and enhanced

  20. Chronic Fatigue Syndrome

    MedlinePlus

    Chronic fatigue syndrome (CFS) is a disorder that causes extreme fatigue. This fatigue is not the kind of tired feeling that ... activities. The main symptom of CFS is severe fatigue that lasts for 6 months or more. You ...

  1. Fibromyalgia, chronic fatigue syndrome, and myofascial pain.

    PubMed

    Goldenberg, D L

    1996-03-01

    The prevalence of fibromyalgia in the general population was found to be 2% and increased with age. Multiple traumatic factors, including sexual and physical abuse, may be important initiating events. The most important pathophysiologic studies in fibromyalgia included evidence of altered blood flow to the brain and hypothalamic-pituitary-adrenal dysfunction. The prevalence of chronic fatigue syndrome is much less than that of fibromyalgia. Epidemiologic studies demonstrated that chronic fatigue and symptoms of fibromyalgia are distributed as continuous variables in the general population. No association between chronic fatigue and initial infections was seen in primary care practices.

  2. Immune System to Brain Signaling: Neuropsychopharmacological Implications

    PubMed Central

    Capuron, Lucile; Miller, Andrew H.

    2011-01-01

    There has been an explosion in our knowledge of the pathways and mechanisms by which the immune system can influence the brain and behavior. In the context of inflammation, pro-inflammatory cytokines can access the central nervous system and interact with a cytokine network in the brain to influence virtually every aspect of brain function relevant to behavior including neurotransmitter metabolism, neuroendocrine function, synaptic plasticity, and neurocircuits that regulate mood, motor activity, motivation, anxiety and alarm. Behavioral consequences of these effects of the immune system on the brain include depression, anxiety, fatigue, psychomotor slowing, anorexia, cognitive dysfunction and sleep impairment; symptoms that overlap with those which characterize neuropsychiatric disorders, especially depression. Pathways that appear to be especially important in immune system effects on the brain include the cytokine signaling molecules, p38 mitogen activated protein kinase and nuclear factor kappa B; indoleamine 2,3 dioxygenase and its down stream metabolites, kynurenine, quinolinic acid and kynurenic acid; the neurotransmitters, serotonin, dopamine and glutamate; and neurocircuits involving the basal ganglia and anterior cingulate cortex. A series of vulnerability factors including aging and obesity as well as chronic stress also appear to interact with immune to brain signaling to exacerbate immunologic contributions to neuropsychiatric disease. The elucidation of the mechanisms by which the immune system influences behavior yields a host of targets for potential therapeutic development as well as informing strategies for the prevention of neuropsychiatric disease in at risk populations. PMID:21334376

  3. 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

  4. 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

  5. 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.

  6. 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. PMID:25915424

  7. Erectile dysfunction.

    PubMed

    Shamloul, Rany; Ghanem, Hussein

    2013-01-12

    Erectile dysfunction is a common clinical entity that affects mainly men older than 40 years. In addition to the classical causes of erectile dysfunction, such as diabetes mellitus and hypertension, several common lifestyle factors, such as obesity, limited or an absence of physical exercise, and lower urinary tract symptoms, have been linked to the development of erectile dysfunction. Substantial steps have been taken in the study of the association between erectile dysfunction and cardiovascular disease. Erectile dysfunction is a strong predictor for coronary artery disease, and cardiovascular assessment of a non-cardiac patient presenting with erectile dysfunction is now recommended. Substantial advances have occurred in the understanding of the pathophysiology of erectile dysfunction that ultimately led to the development of successful oral therapies, namely the phosphodiesterase type 5 inhibitors. However, oral phosphodiesterase type 5 inhibitors have limitations, and present research is thus investigating cutting-edge therapeutic strategies including gene and cell-based technologies with the aim of discovering a cure for erectile dysfunction.

  8. Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome.

    PubMed

    Hornig, M; Gottschalk, G; Peterson, D L; Knox, K K; Schultz, A F; Eddy, M L; Che, X; Lipkin, W I

    2016-02-01

    Myalgic encephalomyelitis/chronic fatigue syndrome is an unexplained debilitating disorder that is frequently associated with cognitive and motor dysfunction. We analyzed cerebrospinal fluid from 32 cases, 40 subjects with multiple sclerosis and 19 normal subjects frequency-matched for age and sex using a 51-plex cytokine assay. Group-specific differences were found for the majority of analytes with an increase in cases of CCL11 (eotaxin), a chemokine involved in eosinophil recruitment. Network analysis revealed an inverse relationship between interleukin 1 receptor antagonist and colony-stimulating factor 1, colony-stimulating factor 2 and interleukin 17F, without effects on interleukin 1α or interleukin 1β, suggesting a disturbance in interleukin 1 signaling. Our results indicate a markedly disturbed immune signature in the cerebrospinal fluid of cases that is consistent with immune activation in the central nervous system, and a shift toward an allergic or T helper type-2 pattern associated with autoimmunity.

  9. Diastolic Dysfunction

    PubMed Central

    Jeong, Euy-Myoung; Dudley, Samuel C.

    2016-01-01

    Despite the growing number of patients affected, the understanding of diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF) is still poor. Clinical trials, largely based on successful treatments for systolic heart failure, have been disappointing, suggesting that HFpEF has a different pathology to that of systolic dysfunction. In this review, general concepts, epidemiology, diagnosis, and treatment of diastolic dysfunction are summarized, with an emphasis on new experiments suggesting that oxidative stress plays a crucial role in the pathogenesis of at least some forms of the disease. This observation has lead to potential new diagnostics and therapeutics for diastolic dysfunction and heart failure caused by diastolic dysfunction. PMID:25746522

  10. 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.

  11. Nivolumab-induced thyroid dysfunction.

    PubMed

    Tanaka, Ryota; Fujisawa, Yasuhiro; Maruyama, Hiroshi; Nakamura, Yasuhiro; Yoshino, Koji; Ohtsuka, Mikio; Fujimoto, Manabu

    2016-06-01

    Nivolumab (ONO-4538) is an anti-programmed death-1 specific monoclonal antibody, which has become a standard treatment for metastatic malignant melanoma. Nivolumab induces autoimmune adverse events, defined as immune-related adverse events. Herein, we report a case of nivolumab-induced thyroid dysfunction in the clinical setting. Fourteen patients were treated with nivolumab at our institute, of which three developed thyroid dysfunction, an incidence higher than previously reported in the initial clinical trials. Interestingly, one patient achieved complete remission; suggesting that in some patients, the occurrence of immune-related adverse events, including thyroid dysfunction, might reflect the drug's antitumour efficacy. No patient died or discontinued nivolumab treatment owing to thyroid dysfunction. Although thyroid dysfunction first appeared to be asymptomatic, two of the three patients developed symptoms related to hypothyroidism soon after, requiring hormone replacement therapy. Another patient developed hyperthyroidism that was initially asymptomatic; the patient subsequently developed myalgia with fever >39.5°C after two additional courses of nivolumab. Treatment with nivolumab was therefore discontinued, and treatment with prednisolone was initiated. Symptoms resolved within a few days, and thyroid function normalized. Thyroid dysfunction is sometimes difficult to diagnose because its symptoms similar to those of many other diseases. In addition, thyroid-related immune-related adverse events may present with unique symptoms such as myalgia with high fever, abruptly worsening patients' quality of life. Consequently, thyroid dysfunction should be considered as a possible immune-related adverse event. Thus, it is important to test for thyroid dysfunction at baseline and before the administration of each nivolumab dose if possible. PMID:27012985

  12. [Gonadal dysfunction].

    PubMed

    Tahara, R; Toma, Y; Yanaihara, T

    1997-11-01

    Function of hypothalamic-pituitary-ovarian axis is an essential factor for the maintenance of regular cycles in mature women. The disturbance of function of those organs causes gonadal dysfunction such as anovulation, amenorrhea and menstrual disorders. Therefore, the correct diagnosis for the assessment of CNS and ovarian function is clinically important to treat the patients those who have an menstrual disorders. In this review, the mechanism of normal gonadal cycles and the diagnostic method and the treatment of gonadal dysfunction are described.

  13. Protective effect of centella triterpene saponins against cyclophosphamide-induced immune and hepatic system dysfunction in rats: its possible mechanisms of action.

    PubMed

    Duggina, Pragathi; Kalla, Chandra Mouli; Varikasuvu, Seshadri Reddy; Bukke, Suman; Tartte, Vijaya

    2015-09-01

    This study was designed to investigate the protective effects of the centella triterpene saponins (EXT) on cyclophosphamide (CYP)-induced hepatotoxicity and immunosuppression in rats. The phytochemical profile of EXT was analyzed for centella saponins by using high-performance liquid chromatographic (HPLC). Therapeutic efficacy of EXT (250 mg/kg/day p.o) on hematological profile of blood, liver function markers, and cytokine profiles in CYP (10 mg/kg/day p.o)-treated rats. In addition, weights of immune organs (spleen and thymus) and histopathological changes in the liver, intestine, and spleen were also evaluated. The active principles in EXT were identified as madecassoside, asiaticoside, and asiatic acid by HPLC analysis. Upon administration of EXT, enhanced levels of glutamate pyruvate transaminase, alkaline phosphatase, and lipid peroxidation were found reduced while the levels of reduced glutathione and hematological parameters and relative weights of immune organs were restored to normal in CYP-treated rats. The hepatic mRNA level of TNF-α, which was increased during CYP administration, was significantly decreased by the EXT treatment. The decreased levels of mRNA expression of other cytokines like IFN-γ, IL-2, GM-CSF, after CYP treatment, were also found elevated upon administration of the EXT. Histopathological examination of the intestine, liver, and spleen indicated that the extract could attenuate the CYP-induced hepatic and immune organ damage. These results indicated that EXT modulated the immune and hepatic system function of rats against CYP-induced immunosuppression and hepatotoxicity by restoring the cytokine production, antioxidant system, and multiorgan injury. Thus, triterpene saponins may provide protective and/or therapeutic alternative against the immune-mediated liver diseases. PMID:26168711

  14. Endocrine-mediated mechanisms of fatigue during treatment with interferon-alpha.

    PubMed

    Jones, T H; Wadler, S; Hupart, K H

    1998-02-01

    Fatigue occurs in more than 70% of patients treated with interferon-alpha (IFN-alpha) and is the most problematic toxicity associated with IFN-based immunotherapy. Abundant evidence suggests that immune-mediated endocrine disease occurs during IFN-alpha therapy, which may contribute to the etiology of fatigue. Autoimmune thyroid disease is a well-recognized consequence of IFN-alpha therapy and may be mediated by the induction of IFN-gamma production by lymphocytes. Administration of exogenous IFN-gamma has been associated with upregulation of class II major histocompatibility antigens in the thyroid and the development of thyroiditis. Interferon-alpha also stimulates the production of interleukin-6; both interleukin-6 and IFN-gamma have specific effects on thyrocyte function. There also is evidence suggesting that IFN-alpha initiates a cytokine cascade that effects the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, thus affecting regulation of glucocorticoid and sex steroid hormone secretion, but the clinical significance of these observations has not been established. Although endocrine disease will not explain the occurrence of fatigue symptoms in all patients, there is clear evidence that hormonal deficiency syndromes occur in a relatively large portion of patients receiving systemic IFN-alpha therapy. Most importantly, the possibility of hypothyroidism must be considered; however, diagnosis of hypothyroidism in cancer patients is complicated by the occurrence of the "sick euthyroid syndrome." Clinical recommendations for assessment and treatment of IFN-alpha-induced fatigue are offered. Most importantly, measurements of thyroid-stimulating hormone and antithyroid autoantibodies should be used to evaluate thyroid status. Acknowledging the limitations of current clinical data, adrenal- and gonadal-axis dysfunction also must be considered in patients with IFN-alpha-induced fatigue.

  15. Gustatory dysfunction

    PubMed Central

    Maheswaran, T.; Abikshyeet, P.; Sitra, G.; Gokulanathan, S.; Vaithiyanadane, V.; Jeelani, S.

    2014-01-01

    Tastes in humans provide a vital tool for screening soluble chemicals for food evaluation, selection, and avoidance of potentially toxic substances. Taste or gustatory dysfunctions are implicated in loss of appetite, unintended weight loss, malnutrition, and reduced quality of life. Dental practitioners are often the first clinicians to be presented with complaints about taste dysfunction. This brief review provides a summary of the common causes of taste disorders, problems associated with assessing taste function in a clinical setting and management options available to the dental practitioner. PMID:25210380

  16. Immune dysfunction in Rett syndrome patients revealed by high levels of serum anti-N(Glc) IgM antibody fraction.

    PubMed

    Papini, Anna Maria; Nuti, Francesca; Real-Fernandez, Feliciana; Rossi, Giada; Tiberi, Caterina; Sabatino, Giuseppina; Pandey, Shashank; Leoncini, Silvia; Signorini, Cinzia; Pecorelli, Alessandra; Guerranti, Roberto; Lavielle, Solange; Ciccoli, Lucia; Rovero, Paolo; De Felice, Claudio; Hayek, Joussef

    2014-01-01

    Rett syndrome (RTT), a neurodevelopmental disorder affecting exclusively (99%) female infants, is associated with loss-of-function mutations in the gene encoding methyl-CpG binding protein 2 (MECP2) and, more rarely, cyclin-dependent kinase-like 5 (CDKL5) and forkhead box protein G1 (FOXG1). In this study, we aimed to evaluate the function of the immune system by measuring serum immunoglobulins (IgG and IgM) in RTT patients (n = 53) and, by comparison, in age-matched children affected by non-RTT pervasive developmental disorders (non-RTT PDD) (n = 82) and healthy age-matched controls (n = 29). To determine immunoglobulins we used both a conventional agglutination assay and a novel ELISA based on antibody recognition by a surrogate antigen probe, CSF114(Glc), a synthetic N-glucosylated peptide. Both assays provided evidence for an increase in IgM titer, but not in IgG, in RTT patients relative to both healthy controls and non-RTT PDD patients. The significant difference in IgM titers between RTT patients and healthy subjects in the CSF114(Glc) assay (P = 0.001) suggests that this procedure specifically detects a fraction of IgM antibodies likely to be relevant for the RTT disease. These findings offer a new insight into the mechanism underlying the Rett disease as they unveil the possible involvement of the immune system in this pathology. PMID:25389532

  17. Transcriptomics: A Step behind the Comprehension of the Polygenic Influence on Oxidative Stress, Immune Deregulation, and Mitochondrial Dysfunction in Chronic Kidney Disease

    PubMed Central

    2016-01-01

    Chronic kidney disease (CKD) is an increasing and global health problem with a great economic burden for healthcare system. Therefore to slow down the progression of this condition is a main objective in nephrology. It has been extensively reported that microinflammation, immune system deregulation, and oxidative stress contribute to CKD progression. Additionally, dialysis worsens this clinical condition because of the contact of blood with bioincompatible dialytic devices. Numerous studies have shown the close link between immune system impairment and CKD but most have been performed using classical biomolecular strategies. These methodologies are limited in their ability to discover new elements and enable measuring the simultaneous influence of multiple factors. The “omics” techniques could overcome these gaps. For example, transcriptomics has revealed that mitochondria and inflammasome have a role in pathogenesis of CKD and are pivotal elements in the cellular alterations leading to systemic complications. We believe that a larger employment of this technique, together with other “omics” methodologies, could help clinicians to obtain new pathogenetic insights, novel diagnostic biomarkers, and therapeutic targets. Finally, transcriptomics could allow clinicians to personalize therapeutic strategies according to individual genetic background (nutrigenomic and pharmacogenomic). In this review, we analyzed the available transcriptomic studies involving CKD patients. PMID:27419142

  18. Delayed neutralization of interleukin 6 reduces organ injury, selectively suppresses inflammatory mediator, and partially normalizes immune dysfunction following trauma and hemorrhagic shock.

    PubMed

    Zhang, Yong; Zhang, Jinxiang; Korff, Sebastian; Ayoob, Faez; Vodovotz, Yoram; Billiar, Timothy R

    2014-09-01

    An excessive and uncontrolled systemic inflammatory response is associated with organ failure, immunodepression, and increased susceptibility to nosocomial infection following trauma. Interleukin 6 (IL-6) plays a particularly prominent role in the host immune response after trauma with hemorrhage. However, as a result of its pleiotropic functions, the effect of IL-6 in trauma and hemorrhage is still controversial. It remains unclear whether suppression of IL-6 after hemorrhagic shock and trauma will attenuate organ injury and immunosuppression. In this study, C57BL/6 mice were treated with anti-mouse IL-6 monoclonal antibody immediately prior to resuscitation in an experimental model combining hemorrhagic shock and lower-extremity injury. Interleukin 6 levels and signaling were transiently suppressed following administrations of anti-IL-6 monoclonal antibody following hemorrhagic shock and lower-extremity injury. This resulted in reduced lung and liver injury, as well as suppression in the levels of key inflammatory mediators including IL-10, keratinocyte-derived chemokine, monocyte chemoattractant protein 1, and macrophage inhibitory protein 1α at both 6 and 24 h. Furthermore, the shift to TH2 cytokine production and suppressed lymphocyte response were partly prevented. These results demonstrate that IL-6 is not only a biomarker but also an important driver of injury-induced inflammation and immune suppression in mice. Rapid measurement of IL-6 levels in the early phase of postinjury care could be used to guide IL-6-based interventions.

  19. Immune Dysfunction in Rett Syndrome Patients Revealed by High Levels of Serum Anti-N(Glc) IgM Antibody Fraction

    PubMed Central

    Papini, Anna Maria; Real-Fernandez, Feliciana; Rossi, Giada; Tiberi, Caterina; Sabatino, Giuseppina; Pandey, Shashank; Lavielle, Solange; Ciccoli, Lucia; Hayek, Joussef

    2014-01-01

    Rett syndrome (RTT), a neurodevelopmental disorder affecting exclusively (99%) female infants, is associated with loss-of-function mutations in the gene encoding methyl-CpG binding protein 2 (MECP2) and, more rarely, cyclin-dependent kinase-like 5 (CDKL5) and forkhead box protein G1 (FOXG1). In this study, we aimed to evaluate the function of the immune system by measuring serum immunoglobulins (IgG and IgM) in RTT patients (n = 53) and, by comparison, in age-matched children affected by non-RTT pervasive developmental disorders (non-RTT PDD) (n = 82) and healthy age-matched controls (n = 29). To determine immunoglobulins we used both a conventional agglutination assay and a novel ELISA based on antibody recognition by a surrogate antigen probe, CSF114(Glc), a synthetic N-glucosylated peptide. Both assays provided evidence for an increase in IgM titer, but not in IgG, in RTT patients relative to both healthy controls and non-RTT PDD patients. The significant difference in IgM titers between RTT patients and healthy subjects in the CSF114(Glc) assay (P = 0.001) suggests that this procedure specifically detects a fraction of IgM antibodies likely to be relevant for the RTT disease. These findings offer a new insight into the mechanism underlying the Rett disease as they unveil the possible involvement of the immune system in this pathology. PMID:25389532

  20. Sexual dysfunction in uremia.

    PubMed

    Palmer, B F

    1999-06-01

    In summary, sexual dysfunction is a common finding in both men and women with chronic renal failure. Common disturbances include erectile dysfunction in men, menstrual abnormalities in women, and decreased libido and fertility in both sexes. These abnormalities are primarily organic in nature and are related to uremia as well as the other comorbid conditions that frequently accompany the chronic renal failure patient. Fatigue and psychosocial factors related to the presence of a chronic disease are also contributory factors. Disturbances in the hypothalamic-pituitary-gonadal axis can be detected before the need for dialysis but continue to worsen once dialytic therapy is initiated. Impaired gonadal function is prominent in uremic men, whereas the disturbances in the hypothalamicpituitary axis are more subtle. By contrast, central disturbances are more prominent in uremic women. Therapy is initially directed toward optimizing the delivery of dialysis, correcting anemia with recombinant erythropoietin, and controlling the degree of secondary hyperparathyroidism with vitamin D. For many practicing nephrologists, sildenafil has become the first-line therapy in the treatment of impotence. In the hypogonadal man whose only complaint is decreased libido, testosterone may be of benefit. Regular gynecologic follow-up is required in uremic women to guard against potential complications of unopposed estrogen effect. Uremic women should be advised against pregnancy while on dialysis. Successful transplantation is the most effective means of restoring normal sexual function in both men and women with chronic renal failure.

  1. Fatigue, Inflammation, and Projected Mortality in Heart Failure

    PubMed Central

    Fink, Anne M.; Gonzalez, Rosalia C.; Lisowski, Tadeusz; Pini, Maria; Fantuzzi, Giamila; Levy, Wayne C.; Piano, Mariann R.

    2012-01-01

    Background Fatigue is a prominent and poorly understood symptom of heart failure with reduced ejection fraction (HFrEF). The purpose of this study was to determine whether fatigue correlated with immune biomarkers and prognosis. Methods/Results In patients with HFrEF (N = 59) and healthy controls (N = 25), we prospectively measured fatigue (Profile of Mood States), depressive symptoms (Patient Health Questionnaire-8), sleep quality (Pittsburgh Sleep Quality Index), and immune biomarkers (plasma C-reactive protein [CRP], tumor necrosis factor-α [TNFα], and interleukins [IL-6 and IL-10]). Seattle Heart Failure Model (SHFM) mortality risk scores were determined. Patients with HFrEF had significantly greater fatigue and depressive symptoms and poorer sleep quality compared to control subjects. When controlling for depressive symptoms, however, fatigue did not differ significantly between patients with HFrEF and controls. Patients with HFrEF had significantly lower levels of IL-10 compared to controls. Cytokines did not correlate significantly with fatigue, but fatigue was significantly associated with higher SHFM scores. Conclusions Depressive symptoms were an important covariate of fatigue in patients with HFrEF. Our study findings were the first to show a positive association between fatigue and the SHFM score, indicating that fatigue was associated with poorer prognosis. PMID:22939040

  2. Erectile Dysfunction

    MedlinePlus

    ... or vascular problems, will have a more difficult time returning to pre-treatment function. Management of Erectile Dysfunction When a man is sexually aroused, the erectile nerves running alongside the penis stimulate the ... blood to rush in. At the same time, tiny valves at the base of the penis ...

  3. Sensory Dysfunction

    MedlinePlus

    ... to Web version Sensory Dysfunction Overview Why are smell and taste important? Your senses of smell and taste let you fully enjoy the scents ... bitter and sour. Flavor involves both taste and smell. For example, because a person is able to ...

  4. A Pathway Proteomic Profile of Ischemic Stroke Survivors Reveals Innate Immune Dysfunction in Association with Mild Symptoms of Depression – A Pilot Study

    PubMed Central

    Nguyen, Vinh A.; Carey, Leeanne M.; Giummarra, Loretta; Faou, Pierre; Cooke, Ira; Howells, David W.; Tse, Tamara; Macaulay, S. Lance; Ma, Henry; Davis, Stephen M.; Donnan, Geoffrey A.; Crewther, Sheila G.

    2016-01-01

    Depression after stroke is a common occurrence, raising questions as to whether depression could be a long-term biological and immunological sequela of stroke. Early explanations for post-stroke depression (PSD) focused on the neuropsychological/psychosocial effects of stroke on mobility and quality of life. However, recent investigations have revealed imbalances of inflammatory cytokine levels in association with PSD, though to date, there is only one published proteomic pathway analysis testing this hypothesis. Thus, we examined the serum proteome of stroke patients (n = 44, mean age = 63.62 years) and correlated these with the Montgomery–Åsberg Depression Rating Scale (MADRS) scores at 3 months post-stroke. Overall, the patients presented with mild depression symptoms on the MADRS, M = 6.40 (SD = 7.42). A discovery approach utilizing label-free relative quantification was employed utilizing an LC-ESI–MS/MS coupled to a LTQ-Orbitrap Elite (Thermo-Scientific). Identified peptides were analyzed using the gene set enrichment approach on several different genomic databases that all indicated significant downregulation of the complement and coagulation systems with increasing MADRS scores. Complement and coagulation systems are traditionally thought to play a key role in the innate immune system and are established precursors to the adaptive immune system through pro-inflammatory cytokine signaling. Both systems are known to be globally affected after ischemic or hemorrhagic stroke. Thus, our results suggest that lowered complement expression in the periphery in conjunction with depressive symptoms post-stroke may be a biomarker for incomplete recovery of brain metabolic needs, homeostasis, and inflammation following ischemic stroke damage. Further proteomic investigations are now required to construct the temporal profile, leading from acute lesion damage to manifestation of depressive symptoms. Overall, the findings provide support for the

  5. 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

  6. Manganese deficiency or excess caused the depression of intestinal immunity, induction of inflammation and dysfunction of the intestinal physical barrier, as regulated by NF-κB, TOR and Nrf2 signalling, in grass carp (Ctenopharyngodon idella).

    PubMed

    Jiang, Wei-Dan; Tang, Ren-Jun; Liu, Yang; Kuang, Sheng-Yao; Jiang, Jun; Wu, Pei; Zhao, Juan; Zhang, Yong-An; Tang, Ling; Tang, Wu-Neng; Zhou, Xiao-Qiu; Feng, Lin

    2015-10-01

    Intestinal mucosal immune components and mRNA levels of inflammatory cytokines, tight junction proteins, antioxidant enzymes and related signalling molecules in young grass carp (Ctenopharyngodon idellus) under dietary manganese (Mn) deficiency or excess were investigated. Fish were fed the diets containing graded levels of Mn [3.65-27.86 mg Mn kg(-1) diet] for 8 weeks. The results demonstrated that Mn deficiency significantly decreased the lysozyme and acid phosphatase (ACP) activities, up-regulated tumour necrosis factor α (TNF-α), interleukin 8 and the signalling factor nuclear factor-κB p65, and down-regulated interleukin 10 (IL-10), transforming growth factor β1, inhibitor of signalling factors κB-α and target of rapamycin mRNA levels in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI). However, Mn deficiency did not change the C3 content in the PI, whereas it decreased the C3 contents in the MI and DI. Additionally, Mn depletion also resulted in significantly low mRNA levels for tight junction proteins (claudin-b, claudin-c, claudin-15, occludin and zonula occludens-1), antioxidant enzymes (MnSOD, GPx and CAT) and NF-E2-related factor-2 in the intestines of fish. Excessive Mn exhibited toxic effects similar to Mn deficiency, where optimal Mn contents reversed those indicators. In conclusion, Mn deficiency or excess causes the depression of intestinal immunity, induction of inflammation and dysfunction of the intestinal physical barrier relating to NF-κB, TOR and Nrf2 signalling in grass carp. Furthermore, quadratic regression analysis at 95% maximum response of lysozyme and acid phosphatase activities in the distal intestine of young grass carp revealed the optimum dietary Mn levels to be 8.90 and 8.99 mg kg(-1) diet, respectively.

  7. 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.

  8. 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

  9. Memory Dysfunction

    PubMed Central

    Matthews, Brandy R.

    2015-01-01

    Purpose of Review: This article highlights the dissociable human memory systems of episodic, semantic, and procedural memory in the context of neurologic illnesses known to adversely affect specific neuroanatomic structures relevant to each memory system. Recent Findings: Advances in functional neuroimaging and refinement of neuropsychological and bedside assessment tools continue to support a model of multiple memory systems that are distinct yet complementary and to support the potential for one system to be engaged as a compensatory strategy when a counterpart system fails. Summary: Episodic memory, the ability to recall personal episodes, is the subtype of memory most often perceived as dysfunctional by patients and informants. Medial temporal lobe structures, especially the hippocampal formation and associated cortical and subcortical structures, are most often associated with episodic memory loss. Episodic memory dysfunction may present acutely, as in concussion; transiently, as in transient global amnesia (TGA); subacutely, as in thiamine deficiency; or chronically, as in Alzheimer disease. Semantic memory refers to acquired knowledge about the world. Anterior and inferior temporal lobe structures are most often associated with semantic memory loss. The semantic variant of primary progressive aphasia (svPPA) is the paradigmatic disorder resulting in predominant semantic memory dysfunction. Working memory, associated with frontal lobe function, is the active maintenance of information in the mind that can be potentially manipulated to complete goal-directed tasks. Procedural memory, the ability to learn skills that become automatic, involves the basal ganglia, cerebellum, and supplementary motor cortex. Parkinson disease and related disorders result in procedural memory deficits. Most memory concerns warrant bedside cognitive or neuropsychological evaluation and neuroimaging to assess for specific neuropathologies and guide treatment. PMID:26039844

  10. Erectile dysfunction.

    PubMed

    McMahon, C G

    2014-01-01

    In the past 30 years, advances in basic science have been instrumental in the evolution of the male sexual health treatment paradigm from a psychosexual model to a new model, which includes oral and intracavernosal injection pharmacotherapy, vacuum constriction devices and penile prostheses for the treatment of erectile dysfunction. This progress has coincided with an increased understanding of the nature of male sexual health problems, and epidemiological data that confirm that these problems are widely prevalent and the source of considerable morbidity, both for individuals and within relationships.

  11. Vestibular dysfunction in occupational chronic solvent intoxication.

    PubMed

    Arlien-Søborg, P; Zilstorff, K; Grandjean, B; Milling Pedersen, L

    1981-08-01

    Neurotoxic volatile organic solvents used by house and car painters may lead to professional toxic encephalopathy after several years of exposure. The symptoms are memory impairment, fatigue, personality changes, headache and dizziness. Vestibular dysfunction was found in 55% of 113 painters examined, mainly in the form of reduced caloric vestibular reactions. No correlation between vestibular dysfunction and the duration of exposure, cerebral atrophy or intellectual impairment could be demonstrated. Vestibular examination may be helpful in detecting early changes in exposed persons and in determining more accurate safety limits for harmful chemicals.

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

    PubMed

    Craddock, Travis J A; Fritsch, Paul; Rice, Mark A; del Rosario, Ryan M; Miller, Diane B; Fletcher, Mary Ann; Klimas, Nancy G; Broderick, Gordon

    2014-01-01

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

  13. Executive Dysfunction

    PubMed Central

    Rabinovici, Gil D.; Stephens, Melanie L.; Possin, Katherine L.

    2015-01-01

    Purpose of Review: Executive functions represent a constellation of cognitive abilities that drive goal-oriented behavior and are critical to the ability to adapt to an ever-changing world. This article provides a clinically oriented approach to classifying, localizing, diagnosing, and treating disorders of executive function, which are pervasive in clinical practice. Recent Findings: Executive functions can be split into four distinct components: working memory, inhibition, set shifting, and fluency. These components may be differentially affected in individual patients and act together to guide higher-order cognitive constructs such as planning and organization. Specific bedside and neuropsychological tests can be applied to evaluate components of executive function. While dysexecutive syndromes were first described in patients with frontal lesions, intact executive functioning relies on distributed neural networks that include not only the prefrontal cortex, but also the parietal cortex, basal ganglia, thalamus, and cerebellum. Executive dysfunction arises from injury to any of these regions, their white matter connections, or neurotransmitter systems. Dysexecutive symptoms therefore occur in most neurodegenerative diseases and in many other neurologic, psychiatric, and systemic illnesses. Management approaches are patient specific and should focus on treatment of the underlying cause in parallel with maximizing patient function and safety via occupational therapy and rehabilitation. Summary: Executive dysfunction is extremely common in patients with neurologic disorders. Diagnosis and treatment hinge on familiarity with the clinical components and neuroanatomic correlates of these complex, high-order cognitive processes. PMID:26039846

  14. [Fatigue and depression].

    PubMed

    Hell, Daniel

    2015-04-22

    Fatigue is characterised in an overview of the literature as a specific phenomenon of depression. Its differential diagnosis is discussed. Distinctions and correspondences to burnout are elaborated. Fatigue is not an obligatory symptom of depressive episodes, although it can contribute to depressive developments. The importance of fatigue in depressive episodes and its therapy is shown with the help of a circular model of depression.

  15. Fatigue of composites

    NASA Technical Reports Server (NTRS)

    Salkind, M. J.

    1972-01-01

    The failure mechanisms in the fatigue of composite materials are analyzed in terms of the requirements for designing fatigue-critical composite structures. Fiber reinforced polymers, fiber reinforced metals, fatigue of composite structures, and composite design considerations are discussed. It is concluded that composite materials offer the engineer the opportunity for tailoring stiffness in different directions for designing dynamic components.

  16. 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

  17. Immune response

    MedlinePlus

    Innate immunity; Humoral immunity; Cellular immunity; Immunity; Inflammatory response; Acquired (adaptive) immunity ... and usually does not react against them. INNATE IMMUNITY Innate, or nonspecific, immunity is the defense system ...

  18. Fatigue in rheumatic diseases

    PubMed Central

    Sandıkçı, Sevinç Can; Özbalkan, Zeynep

    2015-01-01

    Fatigue is a common and important problem in many diseases including rheumatologic illnesses, and it has a negative impact on health-related quality of life. Fatigue is described as having an impact on multiple aspects of a patient’s life. There is a need for knowledge about causes of and treatments for fatigue to ensure that patient outcomes are improved. There are several effective treatment strategies available for fatigue including pharmacological and non-pharmacological therapies. We aim to provide an overview of fatigue in rheumatologic disorders and some recommendations on its optimal management. PMID:27708942

  19. 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

  20. The first report of cabergoline-induced immune hemolytic anemia in an adolescent with prolactinoma.

    PubMed

    Gürbüz, Fatih; Yağcı-Küpeli, Begül; Kör, Yılmaz; Yüksel, Bilgin; Zorludemir, Suzan; Gürbüz, Berrak Bilginer; Küpeli, Serhan

    2014-01-01

    Prolactinomas are common pituitary tumors that can cause gonadal dysfunction and infertility related to hyperprolactinemia. Dopamine agonists are the first-line treatment in these patients. Cabergoline leads to significant reduction in serum prolactin levels and tumor size in patients with prolactinoma. Dopamine agonists have been associated with adverse effects such as nausea, vomiting and psychosis. We report here a case with cabergoline-induced immune hemolytic anemia. The patient had cabergoline treatment history for prolactinoma and presented with weakness, fatigue, nausea, and paleness. Laboratory findings revealed severe anemia-related immune hemolysis. There were no causes identified to explain hemolytic anemia except cabergoline. Therefore, cabergoline therapy was stopped and subsequently hemolytic anemia resolved and did not occur again. This is the first reported pediatric case with prolactinoma and cabergoline-induced hemolytic anemia. Clinicians should be watchful for this rare side effect induced by cabergoline.

  1. Community Immunity (Herd Immunity)

    MedlinePlus

    ... Content Marketing Share this: Main Content Area ​Community Immunity ("Herd" Immunity) Vaccines can prevent outbreaks of disease and save ... disease is contained. This is known as "community immunity." In the illustration below, the top box depicts ...

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

    PubMed Central

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

    2016-01-01

    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. PMID:26921255

  3. Fatigue handbook: Offshore steel structures

    SciTech Connect

    Almarnaess, A.

    1985-01-01

    The contents of this book are: Overview of Offshore Steel Structures; Loads on Ocean Structures; Fracture Mechanics As a Tool in Fatigue Analysis; Basic Fatigue Properties of Welded Joints; Significance of Defects; Improving the Fatigue Strength of Welded Joints; Effects of Marine Environment and Cathodic Protection on Fatigue of Structural Steels Fatigue of Tubular Joints; Unstable Fracture; Fatigue Life Calculations; and Fatigue in Building Codes Background and Applications.

  4. Role of Dendritic Cells in Immune Dysfunction

    NASA Technical Reports Server (NTRS)

    Savary, Cherylyn A.

    1997-01-01

    Specific aims include: (1) Application of the bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC); (2) Based on clues from spaceflight: compare the frequency and function of DC in normal donors and immunocompromised cancer patients; and (3) Initiate studies on the efficiency of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in animal models of experimental fungal infections.

  5. 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

  6. 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

  7. Multiaxial fatigue low cycle fatigue testing

    NASA Technical Reports Server (NTRS)

    Zamrik, S. Y.

    1985-01-01

    Multiaxial testing methods are reviewed. Advantages and disadvantages of each type test is discussed. Significant multiaxial data available in the literature is analyzed. The yield theories are compared for multiaxial fatigue analysis.

  8. Clinical neurophysiology of fatigue.

    PubMed

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

    2008-01-01

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

  9. 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

  10. Thyroid dysfunction from antineoplastic agents.

    PubMed

    Hamnvik, Ole-Petter Riksfjord; Larsen, P Reed; Marqusee, Ellen

    2011-11-01

    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

  11. 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

  12. Aerodynamic Heating and Fatigue

    NASA Technical Reports Server (NTRS)

    Kroll, Wilhelmina D.

    1959-01-01

    A review of the physical condition's under which future airplanes will operate has been made and the necessity for considering fatigue in the design has been established. A survey of the literature shows what phases of elevated-temperature fatigue have been investigated. Other studies that would yield data of particular interest to the designer of aircraft structures are indicated.

  13. 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.

  14. 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...

  15. 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

  16. 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.

  17. Frequent IgG subclass and mannose binding lectin deficiency in patients with chronic fatigue syndrome.

    PubMed

    Guenther, Sabrina; Loebel, Madlen; Mooslechner, Agnes A; Knops, Michael; Hanitsch, Leif G; Grabowski, Patricia; Wittke, Kirsten; Meisel, Christian; Unterwalder, Nadine; Volk, Hans-Dieter; Scheibenbogen, Carmen

    2015-10-01

    Chronic fatigue syndrome (CFS) is a severe disease characterized by various symptoms of immune dysfunction. CFS onset is typically with an infection and many patients suffer from frequently recurrent viral or bacterial infections. Immunoglobulin and mannose binding lectin (MBL) deficiency are frequent causes for increased susceptibility to infections. In this study we retrospectively analysed 300 patients with CFS for immunoglobulin and MBL levels, and B-cell subset frequencies. 25% of the CFS patients had decreased serum levels of at least one antibody class or subclass with IgG3 and IgG4 subclass deficiencies as most common phenotypes. However, we found elevated immunoglobulin levels with an excess of IgM and IgG2 in particular in another 25% of patients. No major alteration in numbers of B cells and B-cell subsets was seen. Deficiency of MBL was found in 15% of the CFS patients in contrast to 6% in a historical control group. In a 2nd cohort of 168 patients similar frequencies of IgG subclass and MBL deficiency were found. Thus, humoral immune defects are frequent in CFS patients and are associated with infections of the respiratory tract.

  18. Neuromarkers of fatigue and cognitive complaints following chemotherapy for breast cancer: a prospective fMRI investigation.

    PubMed

    Askren, Mary K; Jung, Misook; Berman, Marc G; Zhang, Min; Therrien, Barbara; Peltier, Scott; Ossher, Lynn; Hayes, Daniel F; Reuter-Lorenz, Patricia A; Cimprich, Bernadine

    2014-09-01

    The aim of this study is to use functional magnetic resonance imaging (fMRI) to prospectively examine pre-treatment predictors of post-treatment fatigue and cognitive dysfunction in women treated with adjuvant chemotherapy for breast cancer. Fatigue and cognitive dysfunction often co-occur in women treated for breast cancer. We hypothesized that pre-treatment factors, unrelated to chemotherapy per se, might increase vulnerability to post-treatment fatigue and cognitive dysfunction. Patients treated with (n = 28) or without chemotherapy (n = 37) and healthy controls (n = 32) were scanned coincident with pre- and one-month post-chemotherapy during a verbal working memory task (VWMT) and assessed for fatigue, worry, and cognitive dysfunction. fMRI activity measures in the frontoparietal executive network were used in multiple linear regression to predict post-treatment fatigue and cognitive function. The chemotherapy group reported greater pre-treatment fatigue than controls and showed compromised neural response, characterized by higher spatial variance in executive network activity, than the non-chemotherapy group. Also, the chemotherapy group reported greater post-treatment fatigue than the other groups. Linear regression indicated that pre-treatment spatial variance in executive network activation predicted post-treatment fatigue severity and cognitive complaints, while treatment group, age, hemoglobin, worry, and mean executive network activity levels did not predict these outcomes. Pre-treatment neural inefficiency (indexed by high spatial variance) in the executive network, which supports attention and working memory, was a better predictor of post-treatment cognitive and fatigue complaints than exposure to chemotherapy per se. This executive network compromise could be a pre-treatment neuromarker of risk, indicating patients most likely to benefit from early intervention for fatigue and cognitive dysfunction. PMID:25138546

  19. 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

  20. 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.

  1. Sexual Dysfunction and Infertility

    MedlinePlus

    ... American Society for Reproductive Medicine Sexual dysfunction and infertility What is sexual dysfunction and how common is ... and 40% of women. For couples dealing with infertility, it is even more common. Often, people ignore ...

  2. Multiple organ dysfunction syndrome.

    PubMed

    Ramírez, Michelle

    2013-01-01

    Initially known as multiple system organ failure, the term multiple organ dysfunction syndrome (MODS) was first described in the 1960s in adults with bleeding, respiratory failure, and sepsis. It is defined as "the development of potentially reversible physiologic derangement involving two or more organ systems not involved in the disorder that resulted in ICU admission, and arising in the wake of a potentially life threatening physiologic insult."(3) There are many risk factors predisposing to MODS; however, the most common risk factors are shock due to any cause, sepsis, and tissue hypoperfusion. A dysregulated immune response, or immuneparalysis, in which the homeostasis between pro-inflammatory and anti-inflammatory reaction is lost is thought to be key in the development of MODS. The clinical course and evolution of MODS is dependent on a combination of acquired and genetic factors. There are several nonspecific therapies for the prevention and resolution of MODS, mostly care is supportive. Mortality from MODS in septic pediatric patients varies between 11% and 54%.

  3. The measurement of fatigue: a new instrument.

    PubMed

    Schwartz, J E; Jandorf, L; Krupp, L B

    1993-10-01

    Fatigue is a frequent medical symptom which has not been routinely measured. We present a 29-item fatigue assessment instrument, describe its psychometric properties, and use it to differentiate normal fatigue from fatigue related medical disorders. Differences in fatigue across a variety of medical disorders, the reproducibility of the fatigue instrument, and its convergent validity with other fatigue measures are also described.

  4. Silent Burdens in Disease: Fatigue and Depression in SLE.

    PubMed

    Fonseca, R; Bernardes, M; Terroso, G; de Sousa, M; Figueiredo-Braga, M

    2014-01-01

    At a time when health is being recognized as more than just avoiding death, age and comorbidity are becoming increasingly important aspects of chronic disease. Systemic Lupus Erythematous (SLE) is probably one of the best paradigms of modern chronic disease, sitting at the crossroads of numerous somatic health problems, immune activation, depression, pain, and fatigue. One hundred forty-eight female participants were enrolled in the present study: 50 diagnosed with SLE, 45 with major depressive disorder (MDD), and 53 age-matched controls. Statistically significant lower scores in quality-of-life dimensions related to physical impairment were found in SLE. Patients with MDD presented significant levels of pain, reduced physical summary component (PSC), and general health scores different from healthy controls. Fatigue was reported in 90% of women with SLE and 77.8% of the MDD patients in contrast with 39.6% in the control group. Significant correlations were seen among fatigue severity, age, and educational level in SLE. From our own previous work and more recent work on the association of immune activation and depression, unexplained fatigue in SLE may signify an early sign of immune activation flare-up. The search for cytokine markers should perhaps be extended to fatigue in SLE.

  5. Silent Burdens in Disease: Fatigue and Depression in SLE

    PubMed Central

    Fonseca, R.; Bernardes, M.; Terroso, G.; de Sousa, M.; Figueiredo-Braga, M.

    2014-01-01

    At a time when health is being recognized as more than just avoiding death, age and comorbidity are becoming increasingly important aspects of chronic disease. Systemic Lupus Erythematous (SLE) is probably one of the best paradigms of modern chronic disease, sitting at the crossroads of numerous somatic health problems, immune activation, depression, pain, and fatigue. One hundred forty-eight female participants were enrolled in the present study: 50 diagnosed with SLE, 45 with major depressive disorder (MDD), and 53 age-matched controls. Statistically significant lower scores in quality-of-life dimensions related to physical impairment were found in SLE. Patients with MDD presented significant levels of pain, reduced physical summary component (PSC), and general health scores different from healthy controls. Fatigue was reported in 90% of women with SLE and 77.8% of the MDD patients in contrast with 39.6% in the control group. Significant correlations were seen among fatigue severity, age, and educational level in SLE. From our own previous work and more recent work on the association of immune activation and depression, unexplained fatigue in SLE may signify an early sign of immune activation flare-up. The search for cytokine markers should perhaps be extended to fatigue in SLE. PMID:24592329

  6. [Thyroid dysfunction in primary care medicine].

    PubMed

    Wuerzner, Kaisa; Pasche, Olivier; Rodondi, Nicolas; Portmann, Luc

    2010-12-01

    Thyroid function tests include the measuring of the thyroid stimulating hormone (TSH) and free thyroxine (T4) in the case of abnormal TSH. These tests are frequently performed in primary care medicine since many clinical situations can be suggestive of dysthyroidism, as for example fatigue, depressive states or cardiac arthmia. In the case of subclinical thyroid dysfunction, the indications for treatment are controversial there being a lack of significant randomised studies. For primary care physicians faced with abnormal thyroid function tests we propose a diagnostic approach, clinical recommendations, and indications for referral to the specialist. PMID:21207724

  7. Chronic fatigue syndrome

    MedlinePlus

    Bennett RM. Fibromyalgia, chronic fatigue syndrome, and myofascial pain. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 274. Engleberg NC. Chronic ...

  8. Fatigue and Multiple Sclerosis

    MedlinePlus

    Fatigue - National Multiple Sclerosis Society Skip to navigation Skip to content Menu Navigation National Multiple Sclerosis Society Sign In In Your Area ... help* daily life for: positive-mom* The National MS Society is Here to Help Need More Information? ...

  9. Brain Tumors and Fatigue

    MedlinePlus

    ... tiredness. You may experience a profound lack of energy that can come on suddenly and bring dramatic ... to manage the severity. Respect the Fatigue The energy you’re accustomed to having has been transferred ...

  10. Fatigue loading of tendon

    PubMed Central

    Shepherd, Jennifer H; Screen, Hazel R C

    2013-01-01

    Tendon injuries, often called tendinopathies, are debilitating and painful conditions, generally considered to develop as a result of tendon overuse. The aetiology of tendinopathy remains poorly understood, and whilst tendon biopsies have provided some information concerning tendon appearance in late-stage disease, there is still little information concerning the mechanical and cellular events associated with disease initiation and progression. Investigating this in situ is challenging, and numerous models have been developed to investigate how overuse may generate tendon fatigue damage and how this may relate to tendinopathy conditions. This article aims to review these models and our current understanding of tendon fatigue damage. We review the strengths and limitations of different methodologies for characterizing tendon fatigue, considering in vitro methods that adopt both viable and non-viable samples, as well as the range of different in vivo approaches. By comparing data across model systems, we review the current understanding of fatigue damage development. Additionally, we compare these findings with data from tendinopathic tissue biopsies to provide some insights into how these models may relate to the aetiology of tendinopathy. Fatigue-induced damage consistently highlights the same microstructural, biological and mechanical changes to the tendon across all model systems and also correlates well with the findings from tendinopathic biopsy tissue. The multiple testing routes support matrix damage as an important contributor to tendinopathic conditions, but cellular responses to fatigue appear complex and often contradictory. PMID:23837793

  11. Immune System

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Immune System KidsHealth > For Teens > Immune System Print A A ... could put us out of commission. What the Immune System Does The immune (pronounced: ih-MYOON) system, which ...

  12. Bithermal fatigue - A link between isothermal and thermomechanical fatigue

    NASA Technical Reports Server (NTRS)

    Halford, Gary R.; Mcgaw, Michael A.; Bill, Robert C.; Fanti, Paolo D.

    1988-01-01

    A technique for bithermal fatigue testing is presented in which the tensile and compressive halves of the cycle are conducted isothermally at two significantly different temperatures. With reference to experimental results obtained for a nickel-base superalloy, B1900 + Hf, it is shown that bithermal fatigue testing is a simple alternative to thermomechanical fatigue and can provide a conservative determination of thermomechanical fatigue life for creep damage dominated failure modes. Bithermal fatigue results can be directly related to thermomechanical fatigue results through the use of an appropriate damage rule.

  13. Vascular endothelial dysfunction and pharmacological treatment

    PubMed Central

    Su, Jin Bo

    2015-01-01

    The endothelium exerts multiple actions involving regulation of vascular permeability and tone, coagulation and fibrinolysis, inflammatory and immunological reactions and cell growth. Alterations of one or more such actions may cause vascular endothelial dysfunction. Different risk factors such as hypercholesterolemia, homocystinemia, hyperglycemia, hypertension, smoking, inflammation, and aging contribute to the development of endothelial dysfunction. Mechanisms underlying endothelial dysfunction are multiple, including impaired endothelium-derived vasodilators, enhanced endothelium-derived vasoconstrictors, over production of reactive oxygen species and reactive nitrogen species, activation of inflammatory and immune reactions, and imbalance of coagulation and fibrinolysis. Endothelial dysfunction occurs in many cardiovascular diseases, which involves different mechanisms, depending on specific risk factors affecting the disease. Among these mechanisms, a reduction in nitric oxide (NO) bioavailability plays a central role in the development of endothelial dysfunction because NO exerts diverse physiological actions, including vasodilation, anti-inflammation, antiplatelet, antiproliferation and antimigration. Experimental and clinical studies have demonstrated that a variety of currently used or investigational drugs, such as angiotensin-converting enzyme inhibitors, angiotensin AT1 receptors blockers, angiotensin-(1-7), antioxidants, beta-blockers, calcium channel blockers, endothelial NO synthase enhancers, phosphodiesterase 5 inhibitors, sphingosine-1-phosphate and statins, exert endothelial protective effects. Due to the difference in mechanisms of action, these drugs need to be used according to specific mechanisms underlying endothelial dysfunction of the disease. PMID:26635921

  14. Vascular endothelial dysfunction and pharmacological treatment.

    PubMed

    Su, Jin Bo

    2015-11-26

    The endothelium exerts multiple actions involving regulation of vascular permeability and tone, coagulation and fibrinolysis, inflammatory and immunological reactions and cell growth. Alterations of one or more such actions may cause vascular endothelial dysfunction. Different risk factors such as hypercholesterolemia, homocystinemia, hyperglycemia, hypertension, smoking, inflammation, and aging contribute to the development of endothelial dysfunction. Mechanisms underlying endothelial dysfunction are multiple, including impaired endothelium-derived vasodilators, enhanced endothelium-derived vasoconstrictors, over production of reactive oxygen species and reactive nitrogen species, activation of inflammatory and immune reactions, and imbalance of coagulation and fibrinolysis. Endothelial dysfunction occurs in many cardiovascular diseases, which involves different mechanisms, depending on specific risk factors affecting the disease. Among these mechanisms, a reduction in nitric oxide (NO) bioavailability plays a central role in the development of endothelial dysfunction because NO exerts diverse physiological actions, including vasodilation, anti-inflammation, antiplatelet, antiproliferation and antimigration. Experimental and clinical studies have demonstrated that a variety of currently used or investigational drugs, such as angiotensin-converting enzyme inhibitors, angiotensin AT1 receptors blockers, angiotensin-(1-7), antioxidants, beta-blockers, calcium channel blockers, endothelial NO synthase enhancers, phosphodiesterase 5 inhibitors, sphingosine-1-phosphate and statins, exert endothelial protective effects. Due to the difference in mechanisms of action, these drugs need to be used according to specific mechanisms underlying endothelial dysfunction of the disease. PMID:26635921

  15. Review of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: an evidence-based approach to diagnosis and management by clinicians.

    PubMed

    Bested, Alison C; Marshall, Lynn M

    2015-01-01

    This review was written from the viewpoint of the treating clinician to educate health care professionals and the public about Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). It includes: the clinical definition of ME/CFS with emphasis on how to diagnose ME/CFS; the etiology, pathophysiology, management approach, long-term prognosis and economic cost of ME/CFS. After reading this review, you will be better able to diagnose and treat your patients with ME/CFS using the tools and information provided. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, chronic medical condition characterized by symptom clusters that include: pathological fatigue and malaise that is worse after exertion, cognitive dysfunction, immune dysfunction, unrefreshing sleep, pain, autonomic dysfunction, neuroendocrine and immune symptoms. ME/CFS is common, often severely disabling and costly. The Institute of Medicine (IOM) reviewed the ME/CFS literature and estimates that between 836,000 and 2.5 million Americans have ME/CFS at a cost of between 17 and 24 billion dollars annually in the US. The IOM suggested a new name for ME/CFS and called it Systemic Exertion Intolerance Disease (SEID). SEID's diagnostic criteria are less specific and do not exclude psychiatric disorders in the criteria. The 2010 Canadian Community Health Survey discovered that 29% of patients with ME/CFS had unmet health care needs and 20% had food insecurity--lack of access to sufficient healthy foods. ME/CFS can be severely disabling and cause patients to be bedridden. Yet most patients (80%) struggle to get a diagnosis because doctors have not been taught how to diagnose or treat ME/CFS in medical schools or in their post-graduate educational training. Consequently, the patients with ME/CFS suffer. They are not diagnosed with ME/CFS and are not treated accordingly. Instead of compassionate care from their doctors, they are often ridiculed by the very people from whom they seek help

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

    SciTech Connect

    Jereczek-Fossa, Barbara Alicja . E-mail: barbara.fossa@ieo.it; Santoro, Luigi; Alterio, Daniela; Franchi, Benedetta; Fiore, Maria Rosaria; Fossati, Piero; Kowalczyk, Anna; Canino, Paola; Ansarin, Mohssen; Orecchia, Roberto

    2007-06-01

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

  17. Sexual dysfunction in epilepsy.

    PubMed

    Morrell, M J

    1991-01-01

    Sexual dysfunction may arise more frequently in men and women with epilepsy than with other chronic illnesses, manifesting primarily as diminished sexual desire and potency. Studies using retrospective self-report of sexual attitude and behavior find an incidence of sexual dysfunction ranging from 14-66%. Sexual dysfunction may be more common in partial than in generalized epilepsies. Sexual dysfunction in epilepsy may result from a disturbance in social or psychological factors affecting sexual responsiveness. Alternatively, epileptiform discharges may disrupt the function of structures mediating sexual behavior, particularly the limbic cortex, or alter the release of hypothalamic or pituitary hormones. Antiepileptic drugs modulate hormone release from the hypothalamic-pituitary-gonadal axis and may have direct inhibitory effects on sexual behavior. Evidence both supports and refutes each of these etiologies in the sexual dysfunction seen with epilepsy. Specific evaluation and treatment protocols for patients with sexual dysfunction are available.

  18. 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. PMID:19035066

  19. Fatigue of advanced materials

    SciTech Connect

    Dauskardt, R.H.; Ritchie, R.O. . Center for Advanced Materials); Cox, B.N. )

    1993-08-01

    The development of toughened ceramics over the past 10 to 15 years is arguably one of the most important materials breakthroughs of this century. Monolithic and composite ceramic materials having fracture toughnesses up to an order of magnitude higher than those available 20 years ago have been produced using technologies based on scientific understanding and micromechanical models for in situ phase transformation, fiber bridging, ductile-particle toughening, and other toughening mechanisms. The irony of this, however, is that although ceramics can now be seriously considered for many structural applications, they can also, contrary to popular belief, be susceptible to degradation under cyclic fatigue loading. This is true even when the loading is fully compressive. As a result, a great deal of attention is now being paid to ceramic fatigue, largely because of the importance of cyclic loading in many of the potential applications for ceramics, such as gas-turbine and reciprocating engines. However, because the field is in its infancy, only limited fatigue property data have been documented, understanding of salient fatigue mechanisms has not been achieved, and the design of ceramic microstructures for optimum fatigue resistance has yet to be attempted.

  20. Thermal fatigue of beryllium

    SciTech Connect

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

    1995-09-01

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

  1. 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.

  2. Surface contact fatigue and flexural fatigue of dental restorative materials.

    PubMed

    McCabe, J F; Wang, Y; Braem, M

    2000-06-01

    Antagonistic contact on a dental restoration may produce surface and subsurface stresses leading to fatigue wear as well as to bulk stressing, eventually causing catastrophic failure. It was the aim of the present work to study the outcome of two different approaches to fatigue testing of materials involving either surface contact fatigue or flexural fatigue mechanisms. A range of materials was tested, including conventional glass-ionomers, resin-modified glass-ionomers, poly-acid modified composites, and composites. Materials were prepared and tested using both surface contact and flexural fatigue. The results show that conventional glass-ionomers have the least resistance to fatigue under both regimes while composites have the longest fatigue lives and the highest values of flexural fatigue limit. However, the results also support the fact that catastrophic failure should be investigated separately from surface contact fatigue. Within the group of composite products tested, a hybrid composite material had a significantly greater flexural fatigue limit than a microfilled one, but the latter material had a significantly greater surface contact fatigue life, indicating that wear behavior cannot be predicted from bulk fracture characteristics and vice versa. The process of wear occurs by a combination of a number of fundamental processes, and the contribution fatigue makes will vary according to the environment and nature of the material.

  3. An indentation fatigue strength law

    NASA Astrophysics Data System (ADS)

    Xu, Baoxing; Yonezu, Akio; Chen, Xi

    2010-05-01

    Indentation fatigue, where a cyclic load is applied on the sample via an indenter, emerges as an alternative approach for measuring the fatigue properties of materials. We have carried out indentation fatigue tests on a poly(vinyl chloride) (PVC) bulk material, as well as on TiN and NiP films/coatings deposited on SUS304 steel substrates, and demonstrate that a simple power-law relationship can be established between the indentation load amplitude and number of cycles to failure. Such a law is very similar to the conventional fatigue strength law obtained from uniaxial tests. The agreement between the fatigue stress exponents obtained by uniaxial and indentation fatigue tests suggests the potential applicability of the indentation fatigue technique for extracting the fatigue properties of materials.

  4. 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.

  5. Relationship between fatigue and photosensitivity.

    PubMed

    Shigihara, Yoshihito; Tanaka, Masaaki; Watanabe, Yasuyoshi

    2010-01-01

    It is considered that photosensitivity is one of the most important factors to cause video-game epilepsy. Since photosensitivity is thought to cause various signs of hypersensitivity in the central nervous system and hypersensitivity is believed to be related to fatigue, whether fatigue is associated with photosensitivity was determined. The study group consisted of 68 healthy medical students attending Osaka City University Graduate School of Medicine. They completed questionnaires dealing with fatigue (Chalder Fatigue Scale) and photosensitivity. On simple regression analyses, fatigue score was positively associated with photosensitivity score. Similarly, on multiple regression analyses adjusted for age, gender, and sleeping hours, fatigue score was positively associated with photosensitivity score. Fatigue is associated with photosensitivity. Our findings provide new perspectives on fatigue.

  6. Probabilistic Failure Assessment For Fatigue

    NASA Technical Reports Server (NTRS)

    Moore, Nicholas; Ebbeler, Donald; Newlin, Laura; Sutharshana, Sravan; Creager, Matthew

    1995-01-01

    Probabilistic Failure Assessment for Fatigue (PFAFAT) package of software utilizing probabilistic failure-assessment (PFA) methodology to model high- and low-cycle-fatigue modes of failure of structural components. Consists of nine programs. Three programs perform probabilistic fatigue analysis by means of Monte Carlo simulation. Other six used for generating random processes, characterizing fatigue-life data pertaining to materials, and processing outputs of computational simulations. Written in FORTRAN 77.

  7. Symptomatic fatigue in multiple sclerosis.

    PubMed

    Freal, J E; Kraft, G H; Coryell, J K

    1984-03-01

    Symptomatic fatigue has not been investigated previously in a multiple sclerosis population. Potential subjects were the 78% of 656 individuals with multiple sclerosis who indicated in a previous study that they experienced symptomatic fatigue. Three hundred nine subjects (60%) returned a follow-up questionnaire on symptomatic fatigue. Ninety percent described fatigue as "tiredness or the need to rest," but 43% of them indicated that "sleepiness" was part of the symptomatology. In 48% fatigue made other MS symptoms worse. Fatigue tended to occur in the late afternoon and evening. It occurred almost daily for more than 66% of the subjects. In 47% of the subjects fatigue usually subsided within a few hours; in other subjects occurrences were of variable length (40%) or lasted between 6 and 24 hours (8%). Ninety percent said that fatigue was worse at warmer environmental temperatures. Fatigue was worse for 83% after "vigorous exercise" and for 64% after "moderate exercise" although 15% reported that moderate exercise helped to reduce fatigue. Meditation, some drugs, and cooling with water reduced fatigue in a majority of the small proportion of the population trying these techniques. A planned daily schedule of activity and rest seemed to be a partially effective response to symptomatic fatigue for the majority of subjects studied.

  8. 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.

  9. Flibanserin for female sexual dysfunction.

    PubMed

    Reviriego, C

    2014-08-01

    Hypoactive sexual desire disorder (HSDD) is the most commonly described form of female sexual dysfunction. There is currently no pharmacological therapy approved to treat HSDD, and therefore, there is an unmet medical need for the development of efficacious treatment alternatives. Flibanserin is a novel, non-hormonal drug for the treatment of HSDD in pre- and postmenopausal women, although the application submitted to the U.S. Food and Drug Administration by Sprout Pharmaceuticals is only for premenopausal women. Flibanserin works by correcting an imbalance of the levels of the neurotransmitters that affect sexual desire. More specifically, flibanserin increases dopamine and norepinephrine, both responsible for sexual excitement, and decreases serotonin, responsible for sexual inhibition. Clinically, flibanserin has exhibited some encouraging results in terms of its ability to increase the frequency of satisfying sexual events, and the intensity of sexual desire. However, adverse events such as dizziness, nausea, fatigue and somnolence, typical of a centrally acting drug, are also frequently related to flibanserin treatment. PMID:25187905

  10. Fatigue and thermal fatigue of Pb-Sn solder joints

    SciTech Connect

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

    1987-01-01

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

  11. [Effect of diaphragmatic fatigue on ventilatory response to carbon dioxide].

    PubMed

    Wakai, Y; Yoshimura, A; Katagiri, S; Yoshino, K; Konno, K

    1992-12-01

    To clarify the effect of respiratory muscle fatigue on ventilatory response to carbon dioxide, we performed CO2 rebreathing study before and after diaphragmatic fatigue in nine healthy males. Diaphragmatic fatigue was induced by inspiratory resistor loading and confirmed by the increase in Tension Time Index and the decrease in Pdi max at FRC. The effects of diaphragmatic fatigue were as follows: 1) S and B value of VE-CO2 curve did not change. 2) P1-CO2 curve shifted to the left but the slope of the curve did not change. 3) delta Ppl response to CO2 decreased, but delta Pdi response to CO2 did not change. 4) The increase in respiratory accessory muscle EMG was more prominent, compared to diaphragmatic EMG. 5) Rib cage movement became more marked. In conclusion, diaphragmatic fatigue (with 60 percent decrease in Pdi max at FRC) does not affect on ventilatory response to carbon dioxide. To maintain the homeostasis of the chemical ventilatory feedback system, diaphragmatic dysfunction is compensated by the increased activity of respiratory accessory muscles with possible increase in neural drive. PMID:1306216

  12. Powering the Immune System: Mitochondria in Immune Function and Deficiency

    PubMed Central

    Walker, Melissa A.; Sims, Katherine B.; Walter, Jolan E.; Traggiai, Elisabetta

    2014-01-01

    Mitochondria are critical subcellular organelles that are required for several metabolic processes, including oxidative phosphorylation, as well as signaling and tissue-specific processes. Current understanding of the role of mitochondria in both the innate and adaptive immune systems is expanding. Concurrently, immunodeficiencies arising from perturbation of mitochondrial elements are increasingly recognized. Recent observations of immune dysfunction and increased incidence of infection in patients with primary mitochondrial disorders further support an important role for mitochondria in the proper function of the immune system. Here we review current findings. PMID:25309931

  13. Powering the immune system: mitochondria in immune function and deficiency.

    PubMed

    Walker, Melissa A; Volpi, Stefano; Sims, Katherine B; Walter, Jolan E; Traggiai, Elisabetta

    2014-01-01

    Mitochondria are critical subcellular organelles that are required for several metabolic processes, including oxidative phosphorylation, as well as signaling and tissue-specific processes. Current understanding of the role of mitochondria in both the innate and adaptive immune systems is expanding. Concurrently, immunodeficiencies arising from perturbation of mitochondrial elements are increasingly recognized. Recent observations of immune dysfunction and increased incidence of infection in patients with primary mitochondrial disorders further support an important role for mitochondria in the proper function of the immune system. Here we review current findings.

  14. Sleep Dysfunction and Gastrointestinal Diseases.

    PubMed

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

    2015-12-01

    Sleep deprivation and impaired sleep quality have been associated with poor health outcomes. Many patients experience sleep disturbances, which can increase the risk of medical conditions such as hypertension, obesity, stroke, and heart disease as well as increase overall mortality. Recent studies have suggested that there is a strong association between sleep disturbances and gastrointestinal diseases. Proinflammatory cytokines, such as tumor necrosis factor, interleukin-1, and interleukin-6, have been associated with sleep dysfunction. Alterations in these cytokines have been seen in certain gastrointestinal diseases, such as gastroesophageal reflux disease, inflammatory bowel disease, liver disorders, and colorectal cancer. It is important for gastroenterologists to be aware of the relationship between sleep disorders and gastrointestinal illnesses to ensure good care for patients. This article reviews the current research on the interplay between sleep disorders, immune function, and gastrointestinal diseases. PMID:27134599

  15. Sleep Dysfunction and Gastrointestinal Diseases

    PubMed Central

    Khanijow, Vikesh; Prakash, Pia; Emsellem, Helene A.; Borum, Marie L.

    2015-01-01

    Sleep deprivation and impaired sleep quality have been associated with poor health outcomes. Many patients experience sleep disturbances, which can increase the risk of medical conditions such as hypertension, obesity, stroke, and heart disease as well as increase overall mortality. Recent studies have suggested that there is a strong association between sleep disturbances and gastrointestinal diseases. Proinflammatory cytokines, such as tumor necrosis factor, interleukin-1, and interleukin-6, have been associated with sleep dysfunction. Alterations in these cytokines have been seen in certain gastrointestinal diseases, such as gastroesophageal reflux disease, inflammatory bowel disease, liver disorders, and colorectal cancer. It is important for gastroenterologists to be aware of the relationship between sleep disorders and gastrointestinal illnesses to ensure good care for patients. This article reviews the current research on the interplay between sleep disorders, immune function, and gastrointestinal diseases. PMID:27134599

  16. Immune response

    MedlinePlus

    ... cells. T cells are responsible for cell-mediated immunity. This type of immunity becomes deficient in persons with HIV, the virus ... blood. B lymphocytes provide the body with humoral immunity as they circulate in the fluids in search ...

  17. Immune Restoration

    MedlinePlus

    ... marrow cells immune to HIV infection. Letting the immune system repair itself: CD4 counts have increased for many ... have taken ART. Some scientists believe that the immune system might be able to heal and repair itself ...

  18. Probing the Diversity of T Cell Dysfunction in Cancer.

    PubMed

    Sowell, Ryan T; Kaech, Susan M

    2016-09-01

    T cell dysfunction in cancer comes in many forms, with two new varieties reported in this issue. Daley et al. find that T cells expressing γδ T cell receptors (TCR) promote pancreatic tumor growth by inhibiting activation of T cells with conventional TCRs. Singer et al. characterize dysfunctional tumor infiltrating lymphocytes to reveal a role for zinc homeostasis in anti-tumor immunity. PMID:27610560

  19. 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.

  20. Incompatibility and Mental Fatigue

    ERIC Educational Resources Information Center

    Herzog, Thomas R.; Hayes, Lauren J.; Applin, Rebecca C.; Weatherly, Anna M.

    2011-01-01

    A straightforward prediction from attention restoration theory is that the level of incompatibility in a person's life should be positively correlated with that person's level of mental (or directed attention) fatigue. The authors tested this prediction by developing a new self-report measure of incompatibility in which they attempted to isolate…

  1. FATIGUE OF DENTAL CERAMICS

    PubMed Central

    Zhang, Yu; Sailer, Irena; Lawn, Brian R

    2013-01-01

    Objectives Clinical data on survival rates reveal that all-ceramic dental prostheses are susceptible to fracture from repetitive occlusal loading. The objective of this review is to examine the underlying mechanisms of fatigue in current and future dental ceramics. Data/sources The nature of various fatigue modes is elucidated using fracture test data on ceramic layer specimens from the dental and biomechanics literature. Conclusions Failure modes can change over a lifetime, depending on restoration geometry, loading conditions and material properties. Modes that operate in single-cycle loading may be dominated by alternative modes in multi-cycle loading. While post-mortem examination of failed prostheses can determine the sources of certain fractures, the evolution of these fractures en route to failure remains poorly understood. Whereas it is commonly held that loss of load-bearing capacity of dental ceramics in repetitive loading is attributable to chemically-assisted 'slow crack growth' in the presence of water, we demonstrate the existence of more deleterious fatigue mechanisms, mechanical rather than chemical in nature. Neglecting to account for mechanical fatigue can lead to gross overestimates in predicted survival rates. Clinical significance Strategies for prolonging the clinical lifetimes of ceramic restorations are proposed based on a crack-containment philosophy. PMID:24135295

  2. Fatigue of insect cuticle.

    PubMed

    Dirks, Jan-Henning; Parle, Eoin; Taylor, David

    2013-05-15

    Many parts of the insect exoskeleton experience repeated cyclic loading. Although the cuticle of insects and other arthropods is the second most common natural composite material in the world, so far nothing is known about its fatigue properties, despite the fact that fatigue undoubtedly limits the durability of body parts in vivo. For the first time, we here present experimental fatigue data of insect cuticle. Using force-controlled cyclic loading, we determined the number of cycles to failure for hind legs (tibiae) and hind wings of the locust Schistocerca gregaria, as a function of the applied cyclic stress. Our results show that, although both are made from cuticle, these two body parts behave very differently. Wing samples showed a large fatigue range, failing after 100,000 cycles when we applied 46% of the stress needed for instantaneous failure [the ultimate tensile strength (UTS)]. Legs, in contrast, were able to sustain a stress of 76% of the UTS for the same number of cycles to failure. This can be explained by the difference in the composition and structure of the material, two factors that, amongst others, also affect the well-known behaviour of engineering composites. Final failure of the tibiae occurred via one of two different failure modes--propagation in tension or buckling in compression--indicating that the tibia is 'optimized' by evolution to resist both failure modes equally. These results are further discussed in relation to the evolution and normal use of these two body parts.

  3. Fatigue resistance of duralumin

    NASA Technical Reports Server (NTRS)

    1922-01-01

    Where, in the following report, mention is made of fatigue, it always refers to the weakening of the material produced by rapidly changing stresses below the point of elasticity. The alternating stress was obtained by a test bar which was held at one end and subjected to rotation. Most of the tests were conducted on connecting rods.

  4. Immune mediated liver failure

    PubMed Central

    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capacity. Direct damage and immune-mediated liver injury are two major factors involved in this process. Increasing evidence has suggested the essential role of immune-mediated liver injury in the pathogenesis of liver failure. Here, we review the evolved concepts concerning the mechanisms of immune-mediated liver injury in liver failure from human and animal studies. Both innate and adaptive immunity, especially the interaction of various immune cells and molecules as well as death receptor signaling system are discussed. In addition, we highlight the concept of “immune coagulation”, which has been shown to be related to the disease progression and liver injury exacerbation in HBV related acute-on-chronic liver failure. PMID:26417328

  5. Genetics Home Reference: surfactant dysfunction

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions surfactant dysfunction surfactant dysfunction Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Surfactant dysfunction is a lung disorder that causes breathing ...

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

    PubMed Central

    2013-01-01

    Background 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. Methods 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. Results 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. Conclusions Our results support the role of cytokines in the pathophysiology of CFS. PMID:23570606

  7. Different types of fatigue in patients with facioscapulohumeral dystrophy, myotonic dystrophy and HMSN-I. Experienced fatigue and physiological fatigue.

    PubMed

    Kalkman, Joke S; Zwarts, Machiel J; Schillings, Maartje L; van Engelen, Baziel G M; Bleijenberg, Gijs

    2008-09-01

    Although fatigue is a common symptom in neuromuscular disorders, little is known about different types of fatigue. Sixty-five FSHD, 79 adult-onset MD and 73 HMSN type I patients were studied. Experienced fatigue was assessed with the CIS-fatigue subscale. Physiological fatigue was measured during a 2-min sustained maximal voluntary contraction of the biceps brachii muscle using the twitch interpolation technique to assess central activation failure (CAF) and peripheral fatigue. Experienced fatigue, CAF and peripheral fatigue appeared to be predominantly separate types of fatigue. PMID:18690504

  8. Exercise, nutrition and immune function.

    PubMed

    Gleeson, Michael; Nieman, David C; Pedersen, Bente K

    2004-01-01

    Strenuous bouts of prolonged exercise and heavy training are associated with depressed immune cell function. Furthermore, inadequate or inappropriate nutrition can compound the negative influence of heavy exertion on immunocompetence. Dietary deficiencies of protein and specific micronutrients have long been associated with immune dysfunction. An adequate intake of iron, zinc and vitamins A, E, B6 and B12 is particularly important for the maintenance of immune function, but excess intakes of some micronutrients can also impair immune function and have other adverse effects on health. Immune system depression has also been associated with an excess intake of fat. To maintain immune function, athletes should eat a well-balanced diet sufficient to meet their energy requirements. An athlete exercising in a carbohydrate-depleted state experiences larger increases in circulating stress hormones and a greater perturbation of several immune function indices. Conversely, consuming 30-60 g carbohydrate x h(-1) during sustained intensive exercise attenuates rises in stress hormones such as cortisol and appears to limit the degree of exercise-induced immune depression. Convincing evidence that so-called 'immune-boosting' supplements, including high doses of antioxidant vitamins, glutamine, zinc, probiotics and Echinacea, prevent exercise-induced immune impairment is currently lacking. PMID:14971437

  9. Exercise, nutrition and immune function.

    PubMed

    Gleeson, Michael; Nieman, David C; Pedersen, Bente K

    2004-01-01

    Strenuous bouts of prolonged exercise and heavy training are associated with depressed immune cell function. Furthermore, inadequate or inappropriate nutrition can compound the negative influence of heavy exertion on immunocompetence. Dietary deficiencies of protein and specific micronutrients have long been associated with immune dysfunction. An adequate intake of iron, zinc and vitamins A, E, B6 and B12 is particularly important for the maintenance of immune function, but excess intakes of some micronutrients can also impair immune function and have other adverse effects on health. Immune system depression has also been associated with an excess intake of fat. To maintain immune function, athletes should eat a well-balanced diet sufficient to meet their energy requirements. An athlete exercising in a carbohydrate-depleted state experiences larger increases in circulating stress hormones and a greater perturbation of several immune function indices. Conversely, consuming 30-60 g carbohydrate x h(-1) during sustained intensive exercise attenuates rises in stress hormones such as cortisol and appears to limit the degree of exercise-induced immune depression. Convincing evidence that so-called 'immune-boosting' supplements, including high doses of antioxidant vitamins, glutamine, zinc, probiotics and Echinacea, prevent exercise-induced immune impairment is currently lacking.

  10. Chronic fatigue and chronic fatigue syndrome: shifting boundaries and attributions.

    PubMed

    Lloyd, A R

    1998-09-28

    The subjective symptom of "fatigue" is one of the most widespread in the general population and is a major source of healthcare utilization. Prolonged fatigue is often associated with neuropsychological and musculoskeletal symptoms that form the basis of several syndromal diagnoses including chronic fatigue syndrome, fibromyalgia, and neurasthenia, and is clearly not simply the result of a lack of force generation from the muscle. Current epidemiologic research in this area relies predominantly on self-report data to document the prevalence and associations of chronic fatigue. Of necessity, this subjective data source gives rise to uncertain diagnostic boundaries and consequent divergent epidemiologic, clinical, and pathophysiologic research findings. This review will highlight the impact of the case definition and ascertainment methods on the varying prevalence estimates of chronic fatigue syndrome and patterns of reported psychological comorbidty. It will also evaluate the evidence for a true postinfective fatigue syndrome.

  11. Temporomandibular Joint Dysfunction

    MedlinePlus

    The temporomandibular joint (TMJ) connects your jaw to the side of your head. When it works well, it enables you to ... For people with TMJ dysfunction, problems with the joint and muscles around it may cause Pain that ...

  12. Chronic pelvic floor dysfunction.

    PubMed

    Hartmann, Dee; Sarton, Julie

    2014-10-01

    The successful treatment of women with vestibulodynia and its associated chronic pelvic floor dysfunctions requires interventions that address a broad field of possible pain contributors. Pelvic floor muscle hypertonicity was implicated in the mid-1990s as a trigger of major chronic vulvar pain. Painful bladder syndrome, irritable bowel syndrome, fibromyalgia, and temporomandibular jaw disorder are known common comorbidities that can cause a host of associated muscular, visceral, bony, and fascial dysfunctions. It appears that normalizing all of those disorders plays a pivotal role in reducing complaints of chronic vulvar pain and sexual dysfunction. Though the studies have yet to prove a specific protocol, physical therapists trained in pelvic dysfunction are reporting success with restoring tissue normalcy and reducing vulvar and sexual pain. A review of pelvic anatomy and common findings are presented along with suggested physical therapy management.

  13. Velopharyngeal function and dysfunction.

    PubMed

    Jones, D L

    1991-01-01

    The concepts regarding velopharyngeal function, the production of disordered nasalization, and the management of velopharyngeal dysfunction can be summarized as follows: 1. Although the function of the velopharyngeal mechanism is critical to the control of oral-nasal balance, the configuration and function of the speech articulatory system as a whole will determine the degree of nasalized speech that is produced. 2. Velopharyngeal dysfunction can be related to one or a combination of structural and motor limitations within the velopharyngeal mechanism. 3. There are two perceptual manifestations of velopharyngeal dysfunction. One is acoustic (nasality); the other is aerodynamic (nasal emission). For any given speaker, it is possible to hear both, and it is possible to hear one and not the other. 4. Velopharyngeal dysfunction can be treated in a variety of ways. The method of treatment should be determined by the structural characteristics of the velopharyngeal mechanism and the speech-motor abilities of the patient.

  14. Mitochondrial Dysfunction Meets Senescence.

    PubMed

    Gallage, Suchira; Gil, Jesús

    2016-03-01

    Cellular senescence and mitochondrial dysfunction are hallmarks of ageing, but until now their relationship has not been clear. Recent work by Wiley et al. shows that mitochondrial defects can cause a distinct senescence phenotype termed MiDAS (mitochondrial dysfunction-associated senescence). MiDAS has a specific secretome that is able to drive some of the aging phenotypes. These findings suggest novel therapeutic opportunities for treating age-related pathologies. PMID:26874922

  15. Male endocrine dysfunction.

    PubMed

    Hotaling, James M; Patel, Zamip

    2014-02-01

    Evaluation for endocrine function is a pivotal part of the male infertility workup. Endocrine dysfunction may result from endogenous and exogenous sources. This article describes the traditional roles that the hypothalamic-pituitary-gonadal endocrine axis plays in spermatogenesis and testicular dysfunction, as well as other insults that may contribute to hypospermatogenesis. Recent research into the role alternative hormonal axes play in spermatogenesis and promising new technologies that may correct inborn or acquired endocrinopathies leading to impaired sperm growth and maturation are discussed.

  16. [Childhood chronic fatigue syndrome].

    PubMed

    Miike, Teruhisa

    2007-06-01

    Chronic fatigue syndrome in childhood and adolescents(CCFS) is a complex and debilitation with severe morbidity and confusion. It is common condition with up to 3-5% of children and adolescents showing strange fatigue and confusion for more than 30 days. In this condition, four major symptoms are important: sleep disorders, easy fatigability, disturbed learning and memorization and immunological problems. Routine laboratory studies are similar to adult CFS, although abnormalities can be seen on serum pyruvic acid level, OGTT pattern, deep body temperature rhythm, hormonal secretion rhythm, and cerebral blood flow. For a diagnosis of CCFS, a research group supported by Japanese ministry of health, labor and welfare developed CCFS case definition on 2004. Treatment focused to correct disrupted circadian rhythms and supply of energy.

  17. Probabilistic Mesomechanical Fatigue Model

    NASA Technical Reports Server (NTRS)

    Tryon, Robert G.

    1997-01-01

    A probabilistic mesomechanical fatigue life model is proposed to link the microstructural material heterogeneities to the statistical scatter in the macrostructural response. The macrostructure is modeled as an ensemble of microelements. Cracks nucleation within the microelements and grow from the microelements to final fracture. Variations of the microelement properties are defined using statistical parameters. A micromechanical slip band decohesion model is used to determine the crack nucleation life and size. A crack tip opening displacement model is used to determine the small crack growth life and size. Paris law is used to determine the long crack growth life. The models are combined in a Monte Carlo simulation to determine the statistical distribution of total fatigue life for the macrostructure. The modeled response is compared to trends in experimental observations from the literature.

  18. Fatigue syndrome in sarcoidosis.

    PubMed

    Górski, Witold; Piotrowski, Wojciech J

    2016-01-01

    Sarcoidosis is an inflammatory disease of unknown etiology. Most commonly it results in the formation of non-caseating granulomas in intrathoracic lymph nodes and lung parenchyma, but the clinical course and picture may be complicated by extrapulmonary involvement and many non-respiratory signs and symptoms which are directly related to the disease. In addition, sarcoidosis patients may suffer from a plethora of symptoms of uncertain or unknown origin. Fatigue is one of these symptoms, and according to some authors it is reported by the majority of patients with active sarcoidosis, but also by a smaller proportion of patients with inactive sarcoidosis, or even with complete clinical and radiological remission. Therefore the term fatigue syndrome is frequently used to name this clinical problem. The definition of fatigue syndrome in sarcoidosis is imprecise and the syndrome is usually recognized by use of validated questionnaires. In this review the uptodate knowledge in this field was presented and different challenges connected with this syndrome were described.

  19. 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.

  20. Compassion fatigue: a nurse's primer.

    PubMed

    Lombardo, Barbara; Eyre, Caryl

    2011-01-01

    Most nurses enter the field of nursing with the intent to help others and provide empathetic care for patients with critical physical, mental, emotional, and spiritual needs. Empathic and caring nurses, however, can become victims of the continuing stress of meeting the often overwhelming needs of patients and their families, resulting in compassion fatigue. Compassion fatigue affects not only the nurse in terms of job satisfaction and emotional and physical health, but also the workplace environment by decreasing productivity and increasing turnover. We begin this article with a case study of a reactive nurse who did not seek help for her continuing stress. This is followed by a review of Watson's theoretical perspective related to compassion fatigue. Next we delineate symptoms of, and describe interventions for addressing compassion fatigue. We conclude by presenting a case study of a proactive nurse who avoided developing compassion fatigue and a discussion of future research needed to better prevent and ameliorate compassion fatigue. PMID:21800934

  1. Probabilistic Fatigue Damage Program (FATIG)

    NASA Technical Reports Server (NTRS)

    Michalopoulos, Constantine

    2012-01-01

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

  2. 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.

  3. Fatigue of fiberglass beam substructures

    SciTech Connect

    Mandell, J.F.; Combs, D.W.; Samborsky, D.D.

    1995-09-01

    Composite material beams representative of wind turbine blade substructure have been designed, fabricated, and tested under constant amplitude flexural fatigue loading. Beam stiffness, strength, and fatigue life are predicted based on detailed finite element analysis and the materials fatigue database developed using standard test coupons and special high frequency minicoupons.Beam results are in good agreement with predictions when premature adhesive and delamination failures are avoided in the load transfer areas. The results show that fiberglass substructures can be designed and fabricated to withstand maximum strain levels on the order of 8,000 microstrain for about 10{sup 6} cycles with proper structural detail design and the use of fatigue resistant laminate constructions. The study also demonstrates that the materials fatigue database and accurate analysis can be used to predict the fatigue life of composite substructures typical of blades.

  4. Determinants of fatigue and stress

    PubMed Central

    2011-01-01

    Background Fatigue can be triggered by previous perceived stress which may lead to impairment of performance and function. The purpose of the study was to investigate the relationship between fatigue and perceived stress. Method Health determinants including sociodemographic factors for associations between fatigue and perceived stress in the general population (N = 2,483) are outlined. Fatigue and stress were assessed with the Chalder Fatigue Scale (CFS) and the Perceived Stress Questionnaire (PSQ). Results Within the general population, 25.9% of male and 34.5% of female respondents reported moderate fatigue during the last six months; 9.7% of subjects reported substantial fatigue lasting six months or longer. An adjusted regression analysis (R2corr = .28, p < .001) showed that fatigue is highest associated with perceived stress and self-perceived health status. The following factors were correlated with increased rates of fatigue and perceived stress: female gender, divorce/separation, low social class and poor health status. Conclusion We conclude that the two conditions overlap most in terms of socio-economic status and self-perceived health status. PMID:21774803

  5. Gene Expression in Response to Exercise in Patients with Chronic Fatigue Syndrome: A Pilot Study

    PubMed Central

    Keech, Andrew; Vollmer-Conna, Ute; Barry, Benjamin K.; Lloyd, Andrew R.

    2016-01-01

    Chronic fatigue syndrome (CFS) is a debilitating disorder of unknown pathogenesis, characterized by fatigue, which is exacerbated after minimal exercise. We examined the effect of a single bout of aerobic exercise on leucocyte mRNA expression of genes putatively linked to exaggerated afferent signaling as an under-pinning of the fatigue state. A carefully-characterized sample of patients with CFS (N = 10) and healthy matched control participants (N = 12) were included. Participant ratings of fatigue and other symptoms, as well as blood samples, were obtained at baseline, and five other time-points up to 72 h after 25 min of moderate-intensity cycling exercise. Leucocyte mRNA of 19 metabolite-sensing, adrenergic, immune, and neurotransmission genes was examined using quantitative polymerase chain reaction. Patients with CFS reported substantial fatigue, functional impairment, and poor sleep at baseline (all p < 0.02), and exercise immediately induced worsened patients' fatigue (effect size, ES = 1.17). There were no significant changes in gene expression after exercise and patients did not differ from control participants at any time point. Higher levels of expression of ficolin (FCN1) and a purinergic receptor (P2RX4) in patients with CFS were found when all time points were combined. Patients with CFS did not show significant exercise-induced changes in leucocyte mRNA of 19 metabolite-sensing, adrenergic, immune and neurotransmission genes despite a prominent exacerbation of fatigue. PMID:27713703

  6. Marathon training and immune function.

    PubMed

    Nieman, David C

    2007-01-01

    Many components of the immune system exhibit adverse change after marathon-type exertion. These immune changes occur in several compartments of the immune system and body (e.g. the skin, upper respiratory tract mucosal tissue, lung, peritoneal cavity, blood and muscle). Of all immune cells, natural killer (NK) cells, neutrophils and macrophages (of the innate immune system) exhibit the greatest changes in response to marathon competition, both in terms of numbers and function. Many mechanisms appear to be involved, including exercise-induced changes in stress hormone and cytokine concentrations, body temperature changes, increases in blood flow and dehydration. During this 'open window' of immune dysfunction (which may last between 3 and 72 hours, depending on the immune measure), viruses and bacteria may gain a foothold, increasing the risk of subclinical and clinical infection. Of the various nutritional and pharmacological countermeasures to marathon-induced immune perturbations that have been evaluated thus far, ingestion of carbohydrate beverages during intense and prolonged exercise has emerged as the most effective. However, carbohydrate ingestion during a marathon attenuates increases in plasma cytokines and stress hormones, but is largely ineffective against changes in other immune components including suppression of NK and T-cell function, and salivary IgA output. Other countermeasures, such as glutamine, antioxidant supplements and ibuprofen, have had disappointing results and thus the search for companion agents to carbohydrate continues. PMID:17465622

  7. Four Pathways Involving Innate Immunity in the Pathogenesis of Preeclampsia

    PubMed Central

    Bounds, Kelsey R.; Newell-Rogers, M. Karen; Mitchell, Brett M.

    2015-01-01

    The maternal innate immune system plays an important role both in normal pregnancy as well as hypertensive disorders of pregnancy including preeclampsia (PE). We propose four pathways that involve excessive innate immunity that lead to most forms of PE. Pre-existing endothelial dysfunction plus pregnancy leads to an excessive innate immune response resulting in widespread inflammation, placental and renal dysfunction, vasoconstriction, and PE. Placental dysfunction due to shallow trophoblast invasion, inadequate spiral artery remodeling, and/or low placental perfusion initiates an innate immune response leading to excessive inflammation, endothelial and renal dysfunction, and PE. A heightened innate immune system due to pre-existing or acquired infections plus the presence of a paternally derived placenta and semi-allogeneic fetus cause an excessive innate immune response which manifests as PE. Lastly, an abnormal and excessive maternal immune response to pregnancy leads to widespread inflammation, organ dysfunction, and PE. We discuss the potential role of innate immunity in each of these scenarios, as well as the overlap, and how targeting the innate immune system might lead to therapies for the treatment of PE. PMID:26664892

  8. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome

    PubMed Central

    Sullivan, Åsa; Nord, Carl E; Evengård, Birgitta

    2009-01-01

    Disturbances in intestinal microbial ecology and in the immune system of the host have been implicated as a part of the pathogenesis in chronic fatigue syndrome. Probiotic lactic acid producing bacteria have been shown to prevent and alleviate gastrointestinal disturbances and to normalize the cytokine profile which might be of an advantage for patients suffering from chronic fatigue syndrome. The aim of the study was to evaluate the effect of Lactobacillus paracasei ssp. paracasei F19, Lactobacillus acidophilus NCFB 1748 and Bifidobacterium lactis Bb12 on fatigue and physical activity in CFS patients. Fifteen patients fulfilling the criteria set by international researchers in the field at the US Centre for Disease Control and Prevention in 1994 for chronic fatigue syndrome, were included in the study. The patients had high fatigue severity scores and high disability scores. During the first two weeks baseline observations without treatment were assessed, succeeded by four weeks of intake of a probiotic product and a four-week follow-up period. The fatigue, health and physical activity was assessed by the use of the Visual Analogue Scales and the SF-12 Health Survey. Faecal samples were collected and the normal microflora was analysed. Neurocognitive functions improved during the study period while there were no significant changes in fatigue and physical activity scores. No major changes occurred in the gastrointestinal microflora. At the end of the study 6 of 15 patients reported that they had improved according to the assessment described. The findings in this study that improvement of health is possible to achieve should encourage further studies with interventions with probiotics in patients with CFS. PMID:19171024

  9. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome.

    PubMed

    Sullivan, Asa; Nord, Carl E; Evengård, Birgitta

    2009-01-01

    Disturbances in intestinal microbial ecology and in the immune system of the host have been implicated as a part of the pathogenesis in chronic fatigue syndrome. Probiotic lactic acid producing bacteria have been shown to prevent and alleviate gastrointestinal disturbances and to normalize the cytokine profile which might be of an advantage for patients suffering from chronic fatigue syndrome. The aim of the study was to evaluate the effect of Lactobacillus paracasei ssp. paracasei F19, Lactobacillus acidophilus NCFB 1748 and Bifidobacterium lactis Bb12 on fatigue and physical activity in CFS patients. Fifteen patients fulfilling the criteria set by international researchers in the field at the US Centre for Disease Control and Prevention in 1994 for chronic fatigue syndrome, were included in the study. The patients had high fatigue severity scores and high disability scores. During the first two weeks baseline observations without treatment were assessed, succeeded by four weeks of intake of a probiotic product and a four-week follow-up period. The fatigue, health and physical activity was assessed by the use of the Visual Analogue Scales and the SF-12 Health Survey. Faecal samples were collected and the normal microflora was analysed. Neurocognitive functions improved during the study period while there were no significant changes in fatigue and physical activity scores. No major changes occurred in the gastrointestinal microflora. At the end of the study 6 of 15 patients reported that they had improved according to the assessment described. The findings in this study that improvement of health is possible to achieve should encourage further studies with interventions with probiotics in patients with CFS. PMID:19171024

  10. 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.

  11. Influence of catechol-o-methyltransferase genotype (Val158Met) on endocrine, sympathetic nervous and mucosal immune systems in breast cancer survivors.

    PubMed

    Fernández-de-Las-Peñas, César; Cantarero-Villanueva, Irene; Fernández-Lao, Carolina; Ambite-Quesada, Silvia; Díaz-Rodríguez, Lourdes; Rivas-Martínez, Inés; del Moral-Avila, Rosario; Arroyo-Morales, Manuel

    2012-04-01

    Stress can play an important role in development of cancer-related fatigue (CRF) by activating the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic nervous system (SNS), and altering the immune system. This study examined the influence of catechol-O-methyltransferase (COMT) Val158Met genotypes on salivary markers of HPA axis (cortisol), SNS (α-amylase) and immune (IgA) systems, as well as on CRF in breast cancer survivors (BCS). One-hundred BCS participated. After amplifying Val158Met COMT polymorphisms by polymerase chain reaction, three COMT genotypes were considered: Val/Val, Val/Met, Met/Met. Salivary cortisol, α-amylase activity, salivary flow rate, and IgA concentration were collected from non-stimulated saliva. CRF was assessed with the fatigue subscale of the Profile of Mood State (POMS) questionnaire. We found that BCS carrying Met/Met genotype reported higher cortisol concentration, α-amylase activity and greater CRF than those with Val/Met (P < 0.05) and Val/Val (P < 0.001) genotypes. No differences in salivary flow rate or IgA concentration (P > 0.20) were found. The results suggest that BCS carrying Met/Met genotype exhibit greater dysfunction of the HPA axis and SNS system associated with severe CRF. This study is important because it strives to understand biological factors that predispose some BCS to higher levels of CRF. PMID:21974969

  12. 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).

  13. Childhood Immunization

    MedlinePlus

    ... lowest levels in history, thanks to years of immunization. Children must get at least some vaccines before ... child provide protection for many years, adults need immunizations too. Centers for Disease Control and Prevention

  14. Immunizations - diabetes

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000331.htm Immunizations - diabetes To use the sharing features on this page, please enable JavaScript. Immunizations (vaccines or vaccinations) help protect you from some ...

  15. Immunity in arterial hypertension: associations or causalities?

    PubMed

    Anders, Hans-Joachim; Baumann, Marcus; Tripepi, Giovanni; Mallamaci, Francesca

    2015-12-01

    Numerous studies describe associations between markers of inflammation and arterial hypertension (aHT), but does that imply causality? Interventional studies that reduce blood pressure reduced also markers of inflammation, but does immunosuppression improve hypertension? Here, we review the available mechanistic data. Aberrant immunity can trigger endothelial dysfunction but is hardly ever the primary cause of aHT. Innate and adaptive immunity get involved once hypertension has caused vascular wall injury as immunity is a modifier of endothelial dysfunction and vascular wall remodelling. As vascular remodelling progresses, immunity-related mechanisms can become significant cofactors for cardiovascular (CV) disease progression; vice versa, suppressing immunity can improve hypertension and CV outcomes. Innate and adaptive immunity both contribute to vascular wall remodelling. Innate immunity is driven by danger signals that activate Toll-like receptors and other pattern-recognition receptors. Adaptive immunity is based on loss of tolerance against vascular autoantigens and includes autoreactive T-cell immunity as well as non-HLA angiotensin II type 1 receptor-activating autoantibodies. Such processes involve numerous other modulators such as regulatory T cells. Together, immunity is not causal for hypertension but rather an important secondary pathomechanism and a potential therapeutic target in hypertension.

  16. Reversal bending fatigue testing

    SciTech Connect

    Wang, Jy-An John; Wang, Hong; Tan, Ting

    2014-10-21

    Embodiments for apparatuses for testing reversal bending fatigue in an elongated beam are disclosed. Embodiments are configured to be coupled to first and second end portions of the beam and to apply a bending moment to the beam and create a pure bending condition in an intermediate portion of the beam. Embodiments are further configured to cyclically alternate the direction of the bending moment applied to the beam such that the intermediate portion of the beam cyclically bends in opposite directions in a pure bending condition.

  17. Meibomian gland dysfunction.

    PubMed

    Driver, P J; Lemp, M A

    1996-01-01

    Blepharitis is probably the most common disease entity seen in the general ophthalmologist's office. A significant proportion of these cases are secondary to meibomian gland disease. This review outlines our knowledge of the histopathology, lipid abnormalities and role of microorganisms in meibomian gland dysfunction. We will also review the physiology of meibomian gland secretion and present models of meibomian gland dysfunction which have enhanced our knowledge of this condition. The importance of diagnosing associated conditions such as aqueous tear deficiency, contact lens intolerance, rosacea, and seborrheic dermatitis is emphasized. Although this condition causes significant morbidity in the population, there are effective treatments available and these will be discussed.

  18. Fatigue monitoring in Nuclear Power Plants

    SciTech Connect

    Ware, A.G.; Shah, V.N.

    1995-04-01

    This paper summarizes fatigue monitoring methods and surveys their application in the nuclear power industry. The paper is based on a review of the technical literature. Two main reasons for fatigue monitoring are more frequent occurrence of some transients than that assumed in the fatigue design analysis and the discovery of stressors that were not included in the fatigue design analysis but may cause significant fatigue damage at some locations. One fatigue monitoring method involves use of plant operating data and procedures to update the fatigue usage. Another method involves monitoring of plant operating parameters using existing, or if needed, supplementary plant instrumentation for online computation of fatigue usage. Use of fatigue monitoring has better defined the operational transients. Most operational transients have been found less severe and fewer in numbers than anticipated in the design fatigue analysis. Use of fatigue monitoring has assisted in quantifying newly discovered stressors and has helped in detecting the presence of thermal stratification of unsuspected locations.

  19. Bearing fatigue investigation 3

    NASA Technical Reports Server (NTRS)

    Nahm, A. H.; Bamberger, E. N.; Signer, H. R.

    1982-01-01

    The operating characteristics of large diameter rolling-element bearings in the ultra high speed regimes expected in advanced turbine engines for high performance aircraft were investigated. A high temperature lubricant, DuPont Krytox 143 AC, was evaluated at bearing speeds to 3 million DN. Compared to the results of earlier, similar tests using a MIL-L-23699 (Type II) lubricant, bearings lubricated with the high density Krytox fluid showed significantly higher power requirements. Additionally, short bearing lives were observed when this fluid was used with AISI M50 bearings in an air atmosphere. The primary mode of failure was corrosion initiated surface distress (fatigue) on the raceways. The potential of a case-carburized bearing to sustain a combination of high-tangential and hertzian stresses without experiencing race fracture was also investigated. Limited full scale bearing tests of a 120 mm bore ball bearing at a speed of 25,000 rpm (3 million DN) indicated that a carburized material could sustain spalling fatigue without subsequent propagation to fracture. Planned life tests of the carburized material had to be aborted, however, because of apparent processing-induced material defects.

  20. Chronic fatigue syndrome

    PubMed Central

    2008-01-01

    Introduction Chronic fatigue syndrome (CFS) affects between 0.006% and 3% of the population depending on the criteria of definition used, with women being at higher risk than men. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for chronic fatigue syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2007 (BMJ Clinical evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 45 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antidepressants, cognitive behavioural therapy (CBT), corticosteroids, dietary supplements, evening primrose oil, galantamine, graded exercise therapy, homeopathy, immunotherapy, intramuscular magnesium, oral nicotinamide adenine dinucleotide, and prolonged rest. PMID:19445810

  1. Metal fatigue detector

    SciTech Connect

    Veaux, R.C. de la.

    1993-08-24

    A device is described for detecting fatigue of a monitored structure due to flexure, said monitored structure being made of a predetermined material and said device comprising: a substantially flat integral fuse made of said predetermined material and having edges and a plurality of differently configured cut out portions between the edges and defining fuse elements there between designed to fail because of fatigue prior to failure of said monitored structure when said fuse and said monitored structure both experience thee same stress history; means forming parallel elongated slots extending from the cut out portions to one edge to define legs associated with the fuse elements; adhesive means securing said fuse to said monitored structure and extending over at least 75 % of the area of the side of said fuse that is adjacent to said monitored structure but being spaced apart from said fuse elements; whereby said adhesive means ensure that said fuse and said monitored structure are subjected to substantially the same stress history in both tension and compression yet does not inhibit failure of said fuse elements.

  2. Mitochondrial Dysfunction in Cancer

    PubMed Central

    Boland, Michelle L.; Chourasia, Aparajita H.; Macleod, Kay F.

    2013-01-01

    A mechanistic understanding of how mitochondrial dysfunction contributes to cell growth and tumorigenesis is emerging beyond Warburg as an area of research that is under-explored in terms of its significance for clinical management of cancer. Work discussed in this review focuses less on the Warburg effect and more on mitochondria and how dysfunctional mitochondria modulate cell cycle, gene expression, metabolism, cell viability, and other established aspects of cell growth and stress responses. There is increasing evidence that key oncogenes and tumor suppressors modulate mitochondrial dynamics through important signaling pathways and that mitochondrial mass and function vary between tumors and individuals but the significance of these events for cancer are not fully appreciated. We explore the interplay between key molecules involved in mitochondrial fission and fusion and in apoptosis, as well as in mitophagy, biogenesis, and spatial dynamics of mitochondria and consider how these distinct mechanisms are coordinated in response to physiological stresses such as hypoxia and nutrient deprivation. Importantly, we examine how deregulation of these processes in cancer has knock on effects for cell proliferation and growth. We define major forms of mitochondrial dysfunction and address the extent to which the functional consequences of such dysfunction can be determined and exploited for cancer diagnosis and treatment. PMID:24350057

  3. Perceptual-Motor Dysfunction.

    ERIC Educational Resources Information Center

    Pyfer, Jean L.

    Discussed are theoretical and treatment aspects of perceptual motor dysfunction and rehabilitation in 4- to 12-year-old academically failing children involved in a 3-year investigation at the University of Kansas. The program is said to stress increasing the amount of stimulation received by sensory receptors of the vestibular, reflex, and haptic…

  4. Shared Parenting Dysfunction.

    ERIC Educational Resources Information Center

    Turkat, Ira Daniel

    2002-01-01

    Joint custody of children is the most prevalent court ordered arrangement for families of divorce. A growing body of literature indicates that many parents engage in behaviors that are incompatible with shared parenting. This article provides specific criteria for a definition of the Shared Parenting Dysfunction. Clinical aspects of the phenomenon…

  5. Echinoderm immunity.

    PubMed

    Smith, L Courtney; Ghosh, Julie; Buckley, Katherine M; Clow, Lori A; Dheilly, Nolwenn M; Haug, Tor; Henson, John H; Li, Chun; Lun, Cheng Man; Majeske, Audrey J; Matranga, Valeria; Nair, Sham V; Rast, Jonathan P; Raftos, David A; Roth, Mattias; Sacchi, Sandro; Schrankel, Catherine S; Stensvåg, Klara

    2010-01-01

    A survey for immune genes in the genome for the purple sea urchin has shown that the immune system is complex and sophisticated. By inference, immune responses of all echinoderms maybe similar. The immune system is mediated by several types of coelomocytes that are also useful as sensors of environmental stresses. There are a number of large gene families in the purple sea urchin genome that function in immunity and of which at least one appears to employ novel approaches for sequence diversification. Echinoderms have a simpler complement system, a large set of lectin genes and a number of antimicrobial peptides. Profiling the immune genes expressed by coelomocytes and the proteins in the coelomic fluid provide detailed information about immune functions in the sea urchin. The importance of echinoderms in maintaining marine ecosystem stability and the disastrous effects of their removal due to disease will require future collaborations between ecologists and immunologists working towards understanding and preserving marine habitats. PMID:21528703

  6. Understanding and Managing Erectile Dysfunction in Patients Treated for Cancer.

    PubMed

    Annam, Kiran; Voznesensky, Maria; Kreder, Karl J

    2016-04-01

    Cancer can cause sexual adverse effects by direct and indirect pathways. It can involve sexual organs, indirectly affect body image, or cause fatigue or depression with subsequent effects on libido. Erectile dysfunction (ED), the inability to obtain or maintain an erection firm enough for sexual intercourse, can also result from adverse effects of cancer treatment, such as fatigue, pain, or anxiety about therapy. In addition, depressed feelings about having cancer can affect sexuality, causing a range of signs and symptoms that can lead to ED. Chemotherapy, hormone therapy, surgery, and radiation can all cause sexual adverse effects. Additional factors that play a role include patient age and degree of ED before starting cancer treatment. In this article, we discuss how chemotherapy, hormone therapy, surgery, and radiation affect erectile function as well as possible treatment options for ED. PMID:27072383

  7. 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

  8. Programs For Predicting Fatigue And Creep-Fatigue Resistances

    NASA Technical Reports Server (NTRS)

    Saltsman, J. F.

    1994-01-01

    TS-SRP/PACK set of computer programs for characterizing and predicting fatigue and creep-fatigue resistances of metallic materials under isothermal and nonisothermal fatigue conditions in high-temperature, long-life regime. Programs implement total-strain version of strainrange-partitioning (TS-SRP) method. User should be thoroughly familiar with TS-SRP method before attempting to use any of these programs. Five programs included along with alloy data base. Four programs written in FORTRAN 77. One written in BASIC version 3.0.

  9. 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.

  10. Development of the electrochemical fatigue sensor for evaluating fatigue damage

    SciTech Connect

    Li, Y.F.; Wang, J.; Wang, M.Z.; DeLuccia, J.; Laird, C.

    1999-07-01

    The Electrochemical Fatigue Sensor (EFS) is a device which operates by an electrochemical-mechanical interaction and which can sense the type and extent of fatigue damage both before and after crack initiation. It was initially explored through studies on soft metals. Here the authors report efforts to determine the ability of the device to read damage in hardened commercial alloys: 7075 aluminum alloy, 4130 steel and Ti-6Al-4V. They also demonstrate that the device, which uses an electrolytic medium, does not degrade the fatigue properties if care is used in electrolyte selection.

  11. 10 CFR 26.211 - Fatigue assessments.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Fatigue assessments. 26.211 Section 26.211 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Managing Fatigue § 26.211 Fatigue assessments. (a) Licensees shall ensure that fatigue assessments are conducted under the following conditions: (1) For cause....

  12. 10 CFR 26.211 - Fatigue assessments.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Fatigue assessments. 26.211 Section 26.211 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Managing Fatigue § 26.211 Fatigue assessments. (a) Licensees shall ensure that fatigue assessments are conducted under the following conditions: (1) For cause....

  13. 10 CFR 26.211 - Fatigue assessments.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Fatigue assessments. 26.211 Section 26.211 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Managing Fatigue § 26.211 Fatigue assessments. (a) Licensees shall ensure that fatigue assessments are conducted under the following conditions: (1) For cause....

  14. 10 CFR 26.211 - Fatigue assessments.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Fatigue assessments. 26.211 Section 26.211 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Managing Fatigue § 26.211 Fatigue assessments. (a) Licensees shall ensure that fatigue assessments are conducted under the following conditions: (1) For cause....

  15. Fatigue management in the workplace

    PubMed Central

    Sadeghniiat-Haghighi, Khosro; Yazdi, Zohreh

    2015-01-01

    Workers’ fatigue is a significant problem in modern industry, largely because of high demand jobs, long duty periods, disruption of circadian rhythms, and accumulative sleep debt that are common in many industries. Fatigue is the end result of integration of multiple factors such as time awake, time of day, and workload. Then, the full understanding of circadian biologic clock, dynamics of transient and cumulative sleep loss, and recovery is required for effective management of workplace fatigue. It can be more investigated in a new field of sleep medicine called occupational sleep medicine. Occupational sleep medicine is concerned with maintaining best productivity and safety in the industrial settings. The fatigue risk management system (FRMS) is a comprehensive approach that is based on applying scientific evidence of sleep knowledge to manage workers fatigue. It is developing rapidly in the highly safety demand jobs; especially truck drivers, pilots, and power plant workers. The objective of this review is to explain about fatigue in the workplace with emphasis on its association work performance and errors/accidents. Also, we discussed about different methods of fatigue measurement and management. PMID:26257477

  16. Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome.

    PubMed

    Buskila, D

    2000-03-01

    Fibromyalgia and widespread pain were common in Gulf War veterans with unexplained illness referred to a rheumatology clinic. Increased tenderness was demonstrated in the postmenstrual phase of the cycle compared with the intermenstrual phase in normally cycling women but not in users of oral contraceptives. Patients with fibromyalgia had high levels of symptoms that have been used to define silicone implant-associated syndrome. Tender points were found to be a common transient finding associated with acute infectious mononucleosis, but fibromyalgia was an unusual long-term outcome. The common association of fibromyalgia with other rheumatic and systemic illnesses was further explored. A preliminary study revealed a possible linkage of fibromyalgia to the HLA region. Patients with fibromyalgia were found to have an impaired ability to activate the hypothalamic pituitary portion of the hypothalamic pituitary adrenal axis as well as the sympathoadrenal system, leading to reduced corticotropin and epinephrine response to hypoglycemia. Much interest has been expressed in the literature on the possible role of autonomic dysfunction in the development or exacerbation of fatigue and other symptoms in chronic fatigue syndrome. Mycoplasma genus and mycoplasma fermentans were detected by polymerase chain reaction in patients with chronic fatigue syndrome. It was reported that myofascial temporomandibular disorder does not run in families. No major therapeutic trials in fibromyalgia, chronic fatigue syndrome, or myofascial pain syndrome were reported over the past year. The effectiveness of cognitive behavioral therapy and behavior therapy for chronic pain in adults was emphasized. A favorable outcome of fibromyalgia and chronic fatigue syndrome in children and adolescents was reported.

  17. What Is a Dysfunctional School?

    ERIC Educational Resources Information Center

    Bergman, M. M.

    2013-01-01

    Whether or not a school is dysfunctional depends largely on how dysfunctionality in schools is defined and measured. Dysfunctionality, as any construct, is subject to definition and interpretation, and it is thus always marked by perspectivism. But regardless of the definition games occasionally played by academics, some form of reality takes…

  18. 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

  19. Leriche Syndrome Presenting as Depression with Erectile Dysfunction

    PubMed Central

    Gautam, Priyanka; Saha, Rashmita

    2016-01-01

    Leriche syndrome results from thrombotic occlusion of the abdominal aorta immediately above the site of its bifurcation. Impotence in leriche syndrome is caused due to proximal obstruction, commonly involving isolated common iliac, internal iliac, internal pudendal or dorsalis penis artery. The symptoms of Leriche syndrome include intermittent and bilateral claudication, pallor, coldness and fatigue in lower extremities. Data regarding psychiatric morbidity in Leriche syndrome is unavailable. We hereby report the case of Leriche syndrome, presenting to psychiatry outpatient department with depressive disorder and erectile dysfunction (ED) with focus on dilemmas faced in the diagnosis and management in psychiatry. PMID:27134979

  20. The cone dysfunction syndromes

    PubMed Central

    Aboshiha, Jonathan; Dubis, Adam M; Hardcastle, Alison J; Michaelides, Michel

    2016-01-01

    The cone dysfunction syndromes are a heterogeneous group of inherited, predominantly stationary retinal disorders characterised by reduced central vision and varying degrees of colour vision abnormalities, nystagmus and photophobia. This review details the following conditions: complete and incomplete achromatopsia, blue-cone monochromatism, oligocone trichromacy, bradyopsia and Bornholm eye disease. We describe the clinical, psychophysical, electrophysiological and imaging findings that are characteristic to each condition in order to aid their accurate diagnosis, as well as highlight some classically held notions about these diseases that have come to be challenged over the recent years. The latest data regarding the genetic aetiology and pathological changes observed in the cone dysfunction syndromes are discussed, and, where relevant, translational avenues of research, including completed and anticipated interventional clinical trials, for some of the diseases described herein will be presented. Finally, we briefly review the current management of these disorders. PMID:25770143

  1. [Erectile and Ejaculatory Dysfunction].

    PubMed

    Gross, Oliver; Sulser, Tullio; Eberli, Daniel

    2015-11-25

    The inability to achieve an erection of the penis sufficient for sexual activity is called erectile dysfunction (ED). In most cases, the diagnosis can be made by medical history. The prevalence of ED in men at the age of 65 has been reported to be up to 50%. Premature ejaculation has a prevalence, up to 20% and is the most frequent ejaculatory dysfunction. The etiology of ED can involve psychological, vascular, neurogenic, hormonal or urogenital pathologies. The main pathophysiological mechanisms of ED are vascular disorders such as diabetes mellitus and atherosclerosis. Because of the common pathophysiology, patients diagnosed with ED should have a diagnostic work-up for systemic vascular pathologies to prevent concomitant cardiac events. Treatment options include invasive and non-invasive procedures. PMID:26602851

  2. An Exposome Perspective on Environmental Enteric Dysfunction

    PubMed Central

    Mapesa, Job O.; Maxwell, Amy L.; Ryan, Elizabeth P.

    2015-01-01

    Background: Environmental exposures to chemicals have been shown to influence gastrointestinal function, yet little is known regarding whether chemical mixtures may be involved in the development of a subclinical enteric dysfunction found in infants and children born into poor hygiene and sanitation. Advances in gastrointestinal and immunotoxicology fields merit inclusion in complex discussions of environmental enteric dysfunction (EED) that severely affects children in developing countries. Objective: We aimed to highlight exposome approaches for investigating the potential influence of environmental chemical exposures on EED development, including a role for toxicant modulation of gut immune system and microbiome function. Discussion: A major focus on fecal–oral contamination in impoverished living conditions already exists for EED, and should now expand to include environmental chemicals such as pesticides and heavy metals that may be anthropogenic or dietary or from microbial sources. A comprehensive characterization of environmental chemical exposures prenatally and occurring in infants and young children will enhance our knowledge of any associated risks for EED and stunting. Conclusions: Integrating EED, chemical exposure, and stunting at various ages during childhood will enhance our apparent limited view when evaluating EED. Etiology and intervention studies should evaluate the suite of environmental chemical exposures as candidates in the composite of EED biomarkers. Citation: Mapesa JO, Maxwell AL, Ryan EP. 2016. An exposome perspective on environmental enteric dysfunction. Environ Health Perspect 124:1121–1126; http://dx.doi.org/10.1289/ehp.1510459 PMID:26713888

  3. EEG dysfunction in geropsychiatry.

    PubMed

    van Sweden, B

    1987-07-01

    Electro-clinical correlations are reported in 200 elderly patients admitted to a psychiatric ward of a general hospital. Normal EEG characteristics were generally associated with functional psychiatric disorder. Abnormal EEG features correlated with organic brain syndromes (O.B.S.). The diagnostic and pathogenetic considerations and restrictions of EEG foci, intermittent rhythmic delta activity (Irda) and diffuse EEG slowing are discussed. The informative value of EEG dysfunction in geropsychiatry is emphasised.

  4. Sexual dysfunction in diabetes.

    PubMed

    Tamás, Várkonyi; Kempler, Peter

    2014-01-01

    We aimed to summarize the etiology, clinical characteristics, diagnosis, and possible treatment options of sexual dysfunction in diabetic patients of both sexes. Details of dysfunction in diabetic women are less conclusive than in men due to the lack of standardized evaluation of sexual function in women. Male sexual dysfunction is a common complication of diabetes, including abnormalities of orgasmic/ejaculatory function and desire/libido in addition to penile erection. The prevalence of erectile dysfunction (ED) among diabetic men varies from 35% to 75%. Diabetes-induced ED has a multifactorial etiology including metabolic, neurologic, vascular, hormonal, and psychological components. ED should be regarded as the first sign of cardiovascular disease because it can be present before development of symptomatic coronary artery disease, as larger coronary vessels better tolerate the same amount of plaque compared to smaller penile arteries. The diagnosis of ED is based on validated questionnaires and determination of functional and organic abnormalities. First-, second- and third-line therapy may be applied. Phosphodiesterase-5 (PDE-5) inhibitor treatment from the first-line options leads to smooth muscle relaxation in the corpus cavernosum and enhancement in blood flow, resulting in erection during sexual stimulus. The use of PDE-5 inhibitors in the presence of oral nitrates is strictly contraindicated in diabetic men, as in nondiabetic subjects. All PDE-5 inhibitors have been evaluated for ED in diabetic patients with convincing efficacy data. Second-line therapy includes intracavernosal, trans- or intraurethral administration of vasoactive drugs or application of a vacuum device. Third-line therapies are the implantation of penile prosthesis and penile revascularization. PMID:25410225

  5. [Gonadotrophic axis dysfunction in men with HIV-infection/aids].

    PubMed

    Ponte, Clarisse Mourão Melo; Gurgel, Maria Helane Costa; Montenegro, Renan Magalhães

    2009-11-01

    Gonadotrophic axis dysfunction is commonly observed in HIV-infected patients. The pathogenesis is multifactorial and related to duration of HIV infection, direct cytopathic effects of viruses, use of drugs, opportunistic infections, malignancies, and malnutrition, among other factors. In men, reduced levels of testosterone is associated with loss of muscle mass and strength, decreased bone mineral density, lipodystrophy, depression, asthenia, fatigue and sexual dysfunction. In HIV-infected patients with hypogonadism, numerous studies have shown the beneficial effects of testosterone replacement on the metabolic profile and distribution of body fat, with increased body mass weight, and promote better quality of life, reduce the bone mass loss and the rates of depression. Thus, this review aimed to present a brief update of epidemiologic data, pathophysiology aspects and treatment strategies for the major abnormalities of male gonadotrophic axis associated with HIV infection and its treatment.

  6. Mitochondrial dysfunction in inflammatory bowel disease

    PubMed Central

    Novak, Elizabeth A.; Mollen, Kevin P.

    2015-01-01

    Inflammatory Bowel Disease (IBD) represents a group of idiopathic disorders characterized by chronic or recurring inflammation of the gastrointestinal tract. While the exact etiology of disease is unknown, IBD is recognized to be a complex, multifactorial disease that results from an intricate interplay of genetic predisposition, an altered immune response, changes in the intestinal microbiota, and environmental factors. Together, these contribute to a destruction of the intestinal epithelial barrier, increased gut permeability, and an influx of immune cells. Given that most cellular functions as well as maintenance of the epithelial barrier is energy-dependent, it is logical to assume that mitochondrial dysfunction may play a key role in both the onset and recurrence of disease. Indeed several studies have demonstrated evidence of mitochondrial stress and alterations in mitochondrial function within the intestinal epithelium of patients with IBD and mice undergoing experimental colitis. Although the hallmarks of mitochondrial dysfunction, including oxidative stress and impaired ATP production are known to be evident in the intestines of patients with IBD, it is as yet unclear whether these processes occur as a cause of consequence of disease. We provide a current review of mitochondrial function in the setting of intestinal inflammation during IBD. PMID:26484345

  7. Thyroid dysfunction and subfertility.

    PubMed

    Cho, Moon Kyoung

    2015-12-01

    The thyroid hormones act on nearly every cell in the body. Moreover, the thyroid gland continuously interacts with the ovaries, and the thyroid hormones are involved in almost all phases of reproduction. Thyroid dysfunctions are relatively common among women of reproductive age, and can affect fertility in various ways, resulting in anovulatory cycles, high prolactin levels, and sex hormone imbalances. Undiagnosed and untreated thyroid disease can be a cause of subfertility. Subclinical hypothyroidism (SCH), also known as mild thyroid failure, is diagnosed when peripheral thyroid hormone levels are within the normal reference laboratory range, but serum thyroid-stimulating hormone levels are mildly elevated. Thyroid autoimmunity (TAI) is characterized by the presence of anti-thyroid antibodies, which include anti-thyroperoxidase and anti-thyroglobulin antibodies. SCH and TAI may remain latent, asymptomatic, or even undiagnosed for an extended period. It has also been demonstrated that controlled ovarian hyperstimulation has a significant impact on thyroid function, particularly in women with TAI. In the current review, we describe the interactions between thyroid dysfunctions and subfertility, as well as the proper work-up and management of thyroid dysfunctions in subfertile women. PMID:26816871

  8. Thyroid dysfunction and subfertility

    PubMed Central

    2015-01-01

    The thyroid hormones act on nearly every cell in the body. Moreover, the thyroid gland continuously interacts with the ovaries, and the thyroid hormones are involved in almost all phases of reproduction. Thyroid dysfunctions are relatively common among women of reproductive age, and can affect fertility in various ways, resulting in anovulatory cycles, high prolactin levels, and sex hormone imbalances. Undiagnosed and untreated thyroid disease can be a cause of subfertility. Subclinical hypothyroidism (SCH), also known as mild thyroid failure, is diagnosed when peripheral thyroid hormone levels are within the normal reference laboratory range, but serum thyroid-stimulating hormone levels are mildly elevated. Thyroid autoimmunity (TAI) is characterized by the presence of anti-thyroid antibodies, which include anti-thyroperoxidase and anti-thyroglobulin antibodies. SCH and TAI may remain latent, asymptomatic, or even undiagnosed for an extended period. It has also been demonstrated that controlled ovarian hyperstimulation has a significant impact on thyroid function, particularly in women with TAI. In the current review, we describe the interactions between thyroid dysfunctions and subfertility, as well as the proper work-up and management of thyroid dysfunctions in subfertile women. PMID:26816871

  9. Current treatments to counter sleep dysfunction as a pathogenic stimulus of fibromyalgia.

    PubMed

    Choy, Ernest H

    2016-05-01

    Fibromyalgia is characterized by chronic widespread pain, fatigue and nonrestorative sleep. Polysomnography showed reduced short-wave sleep and abnormal alpha rhythms during nonrapid eye movement sleep in patients with fibromyalgia. However, sleep dysfunction might be pathogenic in fibromyalgia since myalgia and fatigue could be induced in healthy individuals by disrupting sleep. Poor sleep quality was a major risk factor for the subsequent development of chronic widespread pain in healthy pain-free individuals. Sleep disruption leads to impairment of the descending pain inhibition pathways. Aside from good sleep, hygiene, exercise can promote sleep. Among currently available pharmacological treatments, evidence suggests amitriptyline and pregabalin can improve sleep in fibromyalgia. PMID:27312978

  10. Coping with cancer - managing fatigue

    MedlinePlus

    ... cause fatigue. Simply having cancer can drain your energy: Some cancers release proteins called cytokines that can ... tumors can change the way your body uses energy and leave you feeling tired. Many cancer treatments ...

  11. Fatigue Fighters in Sjogren's Syndrome

    MedlinePlus

    ... Work with your doctor to find a specific cause and treatment for your fatigue. The possibilities may include systemic inflammation, poor sleep, fibromyalgia, depression, hypothyroidism, muscle inflammation or side-effects of medications. Know ...

  12. Fatigue of internal combustion engines

    NASA Technical Reports Server (NTRS)

    Dumanois, P

    1924-01-01

    The above conditions enable the employment of a criterion of general fatigue which simultaneously takes account of both mechanical and thermal conditions, for the sake of comparing any projected engine with engines of the same type already in use.

  13. Pilot Fatigue and Circadian Desynchronosis

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Pilot fatigue and circadian desynchronosis, its significance to air transport safety, and research approaches, were examined. There is a need for better data on sleep, activity, and other pertinent factors from pilots flying a variety of demanding schedules. Simulation studies of flight crew performance should be utilized to determine the degree of fatigue induced by demanding schedules and to delineate more precisely the factors responsible for performance decrements in flight and to test solutions proposed to resolve problems induced by fatigue and desynchronosis. It was concluded that there is a safety problem of uncertain magnitude due to transmeridian flying and a potential problem due to fatigue associated with various factors found in air transport operations.

  14. Human herpesvirus 6 and 7 are biomarkers for fatigue, which distinguish between physiological fatigue and pathological fatigue.

    PubMed

    Aoki, Ryo; Kobayashi, Nobuyuki; Suzuki, Go; Kuratsune, Hirohiko; Shimada, Kazuya; Oka, Naomi; Takahashi, Mayumi; Yamadera, Wataru; Iwashita, Masayuki; Tokuno, Shinichi; Nibuya, Masashi; Tanichi, Masaaki; Mukai, Yasuo; Mitani, Keiji; Kondo, Kazuhiro; Ito, Hiroshi; Nakayama, Kazuhiko

    2016-09-01

    Fatigue reduces productivity and is a risk factor for lifestyle diseases and mental disorders. Everyone experiences physiological fatigue and recovers with rest. Pathological fatigue, however, greatly reduces quality of life and requires therapeutic interventions. It is therefore necessary to distinguish between the two but there has been no biomarker for this. We report on the measurement of salivary human herpesvirus (HHV-) 6 and HHV-7 as biomarkers for quantifying physiological fatigue. They increased with military training and work and rapidly decreased with rest. Our results suggested that macrophage activation and differentiation were necessary for virus reactivation. However, HHV-6 and HHV-7 did not increase in obstructive sleep apnea syndrome (OSAS), chronic fatigue syndrome (CFS) and major depressive disorder (MDD), which are thought to cause pathological fatigue. Thus, HHV-6 and HHV-7 would be useful biomarkers for distinguishing between physiological and pathological fatigue. Our findings suggest a fundamentally new approach to evaluating fatigue and preventing fatigue-related diseases. PMID:27396623

  15. Threshold fatigue and information transfer

    PubMed Central

    Lindner, Benjamin; Longtin, André

    2016-01-01

    Neurons in vivo must process sensory information in the presence of significant noise. It is thus plausible to assume that neural systems have developed mechanisms to reduce this noise. Theoretical studies have shown that threshold fatigue (i.e. cumulative increases in the threshold during repetitive firing) could lead to noise reduction at certain frequencies bands and thus improved signal transmission as well as noise increases and decreased signal transmission at other frequencies: a phenomenon called noise shaping. There is, however, no experimental evidence that threshold fatigue actually occurs and, if so, that it will actually lead to noise shaping. We analyzed action potential threshold variability in intracellular recordings in vivo from pyramidal neurons in weakly electric fish and found experimental evidence for threshold fatigue: an increase in instantaneous firing rate was on average accompanied by an increase in action potential threshold. We show that, with a minor modification, the standard Hodgkin–Huxley model can reproduce this phenomenon. We next compared the performance of models with and without threshold fatigue. Our results show that threshold fatigue will lead to a more regular spike train as well as robustness to intrinsic noise via noise shaping. We finally show that the increased/reduced noise levels due to threshold fatigue correspond to decreased/increased information transmission at different frequencies. PMID:17436067

  16. Associations between fatigue attributions and fatigue, health, and psychosocial work characteristics: a study among employees visiting a physician with fatigue

    PubMed Central

    Andrea, H; Kant, I.; Beurskens, A; Metsemakers, J; van Schayck, C P

    2003-01-01

    Aims: To study associations between characteristics of employees active at work and making a fatigue related visit to the general practitioner (GP) or occupational physician (OP) in terms of fatigue, physical health problems, mental health problems, psychosocial work characteristics, and attributions of their fatigue complaints. Methods: Self report questionnaires from the Maastricht Cohort Study Fatigue at Work were used to measure fatigue (Checklist Individual Strength, Maslach Burnout Inventory–General Survey), physical health problems (chronic illness), mental health problems (Hospital Anxiety and Depression Scale), psychosocial work characteristics (Job Content Questionnaire), and fatigue attributions (somatic, psychological, none) in employees who made a fatigue related visit to the GP or OP over a six month period. Results: In employees visiting only the GP, fatigue was an important reason to visit in one of seven (13.9%) employees. These fatigue related visits were in particular associated with high fatigue levels and mental health problems. A psychological fatigue attribution was reported by 41.8%, a somatic fatigue attribution by 44.0%. On a multivariate level, mental health problems showed the strongest association with psychological fatigue attributions, over and beyond fatigue itself. No associations were found between fatigue attributions and psychosocial work characteristics. Attributional patterns appeared to be different between visitors of the GP and the OP. Conclusions: Fatigue is a common reason among employees to consult a GP. Asking employees for their own fatigue attributions in terms of somatic or psychological causes may be useful for the GP—and possibly also the OP—to gather information about underlying health problems in employees active at work and making a fatigue related visit. PMID:12782755

  17. Immune System

    EPA Science Inventory

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  18. Subcritical crack-growth behavior of borosilicate glass under cyclic loads: Evidence of a mechanical fatigue effect

    SciTech Connect

    Dill, S.J.; Dauskardt, R.H.; Bennison, S.J.

    1997-03-01

    Amorphous glasses are generally considered immune to mechanical fatigue effects associated with cyclic loading. In this study surprising new evidence is presented for a mechanical fatigue effect in borosilicate glass, in both moist air and dry nitrogen environments. The fatigue effect occurs at near threshold subcritical crack-growth rates (da/dt < 3 {times} 10{sup {minus}8} m/s) as the crack extension per cycle approaches the dimensions of the borosilicate glass network. While subcritical crack growth under cyclic loads at higher load levels is entirely consistent with environmentally assisted crack growth, lower growth rates actually exceed those measured under monotonic loads. This suggests a mechanical fatigue effect which accelerates subcritical crack-growth rates. Likely mechanisms for the mechanical fatigue effect are presented.

  19. Maternal immunization

    PubMed Central

    Moniz, Michelle H; Beigi, Richard H

    2014-01-01

    Maternal immunization holds tremendous promise to improve maternal and neonatal health for a number of infectious conditions. The unique susceptibilities of pregnant women to infectious conditions, as well as the ability of maternally-derived antibody to offer vital neonatal protection (via placental transfer), together have produced the recent increased attention on maternal immunization. The Advisory Committee on Immunization Practices (ACIP) currently recommends 2 immunizations for all pregnant women lacking contraindication, inactivated Influenza and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap). Given ongoing research the number of vaccines recommended during pregnancy is likely to increase. Thus, achieving high vaccination coverage of pregnant women for all recommended immunizations is a key public health enterprise. This review will focus on the present state of vaccine acceptance in pregnancy, with attention to currently identified barriers and determinants of vaccine acceptance. Additionally, opportunities for improvement will be considered. PMID:25483490

  20. Piezomagnetism and fatigue

    NASA Astrophysics Data System (ADS)

    Erber, T.; Guralnick, S. A.; Desai, R. D.; Kwok, W.

    1997-10-01

    Piezomagnetism refers to a change in the intrinsic magnetization of a material subjected to mechanical actions such as tension or compression. In a ferromagnet such as a mild steel these effects are easily measured: typically a stress of 0022-3727/30/20/008/img6 or 140 MPa induces a magnetic moment of the order of 0022-3727/30/20/008/img7 emu or 0022-3727/30/20/008/img8, resulting in flux densities in the range 10 mG or 0022-3727/30/20/008/img9T in the vicinity of the specimen. Since piezomagnetic effects are due to interactions between the mechanical and magnetic mesostructure of materials microplastic processes that alter the arrangement of the ferromagnetic domain structure affect the intensity of the associated magnetic fields. The progressive degradation of such materials under cyclic loading can therefore be tracked by following the evolution of the piezomagnetic field. Specifically, if the measurements are displayed as loci in a three-dimensional stress 0022-3727/30/20/008/img10 - strain 0022-3727/30/20/008/img11 - field (B) space, the approach to fatigue failure is paralleled by a series of conspicuous geometric transformations of these curves. Complementary information also appears in continuous-time records of B(t): these magnetograms clearly show the abrupt incidence of `infarcts' (microcracks) and the cumulation of phase shifts as the material degrades.

  1. Low-cycle fatigue of TiNi shape memory alloy and formulation of fatigue life

    SciTech Connect

    Tobushi, Hisaaki; Nakahara, Takafumi; Shimeno, Yoshirou; Hashimoto, Takahiro

    2000-04-01

    The low-cycle fatigue of a TiNi shape memory alloy was investigated by the rotating-bending fatigue tests in air, in water and in silicone oil. (1) The influence of corrosion fatigue in water does not appear in the region of low-cycle fatigue. (2) The temperature rise measured through an infrared thermograph during the fatigue test in air is four times as large as that measured through a thermocouple. (3) The fatigue life at an elevated temperature in air coincides with the fatigue life at the same elevated temperature in water. (4) The shape memory processing temperature does not affect the fatigue life. (5) The fatigue equation is proposed to describe the fatigue life depending on strain amplitude, temperature and frequency. The fatigue life is estimated well by the proposed equation.

  2. Fatigue in multiple sclerosis is associated with abnormal cortical activation to voluntary movement--EEG evidence.

    PubMed

    Leocani, L; Colombo, B; Magnani, G; Martinelli-Boneschi, F; Cursi, M; Rossi, P; Martinelli, V; Comi, G

    2001-06-01

    Converging evidence is consistent with the view that fatigue in Multiple Sclerosis is independent from pyramidal tract involvement, suggesting a possible involvement of frontal areas. During voluntary movement, changes of the EEG rhythms can be observed over sensorimotor areas. Event-related desynchronization (ERD) of the 10 and 20 Hz frequency bands occurs during motor planning and execution and is followed after movement termination by event-related synchronization (ERS), expressing cortical idling or inhibition. We evaluated the pattern of cortical activation to voluntary movement in MS patients complaining of fatigue assessed using the Fatigue Severity Scale. Fifteen MS patients complaining of fatigue, 18 MS patients without fatigue, and 14 normal controls were studied. The two patients groups were similar for age, sex, disease duration, and were not disabled (score <1.5 at the Expanded Disability Status Scale). Twenty-nine channel EEG was recorded during about 60 self-paced extensions of the right thumb. The onset latency and amount of the contralateral sensorimotor (C3 electrode) 10 and 18--22 Hz ERD were similar in the three groups. ERD was more widespread anteriorly in the fatigue group compared with normal controls (P < 0.01 over Fz electrode). Postmovement contralateral sensorimotor 18--22 Hz ERS was significantly lower in fatigue MS patients compared with normal subjects (P < 0.005) and with nonfatigue MS patients (P = 0.02). These findings are consistent with a central origin of fatigue in MS and indicate cortical dysfunction even during a simple motor task, resulting in hyperactivity during movement execution and failure of the inhibitory mechanisms intervening after movement termination. PMID:11352624

  3. Sleep complaints and fatigue of airline pilots.

    PubMed

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

    2016-01-01

    This work aimed to determine daytime sleepiness and sleep complaints prevalence and the corresponding influence on perceived fatigue and to evaluate the influence of sociodemographic parameters and labour variables on sleep complaints, sleepiness and fatigue. A questionnaire was developed including socio-economic and labour issues and instruments, focused in sleep and fatigue. The response rate was 32% and the final sample had 435 pilots. The prevalence of sleep complaints was 34.9%, daytime sleepiness 59.3% and fatigue 90.6%. The high prevalence of sleep complaints, sleepiness and fatigue was disclosed in pilots, with those who fly short/medium having an added risk of fatigue. PMID:27656269

  4. Sleep complaints and fatigue of airline pilots.

    PubMed

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

    2016-01-01

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

  5. [Somatic comorbidities in irritable bowel syndrome: fibromyalgia, chronic fatigue syndrome, and interstitial cystitis].

    PubMed

    Mathieu, N

    2009-02-01

    Fibromyalgia, chronic fatigue syndrome, and interstitial cystitis frequently overlap with irritable bowel syndrome (IBS). There is a positive correlation between the incidence of these comorbidities and increased health care seeking, reduction in quality of life, and higher levels of mood disorders, which raises the question of a common underlying pathophysiology. A possible central hypersensitization disorder seems to be particularly involved in the dysfunction of bidirectional neural pathways and viscerovisceral cross-interactions within the CNS, thus explaining these many extraintestinal manifestations in IBS.

  6. Respiratory and limb muscle dysfunction in pulmonary arterial hypertension: a role for exercise training?

    PubMed

    Panagiotou, Marios; Peacock, Andrew J; Johnson, Martin K

    2015-09-01

    Respiratory and limb muscle dysfunction is emerging as an important pathophysiological abnormality in pulmonary arterial hypertension (PAH). Muscle abnormalities appear to occur frequently and promote dyspnea, fatigue, and exercise limitation in patients with PAH. Preliminary data suggest that targeted muscle training may be of benefit, although further evidence is required to consolidate these findings into specific recommendations for exercise training in patients with PAH. This article reviews the current evidence on prevalence, risk factors, and implications of respiratory and limb muscle dysfunction in patients with PAH. It also reviews the impact of exercise rehabilitation on morphologic, metabolic, and functional muscle profile and outcomes in PAH. Future research priorities are highlighted.

  7. Fixed belief in cognitive dysfunction despite normal neuropsychological scores: neurocognitive hypochondriasis?

    PubMed

    Boone, Kyle Brauer

    2009-08-01

    A subset of patients who present for neuropsychological testing report dysfunction in daily life activities secondary to cognitive deficits, but are found on formal testing to have no objective abnormalities, raising the possibility of "neurocognitive hypochondriasis." Such a case is presented, and the factors that appear to give rise to this presentation are explored. Cases of hypochondriacal overconcern regarding cognitive function are likely not rare, particularly given research showing there is little correlation between objective report of cognitive dysfunction and actual test scores in such conditions as mild traumatic brain injury, chronic fatigue syndrome, fibromyalgia, toxic mold exposure, and post-polio syndrome. PMID:18923966

  8. Respiratory and limb muscle dysfunction in pulmonary arterial hypertension: a role for exercise training?

    PubMed Central

    2015-01-01

    Abstract Respiratory and limb muscle dysfunction is emerging as an important pathophysiological abnormality in pulmonary arterial hypertension (PAH). Muscle abnormalities appear to occur frequently and promote dyspnea, fatigue, and exercise limitation in patients with PAH. Preliminary data suggest that targeted muscle training may be of benefit, although further evidence is required to consolidate these findings into specific recommendations for exercise training in patients with PAH. This article reviews the current evidence on prevalence, risk factors, and implications of respiratory and limb muscle dysfunction in patients with PAH. It also reviews the impact of exercise rehabilitation on morphologic, metabolic, and functional muscle profile and outcomes in PAH. Future research priorities are highlighted. PMID:26401245

  9. [Epilepsy with higher brain dysfunction].

    PubMed

    Sugimoto, Azusa; Midorikawa, Akira; Koyama, Shinichi; Futamura, Akinori; Kuroda, Takeshi; Fujita, Kazuhisa; Itaya, Kazuhiro; Ishigaki, Seiichiro; Kawamura, Mitsuru

    2013-02-01

    Acquired higher brain dysfunction is for the most part due to cerebral vascular disease, but epilepsy may also be a cause. In this study with five patients, we discuss the advantages of anti-epileptic drugs (AEDs) for persistent higher brain dysfunction. The patients showed chronic amnesia or acute aphasia, with associated symptoms like personality change. All five cases affected automatism or convulsive attack, though only after the emergence of higher brain dysfunction and administration of AEDs. There were underlying diseases like cerebral arteriovenous malformation in four cases, but the other patient had none. Electroencephalogram and single photon emission computed tomography revealed one case of aphasia epilepsy with higher brain dysfunction. These results suggest the potential therapeutic efficacy of AEDs for persistent higher brain dysfunction, and we must differentiate epilepsy with higher brain dysfunction from dementia or cerebral vascular disease. PMID:23399676

  10. Animal models of erectile dysfunction.

    PubMed

    Kapoor, Mandeep Singh; Khan, Samsroz Ahmad; Gupta, Sanjay Kumar; Choudhary, Rajesh; Bodakhe, Surendra H

    2015-01-01

    Erectile dysfunction (ED) is a prevalent male sexual dysfunction with profound adverse effects on the physical and the psychosocial health of men and, subsequently, on their partners. The expanded use of various types of rodent models has produced some advances in the study of ED, and neurophysiological studies using various animal models have provided important insights into human sexual dysfunction. At present, animal models play a key role in exploring and screening novel drugs designed to treat ED.

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

    PubMed

    Bansal, Amolak S

    2016-01-01

    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. PMID:27436349

  12. Female sexual dysfunction.

    PubMed

    Aslan, Erdogan; Fynes, Michelle

    2008-02-01

    Female sexual dysfunction is a common problem with detrimental effects on woman's quality of life. It also has an economical and societal impact. It is defined as disorders of sexual desire, arousal, orgasm, and sexual pain, which lead to personal distress. The etiology of sexual dysfunction is frequently multifactorial as it relates to general physical and mental well-being, quality of relationship, past sexual functioning, social class, education, employment, life stressors, personality factors, the presence of a sexual partner, and partner's age and health. It is very important to adopt the most efficient approach to gather information, and this may be achieved via standardized questionnaires or open-ended questions. Therapy should be tailored according to the patient's needs and may involve a multidisciplinary team approach including psychosexual counselor/sexologist/therapist and the physician. There is still more work needed to optimize the care of women with this problem. Priority should be given to international standardization and training of health care professionals.

  13. Fatigue as it Affects Nursing.

    PubMed

    2016-08-01

    : Editor's note: From its first issue in 1900 through to the present day, AJN has unparalleled archives detailing nurses' work and lives over more than a century. These articles not only chronicle nursing's growth as a profession within the context of the events of the day, but they also reveal prevailing societal attitudes about women, health care, and human rights. Today's nursing school curricula rarely include nursing's history, but it's a history worth knowing. To this end, From the AJN Archives highlights articles selected to fit today's topics and times.In this month's article from the January 1935 issue, Lillian M. Gilbreth, a highly respected psychologist and industrial engineer, examines the problem of fatigue in nursing. A nonnurse expert, Gilbreth notes the negative effects of fatigue on skills, a problem "enormously more serious when the product of the work is human comfort and sometimes even human life, as it often is with the work of the nurse." In their article in this issue, "Health Care Worker Fatigue," Lea Anne Gardner and Deborah Dubeck of the Pennsylvania Patient Safety Authority share examples of fatigue-related adverse events and discuss the need for both personal and institutional fatigue risk management strategies. PMID:27466935

  14. Olfactory dysfunction in Alzheimer's disease.

    PubMed

    Zou, Yong-Ming; Lu, Da; Liu, Li-Ping; Zhang, Hui-Hong; Zhou, Yu-Ying

    2016-01-01

    Alzheimer's disease (AD) is a common neurodegenerative disorder with the earliest clinical symptom of olfactory dysfunction, which is a potential clinical marker for AD severity and progression. However, many questions remain unanswered. This article reviews relevant research on olfactory dysfunction in AD and evaluates the predictive value of olfactory dysfunction for the epidemiological, pathophysiological, and clinical features of AD, as well as for the conversion of cognitive impairment to AD. We summarize problems of existing studies and provide a useful reference for further studies in AD olfactory dysfunction and for clinical applications of olfactory testing. PMID:27143888

  15. HIV-1 infection, microenvironment and endothelial cell dysfunction.

    PubMed

    Mazzuca, Pietro; Caruso, Arnaldo; Caccuri, Francesca

    2016-09-01

    HIV-1 promotes a generalized immune activation that involves the main targets of HIV-1 infection but also cells that are not sensitive to viral infection. ECs display major dysfunctions in HIV+ patients during long-standing viral infection that persist even in the current cART era, in which new-generation drugs have reduced dysmetabolic side effects and successfully impeded viral replication. In vivo studies have failed to demonstrate the presence of replicating virus in ECs suggesting that a direct role of the virus is unlikely, and implying that the mechanism accounting for vascular dysfunction may rely on the indirect action of molecules released in the microenvironment by HIV-1-infected cells. This article reviews the current understanding of how HIV-1 infection can contribute to vascular dysfunction. In particular, we discuss the emerging role played by different HIV-1 proteins in driving inflammation and EC dysregulation, and highlight the need to target them for therapeutic benefit. PMID:27602413

  16. Ischemia causes muscle fatigue

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

    The purpose of this investigation was to determine whether ischemia, which reduces oxygenation in the extensor carpi radialis (ECR) muscle, causes a reduction in muscle force production. In eight subjects, muscle oxygenation (TO2) of the right ECR was measured noninvasively and continuously using near infrared spectroscopy (NIRS) while muscle twitch force was elicited by transcutaneous electrical stimulation (1 Hz, 0.1 ms). Baseline measurements of blood volume, muscle oxygenation and twitch force were recorded continuously, then a tourniquet on the upper arm was inflated to one of five different pressure levels: 20, 40, 60 mm Hg (randomized order) and diastolic (69 +/- 9.8 mm Hg) and systolic (106 +/- 12.8 mm Hg) blood pressures. Each pressure level was maintained for 3-5 min, and was followed by a recovery period sufficient to allow measurements to return to baseline. For each respective tourniquet pressure level, mean TO2 decreased from resting baseline (100% TO2) to 99 +/- 1.2% (SEM), 96 +/- 1.9%, 93 +/- 2.8%, 90 +/- 2.5%, and 86 +/- 2.7%, and mean twitch force decreased from resting baseline (100% force) to 99 +/- 0.7% (SEM), 96 +/- 2.7%, 93 +/- 3.1%, 88 +/- 3.2%, and 86 +/- 2.6%. Muscle oxygenation and twitch force at 60 mm Hg tourniquet compression and above were significantly lower (P < 0.05) than baseline value. Reduced twitch force was correlated in a dose-dependent manner with reduced muscle oxygenation (r = 0.78, P < 0.001). Although the correlation does not prove causation, the results indicate that ischemia leading to a 7% or greater reduction in muscle oxygenation causes decreased muscle force production in the forearm extensor muscle. Thus, ischemia associated with a modest decline in TO2 causes muscle fatigue.

  17. Defeating feature fatigue.

    PubMed

    Rust, Roland T; Thompson, Debora Viana; Hamilton, Rebecca W

    2006-02-01

    Consider a coffeemaker that offers 12 drink options, a car with more than 700 features on the dashboard, and a mouse pad that's also a clock, calculator, and FM radio. All are examples of "feature bloat", or "featuritis", the result of an almost irresistible temptation to load products with lots of bells and whistles. The problem is that the more features a product boasts, the harder it is to use. Manufacturers that increase a product's capability--the number of useful functions it can perform--at the expense of its usability are exposing their customers to feature fatigue. The authors have conducted three studies to gain a better understanding of how consumers weigh a product's capability relative to its usability. They found that even though consumers know that products with more features are harder to use, they initially choose high-feature models. They also pile on more features when given the chance to customize a product for their needs. Once consumers have actually worked with a product, however, usability starts to matter more to them than capability. For managers in consumer products companies, these findings present a dilemma: Should they maximize initial sales by designing high-feature models, which consumers consistently choose, or should they limit the number of features in order to enhance the lifetime value of their customers? The authors' analytical model guides companies toward a happy middle ground: maximizing the net present value of the typical customer's profit stream. The authors also advise companies to build simpler products, help consumers learn which products suit their needs, develop products that do one thing very well, and design market research in which consumers use actual products or prototypes.

  18. Immunization Coverage

    MedlinePlus

    ... underused vaccines is increasing. Immunization currently averts an estimated 2 to 3 million deaths every year. An ... avoided, however, if global vaccination coverage improves. An estimated 19.4 million infants worldwide are still missing ...

  19. Adolescent immunization.

    PubMed

    Handal, G A

    2000-06-01

    The dramatic improvements achieved in the control of vaccine-preventable diseases in children have only been shared partially by adolescents and young adults, as today several million adolescents are not receiving the full complement of vaccines recommended by the Advisory Committee on Immunization Practices (ACIP). This article discusses the reasons for this problem and the tools to bridge this gap. In particular, medical societies and the Centers for Disease Control and Prevention (CDC) recommend a close assessment of the adolescentís immunization status between 11 and 12 years of age, inclusion of school immunization, and providing missing immunizations at any opportunity. The article also addresses other vaccines recommended for groups of adolescents with special needs, reporting information, and provides an update on the vaccines of the future.

  20. Neuroendocrine dysfunction in Sjogren's syndrome.

    PubMed

    Tzioufas, Athanasios G; Tsonis, John; Moutsopoulos, Haralampos M

    2008-01-01

    Interactions among the immune, nervous and endocrine systems, which are mediated by hormones, neuropeptides, neurotransmitters, cytokines and their receptors, appear to play an important role in modulating host susceptibility and resistance to inflammatory disease. The neuroendocrine system has two main components: the central and the peripheral. The central compartment is located in the locus ceruleus, the brainstem centers of the autonomic system and the paraventricular nucleus; the peripheral mainly consists of the sympathetic/adrenomedullary system, the hypothalamic-pituitary-adrenal axis (HPA), the hypothalamic-pituitary-gonadal (HPG) axis, and the neuroendocrine tissue located in several organs throughout the body. Hormones and neuropeptides may influence the activities of lymphoid organs and cells via endocrine and local autocrine/paracrine pathways or alter the function of different cell types in target organs. Recent studies highlighted alterations of the neuroendocrine system in systemic autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus and Sjogren's syndrome (SS). SS, a prototype autoimmune disorder, has a wide clinical spectrum, extending from organ involvement (autoimmune exocrinopathy) to systemic disease and B cell lymphoma. In SS, several functions of the neuroendocrine system are impaired. First, the HPA axis appears to be disturbed, since significantly lower basal ACTH and cortisol levels were found in patients with SS and were associated with a blunted pituitary and adrenal response to ovine corticotropin-releasing factor compared to normal controls. Second, HPG axis is also involved, since lack of estrogens is associated with human disease and the development of autoimmune exocrinopathy in several experimental models. Finally, exocrine glands are enriched with neuroendocrine-related molecules, adjacent to local autoimmune lesions. Certain clinical manifestations of the disease, including the sicca manifestations

  1. The analysis of fatigue crack growth mechanism and oxidation and fatigue life at elevated temperatures

    NASA Technical Reports Server (NTRS)

    Liu, H. W.

    1988-01-01

    Two quantitative models based on experimentally observed fatigue damage processes have been made: (1) a model of low cycle fatigue life based on fatigue crack growth under general-yielding cyclic loading; and (2) a model of accelerated fatigue crack growth at elevated temperatures based on grain boundary oxidation. These two quantitative models agree very well with the experimental observations.

  2. Fatigue life of laser cut metals

    NASA Technical Reports Server (NTRS)

    Martin, M. R.

    1986-01-01

    Fatigue tests were conducted to determine the actual reduction in fatigue life due to weight removal for balancing by: hand grinding, low power (20 watt) Nd:glass laser, and high power (400 watt) Nd:YAG laser.

  3. High Speed Research Program Sonic Fatigue

    NASA Technical Reports Server (NTRS)

    Rizzi, Stephen A. (Technical Monitor); Beier, Theodor H.; Heaton, Paul

    2005-01-01

    The objective of this sonic fatigue summary is to provide major findings and technical results of studies, initiated in 1994, to assess sonic fatigue behavior of structure that is being considered for the High Speed Civil Transport (HSCT). High Speed Research (HSR) program objectives in the area of sonic fatigue were to predict inlet, exhaust and boundary layer acoustic loads; measure high cycle fatigue data for materials developed during the HSR program; develop advanced sonic fatigue calculation methods to reduce required conservatism in airframe designs; develop damping techniques for sonic fatigue reduction where weight effective; develop wing and fuselage sonic fatigue design requirements; and perform sonic fatigue analyses on HSCT structural concepts to provide guidance to design teams. All goals were partially achieved, but none were completed due to the premature conclusion of the HSR program. A summary of major program findings and recommendations for continued effort are included in the report.

  4. 14 CFR 23.627 - Fatigue strength.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Fatigue strength. The structure must be designed, as far as practicable, to avoid points of stress concentration where variable stresses above the fatigue limit are likely to occur in normal service....

  5. 14 CFR 23.627 - Fatigue strength.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Fatigue strength. The structure must be designed, as far as practicable, to avoid points of stress concentration where variable stresses above the fatigue limit are likely to occur in normal service....

  6. 14 CFR 23.627 - Fatigue strength.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Fatigue strength. The structure must be designed, as far as practicable, to avoid points of stress concentration where variable stresses above the fatigue limit are likely to occur in normal service....

  7. 14 CFR 23.627 - Fatigue strength.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Fatigue strength. The structure must be designed, as far as practicable, to avoid points of stress concentration where variable stresses above the fatigue limit are likely to occur in normal service....

  8. 14 CFR 23.627 - Fatigue strength.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Fatigue strength. The structure must be designed, as far as practicable, to avoid points of stress concentration where variable stresses above the fatigue limit are likely to occur in normal service....

  9. 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

  10. Investigations concerning cavitation and frost fatigue in clonal 84K poplar using high-resolution cavitron measurements.

    PubMed

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

    2015-05-01

    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.

  11. Fatigue of bovine trabecular bone.

    PubMed

    Moore, Tara L; Gibson, Lorna J

    2003-12-01

    Fatigue loading of bone, from the activities of daily living in the elderly, or from prolonged exercise in the young, can lead to increased risk of fracture. Elderly patients with osteoporosis are particularly prone to fragility fractures of the vertebrae, where load is carried primarily by trabecular bone. In this study, specimens of bovine trabecular bone were loaded in compressive fatigue at four different normalized stresses to one of six maximum strains. The resulting change in modulus and residual strain accumulation were measured over the life of the fatigue test. The number of cycles to reach a given maximum compressive strain increased with decreasing normalized stress. Modulus reduction and specimen residual strain increased with increasing maximum compressive strain, but few differences were observed between specimens loaded to the same maximum strain at different normalized stresses.

  12. Neuromuscular fatigue in racquet sports.

    PubMed

    Girard, Olivier; Millet, Grégoire P

    2008-02-01

    This article describes the physiologic and neural mechanisms that cause neuromuscular fatigue in racquet sports: table tennis, tennis, squash, and badminton. In these intermittent and dual activities, performance may be limited as a match progresses because of a reduced central activation, linked to changes in neurotransmitter concentration or in response to afferent sensory feedback. Alternatively, modulation of spinal loop properties may occur because of changes in metabolic or mechanical properties within the muscle. Finally, increased fatigue manifested by mistimed strokes, lower speed, and altered on-court movements may be caused by ionic disturbances and impairments in excitation-contraction coupling properties. These alterations in neuromuscular function contribute to decrease in racquet sports performance observed under fatigue.

  13. Peridynamic model for fatigue cracking.

    SciTech Connect

    Silling, Stewart Andrew; Abe Askari

    2014-10-01

    The peridynamic theory is an extension of traditional solid mechanics in which the field equations can be applied on discontinuities, such as growing cracks. This paper proposes a bond damage model within peridynamics to treat the nucleation and growth of cracks due to cyclic loading. Bond damage occurs according to the evolution of a variable called the "remaining life" of each bond that changes over time according to the cyclic strain in the bond. It is shown that the model reproduces the main features of S-N data for typical materials and also reproduces the Paris law for fatigue crack growth. Extensions of the model account for the effects of loading spectrum, fatigue limit, and variable load ratio. A three-dimensional example illustrates the nucleation and growth of a helical fatigue crack in the torsion of an aluminum alloy rod.

  14. Neuromuscular fatigue in racquet sports.

    PubMed

    Girard, Olivier; Millet, Grégoire P

    2009-02-01

    This article describes the physiologic and neural mechanisms that cause neuromuscular fatigue in racquet sports: table tennis, tennis, squash, and badminton. In these intermittent and dual activities, performance may be limited as a match progresses because of a reduced central activation, linked to changes in neurotransmitter concentration or in response to afferent sensory feedback. Alternatively, modulation of spinal loop properties may occur because of changes in metabolic or mechanical properties within the muscle. Finally, increased fatigue manifested by mistimed strokes, lower speed, and altered on-court movements may be caused by ionic disturbances and impairments in excitation-contraction coupling properties. These alterations in neuromuscular function contribute to decrease in racquet sports performance observed under fatigue.

  15. [Thyroid dysfunction in pregnancy].

    PubMed

    Führer, D; Mann, K; Feldkamp, J; Krude, H; Spitzweg, C; Kratzsch, J; Schott, M

    2014-10-01

    Thyroid dysfunction may impair fertility, course of pregnancy and fetal development. Physiological alterations of thyroid function parameters, that occur during pregnancy need to be distinguished from pathophysiological states of hypo- and hyperthyroidism. We performed a literature search (PubMed 1990-2013) and review relevant publications as well as consensus and practice guidelines of international thyroid/endocrine societies. Interpretation of thyroid function values in pregnancy must be based on trimester-specific TSH and T4 ranges. Alterations in thyroid function are present in up to 15% of pregnancies (0.4% overt hypothyroidism, 0.1-0.4% hyperthyroidism) and may lead to preventable complications in the pregnant woman and the fetus. Hypothyroidism is associated with an increased risk for abortion, premature delivery and stillbirth, besides impairment of neurocognitive development. The latter has also been shown in situations of grave iodine deficiency. In addition to new-born screening directed at early recognition of congenital hypothyroidism (incidence 0.03%), universal screening of all pregnant women should be implemented in health care guidelines. Newly diagnosed overt hypothyroidism in a pregnant woman requires immediate levothyroxine substitution at adequate doses. In subclinical hypothyroidism thyroid hormone replacement should be considered. Iodine supplementation is strongly recommended in all pregnant and breast-feeding women. Pregnancy causes a number of, that need to be of thyroid dysfunction. Both hypothyroidism and thyrotoxicosis may impair the course of pregnancy and may negatively affect the fetus. In particular, maternal hypothyroidism may lead to irreparable and detrimental deficits in the neurocognitive development of the fetus. Autoimmune thyroid disease is the most common cause of thyroid dysfunction in pregnancy. Hashimoto's thyroiditis is associated with impaired fertility and miscarriage, and may first manifest in pregnancy due to the

  16. 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

  17. Fatigue and Comorbidities in Multiple Sclerosis

    PubMed Central

    Fiest, Kirsten M.; Fisk, John D.; Patten, Scott B.; Tremlett, Helen; Wolfson, Christina; Warren, Sharon; McKay, Kyla A.; Berrigan, Lindsay I.

    2016-01-01

    Abstract Background: Fatigue is commonly reported by people with multiple sclerosis (MS). Comorbidity is also common in MS, but its association with the presence of fatigue or fatigue changes over time is poorly understood. Methods: Nine hundred forty-nine people with definite MS were recruited from four Canadian centers. The Fatigue Impact Scale for Daily Use and a validated comorbidity questionnaire were completed at three visits over 2 years. Participants were classified into groups with no fatigue versus any fatigue. Logistic regression was used to determine the relationship between fatigue and each comorbidity at baseline, year 1, year 2, and overall. Results: The incidence of fatigue during the study was 38.8%. The prevalence of fatigue was greater in those who were older (P = .0004), had a longer time since symptom onset (P = .005), and had greater disability (P < .0001). After adjustment, depression (odds ratio [OR], 2.58; 95% confidence interval [CI], 2.03–3.27), irritable bowel syndrome (OR, 1.71; 95% CI, 1.18–2.48), migraine (OR, 1.69; 95% CI, 1.27–2.27), and anxiety (OR, 1.57; 95% CI, 1.15–2.16) were independently associated with fatigue that persisted during the study. There was also an individual-level effect of depression on worsening fatigue (OR, 1.49; 95% CI, 1.08–2.07). Conclusions: Comorbidity is associated with fatigue in MS. Depression is associated with fatigue and with increased risk of worsening fatigue over 2 years. However, other comorbid conditions commonly associated with MS are also associated with persistent fatigue, even after accounting for depression. Further investigation is required to understand the mechanisms by which comorbidities influence fatigue. PMID:27134583

  18. Fatigue and related factors after liver transplantation

    PubMed Central

    Hong, Kwangpyo; Kim, Hyeyoung; Lee, Jeong-Moo; Lee, Kwang-Woong; Yi, Nam-Joon; Lee, Hae Won; Choi, YoungRok; Suh, Suk-Won; Hong, Suk Kyun; Yoon, Kyung Chul; Kim, Hyo-Sin

    2015-01-01

    Backgrounds/Aims Fatigue is common in chronic hepatitis and end-stage liver disease. However, little is known about fatigue after liver transplantation (LT). We therefore evaluated the prevalence, severity, and related factors of fatigue after LT. Methods We retrospectively reviewed adult recipients who responded to our survey at outpatient clinics between April and May 2013. Fatigue and its severity were assessed using a questionnaire with the Fatigue Severity Scale (FSS). We defined fatigue as FSS of 4.0 or more and severe fatigue as FSS of 5.1 or more. The related factors including hepatocellular carcinoma and complications were analyzed. Results A total of 93 patients were included in this study. The mean age was 54.9 (19-76) years and two-thirds were men (67.7%). Living donor LT was 77.4%. Hepatitis B related liver disease was the main underlying disease (77.4%), with hepatocellular carcinoma accompanied in 33.3%. The mean follow-up period was 66.8±43.2 (2-171) months. The mean FFS was 2.83±1.48 (1.0-6.7) overall and 5.10±0.82 (4.0-6.7) in the fatigue group. Of the 93 adult patients, fatigue was presented in 20 patients (21.5%). Among these, 9 patients (45.0%) showed severe fatigue. Even though post-LT complications tended to be greater in the fatigue group (50.0% vs. 30.1% in the non-fatigue group, p=0.098), there were no significant related factors of fatigue after LT, including hepatocellular carcinoma and major complication. Conclusions Fatigue is present in a considerable portion of recipients after LT, and almost half of them have severe fatigue. Further efforts are needed to decrease fatigue in LT recipients. PMID:26693233

  19. [Revisiting meibomian gland dysfunction].

    PubMed

    Baudouin, C

    2014-12-01

    Meibomian gland dysfunctions (MGD) are frequent affections, sometimes asymptomatic, more often responsible for disabling, potentially severe, manifestations. MGD is indeed the most frequent cause of dry eye, through the induction of tear film instability. However, eyelid inflammation, microbial proliferation that modifies melting temperature of meibum, frequent association with skin diseases, as well as potentially severe corneal complications make them complex multifactorial disorders. Complementary mechanisms combine to actually result in a vicious circle, or more accurately a double vicious cycle. The first one is self-stimulated by the microbiological changes, which create their own conditions for MGD development. The second one is related to tear film instability that results from MGD and is also self-stimulated through hyperosmolarity and inflammatory phenomena, which are both consequence and cause of dry eye. We herein propose a new pathophysiological schema on MGD, in order to better identify mechanisms and more efficiently target therapeutics.

  20. Investigation of erectile dysfunction.

    PubMed

    Patel, D V; Halls, J; Patel, U

    2012-11-01

    Erectile dysfunction (ED) represents a common and debilitating condition with a wide range of organic and non-organic causes. Physical aetiologies can be divided into disorders affecting arterial inflow, the venous occlusion mechanism or the penile structure itself. Various imaging modalities can be utilised to investigate the physical causes of ED, but penile Doppler sonography (PDS) is the most informative technique, indicated in those patients with ED who do not respond to oral pharmacological agents (e.g. phosphodiesterase type 5 inhibitors). This review will examine the anatomical and physiological basis of penile erection, the method for performing PDS and features of specific causes of ED, and will also consider the alternative imaging modalities available.

  1. Telomere dysfunction and chromothripsis.

    PubMed

    Ernst, Aurélie; Jones, David T W; Maass, Kendra K; Rode, Agata; Deeg, Katharina I; Jebaraj, Billy Michael Chelliah; Korshunov, Andrey; Hovestadt, Volker; Tainsky, Michael A; Pajtler, Kristian W; Bender, Sebastian; Brabetz, Sebastian; Gröbner, Susanne; Kool, Marcel; Devens, Frauke; Edelmann, Jennifer; Zhang, Cindy; Castelo-Branco, Pedro; Tabori, Uri; Malkin, David; Rippe, Karsten; Stilgenbauer, Stephan; Pfister, Stefan M; Zapatka, Marc; Lichter, Peter

    2016-06-15

    Chromothripsis is a recently discovered form of genomic instability, characterized by tens to hundreds of clustered DNA rearrangements resulting from a single dramatic event. Telomere dysfunction has been suggested to play a role in the initiation of this phenomenon, which occurs in a large number of tumor entities. Here, we show that telomere attrition can indeed lead to catastrophic genomic events, and that telomere patterns differ between cells analyzed before and after such genomic catastrophes. Telomere length and telomere stabilization mechanisms diverge between samples with and without chromothripsis in a given tumor subtype. Longitudinal analyses of the evolution of chromothriptic patterns identify either stable patterns between matched primary and relapsed tumors, or loss of the chromothriptic clone in the relapsed specimen. The absence of additional chromothriptic events occurring between the initial tumor and the relapsed tumor sample points to telomere stabilization after the initial chromothriptic event which prevents further shattering of the genome. PMID:26856307

  2. [Revisiting meibomian gland dysfunction].

    PubMed

    Baudouin, C

    2014-12-01

    Meibomian gland dysfunctions (MGD) are frequent affections, sometimes asymptomatic, more often responsible for disabling, potentially severe, manifestations. MGD is indeed the most frequent cause of dry eye, through the induction of tear film instability. However, eyelid inflammation, microbial proliferation that modifies melting temperature of meibum, frequent association with skin diseases, as well as potentially severe corneal complications make them complex multifactorial disorders. Complementary mechanisms combine to actually result in a vicious circle, or more accurately a double vicious cycle. The first one is self-stimulated by the microbiological changes, which create their own conditions for MGD development. The second one is related to tear film instability that results from MGD and is also self-stimulated through hyperosmolarity and inflammatory phenomena, which are both consequence and cause of dry eye. We herein propose a new pathophysiological schema on MGD, in order to better identify mechanisms and more efficiently target therapeutics. PMID:25455142

  3. 10 CFR 26.211 - Fatigue assessments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Fatigue assessments. 26.211 Section 26.211 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Managing Fatigue § 26.211 Fatigue assessments. (a) Licensees... addition to any other test or determination of fitness that may be required under §§ 26.31(c) and 26.77,...

  4. Endothelins & erectile dysfunction.

    PubMed

    Ritchie, Robert; Sullivan, Mark

    2011-06-01

    Erectile dysfunction (ED) is common and a significant contributor to poor quality of life and psychosocial morbidity in men. Normal erectile function requires effective co-ordination between a number of complex neural pathways. Penile tumescence occurs in response to rapid arterial inflow to the corpora cavernosa with simultaneous venous outflow restriction due to expansion of the lacunar spaces. This process is under both central and local neuromediation. Endothelins are potent vasoconstrictor peptides that cause strong, slowly developing but sustained contraction of trabecular smooth muscles cells of the corpora cavernosa. Multiple mechanisms of action are proposed, including transmembrane calcium flux, mobilisation of inositol triphosphate sensitive intracellular calcium stores and calcium sensitisation through the Rho-Rho kinase pathway. The exact role of endothelins in the pathogenesis of ED currently remains unclear. Elevated endothelin-1 levels are found in patients with diabetes mellitus and this alone may be sufficient to cause ED. However, this is not borne out in clinical studies. The resultant elevated intracellular calcium may, however, modulate gene expression sufficiently to cause smooth muscle proliferation. Alternatively, alterations in endothelin receptor sensitivity in conditions such as diabetes and hypertension may enhance vasoconstrictor processes. Currently there is contradictory evidence for the role of endothelin receptor antagonists in ED. Animals studies suggest they inhibit corporal vasoconstriction, improve erectile function and protect against diabetes-induced smooth muscle apoptosis. However, the results of clinical studies in ED have been less promising. Uncertainty regarding the exact role of endothelin in penile erection hampers progress in this area. It is possible that the endothelin system may only be relevant to ED in certain conditions where global endothelial dysfunction exists (e.g. diabetes mellitus, systemic sclerosis) and

  5. Cognitive dysfunction in pediatric multiple sclerosis

    PubMed Central

    Suppiej, Agnese; Cainelli, Elisa

    2014-01-01

    Cognitive and neuropsychological impairments are well documented in adult multiple sclerosis (MS). Research has only recently focused on cognitive disabilities in pediatric cases, highlighting some differences between pediatric and adult cases. Impairments in several functions have been reported in children, particularly in relation to attention, processing speed, visual–motor skills, and language. Language seems to be particularly vulnerable in pediatric MS, unlike in adults in whom it is usually preserved. Deficits in executive functions, which are considered MS-specific in adults, have been inconsistently reported in children. In children, as compared to adults, the relationship between cognitive dysfunctions and the two other main symptoms of MS, fatigue and psychiatric disorders, was poorly explored. Furthermore, data on the correlations of cognitive impairments with clinical and neuroimaging features are scarce in children, and the results are often incongruent; interestingly, involvement of corpus callosum and reduced thalamic volume differentiated patients identified as having a cognitive impairment from those without a cognitive impairment. Further studies about pediatric MS are needed in order to better understand the impact of the disease on brain development and the resulting effect on cognitive functions, particularly with respect to different therapeutic strategies. PMID:25092984

  6. Bladder Dysfunction and Vesicoureteral Reflux

    PubMed Central

    Sillén, Ulla

    2008-01-01

    In this overview the influence of functional bladder disturbances and of its treatment on the resolution of vesicoureteral reflux (VUR) in children is discussed. Historically both bladder dysfunction entities, the overactive bladder (OAB) and the dysfunctional voiding (DV), have been described in conjunction with VUR. Treatment of the dysfunction was also considered to influence spontaneous resolution in a positive way. During the last decades, however, papers have been published which could not support these results. Regarding the OAB, a prospective study with treatment of the bladder overactivity with anticholinergics, did not influence spontaneous resolution rate in children with a dysfunction including also the voiding phase, DV and DES (dysfunctional elimination syndrome), most studies indicate a negative influence on the resolution rate of VUR in children, both before and after the age for bladder control, both with and without treatment. However, a couple of uncontrolled studies indicate that there is a high short-term resolution rate after treatment with flow biofeedback. It should be emphasized that the voiding phase dysfunctions (DV and DES) are more severe than the genuine filling phase dysfunction (OAB), with an increased frequency of UTI and renal damage in the former groups. To be able to answer the question if treatment of bladder dysfunction influence the resolution rate of VUR in children, randomized controlled studies must be performed. PMID:19009037

  7. Immune Mechanisms in Arterial Hypertension.

    PubMed

    Wenzel, Ulrich; Turner, Jan Eric; Krebs, Christian; Kurts, Christian; Harrison, David G; Ehmke, Heimo

    2016-03-01

    Traditionally, arterial hypertension and subsequent end-organ damage have been attributed to hemodynamic factors, but increasing evidence indicates that inflammation also contributes to the deleterious consequences of this disease. The immune system has evolved to prevent invasion of foreign organisms and to promote tissue healing after injury. However, this beneficial activity comes at a cost of collateral damage when the immune system overreacts to internal injury, such as prehypertension. Renal inflammation results in injury and impaired urinary sodium excretion, and vascular inflammation leads to endothelial dysfunction, increased vascular resistance, and arterial remodeling and stiffening. Notably, modulation of the immune response can reduce the severity of BP elevation and hypertensive end-organ damage in several animal models. Indeed, recent studies have improved our understanding of how the immune response affects the pathogenesis of arterial hypertension, but the remarkable advances in basic immunology made during the last few years still await translation to the field of hypertension. This review briefly summarizes recent advances in immunity and hypertension as well as hypertensive end-organ damage.

  8. Adipose tissue immunity and cancer.

    PubMed

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

    2013-10-02

    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.

  9. Dysfunctional stress responses in chronic pain.

    PubMed

    Woda, Alain; Picard, Pascale; Dutheil, Frédéric

    2016-09-01

    Many dysfunctional and chronic pain conditions overlap. This review describes the different modes of chronic deregulation of the adaptive response to stress which may be a common factor for these conditions. Several types of dysfunction can be identified within the hypothalamo-pituitary-adrenal axis: basal hypercortisolism, hyper-reactivity, basal hypocortisolism and hypo-reactivity. Neuroactive steroid synthesis is another component of the adaptive response to stress. Dehydroepiandrosterone (DHEA) and its sulfated form DHEA-S, and progesterone and its derivatives are synthetized in cutaneous, nervous, and adipose cells. They are neuroactive factors that act locally. They may have a role in the localization of the symptoms and their levels can vary both in the central nervous system and in the periphery. Persistent changes in neuroactive steroid levels or precursors can induce localized neurodegeneration. The autonomic nervous system is another component of the stress response. Its dysfunction in chronic stress responses can be expressed by decreased basal parasympathethic activity, increased basal sympathetic activity or sympathetic hyporeactivity to a stressful stimulus. The immune and genetic systems also participate. The helper-T cells Th1 secrete pro-inflammatory cytokines such as IL-1-β, IL-2, IL-6, IL-8, IL-12, IFN-γ, and TNF-α, whereas Th2 secrete anti-inflammatory cytokines: IL-4, IL-10, IGF-10, IL-13. Chronic deregulation of the Th1/Th2 balance can occur in favor of anti- or pro-inflammatory direction, locally or systemically. Individual vulnerability to stress can be due to environmental factors but can also be genetically influenced. Genetic polymorphisms and epigenetics are the main keys to understanding the influence of genetics on the response of individuals to constraints. PMID:27262345

  10. [Cytokines, endothelial dysfunction, and insulin resistance].

    PubMed

    de Carvalho, Maria Helena C; Colaço, André Luiz; Fortes, Zuleica Bruno

    2006-04-01

    Endothelial dysfunction is associated with several vascular conditions as atherosclerosis, hypertension, hyperlipidemia and diabetes mellitus. In all these conditions insulin resistance (IR) is present. Cytokines are low molecular weight proteins with several endocrine and metabolic functions that participate of inflammation and immune response. Several of these cytokines are independent risk factors for cerebrovascular and coronary artery disease. The major sources of cytokines (adipokines) are the visceral and subcutaneous adipose tissues. Thus, increased adipose tissue mass is associated with alteration in adipokine production as over expression of tumor necrosis factor alpha, interleukin 6, plasminogen activator inhibitor 1, and under expression of adiponectin in adipocite tissue. The pro-inflammatory status associated with these changes provides a potential link between IR and endothelial dysfunction, the early stage in the atherosclerotic process, in obese individuals, and type 2 diabetic patients. Reduction of adipose tissue mass through weight reduction in association with exercise reduces TNF-alpha, IL-6, and PAI-1, increases adiponectin, and is associated with improved insulin sensitivity and endothelial function. This review will focus on the evidence for regulation of endothelial function by insulin and the adypokines such as adyponectin, leptin, resistin, IL-6 and TNF-alpha. Interaction between insulin signaling and adypokines will be discussed, as well as the concept that aberrant adypokine secretion in IR and/or obesity impairs endothelial function and contributes further to reduce insulin sensitivity.

  11. Telomere dysfunction causes alveolar stem cell failure.

    PubMed

    Alder, Jonathan K; Barkauskas, Christina E; Limjunyawong, Nathachit; Stanley, Susan E; Kembou, Frant; Tuder, Rubin M; Hogan, Brigid L M; Mitzner, Wayne; Armanios, Mary

    2015-04-21

    Telomere syndromes have their most common manifestation in lung disease that is recognized as idiopathic pulmonary fibrosis and emphysema. In both conditions, there is loss of alveolar integrity, but the underlying mechanisms are not known. We tested the capacity of alveolar epithelial and stromal cells from mice with short telomeres to support alveolar organoid colony formation and found that type 2 alveolar epithelial cells (AEC2s), the stem cell-containing population, were limiting. When telomere dysfunction was induced in adult AEC2s by conditional deletion of the shelterin component telomeric repeat-binding factor 2, cells survived but remained dormant and showed all the hallmarks of cellular senescence. Telomere dysfunction in AEC2s triggered an immune response, and this was associated with AEC2-derived up-regulation of cytokine signaling pathways that are known to provoke inflammation in the lung. Mice uniformly died after challenge with bleomycin, underscoring an essential role for telomere function in AEC2s for alveolar repair. Our data show that alveoloar progenitor senescence is sufficient to recapitulate the regenerative defects, inflammatory responses, and susceptibility to injury that are characteristic of telomere-mediated lung disease. They suggest alveolar stem cell failure is a driver of telomere-mediated lung disease and that efforts to reverse it may be clinically beneficial. PMID:25840590

  12. A new quantitative indicator of visual fatigue

    NASA Technical Reports Server (NTRS)

    Goussard, Yves; Martin, Bernard; Stark, Lawrence

    1987-01-01

    Ocular-motor correlates of visual fatigue have remained elusive. Performance of ocular-motor tracking with a wide-band white noise input and the response of the dual-mode, smooth pursuit-saccadic eye movement system as output was used to test visual fatigue. A new visual fatigue indicator, VFI, was defined as the nonlinear remnant after subtracting an identified impulse response contribution to the output. Subjects were required to perform very fatiguing CRT screen reading tasks, and the VFI correlated well with the subjective reports of visual fatigue.

  13. FATIGUE OF BIOMATERIALS: HARD TISSUES.

    PubMed

    Arola, D; Bajaj, D; Ivancik, J; Majd, H; Zhang, D

    2010-09-01

    The fatigue and fracture behavior of hard tissues are topics of considerable interest today. This special group of organic materials comprises the highly mineralized and load-bearing tissues of the human body, and includes bone, cementum, dentin and enamel. An understanding of their fatigue behavior and the influence of loading conditions and physiological factors (e.g. aging and disease) on the mechanisms of degradation are essential for achieving lifelong health. But there is much more to this topic than the immediate medical issues. There are many challenges to characterizing the fatigue behavior of hard tissues, much of which is attributed to size constraints and the complexity of their microstructure. The relative importance of the constituents on the type and distribution of defects, rate of coalescence, and their contributions to the initiation and growth of cracks, are formidable topics that have not reached maturity. Hard tissues also provide a medium for learning and a source of inspiration in the design of new microstructures for engineering materials. This article briefly reviews fatigue of hard tissues with shared emphasis on current understanding, the challenges and the unanswered questions.

  14. "Holocaust Fatigue" in Teaching Today

    ERIC Educational Resources Information Center

    Schweber, Simone

    2006-01-01

    In this article, the author discusses the problems faced by educators in teaching about the Holocaust. She relates that because the Holocaust is now frequently taught in middle schools and in upper elementary grades, by the time it is taught in high schools, students will experience "Holocaust fatigue." As such, teachers face the challenge of…

  15. TV fatigue crack monitoring system

    NASA Technical Reports Server (NTRS)

    Exton, R. J. (Inventor)

    1977-01-01

    An apparatus is disclosed for monitoring the development and growth of fatigue cracks in a test specimen subjected to a pulsating tensile load. A plurality of television cameras photograph a test specimen which is illuminated at the point of maximum tensile stress. The television cameras have a modified vidicon tube which has an increased persistence time thereby eliminating flicker in the displayed images.

  16. FATIGUE OF BIOMATERIALS: HARD TISSUES

    PubMed Central

    Arola, D.; Bajaj, D.; Ivancik, J.; Majd, H.; Zhang, D.

    2009-01-01

    The fatigue and fracture behavior of hard tissues are topics of considerable interest today. This special group of organic materials comprises the highly mineralized and load-bearing tissues of the human body, and includes bone, cementum, dentin and enamel. An understanding of their fatigue behavior and the influence of loading conditions and physiological factors (e.g. aging and disease) on the mechanisms of degradation are essential for achieving lifelong health. But there is much more to this topic than the immediate medical issues. There are many challenges to characterizing the fatigue behavior of hard tissues, much of which is attributed to size constraints and the complexity of their microstructure. The relative importance of the constituents on the type and distribution of defects, rate of coalescence, and their contributions to the initiation and growth of cracks, are formidable topics that have not reached maturity. Hard tissues also provide a medium for learning and a source of inspiration in the design of new microstructures for engineering materials. This article briefly reviews fatigue of hard tissues with shared emphasis on current understanding, the challenges and the unanswered questions. PMID:20563239

  17. Sexual dysfunction in rheumatoid arthritis: a hot but sensitive issue.

    PubMed

    Palmer, Deborah; El Miedany, Yasser

    Rheumatoid arthritis (RA) has considerable personal impact for sufferers and their families. Those with RA suffer from pain, restricted joint movements, and fatigue, and can have problems with self-esteem and body image. It is also possible that medication causes sexual problems. Research on the subject is limited, and shows a divergent picture. Assessment for sexual dysfunction in clinical practice might be another hurdle, as patients and health professionals are reluctant to discuss this issue face to face. The aim of the work carried out and described in this article was to study the possibility of implementing sexual dysfunction assessment into standard rheumatology clinical practice. Results revealed that the multidimensional patient-reported outcome measures questionnaire offered the opportunity to assess the disease activity parameters, functional disability, quality of life, sexual dysfunction, and self-helplessness in one format. The patients appeared willing to complete questionnaires and this may be an acceptable tool for assessment. Improving patient education, as well as nurse-patient communication, through discussions about available options may minimize patients' feelings of isolation in addressing the problem and could help compensate for negative effects resulting from the disease. PMID:22067584

  18. Dynamic fatigue of feldspathic porcelain.

    PubMed

    Fairhurst, C W; Lockwood, P E; Ringle, R D; Twiggs, S W

    1993-07-01

    Several studies (Sherrill and O'Brien, 1974; Southan and Jørgensen, 1974; Jones, 1983) have shown that stress corrosion fatigue occurs in dental porcelains. Morena et al. (1986) reported on an assessment of slow crack growth parameters for dental ceramics. The purpose of the study reported here was to evaluate the fatigue parameters of a model experimental porcelain using dynamic fatigue testing. This test procedure makes use of several constant stressing rates to perform strength tests. Dynamic stress testing was first described by Evans (1974) and later defined as a distinct test modality by Ritter (1978). From such data, the fatigue parameters can be calculated. These fatigue parameters, n and sigma f0, are, respectively, the crack growth exponent from the crack velocity expression and a materials constant which is dependent on the test environment and the inert (moisture-free) strength. The model porcelain was made from 60% component 1 and 40% component 3 according to the Weinstein patent (Weinstein, et al., 1962). The biaxial flexure strength of 300 specimens 1 mm thick was tested in 37 degrees C water by testing 50 samples at each of 6 constant stressing rates: 100, 10, 1, 0.1, 0.01, and 0.001 MPa/s. One hundred specimens were tested in a moisture-free environment at 100 MPa/s using a servo-mechanical testing machine. A commercial porcelain (Jelenko Gingival-Lot # 2012, Jelenko Dental Health Products, Armonk, NY, USA) was chosen as a reference material. One hundred twenty specimens were tested using the same procedures as those used for the model porcelain; however, only 20 samples were tested for 5 stressing rate groups and an inert group.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Disease, dysfunction, and synthetic biology.

    PubMed

    Holm, Sune

    2014-08-01

    Theorists analyzing the concept of disease on the basis of the notion of dysfunction consider disease to be dysfunction requiring. More specifically, dysfunction-requiring theories of disease claim that for an individual to be diseased certain biological facts about it must be the case. Disease is not wholly a matter of evaluative attitudes. In this paper, I consider the dysfunction-requiring component of Wakefield's hybrid account of disease in light of the artifactual organisms envisioned by current research in synthetic biology. In particular, I argue that the possibility of artifactual organisms and the case of oncomice and other bred or genetically modified strains of organism constitute a significant objection to Wakefield's etiological account of the dysfunction requirement. I then develop a new alternative understanding of the dysfunction requirement that builds on the organizational theory of function. I conclude that my suggestion is superior to Wakefield's theory because it (a) can accommodate both artifactual and naturally evolved organisms, (b) avoids the possibility of there being a conflict between what an organismic part is supposed to do and the health of the organism, and (c) provides a nonarbitrary and practical way of determining whether dysfunction occurs.

  20. Understanding brain dysfunction in sepsis

    PubMed Central

    2013-01-01

    Sepsis often is characterized by an acute brain dysfunction, which is associated with increased morbidity and mortality. Its pathophysiology is highly complex, resulting from both inflammatory and noninflammatory processes, which may induce significant alterations in vulnerable areas of the brain. Important mechanisms include excessive microglial activation, impaired cerebral perfusion, blood–brain-barrier dysfunction, and altered neurotransmission. Systemic insults, such as prolonged inflammation, severe hypoxemia, and persistent hyperglycemia also may contribute to aggravate sepsis-induced brain dysfunction or injury. The diagnosis of brain dysfunction in sepsis relies essentially on neurological examination and neurological tests, such as EEG and neuroimaging. A brain MRI should be considered in case of persistent brain dysfunction after control of sepsis and exclusion of major confounding factors. Recent MRI studies suggest that septic shock can be associated with acute cerebrovascular lesions and white matter abnormalities. Currently, the management of brain dysfunction mainly consists of control of sepsis and prevention of all aggravating factors, including metabolic disturbances, drug overdoses, anticholinergic medications, withdrawal syndromes, and Wernicke’s encephalopathy. Modulation of microglial activation, prevention of blood–brain-barrier alterations, and use of antioxidants represent relevant therapeutic targets that may impact significantly on neurologic outcomes. In the future, investigations in patients with sepsis should be undertaken to reduce the duration of brain dysfunction and to study the impact of this reduction on important health outcomes, including functional and cognitive status in survivors. PMID:23718252

  1. The immune system in hypertension.

    PubMed

    Trott, Daniel W; Harrison, David G

    2014-03-01

    While hypertension has predominantly been attributed to perturbations of the vasculature, kidney, and central nervous system, research for almost 50 yr has shown that the immune system also contributes to this disease. Inflammatory cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension and likely contribute to end-organ damage. We and others have shown that mice lacking adaptive immune cells, including recombinase-activating gene-deficient mice and rats and mice with severe combined immunodeficiency have blunted hypertension to stimuli such as ANG II, high salt, and norepinephrine. Adoptive transfer of T cells restores the blood pressure response to these stimuli. Agonistic antibodies to the ANG II receptor, produced by B cells, contribute to hypertension in experimental models of preeclampsia. The central nervous system seems important in immune cell activation, because lesions in the anteroventral third ventricle block hypertension and T cell activation in response to ANG II. Likewise, genetic manipulation of reactive oxygen species in the subfornical organ modulates both hypertension and immune cell activation. Current evidence indicates that the production of cytokines, including tumor necrosis factor-α, interleukin-17, and interleukin-6, contribute to hypertension, likely via effects on both the kidney and vasculature. In addition, the innate immune system also appears to contribute to hypertension. We propose a working hypothesis linking the sympathetic nervous system, immune cells, production of cytokines, and, ultimately, vascular and renal dysfunction, leading to the augmentation of hypertension. Studies of immune cell activation will clearly be useful in understanding this common yet complex disease.

  2. [Thyroid dysfunction during pregnancy].

    PubMed

    Díez, Juan J; Iglesias, Pedro; Donnay, Sergio

    2015-10-21

    Recent clinical practice guidelines on thyroid dysfunction and pregnancy have changed health care provided to pregnant women, although their recommendations are under constant revision. Trimester- and area-specific reference ranges for serum thyroid-stimulating hormone are required for proper diagnosis of hypothyroidism and hyperthyroidism. There is no doubt on the need of therapy for overt hypothyroidism, while therapy for subclinical hypothyroidism is controversial. Further research is needed to settle adverse effects of isolated hypothyroxinemia and thyroid autoimmunity. Differentiation between hyperthyroidism due to Graves' disease and the usually self-limited gestational transient thyrotoxicosis is critical. It is also important to recognize risk factors for postpartum thyroiditis. Supplementation with iodine is recommended to maintain adequate iodine nutrition during pregnancy and avoid serious consequences in offspring. Controversy remains about universal screening for thyroid disease during pregnancy or case-finding in high-risk women. Opinions of some scientific societies and recent cost-benefit studies favour universal screening. Randomized controlled studies currently under development should reduce the uncertainties that still remain in this area. PMID:25433782

  3. Psychoanalysis: a dysfunctional family?

    PubMed

    Grosskurth, P

    1998-01-01

    The discussion opens with an account of the author's mother's bizarre family in which a strong, charismatic grandmother maintained absolute control over her large family by encouraging a neurotic dependence in them through daily reports of their complaints. Getting interested in psychoanalysis in an effort to understand the dynamics of this dysfunctional family, the author, a biographer, turned to the study of Melanie Klein, becoming entranced by her ideas. Her research also revealed how Klein had discouraged her followers from developing ideas that diverged in any way from her own. Her portrait of the pioneer analyst provoked intense indignation. A similar pattern of absolute loyalty to his person and theories was to be found in Freud's Secret Committee, formed primarily as a means of getting rid of Jung who had been showing disturbing signs of independence. When Ferenczi and Rank began to pursue independent lines of enquiry in their work, they too were though to be undermining the foundations of classical psychoanalysis. Finally, the author concludes that though there have been sorry incidents in psychoanalysis, we should be mature enough to accept both the contributions of the early pioneers and the realizations that new ideas must be permitted to evolve.

  4. [Meibomian gland dysfunction].

    PubMed

    Finis, D; Schrader, S; Geerling, G

    2012-05-01

    Meibomian gland dysfunction (MGD) is a chronic disease, usually caused by obstruction of the secretory Meibomian glands. The subsequent reduction of gland secretion results in a decreased amount of lipids in the tear film. This results in a faster evaporation of the tear film and thus an evaporative dry eye. MGD alone is responsible for about 60% of all cases in combination with aqueous deficiency for a further 20% of dry eyes. While in Europe up to 20% of the population are suffering from MDD, this is true in Asia for over 60% of the population. MGD is more common in women and it incidence increases with age. It is influenced by the hormonal status as well as chemical and mechanical noxious stimuli. Additional risk factors include various skin diseases such as rosacea, acne or atopy. To diagnose MGD, particular attention should be paid to changes in the lid margin such as plugging or pouting of the ducts, thickening and telangiectasia. However, most important is the diagnostic expression of the glands. At first it should be assessed whether secretion can be caused by pressure to the eyelid against the globe and secondly the quality of the expressed secretions should be evaluated. MGD should be treated according to the severity of the disease. While in mild stages instructions for lid margin hygiene, warming and massage in combination with artificial tears might be sufficient, in more severe stages oral tetracyclin derivatives and anti-inflammatory eye drops such as steroids or CSA are necessary for successful treatment.

  5. Liver dysfunction in haemophilia.

    PubMed

    Steven, M M; Small, M; Pettigrew, A; Lowe, G D; Sturrock, R D; Follett, E A; Forbes, C D

    1986-04-01

    Liver function was studied in 139 of 291 haemophiliacs known to a single Regional Haemophilia Centre including patients with classical haemophilia, Christmas disease and von Willebrand's disease. In 57 patients, six-monthly liver function tests over a five year period were also available. Thirty-nine of the 139 patients had had jaundice or hepatitis and 56 had a positive test for HBsAb in the blood although few of these had had an identifiable clinical illness. Fifty-eight haemophiliacs had elevated serum aminotransferases at the time of study, but the five year review revealed only six patients who had had persistently abnormal results, although none had clinically evident liver disease. Liver dysfunction was unrelated to a history of hepatitis, to a positive HBsAb test, or to age, type of haemophilia, factor level or frequency of factor replacement treatment. Abnormalities of liver function in haemophilia appear to be unrelated to past or present hepatitis B infection in most cases and may not be related to any single transmitted infectious agent.

  6. Psychoanalysis: a dysfunctional family?

    PubMed

    Grosskurth, P

    1998-01-01

    The discussion opens with an account of the author's mother's bizarre family in which a strong, charismatic grandmother maintained absolute control over her large family by encouraging a neurotic dependence in them through daily reports of their complaints. Getting interested in psychoanalysis in an effort to understand the dynamics of this dysfunctional family, the author, a biographer, turned to the study of Melanie Klein, becoming entranced by her ideas. Her research also revealed how Klein had discouraged her followers from developing ideas that diverged in any way from her own. Her portrait of the pioneer analyst provoked intense indignation. A similar pattern of absolute loyalty to his person and theories was to be found in Freud's Secret Committee, formed primarily as a means of getting rid of Jung who had been showing disturbing signs of independence. When Ferenczi and Rank began to pursue independent lines of enquiry in their work, they too were though to be undermining the foundations of classical psychoanalysis. Finally, the author concludes that though there have been sorry incidents in psychoanalysis, we should be mature enough to accept both the contributions of the early pioneers and the realizations that new ideas must be permitted to evolve. PMID:9531859

  7. Adult immunization

    PubMed Central

    Mehta, Bharti; Chawla, Sumit; Kumar Dharma, Vijay; Jindal, Harashish; Bhatt, Bhumika

    2014-01-01

    Vaccination is recommended throughout life to prevent vaccine-preventable diseases and their sequel. The primary focus of vaccination programs has historically been directed to childhood immunizations. For adults, chronic diseases have been the primary focus of preventive and medical health care, though there has been increased emphasis on preventing infectious diseases. Adult vaccination coverage, however, remains low for most of the routinely recommended vaccines. Though adults are less susceptible to fall prey to traditional infectious agents, the probability of exposure to infectious agents has increased manifold owing to globalization and increasing travel opportunities both within and across the countries. Thus, there is an urgent need to address the problem of adult immunization. The adult immunization enterprise is more complex, encompassing a wide variety of vaccines and a very diverse target population. There is no coordinated public health infrastructure to support an adult immunization program as there is for children. Moreover, there is little coordination among adult healthcare providers in terms of vaccine provision. Substantial improvement in adult vaccination is needed to reduce the health consequences of vaccine-preventable diseases among adults. Routine assessment of adult patient vaccination needs, recommendation, and offer of needed vaccines for adults should be incorporated into routine clinical care of adults. PMID:24128707

  8. Plant Immunity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plants are faced with defending themselves against a multitude of pathogens, including bacteria, fungi, viruses, nematodes, etc. Immunity is multi-layered and complex. Plants can induce defenses when they recognize small peptides, proteins or double-stranded RNA associated with pathogens. Recognitio...

  9. [Meibomian gland dysfunction--review].

    PubMed

    Nowińska, Anna; Wylegała, Edward; Tarnawska, Dorota; Janiszewska, Dominika; Dobrowolskia, Dariusz

    2012-01-01

    Meibomian gland dysfunction is a common ocular disorder affecting from 39 to 50% of population. Despite that, so far a pathophysiology path of the disease remains unknown, moreover there is no distinct border between physiology and the disease. There has been no clear diagnostic criteria. The purpose of this review was to combine a current knowledge of Meibomian gland anatomy, Meibomian gland dysfunction epidemiology, as well as presenting current definition, nomenclature, classification and diagnostic criteria. The importance of diagnosis associated with conditions such as aqueous tear deficiency, seborrheic dermatitis, and rosacea is emphasized. The available treatment methods are discussed. Meibomian gland dysfunction, blepharitis, dry eye syndrome.

  10. 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.

  11. Interleukin 10 knockout frail mice develop cardiac and vascular dysfunction with increased age☆

    PubMed Central

    Sikka, Gautam; Miller, Karen L.; Steppan, Jochen; Pandey, Deepesh; Jung, Sung M.; Fraser, Charles D.; Ellis, Carla; Ross, Daniel; Vandegaer, Koenraad; Bedja, Djahida; Gabrielson, Kathleen; Walston, Jeremy D.; Berkowitz, Dan E.; Barouch, Lili A.

    2013-01-01

    Cardiovascular dysfunction is a primary independent predictor of age-related morbidity and mortality. Frailty is associated with activation of inflammatory pathways and fatigue that commonly presents and progresses with age. Interleukin 10 (IL-10), the cytokine synthesis inhibitory factor, is an anti-inflammatory cytokine produced by immune and non-immune cells. Homozygous deletion of IL-10 in mice yields a phenotype that is consistent with human frailty, including age-related increases in serum inflammatory mediators, muscular weakness, higher levels of IGF-1 at midlife, and early mortality. While emerging evidence suggests a role for IL-10 in vascular protection, a clear mechanism has not yet been elucidated. Methods In order to evaluate the role of IL-10 in maintenance of vascular function, force tension myography was utilized to access ex-vivo endothelium dependent vasorelaxation in vessels isolated from IL-10 knockout IL-10(tm/tm) and control mice. Pulse wave velocity ((PWV), index of stiffness) of vasculature was measured using ultrasound and blood pressure was measured using the tail cuff method. Echocardiography was used to elucidated structure and functional changes in the heart. Results Mean arterial pressures were significantly higher in IL-10(tm/tm) mice as compared to C57BL6/wild type (WT) controls. PWV was increased in IL-10(tm/tm) indicating stiffer vasculature. Endothelial intact aortic rings isolated from IL-10(tm/tm) mice demonstrated impaired vasodilation at low acetylcholine doses and vasoconstriction at higher doses whereas vasorelaxation responses were preserved in rings from WT mice. Cyclo-oxygenase (COX-2)/thromboxane A2 inhibitors improved endothelial dependent vasorelaxation and reversed vasoconstriction. Left ventricular end systolic diameter, left ventricular mass, isovolumic relaxation time, fractional shortening and ejection fraction were all significantly different in the aged IL-10(tm/tm) mice compared to WT mice. Conclusion Aged IL

  12. Sexual dysfunction following radical prostatectomy.

    PubMed

    Benson, Cooper R; Serefoglu, Ege Can; Hellstrom, Wayne J G

    2012-01-01

    Prostate cancer is the most common solid cancer in men and the second leading cause of cancer death in men. A favored treatment option for organ-confined prostate cancer in a middle-aged healthy man is radical prostatectomy (RP). Despite advances in techniques for RP, there remain concerns among physicians and patients alike on its adverse effects on sexual function. Although post-RP erectile dysfunction has been extensively studied, little attention has been focused on the other domains of sexual function, namely loss of libido, ejaculatory dysfunction, orgasmic dysfunction, penile shortening, and Peyronie disease. The aim of this review is to discuss the most recent literature regarding post-RP sexual dysfunctions. PMID:22744864

  13. Surgical Procedures for Vestibular Dysfunction

    MedlinePlus

    ... Rated Nonprofit! Volunteer. Donate. Review. Surgical Procedures for Vestibular Dysfunction When is surgery necessary? When medical treatment ... organ (cochlea) is also sacrificed with this procedure. Vestibular nerve section A vestibular nerve section is a ...

  14. Fatiguing exercise enhances hyperalgesia to muscle inflammation.

    PubMed

    Sluka, Kathleen A; Rasmussen, Lynn A

    2010-02-01

    Since many people with chronic fatigue present with pain and many people with chronic pain present with fatigue, we tested if fatigue would enhance the response to pain in male and female mice. We further tested for the activation of brainstem nuclei by the fatigue task using c-fos as a marker. Fatigue was induced by having mice spontaneously run in running wheel for 2h. Carrageenan (0.03%) was injected into the gastrocnemius muscle either 2h before or 2h after the fatigue task. The mechanical sensitivity of the paw (von Frey filaments), muscle (tweezers), grip force and running wheel activity was assessed before and 24h after injection of carrageenan. Both male and female mice that performed the fatigue task, either before or after intramuscular injection of carrageenan, showed an enhanced mechanical sensitivity of the paw, but not the muscle. Ovariectomized mice showed a similar response to male mice. There was a decrease in running wheel activity after carrageenan injection, but no change in grip force suggesting that mice had no deficit in motor performance induced by the carrageenan. C-fos expression was observed in the nucleus raphe pallidus, obscurus, and magnus after the fatigue task suggesting an increased activity in the raphe nuclei in response to the fatigue task. Therefore, widespread hyperalgesia is enhanced by the fatigue response but not hyperalgesia at the site of insult. We suggest that this effect is sex-dependent and involves mechanisms in the brainstem to result in an enhanced hyperalgesia.

  15. Probabilistic fatigue methodology for six nines reliability

    NASA Technical Reports Server (NTRS)

    Everett, R. A., Jr.; Bartlett, F. D., Jr.; Elber, Wolf

    1990-01-01

    Fleet readiness and flight safety strongly depend on the degree of reliability that can be designed into rotorcraft flight critical components. The current U.S. Army fatigue life specification for new rotorcraft is the so-called six nines reliability, or a probability of failure of one in a million. The progress of a round robin which was established by the American Helicopter Society (AHS) Subcommittee for Fatigue and Damage Tolerance is reviewed to investigate reliability-based fatigue methodology. The participants in this cooperative effort are in the U.S. Army Aviation Systems Command (AVSCOM) and the rotorcraft industry. One phase of the joint activity examined fatigue reliability under uniquely defined conditions for which only one answer was correct. The other phases were set up to learn how the different industry methods in defining fatigue strength affected the mean fatigue life and reliability calculations. Hence, constant amplitude and spectrum fatigue test data were provided so that each participant could perform their standard fatigue life analysis. As a result of this round robin, the probabilistic logic which includes both fatigue strength and spectrum loading variability in developing a consistant reliability analysis was established. In this first study, the reliability analysis was limited to the linear cumulative damage approach. However, it is expected that superior fatigue life prediction methods will ultimately be developed through this open AHS forum. To that end, these preliminary results were useful in identifying some topics for additional study.

  16. Recovery of gait after quadriceps muscle fatigue.

    PubMed

    Barbieri, Fabio Augusto; Beretta, Stephannie Spiandor; Pereira, Vinicius A I; Simieli, Lucas; Orcioli-Silva, Diego; dos Santos, Paulo Cezar Rocha; van Dieën, Jaap H; Gobbi, Lilian Teresa Bucken

    2016-01-01

    The aim of this study was to investigate the effect of recovery time after quadriceps muscle fatigue on gait in young adults. Forty young adults (20-40 years old) performed three 8-m gait trials at preferred velocity before and after muscle fatigue, and after 5, 10 and 20min of passive rest. In addition, at each time point, two maximal isometric voluntary contractions were preformed. Muscle fatigue was induced by repeated sit-to-stand transfers until task failure. Spatio-temporal, kinetic and muscle activity parameters, measured in the central stride of each trial, were analyzed. Data were compared between before and after the muscle fatigue protocol and after the recovery periods by one-way repeated measures ANOVA. The voluntary force was decreased after the fatigue protocol (p<0.001) and after 5, 10 and 20min of recovery compared to before the fatigue protocol. Step width (p<0.001) and RMS of biceps femoris (p<0.05) were increased immediately after the fatigue protocol and remained increased after the recovery periods. In addition, stride duration was decreased immediately after the fatigue protocol compared to before and to after 10 and 20min of rest (p<0.001). The anterior-posterior propulsive impulse was also decreased after the fatigue protocol (p<0.001) and remained low after 5, 10 and 20min of rest. We conclude that 20min is not enough to see full recovery of gait after exhaustive quadriceps muscle fatigue.

  17. Randomized Controlled Trial of Qigong/Tai Chi Easy on Cancer-Related Fatigue in Breast Cancer Survivors

    PubMed Central

    Larkey, Linda K.; Roe, Denise J.; Weihs, Karen L.; Jahnke, Roger; Lopez, Ana Maria; Rogers, Carol E.; Oh, Byeongsang; Guillen-Rodriguez, Jose

    2014-01-01

    Background Many breast cancer survivors experience fatigue, mood, and sleep disturbances. Purpose To compare a Meditative Movement practice, Qigong/Tai Chi Easy (QG/TCE), with sham Qigong (SQG), testing effects of meditation/breath aspects of QG/TCE on breast cancer survivors' persistent fatigue and other symptoms. Methods A double-blind, randomized controlled trial tested 12-weeks of QG/TCE versus SQG on fatigue, depression and sleep among 87 post-menopausal, fatigued breast cancer survivors, Stage 0-III, age 40–75. Results Fatigue decreased significantly in the QG/TCE group compared to control at post-intervention (p = 0.005) and 3 month follow-up (p = 0.024), but not depression and sleep quality. Improvement occurred over time for both interventions in depression and sleep quality (all p < 0.05). Conclusions QG/TCE showed significant improvement over time compared to SQG for fatigue, but not depression or sleep. Both QG/TCE and SQG showed improvement for two prevalent symptoms among breast cancer survivors, depression and sleep dysfunction. PMID:25124456

  18. Thyroid dysfunction and pregnancy outcomes

    PubMed Central

    Nazarpour, Sima; Ramezani Tehrani, Fahimeh; Simbar, Masoumeh; Azizi, Fereidoun

    2015-01-01

    Background: Pregnancy has a huge impact on the thyroid function in both healthy women and those that have thyroid dysfunction. The prevalence of thyroid dysfunction in pregnant women is relatively high. Objective: The objective of this review was to increase awareness and to provide a review on adverse effect of thyroid dysfunction including hyperthyroidism, hypothyroidism and thyroid autoimmune positivity on pregnancy outcomes. Materials and Methods: In this review, Medline, Embase and the Cochrane Library were searched with appropriate keywords for relevant English manuscript. We used a variety of studies, including randomized clinical trials, cohort (prospective and retrospective), case-control and case reports. Those studies on thyroid disorders among non-pregnant women and articles without adequate quality were excluded. Results: Overt hyperthyroidism and hypothyroidism has several adverse effects on pregnancy outcomes. Overt hyperthyroidism was associated with miscarriage, stillbirth, preterm delivery, intrauterine growth retardation, low birth weight, preeclampsia and fetal thyroid dysfunction. Overt hypothyroidism was associated with abortion, anemia, pregnancy-induced hypertension, preeclampsia, placental abruption, postpartum hemorrhage, premature birth, low birth weight, intrauterine fetal death, increased neonatal respiratory distress and infant neuro developmental dysfunction. However the adverse effect of subclinical hypothyroidism, and thyroid antibody positivity on pregnancy outcomes was not clear. While some studies demonstrated higher chance of placental abruption, preterm birth, miscarriage, gestational hypertension, fetal distress, severe preeclampsia and neonatal distress and diabetes in pregnant women with subclinical hypothyroidism or thyroid autoimmunity; the other ones have not reported these adverse effects. Conclusion: While the impacts of overt thyroid dysfunction on feto-maternal morbidities have been clearly identified and its long

  19. Lymphatic Vessels, Inflammation, and Immunity in Skin Cancer

    PubMed Central

    Lund, Amanda W.; Medler, Terry R.; Leachman, Sancy A.; Coussens, Lisa M.

    2015-01-01

    Skin is a highly ordered immune organ that coordinates rapid responses to external insult while maintaining self-tolerance. In healthy tissue, lymphatic vessels drain fluid and coordinate local immune responses; however, environmental factors induce lymphatic vessel dysfunction, leading to lymph stasis and perturbed regional immunity. These same environmental factors drive the formation of local malignancies, which are also influenced by local inflammation. Herein, we discuss clinical and experimental evidence supporting the tenet that lymphatic vessels participate in regulation of cutaneous inflammation and immunity, are important contributors to malignancy and potential biomarkers and targets for immunotherapy. PMID:26552413

  20. Mental fatigue: costs and benefits.

    PubMed

    Boksem, Maarten A S; Tops, Mattie

    2008-11-01

    A framework for mental fatigue is proposed, that involves an integrated evaluation of both expected rewards and energetical costs associated with continued performance. Adequate evaluation of predicted rewards and potential risks of actions is essential for successful adaptive behaviour. However, while both rewards and punishments can motivate to engage in activities, both types of motivated behaviour are associated with energetical costs. We will review findings that suggest that the nucleus accumbens, orbitofrontal cortex, amygdala, insula and anterior cingulate cortex are involved evaluating both the potential rewards associated with performing a task, as well as assessing the energetical demands involved in task performance. Behaviour will only proceed if this evaluation turns out favourably towards spending (additional) energy. We propose that this evaluation of predicted rewards and energetical costs is central to the phenomenon of mental fatigue: people will no longer be motivated to engage in task performance when energetical costs are perceived to outweigh predicted rewards.

  1. Review of sonic fatigue technology

    NASA Technical Reports Server (NTRS)

    Clarkson, B. L.

    1994-01-01

    From the early-1960s until the mid-1980s, there was very little theoretical development for sonic fatigue prediction. Design nomographs based on simple theoretical models and results of specially designed tests were developed for most common aircraft structures. The use of advanced composites in the 1980s, however, generated an increased interest in development of more sophisticated theoretical models because of the possibilities for a much wider range of structural designs. The purpose of this report is to review sonic fatigue technology and, in particular, to assess recent developments. It also suggests a plan for a coordinated program of theoretical and experimental work to meet the anticipated needs of future aerospace vehicles.

  2. How the Innate Immune System Senses Trouble and Causes Trouble.

    PubMed

    Hato, Takashi; Dagher, Pierre C

    2015-08-01

    The innate immune system is the first line of defense in response to nonself and danger signals from microbial invasion or tissue injury. It is increasingly recognized that each organ uses unique sets of cells and molecules that orchestrate regional innate immunity. The cells that execute the task of innate immunity are many and consist of not only "professional" immune cells but also nonimmune cells, such as renal epithelial cells. Despite a high level of sophistication, deregulated innate immunity is common and contributes to a wide range of renal diseases, such as sepsis-induced kidney injury, GN, and allograft dysfunction. This review discusses how the innate immune system recognizes and responds to nonself and danger signals. In particular, the roles of renal epithelial cells that make them an integral part of the innate immune apparatus of the kidney are highlighted.

  3. Dynamic Fatigue of ULE Glass

    NASA Technical Reports Server (NTRS)

    Tucker, Dennis S.; Nettles, Alan T.; Brantley, Lott W. (Technical Monitor)

    2001-01-01

    Ultra Low Expansion (ULE) glass is used in a number of applications which require a low thermal expansion coefficient. One such application is telescope mirror elements. An allowable stress can be calculated for this material based upon modulus of rupture data; however, this does not take into account the problem of delayed failure. Delayed failure, due to stress corrosion can significantly shorten the lifetime of a glass article. Knowledge of the factors governing the rate of subcritical flaw growth in a given environment enables the development of relations between lifetime, applied stress and failure probability for the material under study. Dynamic fatigue is one method of obtaining the necessary information to develop these relationships. In this study, the dynamic fatigue method was used to construct time-to-failure diagrams for both 230/270 ground and optically polished samples. The grinding and polishing process reduces the surface flaw size and subsurface damage, and relieves residual stress by removing materials with successively smaller grinding media. This resulted in an increase in the strength of the optic during the grinding and polishing sequence. There was also an increase in the lifetime due to grinding and polishing. It was found that using the fatigue parameters determined from the 230/270 grit surface are not significantly different from the optically polished values. Although the lower bound of the polished samples is more conservative, neither time-to-failure curves lie beyond the upper or lower bound of the confidence limits. Therefore, designers preferring conservative limits could use samples without residual stress present (polished samples) to determine the fatigue parameters and inert Weibull parameters from samples with the service condition surface, to determine time-to-failure of the optical element.

  4. Low cycle fatigue in turbines

    NASA Technical Reports Server (NTRS)

    Brun, M.

    1978-01-01

    Behavior of certain components at low-cycle fatigue is a parameter related to the conditions of use of turbines, to the technology of engine production and to the precision of its regulation. The laboratory takes this into account using data from sophisticated tests and rigorous analyses. The production plan includes careful examination of possible causes of premature rupture. This parameter has motivated the metallurgy industry to develop new materials and new technology.

  5. Electroencephalographic Monitoring of Cognitive Fatigue

    NASA Technical Reports Server (NTRS)

    Montgomery, Leslie D.; Montgomery, Richard W.; Ku, Yu-Tsuan E.; Luna, Bernadette

    2000-01-01

    Mental exhaustion often poses a serious risk, even when performance is not apparently degraded. When such fatigue is associated with sustained performance of a single type of cognitive task it may be related to the metabolic energy required for sustained activation of cortical fields specialized for that task. The objective of this study was to adapt EEG to monitor cortical energy dissipation at a functionally specialized site over a long period of repetitive performance of a cognitive task.

  6. Immunization Schedules for Adults

    MedlinePlus

    ... ACIP Vaccination Recommendations Why Immunize? Vaccines: The Basics Immunization Schedules for Adults in Easy-to-read Formats ... previous immunizations. View or Print a Schedule Recommended Immunizations for Adults (19 Years and Older) by Age ...

  7. Fatigue Management in Spaceflight Operations

    NASA Technical Reports Server (NTRS)

    Whitmire, Alexandra

    2011-01-01

    Sleep loss and fatigue remain an issue for crewmembers working on the International Space Station, and the ground crews who support them. Schedule shifts on the ISS are required for conducting mission operations. These shifts lead to tasks being performed during the biological night, and sleep scheduled during the biological day, for flight crews and the ground teams who support them. Other stressors have been recognized as hindering sleep in space; these include workload, thinking about upcoming tasks, environmental factors, and inadequate day/night cues. It is unknown if and how other factors such as microgravity, carbon dioxide levels, or increased radiation, may also play a part. Efforts are underway to standardize and provide care for crewmembers, ground controllers and other support personnel. Through collaborations between research and operations, evidenced-based clinical practice guidelines are being developed to equip flight surgeons with the tools and processes needed for treating circadian desynchrony (and subsequent sleep loss) caused by jet lag and shift work. The proper implementation of countermeasures such as schedules, lighting protocols, and cognitive behavioral education can hasten phase shifting, enhance sleep and optimize performance. This panel will focus on Fatigue Management in Spaceflight Operations. Speakers will present on research-based recommendations and technologies aimed at mitigating sleep loss, circadian desynchronization and fatigue on-orbit. Gaps in current mitigations and future recommendations will also be discussed.

  8. Mental fatigue impairs emotion regulation.

    PubMed

    Grillon, Christian; Quispe-Escudero, David; Mathur, Ambika; Ernst, Monique

    2015-06-01

    Because healthy physical and mental functioning depends on the ability to regulate emotions, it is important to identify moderators of such regulations. Whether mental fatigue, subsequent to the depletion of cognitive resources, impairs explicit emotion regulation to negative stimuli is currently unknown. This study explored this possibility. In a within-subject design over 2 separate sessions, healthy individuals performed easy (control session) or difficult (depletion session) cognitive tasks. Subsequently, they were presented with neutral and negative pictures, with instructions to either maintain or regulate (i.e., reduce) the emotions evoked by the pictures. Emotional reactivity was probed with the startle reflex. The negative pictures evoked a similar aversive state in the control and depletion sessions as measured by startle potentiation. However, subjects were able to down-regulate their aversive state only in the control session, not in the depletion session. These results indicate that mental fatigue following performance of cognitive tasks impairs emotion regulation without affecting emotional reactivity. These findings suggest that mental fatigue needs to be incorporated into models of emotion regulation.

  9. A Pair of Identical Twins Discordant for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Differ in Physiological Parameters and Gut Microbiome Composition

    PubMed Central

    Giloteaux, Ludovic; Hanson, Maureen R.; Keller, Betsy A.

    2016-01-01

    Patient: Male, 34 Final Diagnosis: ME/CFS Symptoms: Exertion intolerance • loss of functional capacity • pain • severe fatigue Medication: — Clinical Procedure: Cardiopulmonary exercise test Specialty: Sports Medicine Objective: Unknown ethiology Background: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with profound fatigue, flu-like symptoms, pain, cognitive impairment, orthostatic intolerance, post-exertional malaise (PEM), and exacerbation of some or all of the baseline symptoms. Case Report: We report on a pair of 34-year-old monozygotic twins discordant for ME/CFS, with WELL, the non-affected twin, and ILL, the affected twin. Both twins performed a two-day cardiopulmonary exercise test (CPET), preand post-exercise blood samples were drawn, and both provided stool samples for biochemical and molecular analyses. At peak exertion for both CPETs, ILL presented lower VO2peak and peak workload compared to WELL. WELL demonstrated normal reproducibility of VO2@ventilatory/anaerobic threshold (VAT) during CPET2, whereas ILL experienced an abnormal reduction of 13% in VAT during CPET2. A normal rise in lactate dehydrogenase (LDH), creatine kinase (CK), adrenocorticotropic hormone (ACTH), cortisol, creatinine, and ferritin content was observed following exercise for both WELL and ILL at each CPET. ILL showed higher increases of resistin, soluble CD40 ligand (sCD40L), and soluble Fas ligand (sFasL) after exercise compared to WELL. The gut bacterial microbiome and virome were examined and revealed a lower microbial diversity in ILL compared to WELL, with fewer beneficial bacteria such as Faecalibacterium and Bifidobacterium, and an expansion of bacteriophages belonging to the tailed dsDNA Caudovirales order. Conclusions: Results suggest dysfunctional immune activation in ILL following exercise and that prokaryotic viruses may contribute to mucosal inflammation and bacterial dysbiosis. Therefore, a two-day CPET and molecular

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

    PubMed

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

    2015-03-01

    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.

  11. New insights into upper airway innate immunity

    PubMed Central

    Hariri, Benjamin M.

    2016-01-01

    Background: Protecting the upper airway from microbial infection is an important function of the immune system. Proper detection of these pathogens is paramount for sinonasal epithelial cells to be able to prepare a defensive response. Toll-like receptors and, more recently, bitter taste receptors and sweet taste receptors have been implicated as sensors able to detect the presence of these pathogens and certain compounds that they secrete. Activation of these receptors also triggers innate immune responses to prevent or counteract infection, including mucociliary clearance and the production and secretion of antimicrobial compounds (e.g., defensins). Objective: To provide an overview of the current knowledge of the role of innate immunity in the upper airway, the mechanisms by which it is carried out, and its clinical relevance. Methods: A literature review of the existing knowledge of the role of innate immunity in the human sinonasal cavity was performed. Results: Clinical and basic science studies have shown that the physical epithelial cell barrier, mucociliary clearance, and antimicrobial compound secretion play pivotal innate immune roles in defending the sinonasal cavity from infection. Clinical findings have also linked dysfunction of these defense mechanisms with diseases, such as chronic rhinosinusitis and cystic fibrosis. Recent discoveries have elucidated the significance of bitter and sweet taste receptors in modulating immune responses in the upper airway. Conclusion: Numerous innate immune mechanisms seem to work in a concerted fashion to keep the sinonasal cavity free of infection. Understanding sinonasal innate immune function and dysfunction in health and disease has important implications for patients with respiratory ailments, such as chronic rhinosinusitis and cystic fibrosis.

  12. New insights into upper airway innate immunity

    PubMed Central

    Hariri, Benjamin M.

    2016-01-01

    Background: Protecting the upper airway from microbial infection is an important function of the immune system. Proper detection of these pathogens is paramount for sinonasal epithelial cells to be able to prepare a defensive response. Toll-like receptors and, more recently, bitter taste receptors and sweet taste receptors have been implicated as sensors able to detect the presence of these pathogens and certain compounds that they secrete. Activation of these receptors also triggers innate immune responses to prevent or counteract infection, including mucociliary clearance and the production and secretion of antimicrobial compounds (e.g., defensins). Objective: To provide an overview of the current knowledge of the role of innate immunity in the upper airway, the mechanisms by which it is carried out, and its clinical relevance. Methods: A literature review of the existing knowledge of the role of innate immunity in the human sinonasal cavity was performed. Results: Clinical and basic science studies have shown that the physical epithelial cell barrier, mucociliary clearance, and antimicrobial compound secretion play pivotal innate immune roles in defending the sinonasal cavity from infection. Clinical findings have also linked dysfunction of these defense mechanisms with diseases, such as chronic rhinosinusitis and cystic fibrosis. Recent discoveries have elucidated the significance of bitter and sweet taste receptors in modulating immune responses in the upper airway. Conclusion: Numerous innate immune mechanisms seem to work in a concerted fashion to keep the sinonasal cavity free of infection. Understanding sinonasal innate immune function and dysfunction in health and disease has important implications for patients with respiratory ailments, such as chronic rhinosinusitis and cystic fibrosis. PMID:27657896

  13. Fatigue properties of acrylic denture base resins.

    PubMed

    Fujii, K

    1989-12-01

    Observations were made of fractured surfaces caused by flexural and tensile fatigue tests made in polymethyl methacrylate denture base resins (PMMA). In addition, the changes in dynamic viscoelastic and tensile properties of the materials along with fatigue propagation were investigated. In the tensile and flexural fatigue tests, both the fractured surfaces, which had striations on their surfaces and cracks near the fractured section, closely resembled each other in appearance. On the other hand, all of the tensile properties, such as elastic modulus, toughness and tensile strength, decreased with the increase of the number of stress cycles in the fatigue test. The storage modulus (E') of the material decreased gradually along with fatigue propagation over the whole range of temperatures tested. The loss modulus (E") and mechanical loss tangent (tan delta) increased slightly. The fatigue limit of four commercial denture base resins varied widely from one product to another.

  14. Immune regulation during chronic visceral leishmaniasis.

    PubMed

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

    2014-07-01

    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.

  15. Polysaccharide of Radix Pseudostellariae Improves Chronic Fatigue Syndrome Induced by Poly I:C in Mice

    PubMed Central

    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. PMID:20008077

  16. Serotonergic dysfunction in Parkinson's disease and its relevance to disability.

    PubMed

    Politis, Marios; Loane, Clare

    2011-01-01

    Growing evidence suggests that Parkinson's disease is not solely affecting the dopaminergic system. Results from biochemical, animal, postmortem, and functional imaging studies have revealed that other neurotransmitter systems are affected as well, including the serotonergic system. With the use of in vivo positron emission tomography functional imaging, it has been shown that serotonergic terminals are affected at a varying, nonlinear degree starting early in the clinical course of Parkinson's disease. Tremor and the majority of nonmotor symptoms do not seem to respond adequately to dopaminergic medication. Recent studies suggest that serotonergic dysfunction has a direct relevance to Parkinson's disease symptoms, the so-called nonmotor symptoms, including depression, fatigue, weight changes, and visual hallucinations. These in vivo findings indicate that agents acting on the serotonergic system could help towards alleviating these symptoms. This paper aims to review the current literature and to highlight the need for further in vivo investigations.

  17. The aging male: androgens, erectile dysfunction, and depression.

    PubMed

    Seidman, Stuart N

    2003-01-01

    In contrast to women, men do not experience a sudden cessation of gonadal function comparable to menopause. However, there is a progressive reduction in hypothalamic-pituitary-gonadal (HPG) axis activity in aging men: testosterone levels decline and there is a loss of the circadian rhythm of testosterone secretion. Such progressive HPG-axis hypofunctioning is thought to be responsible for some signs and symptoms that are common in elderly men such as fatigue, reduced muscle and bone mass, sexual dysfunction, and depression. Yet, such presumed hypogonadal sequelae have not been correlated with testosterone levels. Unlike the profound effects of replacement therapy in young men with frank hypogonadism, testosterone replacement in men with age-related mild hypogonadism is not apparently effective in reversing these symptoms. This article reviews the relationship between androgens, sexual function, and depression in aging men.

  18. Exercise-induced mitochondrial dysfunction: a myth or reality?

    PubMed

    Ostojic, Sergej M

    2016-08-01

    Beneficial effects of physical activity on mitochondrial health are well substantiated in the scientific literature, with regular exercise improving mitochondrial quality and quantity in normal healthy population, and in cardiometabolic and neurodegenerative disorders and aging. However, several recent studies questioned this paradigm, suggesting that extremely heavy or exhaustive exercise fosters mitochondrial disturbances that could permanently damage its function in health and disease. Exercise-induced mitochondrial dysfunction (EIMD) might be a key proxy for negative outcomes of exhaustive exercise, being a pathophysiological substrate of heart abnormalities, chronic fatigue syndrome (CFS) or muscle degeneration. Here, we overview possible factors that mediate negative effects of exhaustive exercise on mitochondrial function and structure, and put forward alternative solutions for the management of EIMD. PMID:27389587

  19. Bonded joint strength - Static versus fatigue

    NASA Technical Reports Server (NTRS)

    Johnson, W. S.; Mall, S.

    1984-01-01

    Adhesives are commonly characterized only by their static strength even though they are used in structural joints that are subjected to fatigue loads. This paper reviews the relationship between static and fatigue strength for four different specimen types: single-lap-shear, edge-delamination, double cantilever beam, and cracked-lap-shear. It was found that the ratio of static strength to fatigue strength varied from 2.3 to 4.7, depending on the adhesive and specimen configuration.

  20. Does Fatigue Alter Pitching Mechanics?

    PubMed Central

    Chalmers, Peter Nissen; Erickson, Brandon J.; Sgroi, Terrance; Vignona, Peter; Lesniak, Matthew; Bush-Joseph, Charles A.; Verma, Nikhil N.; Romeo, Anthony A.

    2016-01-01

    Objectives: Background: Injuries of the adolescent shoulder and elbow are common in baseball pitchers. Fatigue has been demonstrated to be a risk factor for injury. Purpose: To determine if shoulder and elbow kinematics, pitching velocity, accuracy, and pain change during a simulated full baseball game in adolescent pitchers. Methods: Methods: Adolescent pitchers between the ages of 13-16 were recruited to throw a 90 pitch simulated game. Shoulder range of motion was assessed before and after the game. Velocity and accuracy were measured for every pitch and every 15th pitch was videotaped from two orthogonal views in high definition at 240 Hz. Quantitative and qualitative mechanics were measured from these videos. Perceived fatigue and pain were assessed after each inning using the visual analog scale. Data was statistically analyzed using a repeated-measures analysis of variance. Results: Results: Twenty-eight elite adolescent pitchers were included. These pitchers, on average, were 14.6±0.9 years old (mean ± standard deviation), had been pitching for 6.3±1.7 years, and threw 94±58 pitches per week. Our experimental model functioned as expected in that pitchers became progressively more fatigued and painful and pitched with a lower velocity as pitch number increased (p<0.001, 0.001, and <0.001 respectively). Knee flexion at ball release progressively increased with pitch number (p=0.008). Hip and shoulder separation significantly decreased as pitch number increased, from 90%±40% at pitch 15 to 40%±50% at pitch 90 (p0.271 in all cases, 91% power for elbow flexion at ball release). External rotation and total range of motion in the pitching shoulder significantly increased post-pitching (p=0.007 and 0.047 respectively). Conclusion: Conclusion: As pitchers progress through a simulated game they throw lower velocity pitches and become fatigued and painful. Core and leg musculature becomes fatigued before upper extremity kinematics change. Based upon these

  1. Lupus brain fog: a biologic perspective on cognitive impairment, depression, and fatigue in systemic lupus erythematosus.

    PubMed

    Mackay, Meggan

    2015-12-01

    Cognitive disturbances, mood disorders and fatigue are common in SLE patients with substantial adverse effects on function and quality of life. Attribution of these clinical findings to immune-mediated disturbances associated with SLE remains difficult and has compromised research efforts in these areas. Improved understanding of the role of the immune system in neurologic processes essential for cognition including synaptic plasticity, long term potentiation and adult neurogenesis suggests multiple potential mechanisms for altered central nervous system function associated with a chronic inflammatory illness such as SLE. This review will focus on the biology of cognition and neuroinflammation in normal circumstances and potential biologic mechanisms for cognitive impairment, depression and fatigue attributable to SLE.

  2. Bioactivity-guided fractionation of physical fatigue-attenuating components from Rubus parvifolius L.

    PubMed

    Chen, Jianhong; Wang, Xianfeng; Cai, Yongqing; Tang, Ming; Dai, Qing; Hu, Xiaogang; Huang, Mingchun; Sun, Fengjun; Liu, Yao; Xia, Peiyuan

    2013-01-01

    Alleviation of fatigue has been emerging as a serious issue that requires urgent attention. Health professionals and sports physiologists have been looking for active natural products and synthetic compounds to overcome fatigue in humans. This study was designed to define the anti-fatigue property of Rubus parvifolius L. (RPL) by characterization of active constituents using a mouse forced swimming test model. Four RPL fractions with different polarities containing anti-fatigue activity were sequentially isolated from the n-butanol RPL extract, followed by elution of 50% ethanol-water fraction from D101 macroporous resin chromatography to obtain nigaichigoside F1, suavissimoside R1 and coreanoside F1. Active constituents of the 50% ethanol-water eluate of RPL were total saponins. The fractions were examined based on the effect on weight-loaded swimming capacity of mice. Serum levels of urea nitrogen (SUN), triglyceride fatty acids (TG), lactate dehydrogenase (LDH), lactic acid (LA), ammonia and hepatic glycogen (HG) were also examined for potential mechanisms underlying the anti-fatigue effect of RPL extracts. During the experiment, two inflammatory markers, interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) in serum, were measured. We found that total saponins from RPL possess potent capabilities to alleviate mouse fatigue induced by forced swimming and that nigaichigoside F1 was responsible for the pharmacological effect. The underlying mechanisms include delays of SUN and LA accumulation, a decrease in TG level by increasing fat consumption, increases in HG and LDH so that lactic acid accumulation and ammonia in the muscle were reduced, and suppression of increased immune activation and inflammatory cytokine production. Our findings will be helpful for functional identification of novel anti-fatigue components from natural medicinal herbs. PMID:24064456

  3. Corticosteroid-binding globulin gene polymorphisms: clinical implications and links to idiopathic chronic fatigue disorders.

    PubMed

    Torpy, D J; Ho, J T

    2007-08-01

    Corticosteroid-binding globulin (CBG) binds cortisol with high affinity, facilitating transport of cortisol in blood, although tissue-specific CBG-cortisol interactions have long been postulated. There are three heritable, human CBG gene mutations that can reduce CBG-cortisol binding affinity and/or reduce circulating CBG levels. In some families, fatigue and low blood pressure have been associated with affinity altering or CBG level reducing mutations. The limited numbers of reports raise the possibility of ascertainment bias as many cases presented with features suggesting cortisol deficiency. The recent description of a genetically CBG-deficient mouse listed fatigue, manifest as reduced activity levels, as part of the phenotype, which also included immune aberrations. Severe CBG mutations may produce fatigue, but one study suggests that these are a rare cause of idiopathic fatigue. A mechanism for the effect of CBG mutations on fatigue is not readily apparent because free cortisol levels are normal, although we speculate that CBG may have an effect on cortisol-brain transport.

  4. Uncovering cortico-striatal correlates of cognitive fatigue in pediatric acquired brain disorder: Evidence from traumatic brain injury.

    PubMed

    Ryan, Nicholas P; Beauchamp, Miriam H; Beare, Richard; Coleman, Lee; Ditchfield, Michael; Kean, Michael; Silk, Timothy J; Genc, Sila; Catroppa, Cathy; Anderson, Vicki A

    2016-10-01

    Cognitive fatigue is among the most profound and disabling sequelae of pediatric acquired brain disorders, however the neural correlates of these symptoms in children remains unexplored. One hypothesis suggests that cognitive fatigue may arise from dysfunction of cortico-striatal networks (CSNs) implicated in effort output and outcome valuation. Using pediatric traumatic brain injury (TBI) as a model, this study investigated (i) the sub-acute effect of brain injury on CSN volume; and (ii) potential relationships between cognitive fatigue and sub-acute volumetric abnormalities of the CSN. 3D T1 weighted magnetic resonance imaging sequences were acquired sub-acutely in 137 children (TBI: n = 103; typically developing - TD children: n = 34). 67 of the original 137 participants (49%) completed measures of cognitive fatigue and psychological functioning at 24-months post-injury. Results showed that compared to TD controls and children with milder injuries, children with severe TBI showed volumetric reductions in the overall CSN package, as well as regional gray matter volumetric change in cortical and subcortical regions of the CSN. Significantly greater cognitive fatigue in the TBI patients was associated with volumetric reductions in the CSN and its putative hub regions, even after adjusting for injury severity, socioeconomic status (SES) and depression. In the first study to evaluate prospective neuroanatomical correlates of cognitive fatigue in pediatric acquired brain disorder, these findings suggest that post-injury cognitive fatigue is related to structural abnormalities of cortico-striatal brain networks implicated in effort output and outcome valuation. Morphometric magnetic resonance imaging (MRI) may have potential to unlock early prognostic markers that may assist to identify children at elevated risk for cognitive fatigue post-TBI.

  5. Objective assessment of motor fatigue in multiple sclerosis: the Fatigue index Kliniken Schmieder (FKS).

    PubMed

    Sehle, Aida; Vieten, Manfred; Sailer, Simon; Mündermann, Annegret; Dettmers, Christian

    2014-09-01

    Fatigue is a common and frequently disabling symptom of multiple sclerosis (MS). The aim of this study was to develop the Fatigue index Kliniken Schmieder (FKS) for detecting motor fatigue in patients with MS using kinematic gait analysis. The FKS relies on the chaos theoretical term "attractor", which, if unchanged, is a necessary and sufficient indicator of a stable dynamical system. We measured the acceleration of the feet at the beginning of and shortly before stopping a treadmill walking task in 20 healthy subjects and 40 patients with multiple sclerosis. The attractor and movement variability were calculated. In the absence of muscular exhaustion a significant difference in the attractor and movement variability between the two time points demonstrates altered motor control indicating fatigue. Subjects were classified using the FKS. All healthy subjects had normal FKS and thus no fatigue. 29 patients with MS were classified into a fatigue group and 11 patients into a non-fatigue group. This classification agreed with the physician's observation and video analyses in up to 97 % of cases. The FKS did not correlate significantly with the overall and motor dimensions of the fatigue questionnaire scores in patients with MS and motor fatigue. The common concept of fatigue as overall subjective sensation of exhaustion can be affected by conditions including depression, sleep disorder and others. FKS constitutes a robust and objective measure of changes in motor performance. Therefore, the FKS allows correct identification of motor fatigue even in cases where common comorbidities mask motor fatigue. PMID:24952620

  6. [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.

  7. Classification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome by Types of Fatigue

    PubMed Central

    Jason, Leonard A.; Boulton, Aaron; Porter, Nicole S.; Jessen, Tricia; Njoku, Mary Gloria

    2016-01-01

    Persons with Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS) often complain of fatigue states (e.g. post-exertional malaise, brain fog) that are qualitatively different than normal, daily fatigue. Given the heterogeneous nature of ME/CFS, it is likely that individuals with this illness experience these fatigue types differently in terms of severity and frequency. It is also possible that meaningful subgroups of patients exist regarding different patterns of the fatigue experience. The purpose of this study was to investigate whether individuals with ME/CFS can be classified in a meaningful way according to the different types of fatigue they experience. One hundred individuals with ME/CFS participated in the study. Individuals that met inclusion criteria were administered the Multiple Fatigue Types Questionnaire (MFTQ), a five-factor instrument that distinguishes between different types of fatigue. A cluster analysis was used to classify patients into various clusters based upon factor subscale scores. Using a three-factor solution, individuals were classified according to illness severity (low, moderate, severe) across the different fatigue factors. However, a 5-cluster solution enabled participants with moderate to severe fatigue levels to fall out into more differentiated clusters and demonstrate distinct fatigue state patterns. These results suggest that fatigue patterns of individuals with ME/CFS are heterogeneous and patients may be classified into meaningful subgroups. PMID:20185398

  8. Fatigue Risk Management: A Maritime Framework

    PubMed Central

    Grech, Michelle Rita

    2016-01-01

    It is evident that despite efforts directed at mitigating the risk of fatigue through the adoption of hours of work and rest regulations and development of codes and guidelines, fatigue still remains a concern in shipping. Lack of fatigue management has been identified as a contributory factor in a number of recent accidents. This is further substantiated through research reports with shortfalls highlighted in current fatigue management approaches. These approaches mainly focus on prescriptive hours of work and rest and include an individualistic approach to managing fatigue. The expectation is that seafarers are responsible to manage and tolerate fatigue as part of their working life at sea. This attitude is an accepted part of a seafarer’s role. Poor compliance is one manifest of this problem with shipboard demands making it hard for seafarers to follow hours of work and rest regulations, forcing them into this “poor compliance” trap. This makes current fatigue management approaches ineffective. This paper proposes a risk based approach and way forward for the implementation of a fatigue risk management framework for shipping, aiming to support the hours of work and rest requirements. This forms part of the work currently underway to review and update the International Maritime Organization, Guidelines on Fatigue. PMID:26840326

  9. Survivorship: Fatigue, Version 1.2014

    PubMed Central

    Denlinger, Crystal S.; Ligibel, Jennifer A.; Are, Madhuri; Baker, K. Scott; Demark-Wahnefried, Wendy; Friedman, Debra L.; Goldman, Mindy; Jones, Lee; King, Allison; Ku, Grace H.; Kvale, Elizabeth; Langbaum, Terry S.; Leonardi-Warren, Kristin; McCabe, Mary S.; Melisko, Michelle; Montoya, Jose G.; Mooney, Kathi; Morgan, Mary Ann; Moslehi, Javid J.; O’Connor, Tracey; Overholser, Linda; Paskett, Electra D.; Raza, Muhammad; Syrjala, Karen L.; Urba, Susan G.; Wakabayashi, Mark T.; Zee, Phyllis; McMillian, Nicole; Freedman-Cass, Deborah

    2015-01-01

    Many cancer survivors report that fatigue is a disruptive symptom even after treatment ends. Persistent cancer-related fatigue affects quality of life, because individuals become too tired to fully participate in the roles and activities that make life meaningful. Identification and management of fatigue remains an unmet need for many cancer survivors. This section of the NCCN Guidelines for Survivorship provides screening, evaluation, and management recommendations for fatigue in survivors. Management includes education and counseling, physical activity, psychosocial interventions, and pharmacologic treatments. PMID:24925198

  10. Fatigue of niobium. Technical progress report

    SciTech Connect

    Stoloff, N. S.

    1980-01-31

    Tests to determine the effects of frequency, test temperature, and hydrogen content on the fatigue life and crack propagation behavior of polycrystalline niobium are described. Unalloyed niobium is nearly insensitive to test frequency at 25/sup 0/C, while hydrided alloys exhibit a strong frequency effect. Increasing test temperature decreases fatigue life, consistent with decreasing tensile strength. A brief survey of irradiation effects on fatigue of refractory metal alloys suggests that fatigue resistance of irradiated niobium should increase in proportion to effects on strength.

  11. Fatigue tests on the ITER PF jacket

    NASA Astrophysics Data System (ADS)

    Qin, Jinggang; Weiss, Klaus-Peter; Wu, Yu; Wu, Zhixiong; Li, Laifeng; Liu, Sheng

    2012-10-01

    This paper focuses on fatigue tests on the ITER Poloidal Field (PF) jacket made of 316L stainless steel material. During manufacture, the conductor will be compacted and spooled after cable insertion. Therefore, sample jackets were prepared under compaction, bending and straightening in order to simulate the status of PF conductor during manufacturing and winding. The fatigue properties of materials were measured at T < 7 K, including S-N and fatigue crack growth rate (FCGR). The testing results show that the present Chinese PF jacket has good fatigue properties, which conclude that the results are accordant with the requirements of ITER.

  12. Fatigue Risk Management: A Maritime Framework.

    PubMed

    Grech, Michelle Rita

    2016-02-01

    It is evident that despite efforts directed at mitigating the risk of fatigue through the adoption of hours of work and rest regulations and development of codes and guidelines, fatigue still remains a concern in shipping. Lack of fatigue management has been identified as a contributory factor in a number of recent accidents. This is further substantiated through research reports with shortfalls highlighted in current fatigue management approaches. These approaches mainly focus on prescriptive hours of work and rest and include an individualistic approach to managing fatigue. The expectation is that seafarers are responsible to manage and tolerate fatigue as part of their working life at sea. This attitude is an accepted part of a seafarer's role. Poor compliance is one manifest of this problem with shipboard demands making it hard for seafarers to follow hours of work and rest regulations, forcing them into this "poor compliance" trap. This makes current fatigue management approaches ineffective. This paper proposes a risk based approach and way forward for the implementation of a fatigue risk management framework for shipping, aiming to support the hours of work and rest requirements. This forms part of the work currently underway to review and update the International Maritime Organization, Guidelines on Fatigue.

  13. Tendon fatigue in response to mechanical loading

    PubMed Central

    Andarawis-Puri, N.; Flatow, E. L.

    2015-01-01

    Tendinopathies are commonly attributable to accumulation of sub-rupture fatigue damage from repetitive use. Data is limited to late stage disease from patients undergoing surgery, motivating development of animal models, such as ones utilizing treadmill running or repetitive reaching, to investigate the progression of tendinopathies. We developed an in vivo model using the rat patellar tendon that allows control of the loading directly applied to the tendon. This manuscript discusses the response of tendons to fatigue loading and applications of our model. Briefly, the fatigue life of the tendon was used to define low, moderate and high levels of fatigue loading. Morphological assessment showed a progression from mild kinks to fiber disruption, for low to high level fatigue loading. Collagen expression, 1 and 3 days post loading, showed more modest changes for low and moderate than high level fatigue loading. Protein and mRNA expression of Ineterleukin-1β and MMP-13 were upregulated for moderate but not low level fatigue loading. Moderate level (7200 cycles) and 100 cycles of fatigue loading resulted in a catabolic and anabolic molecular profile respectively, at both 1 and 7 days post loading. Results suggest unique mechanisms for different levels of fatigue loading that are distinct from laceration. PMID:21625047

  14. Exercise and Cancer-related Fatigue

    PubMed Central

    Mustian, Karen M; Peppone, Luke J; Palesh, Oxana G; Janelsins, Michelle C; Mohile, Supriya G; Purnell, Jason Q; Darling, Tom V

    2011-01-01

    Cancer-related fatigue is the most common side effect reported by cancer patients during and after treatment. Cancer-related fatigue significantly interferes with a patient’s ability to perform activities of daily living and maintain functional independence and quality of life. Cancer-related fatigue can also interfere with a patient’s ability to complete treatments. The purpose of this article is to provide an overview of cancer-related fatigue, its pathopsychophysiology, and the role of exercise in the management of this side effect. PMID:21853012

  15. Contractile dysfunction in muscle may underlie androgen-dependent motor dysfunction in spinal bulbar muscular atrophy

    PubMed Central

    Oki, Kentaro; Halievski, Katherine; Vicente, Laura; Xu, Youfen; Zeolla, Donald; Poort, Jessica; Katsuno, Masahisa; Adachi, Hiroaki; Sobue, Gen; Wiseman, Robert W.; Breedlove, S. Marc

    2015-01-01

    Spinal and bulbar muscular atrophy (SBMA) is characterized by progressive muscle weakness linked to a polyglutamine expansion in the androgen receptor (AR). Current evidence indicates that mutant AR causes SBMA by acting in muscle to perturb its function. However, information about how muscle function is impaired is scant. One fundamental question is whether the intrinsic strength of muscles, an attribute of muscle independent of its mass, is affected. In the current study, we assess the contractile properties of hindlimb muscles in vitro from chronically diseased males of three different SBMA mouse models: a transgenic (Tg) model that broadly expresses a full-length human AR with 97 CAGs (97Q), a knock-in (KI) model that expresses a humanized AR containing a CAG expansion in the first exon, and a Tg myogenic model that overexpresses wild-type AR only in skeletal muscle fibers. We found that hindlimb muscles in the two Tg models (97Q and myogenic) showed marked losses in their intrinsic strength and resistance to fatigue, but were minimally affected in KI males. However, diseased muscles of all three models showed symptoms consistent with myotonic dystrophy type 1, namely, reduced resting membrane potential and deficits in chloride channel mRNA. These data indicate that muscle dysfunction is a core feature of SBMA caused by at least some of the same pathogenic mechanisms as myotonic dystrophy. Thus mechanisms controlling muscle function per se independent of mass are prime targets for SBMA therapeutics. PMID:25663674

  16. Contractile dysfunction in muscle may underlie androgen-dependent motor dysfunction in spinal bulbar muscular atrophy.

    PubMed

    Oki, Kentaro; Halievski, Katherine; Vicente, Laura; Xu, Youfen; Zeolla, Donald; Poort, Jessica; Katsuno, Masahisa; Adachi, Hiroaki; Sobue, Gen; Wiseman, Robert W; Breedlove, S Marc; Jordan, Cynthia L

    2015-04-01

    Spinal and bulbar muscular atrophy (SBMA) is characterized by progressive muscle weakness linked to a polyglutamine expansion in the androgen receptor (AR). Current evidence indicates that mutant AR causes SBMA by acting in muscle to perturb its function. However, information about how muscle function is impaired is scant. One fundamental question is whether the intrinsic strength of muscles, an attribute of muscle independent of its mass, is affected. In the current study, we assess the contractile properties of hindlimb muscles in vitro from chronically diseased males of three different SBMA mouse models: a transgenic (Tg) model that broadly expresses a full-length human AR with 97 CAGs (97Q), a knock-in (KI) model that expresses a humanized AR containing a CAG expansion in the first exon, and a Tg myogenic model that overexpresses wild-type AR only in skeletal muscle fibers. We found that hindlimb muscles in the two Tg models (97Q and myogenic) showed marked losses in their intrinsic strength and resistance to fatigue, but were minimally affected in KI males. However, diseased muscles of all three models showed symptoms consistent with myotonic dystrophy type 1, namely, reduced resting membrane potential and deficits in chloride channel mRNA. These data indicate that muscle dysfunction is a core feature of SBMA caused by at least some of the same pathogenic mechanisms as myotonic dystrophy. Thus mechanisms controlling muscle function per se independent of mass are prime targets for SBMA therapeutics.

  17. 14 CFR 117.7 - Fatigue risk management system.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... fatigue risk management policy. (2) An education and awareness training program. (3) A fatigue reporting system. (4) A system for monitoring flightcrew fatigue. (5) An incident reporting process. (6) A performance evaluation....

  18. [Treatment Options for Executive Dysfunction].

    PubMed

    Müller, S V

    2016-09-01

    The concept of executive function is a so-called umbrella concept, so that it includes many different and in some cases mutually contradictory higher-level organizational abilities such as planning, monitoring, inhibition and control of action. Typically, the cause of an executive dysfunction is an underlying lesion in the prefrontal cortex or subcortical regions. Deficits in executive functions appear in the fields of cognition as well as behavior. Diagnosis requires the use of a wide-ranging repertoire of tests and questionnaires making it a time-consuming process. Different therapeutic approaches addressing the diverse symptoms of executive dysfunction, both positive and negative, are available. These include modification and manipulation of the environment and practice of cognitive repetitive procedures. The former are implemented particularly in cases of severely impaired persons. The latter are used in persons in whom cognitive dysfunctions are the dominating symptoms of the disorder.The operational area of therapeutic approaches using paper and pencil as well as computer programs limits them to treatment of cognitive dysfunction. If behavioral disturbances dominate the clinical picture, other procedures should be used.The effectiveness of cognitive therapy of executive dysfunction is well demonstrated according to the criteria of evidence-based medicine (EBM). PMID:27607068

  19. Feeling Worn Out? PGC1α to the Rescue for Dysfunctional Mitochondria in T Cell Exhaustion.

    PubMed

    Balmer, Maria L; Hess, Christoph

    2016-08-16

    In chronic viral infections and cancer, T cells acquire a functional state characterized by reduced effector functionality, termed exhaustion. In two related studies by Scharping et al. (2016) and Bengsch et al. (2016) in this issue of Immunity, dysfunctional mitochondria are identified as a key correlate of CD8(+) T cell exhaustion. PMID:27533009

  20. Exercise and fatigue in rheumatoid arthritis.

    PubMed

    Balsamo, Sandor; Diniz, Leonardo R; dos Santos-Neto, Leopoldo L; da Mota, Licia M H

    2014-01-01

    Fatigue, the enduring sensation of weakness, lack of energy, tiredness or exhaustion, is described by 40%-80% of patients with rheumatoid arthritis as their most disabling symptom with wide-ranging consequences for quality of life. Little attention has been paid to its multidimensional nature or to its reliability as a measure to evaluate progression of the disease. Low impact aerobic exercise affects the level of fatigue, and this same level of fatigue influences the exercise itself. We searched Medline, Cochrane Collaboration Register of Controlled Trials (CCRCT), Lilacs, PubMed and Scopus databases for randomized controlled trials (with appropriate description of methods, materials and results) on the assessment of fatigue and exercise. Review articles, case reports, letters to the editor and editorials were excluded. Of 121 references initially identified, 4 randomized controlled trials met the inclusion criteria. Two studies used the MAF scale (Multidimensional Assessment of Fatigue), one used the MAC (Mental Adjustment to Cancer) fatigue scale, and all trials used POMS (Profile of Mood States) to assess fatigue. All four trials conducted a 12 week program of two to three times/ week and different periods of follow-up. Two studies used low impact aerobic exercise, one used dance-based exercise, and another study followed a home cardiopulmonary conditioning program using a stationary bicycle. While fatigue appears to be a reliable outcome measure in the clinical management of RA, especially when related to exercise prescription, further research is needed to evaluate the correlation between exercise, fatigue and quality of life, using fatigue scales validated to explore the different components of fatigue and its wide-ranging consequences.

  1. Clinical neurology and executive dysfunction.

    PubMed

    Filley, C M

    2000-01-01

    Executive function is a uniquely human ability that permits an individual to plan, carry out, and monitor a sequence of actions that is intended to accomplish a goal. This crucial neurobehavioral capacity depends on the integrity of the frontal lobes, most importantly the dorsolateral prefrontal cortices and their connections. Executive dysfunction is associated with a wide range of neurologic disorders that affect these regions. In this paper, executive dysfunction is considered from the perspective of behavioral neurology, and the lesion method is employed to illustrate this impairment in a diverse group of disorders. Frontal system damage leading to disturbed executive function is common and clinically significant. Recognition of this syndrome is critical for ensuring the correct diagnosis, accurate prognosis, and appropriate treatment of affected patients. Executive dysfunction also represents an intriguing aspect of brain-behavior relationships and offers important insights into one of the highest cerebral functions. PMID:10879543

  2. [Sexual dysfunctions in selected endocrinopathies].

    PubMed

    Skrzypulec, Violetta; Nowosielski, Krzysztof; Drosdzol, Agnieszka; Kowalaczyk, Robert

    2005-01-01

    According to the socio-sexological reports approximately 40-45% of women and up to 30% of males may suffer from different sexual dysfunctions. The prevalence of those disorders is gradually increasing with age. Multiply numbers of endocrinopathies may influence the human sexual life. In diabetic patients all phases of the sexual responses cycle, especially orgasm, might be affected. Women diagnosed with PCOS have decreased adaptation to the sexual life, low self-esteem and perception of self sexual attractiveness. The intimacy of infertile couples has not been well described and the characteristic of particular dysfunction in sex life has not been established yet. Interdisciplinary approach, understood as treatment of the endocrinopathy accompanied with psychological and sexological counseling, seems to be the fundamental issue in the therapy of sexual dysfunctions in patients with endocrinological disorders. PMID:16821220

  3. Integrated Circuit Immunity

    NASA Technical Reports Server (NTRS)

    Sketoe, J. G.; Clark, Anthony

    2000-01-01

    This paper presents a DOD E3 program overview on integrated circuit immunity. The topics include: 1) EMI Immunity Testing; 2) Threshold Definition; 3) Bias Tee Function; 4) Bias Tee Calibration Set-Up; 5) EDM Test Figure; 6) EMI Immunity Levels; 7) NAND vs. and Gate Immunity; 8) TTL vs. LS Immunity Levels; 9) TP vs. OC Immunity Levels; 10) 7805 Volt Reg Immunity; and 11) Seventies Chip Set. This paper is presented in viewgraph form.

  4. Subcritical fatigue in fuse networks

    NASA Astrophysics Data System (ADS)

    Oliveira, C. L. N.; Vieira, A. P.; Herrmann, H. J.; Andrade, J. S., Jr.

    2012-11-01

    We obtain the Paris law of fatigue crack propagation in a fuse network model where the accumulated damage in each resistor increases with time as a power law of the local current amplitude. When a resistor reaches its fatigue threshold, it burns irreversibly. Over time, this drives cracks to grow until the system is fractured into two parts. We study the relation between the macroscopic exponent of the crack-growth rate —entering the phenomenological Paris law— and the microscopic damage accumulation exponent, γ, under the influence of disorder. The way the jumps of the growing crack, Δa, and the waiting time between successive breaks, Δt, depend on the type of material, via γ, are also investigated. We find that the averages of these quantities, \\left \\langle \\Delta a\\right \\rangle and \\left \\langle \\Delta t\\right \\rangle /\\left \\langle t_r\\right \\rangle , scale as power laws of the crack length a, \\left \\langle \\Delta a\\right \\rangle \\propto a^{\\alpha } and \\left \\langle \\Delta t\\right \\rangle /\\left \\langle t_r\\right \\rangle \\propto a^{-\\beta } , where \\left \\langle t_r\\right \\rangle is the average rupture time. Strikingly, our results show, for small values of γ, a decrease in the exponent of the Paris law in comparison with the homogeneous case, leading to an increase in the lifetime of breaking materials. For the particular case of γ = 0, when fatigue is exclusively ruled by disorder, an analytical treatment confirms the results obtained by simulation.

  5. Chronic Fatigue Syndrome: How Vulnerable Are Athletes?

    ERIC Educational Resources Information Center

    Eichner, Edward R.

    1989-01-01

    Discusses chronic fatigue syndrome as it affects elite athletes, noting that overtraining may mimic it. In some cases, athletes who have it perform exceedingly well in the face of debilitating fatigue. Among athletes and nonathletes, the cause and the mind-body connection are areas of controversy and research. (Author/SM)

  6. Attention, effort, and fatigue: Neuropsychological perspectives

    NASA Technical Reports Server (NTRS)

    Cohen, Ronald A.; Odonnell, Brian F.

    1988-01-01

    Models of attention, effort, and fatigue are reviewed. Methods are discussed for measuring these phenomena from a neuropsychological and psychophysiological perspective. The following methodologies are included: (1) the autonomic measurement of cognitive effort and quality of encoding; (2) serial assessment approaches to neurophysiological assessment; and (3) the assessment of subjective reports of fatigue using multidimensional ratings and their relationship to neurobehavioral measures.

  7. Compact bone fatigue damage: a microscopic examination.

    PubMed

    Carter, D R; Hayes, W C

    1977-01-01

    Flexural fatigue tests of bovine bone specimens produced fracture surfaces that were transverse on the tension side and oblique on the compression side. Similar fracture patterns were produced by bending tests with a single applied loading. Microscopic examination of flexural fatigue specimens prior to complete established that fatigue fracture is caused by the progressive accumulation of diffuse structural damage. The microdamage observed on the tension side consisted primarily of separation (or debonding) at cement lines and interlamellar cement bands. Tensile cracks in interstitial bone were also observed. The major damage modes on the compression side were oblique cracking and longitudinal splitting. The fatigue fracture patterns observed for the bone specimens correspond to the types of fatigue fractures observed clinically. Compact bone fatigue fractures in areas of longitudinal tensile stresses are generally seen as transverse lesions, whereas fatigue fractures in areas of longitudinal compressive stresses are normally oblique fractures. The diffuse nature of the observed fatigue damage is consistent with the hypothesis that microdamage caused by mechanical loading may serve as a stimulus for in vivo bone remodeling.

  8. Cerebrovascular complications of diabetes: focus on cognitive dysfunction.

    PubMed

    Hardigan, Trevor; Ward, Rebecca; Ergul, Adviye

    2016-10-01

    The incidence of diabetes has more than doubled in the United States in the last 30 years and the global disease rate is projected to double by 2030. Cognitive impairment has been associated with diabetes, worsening quality of life in patients. The structural and functional interaction of neurons with the surrounding vasculature is critical for proper function of the central nervous system including domains involved in learning and memory. Thus, in this review we explore cognitive impairment in patients and experimental models, focusing on links to vascular dysfunction and structural changes. Lastly, we propose a role for the innate immunity-mediated inflammation in neurovascular changes in diabetes. PMID:27634842

  9. Environmental fatigue in aluminum-lithium alloys

    SciTech Connect

    Piascik, R.S.

    1992-07-01

    Aluminum-lithium alloys exhibit similar environmental fatigue crack growth characteristics compared to conventional 2000 series alloys and are more resistant to environmental fatigue compared to 7000 series alloys. The superior fatigue crack growth behavior of Al-Li alloys 2090, 2091, 8090, and 8091 is due to crack closure caused by tortuous crack path morphology and crack surface corrosion products. At high R and reduced closure, chemical environment effects are pronounced resulting in accelerated near threshold da/dN. The beneficial effects of crack closure are minimized for small cracks resulting in rapid growth rates. Limited data suggest that the 'chemically small crack' effect, observed in other alloy system, is not pronounced in Al-Li alloys. Modeling of environmental fatigue in Al-Li-Cu alloys related accelerated fatigue crack growth in moist air and salt water to hydrogen embrittlement.

  10. On the Fatigue Analysis of Wind Turbines

    SciTech Connect

    Sutherland, Herbert J.

    1999-06-01

    Modern wind turbines are fatigue critical machines that are typically used to produce electrical power from the wind. Operational experiences with these large rotating machines indicated that their components (primarily blades and blade joints) were failing at unexpectedly high rates, which led the wind turbine community to develop fatigue analysis capabilities for wind turbines. Our ability to analyze the fatigue behavior of wind turbine components has matured to the point that the prediction of service lifetime is becoming an essential part of the design process. In this review paper, I summarize the technology and describe the ''best practices'' for the fatigue analysis of a wind turbine component. The paper focuses on U.S. technology, but cites European references that provide important insights into the fatigue analysis of wind turbines.

  11. Activity and post-polio fatigue.

    PubMed

    Packer, T L; Martins, I; Krefting, L; Brouwer, B

    1991-11-01

    Fatigue was studied in 12 subjects with post-polio sequelae (PPS). Results of the Fatigue Severity Scale (FSS) demonstrated a mean score of 4.8 +/- 1.6 (non-disabled scores = 2.3 +/- 0.7). The Human Activity Profile (HAP) was not sensitive enough to measure fatigue. Fifty percent of subjects scored below the first percentile based on age and sex matched norms. The Activity Record (ACTRE) results revealed that subjects spent 5% of their time resting and 1% in planning or preparation activities. Fatigue peaked in the late morning or early afternoon and was relieved by rest periods. Use of energy conservation and work simplification skills along with frequent rest periods was suggested as a possible method for managing PPS fatigue.

  12. Interconnect fatigue design for terrestrial photovoltaic modules

    NASA Technical Reports Server (NTRS)

    Mon, G. R.; Moore, D. M.; Ross, R. G., Jr.

    1982-01-01

    The results of comprehensive investigation of interconnect fatigue that has led to the definition of useful reliability-design and life-prediction algorithms are presented. Experimental data indicate that the classical strain-cycle (fatigue) curve for the interconnect material is a good model of mean interconnect fatigue performance, but it fails to account for the broad statistical scatter, which is critical to reliability prediction. To fill this shortcoming the classical fatigue curve is combined with experimental cumulative interconnect failure rate data to yield statistical fatigue curves (having failure probability as a parameter) which enable (1) the prediction of cumulative interconnect failures during the design life of an array field, and (2) the unambiguous--ie., quantitative--interpretation of data from field-service qualification (accelerated thermal cycling) tests. Optimal interconnect cost-reliability design algorithms are derived based on minimizing the cost of energy over the design life of the array field.

  13. Multiscale Fatigue Life Prediction for Composite Panels

    NASA Technical Reports Server (NTRS)

    Bednarcyk, Brett A.; Yarrington, Phillip W.; Arnold, Steven M.

    2012-01-01

    Fatigue life prediction capabilities have been incorporated into the HyperSizer Composite Analysis and Structural Sizing Software. The fatigue damage model is introduced at the fiber/matrix constituent scale through HyperSizer s coupling with NASA s MAC/GMC micromechanics software. This enables prediction of the micro scale damage progression throughout stiffened and sandwich panels as a function of cycles leading ultimately to simulated panel failure. The fatigue model implementation uses a cycle jumping technique such that, rather than applying a specified number of additional cycles, a specified local damage increment is specified and the number of additional cycles to reach this damage increment is calculated. In this way, the effect of stress redistribution due to damage-induced stiffness change is captured, but the fatigue simulations remain computationally efficient. The model is compared to experimental fatigue life data for two composite facesheet/foam core sandwich panels, demonstrating very good agreement.

  14. Effects of two neuromuscular fatigue protocols on landing performance.

    PubMed

    James, C Roger; Scheuermann, Barry W; Smith, Michael P

    2010-08-01

    The purpose of the study was to investigate the effects of two fatigue protocols on landing performance. A repeated measures design was used to examine the effects of fatigue and fatigue protocol on neuromuscular and biomechanical performance variables. Ten volunteers performed non-fatigued and fatigued landings on two days using different fatigue protocols. Repeated maximum isometric squats were used to induce fatigue on day one. Sub-maximum cycling was used to induce fatigue on day two. Isometric squat maximum voluntary contraction (MVC) was measured before and after fatigued landings on each day. During the landings, ground reaction force (GRF), knee kinematics, and electromyographic (EMG) data were recorded. Isometric MVC, GRF peaks, loading rates, impulse, knee flexion at contact, range of motion, max angular velocity, and EMG root mean square (RMS) values were compared pre- and post-fatiguing exercise and between fatigue protocols using repeated ANOVA. Fatigue decreased MVC strength (p0.05), GRF second peak, and initial impulse (p0.01), but increased quadriceps medium latency stretch reflex EMG activity (p0.012). Knee flexion at contact was 5.2 degrees greater (p0.05) during fatigued landings following the squat exercise compared to cycling. Several variables exhibited non-significant but large effect sizes when comparing the effects of fatigue and fatigue protocol. In conclusion, fatigue alters landing performance and different fatigue protocols result in different performance changes.

  15. Notched Fatigue Behavior of PEEK

    PubMed Central

    Murphy, JE; Brinkman, JG; Kurtz, SM; Rimnac, CM

    2013-01-01

    Poly(ether-ether-ketone) (PEEK) has been used as a load bearing orthopaedic implant material with clinical success. All of the orthopaedic applications contain stress concentrations (notches) in their design; however, little work has been done to examine the fatigue behavior of PEEK in the presence of a notch. This work examines both stress-life (SN) fatigue behavior and the fracture behavior of unfilled PEEK under tension tension loading in circumferentially grooved round bar specimens with different elastic stress concentration factors. It was found that the majority of the loading was elastic in nature, and that there was only a small portion on the lifetime where there was a detectable change in structural behavior prior to gross fracture. Fractographic analysis via SEM further elucidated the potential fracture micromechanisms. Additional analysis was conducted to estimate the percent of the lifetime spent in crack initiation vs propagation, and it was found that the specimens spent the majority of the time in the crack initiation phase. PMID:20864160

  16. Muscle glycogen stores and fatigue.

    PubMed

    Ørtenblad, Niels; Westerblad, Håkan; Nielsen, Joachim

    2013-09-15

      Studies performed at the beginning of the last century revealed the importance of carbohydrate as a fuel during exercise, and the importance of muscle glycogen on performance has subsequently been confirmed in numerous studies. However, the link between glycogen depletion and impaired muscle function during fatigue is not well understood and a direct cause-and-effect relationship between glycogen and muscle function remains to be established. The use of electron microscopy has revealed that glycogen is not homogeneously distributed in skeletal muscle fibres, but rather localized in distinct pools. Furthermore, each glycogen granule has its own metabolic machinery with glycolytic enzymes and regulating proteins. One pool of such glycogenolytic complexes is localized within the myofibrils in close contact with key proteins involved in the excitation-contraction coupling and Ca2+ release from the sarcoplasmic reticulum (SR). We and others have provided experimental evidence in favour of a direct role of decreased glycogen, localized within the myofibrils, for the reduction in SR Ca2+ release during fatigue. This is consistent with compartmentalized energy turnover and distinctly localized glycogen pools being of key importance for SR Ca2+ release and thereby affecting muscle contractility and fatigability.

  17. Muscle glycogen stores and fatigue

    PubMed Central

    Ørtenblad, Niels; Westerblad, Håkan; Nielsen, Joachim

    2013-01-01

    Studies performed at the beginning of the last century revealed the importance of carbohydrate as a fuel during exercise, and the importance of muscle glycogen on performance has subsequently been confirmed in numerous studies. However, the link between glycogen depletion and impaired muscle function during fatigue is not well understood and a direct cause-and-effect relationship between glycogen and muscle function remains to be established. The use of electron microscopy has revealed that glycogen is not homogeneously distributed in skeletal muscle fibres, but rather localized in distinct pools. Furthermore, each glycogen granule has its own metabolic machinery with glycolytic enzymes and regulating proteins. One pool of such glycogenolytic complexes is localized within the myofibrils in close contact with key proteins involved in the excitation–contraction coupling and Ca2+ release from the sarcoplasmic reticulum (SR). We and others have provided experimental evidence in favour of a direct role of decreased glycogen, localized within the myofibrils, for the reduction in SR Ca2+ release during fatigue. This is consistent with compartmentalized energy turnover and distinctly localized glycogen pools being of key importance for SR Ca2+ release and thereby affecting muscle contractility and fatigability. PMID:23652590

  18. Mitochondrial dysfunction in Parkinson's disease.

    PubMed

    Hu, Qingsong; Wang, Guanghui

    2016-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease, which is characterized by loss of dopaminergic (DA) neurons in the substantia nigra pars compacta and the formation of Lewy bodies and Lewy neurites in surviving DA neurons in most cases. Although the cause of PD is still unclear, the remarkable advances have been made in understanding the possible causative mechanisms of PD pathogenesis. Numerous studies showed that dysfunction of mitochondria may play key roles in DA neuronal loss. Both genetic and environmental factors that are associated with PD contribute to mitochondrial dysfunction and PD pathogenesis. The induction of PD by neurotoxins that inhibit mitochondrial complex I provides direct evidence linking mitochondrial dysfunction to PD. Decrease of mitochondrial complex I activity is present in PD brain and in neurotoxin- or genetic factor-induced PD cellular and animal models. Moreover, PINK1 and parkin, two autosomal recessive PD gene products, have important roles in mitophagy, a cellular process to clear damaged mitochondria. PINK1 activates parkin to ubiquitinate outer mitochondrial membrane proteins to induce a selective degradation of damaged mitochondria by autophagy. In this review, we summarize the factors associated with PD and recent advances in understanding mitochondrial dysfunction in PD. PMID:27453777

  19. Sexual dysfunction in infertile women

    PubMed Central

    Zare, Zahra; Amirian, Malihe; Golmakani, Nahid; Mazlom, Reza; Laal Ahangar, Mojtaba

    2016-01-01

    Background: Sexual problems have different effects on the life of people by influencing their interpersonal and marital relationships and satisfaction. Relationship between sexual dysfunctions and infertility can be mutual. Sexual dysfunction may cause difficulty conceiving but also attempts to conceive, may cause sexual dysfunction. Objective: This paper compares sexual dysfunction in fertile and infertile women. Materials and Methods: In this cross-sectional study, 110 infertile couples referring to Montasarieh Infertility Clinic and 110 fertile couples referring to five healthcare centers in Mashhad were selected by class cluster sampling method. Data collection tools included demographic questionnaire and Glombok-Rust Inventory of Sexual Satisfaction. Data were analyzed through descriptive and analytical statistical methods by SPSS. Results: There was no significant difference in total score of sexual problems and other dimensions of sexual problems (except infrequency) in fertile 28.9 (15.5) and infertile 29.0 (15.4) women. Fertile women had more infrequency than infertile women (p=0.002). Conclusion: There was no significant difference between fertile and infertile women in terms of sexual problems. Paying attention to sexual aspects of infertility and presence of programs for training of sexual skills seems necessary for couples. PMID:27200422

  20. Current Concepts in Ejaculatory Dysfunction

    PubMed Central

    Wolters, Jeffrey P; Hellstrom, Wayne J. G

    2006-01-01

    Although erectile dysfunction has recently become the most well-known aspect of male sexual dysfunction, the most prevalent male sexual disorders are ejaculatory dysfunctions. Ejaculatory disorders are divided into 4 categories: premature ejaculation (PE), delayed ejaculation, retrograde ejaculation, and anejaculation/anorgasmia. Pharmacologic treatment for certain ejaculatory disorders exists, for example the off-label use of selective serotonin reuptake inhibitors for PE. Unfortunately, the other ejaculatory disorders are less studied and not as well understood. This review revisits the physiology of the normal ejaculatory response, specifically explores the mechanisms of anejaculation, and presents emerging data. The neurophysiology of the ejaculatory reflex is complex, making classification of the role of individual neurotransmitters extremely difficult. However, recent research has elucidated more about the role of serotonin and dopamine at the central level in the physiology of both arousal and orgasm. Other recent studies that look at differing pharmacokinetic profiles and binding affinities of the α1-antagonists serve as an indication of the centrally mediated role of ejaculation and orgasm. As our understanding of the interaction between central and peripheral modulations and regulation of the process of ejaculation increases, the probability of developing centrally acting pharmaceutical agents for the treatment of sexual dysfunction approaches reality. PMID:17215997

  1. Photobiomodulation on alcohol induced dysfunction

    NASA Astrophysics Data System (ADS)

    Yang, Zheng-Ping; Liu, Timon C.; Zhang, Yan; Wang, Yan-Fang

    2007-05-01

    Alcohol, which is ubiquitous today, is a major health concern. Its use was already relatively high among the youngest respondents, peaked among young adults, and declined in older age groups. Alcohol is causally related to more than 60 different medical conditions. Overall, 4% of the global burden of disease is attributable to alcohol, which accounts for about as much death and disability globally as tobacco and hypertension. Alcohol also promotes the generation of reactive oxygen species (ROS) and/or interferes with the body's normal defense mechanisms against these compounds through numerous processes, particularly in the liver. Photobiomodulation (PBM) is a cell-specific effect of low intensity monochromatic light or low intensity laser irradiation (LIL) on biological systems. The cellular effects of both alcohol and LIL are ligand-independent so that PBM might rehabilitate alcohol induced dysfunction. The PBM on alcohol induced human neutrophil dysfunction and rat chronic atrophic gastritis, the laser acupuncture on alcohol addiction, and intravascular PBM on alcoholic coma of patients and rats have been observed. The endonasal PBM (EPBM) mediated by Yangming channel, autonomic nervous systems and blood cells is suggested to treat alcohol induced dysfunction in terms of EPBM phenomena, the mechanism of alcohol induced dysfunction and our biological information model of PBM. In our opinion, the therapeutic effects of PBM might also be achieved on alcoholic myopathy.

  2. Acute Changes in Striatal Microstructure Predict the Development of Interferon-Alpha Induced Fatigue

    PubMed Central

    Dowell, Nicholas G.; Cooper, Ella A.; Tibble, Jeremy; Voon, Valerie; Critchley, Hugo D.; Cercignani, Mara; Harrison, Neil A.

    2016-01-01

    Background Interferon-alpha (IFN-α) is a key mediator of antiviral immune responses used clinically for hepatitis C treatment. Though effective, IFN-α induces marked behavioral changes that, when severe, can appear indistinguishable from major depression. Curiously, fatigue and motivational impairment evolve rapidly, suggesting acute engagement of immune-brain communicatory pathways, yet mood impairments typically emerge later, after weeks of treatment. Whether this reflects prolonged modulation of motivational processes underpinning fatigue or separate neurobiological mechanisms is currently unclear. Methods Here, we used quantitative magnetization transfer (qMT) imaging, an advanced microstructural neuroimaging technique sensitive to effects of inflammation, in a prospective study design to measure acute brain changes to IFN-α and relate these to later development of discrete behavioral changes. Twenty-three patients initiating IFN-α treatment for hepatitis C underwent qMT imaging and blood sampling at baseline and 4 hours after their first IFN-α injection. Comprehensive behavioral and psychological assessments were completed at both scanning sessions and at treatment weeks 4, 8, 12, and 24. Results IFN-α injection stimulated an acute inflammatory cytokine response and evoked fatigue that peaked between 4 and 12 weeks, preceding mood change by 4 weeks. In the brain, IFN-α induced an acute change in striatal microstructure that additionally predicted development of fatigue but not mood symptoms. Conclusions Our findings highlight qMT as an in vivo biomarker of central effects of peripheral inflammation. We demonstrate exquisite sensitivity of the striatum to IFN-α, implicate striatal perturbation in IFN-α-induced fatigue, and dissociate this from mechanisms underlying IFN-α-induced mood symptoms, providing empirical support for distinct neural substrates mediating actions on motivation and mood. PMID:26169252

  3. Endothelial cell dysfunction in viral hemorrhage and edema

    PubMed Central

    Mackow, Erich R.; Gorbunova, Elena E.; Gavrilovskaya, Irina N.

    2015-01-01

    The endothelium maintains a vascular barrier by controlling platelet and immune cell interactions, capillary tone and interendothelial cell (EC) adherence. Here we suggest common elements in play during viral infection of the endothelium that alter normal EC functions and contribute to lethal hemorrhagic or edematous diseases. In viral reservoir hosts, infection of capillaries and lymphatic vessels may direct immunotolerance without disease, but in the absence of these cognate interactions they direct the delayed onset of human disease characterized by thrombocytopenia and vascular leakage in a severe endothelial dysfunction syndrome. Here we present insight into EC controls of hemostasis, immune response and capillary permeability that are altered by viral infection of the endothelium. PMID:25601858

  4. German experiences in local fatigue monitoring

    SciTech Connect

    Abib, E.; Bergholz, S.; Rudolph, J.

    2012-07-01

    The ageing management of nuclear power plants (NPP) has gained an increasing importance in the last years. The reasons are mainly due to the international context of extending period of plants operation. Moreover, new scientific discoveries, such as the corrosive influence of the medium on the fatigue process (environmentally assisted fatigue - EAF) play an important role and influence the code development (ASME, EAF code cases). The fatigue damage process takes a central position in ageing mechanisms of components. It must be ensured through appropriate evidence that facilities are being operated under allowable boundary conditions. In the design phase of NPP, fatigue analyses are still based on theoretical considerations and empirical values, which are summarized in the design transient catalogue, necessary for licensing. These analyses aim at proving the admissibility of the loads in terms of stress and fatigue usage. These analyses will also provide the fatigue-relevant positions in the NPP and give a basis for future design improvements and optimization of operating modes. The design transients are in practice conservatively correlated with the real transients occurring during operation. Uncertainties reveal very conservative assumptions regarding forecast temperatures, temperature gradients and frequencies of events. During operation of the plant, it has to be recurrently proved, that the plant is being operated under designed boundary conditions. Moreover, operating signals are constantly acquired to enable a fatigue evaluation. For example, in Germany fatigue evaluation is based on decades of experience and regulatory requirements. The rule KTA 3201.4 [1] establishes the rules for qualified fatigue monitoring. The rule DIN 25475-3 [2] on fatigue monitoring systems is available in draft version. Experience shows that some significant differences occur between the design transients and the real occurred transients during plant operation. The reasons for it

  5. Central Nervous System-Peripheral Immune System Dialogue in Neurological Disorders: Possible Application of Neuroimmunology in Urology.

    PubMed

    Park, Hyun-Sun; Park, Min-Jung; Kwon, Min-Soo

    2016-05-01

    Previous concepts of immune-privileged sites obscured the role of peripheral immune cells in neurological disorders and excluded the consideration of the potential benefits of immunotherapy. Recently, however, numerous studies have demonstrated that the blood-brain barrier in the central nervous system is an educational barrier rather than an absolute barrier to peripheral immune cells. Emerging knowledge of immune-privileged sites suggests that peripheral immune cells can infiltrate these sites via educative gates and that crosstalk can occur between infiltrating immune cells and the central nervous system parenchyma. This concept can be expanded to the testis, which has long been considered an immune-privileged site, and to neurogenic bladder dysfunction. Thus, we propose that the relationship between peripheral immune cells, the brain, and the urologic system should be considered as an additional possible mechanism in urologic diseases, and that immunotherapy might be an alternative therapeutic strategy in treating neurogenic bladder dysfunction.

  6. Central Nervous System-Peripheral Immune System Dialogue in Neurological Disorders: Possible Application of Neuroimmunology in Urology

    PubMed Central

    2016-01-01

    Previous concepts of immune-privileged sites obscured the role of peripheral immune cells in neurological disorders and excluded the consideration of the potential benefits of immunotherapy. Recently, however, numerous studies have demonstrated that the blood–brain barrier in the central nervous system is an educational barrier rather than an absolute barrier to peripheral immune cells. Emerging knowledge of immune-privileged sites suggests that peripheral immune cells can infiltrate these sites via educative gates and that crosstalk can occur between infiltrating immune cells and the central nervous system parenchyma. This concept can be expanded to the testis, which has long been considered an immune-privileged site, and to neurogenic bladder dysfunction. Thus, we propose that the relationship between peripheral immune cells, the brain, and the urologic system should be considered as an additional possible mechanism in urologic diseases, and that immunotherapy might be an alternative therapeutic strategy in treating neurogenic bladder dysfunction. PMID:27230462

  7. Fatigue

    MedlinePlus

    ... depression. The chances that you are depressed are higher if you have previously been diagnosed with depression, if you have a history of heavy alcohol or recreational drug use, or if you have ...

  8. Cytomegalovirus driven immunosenescence-An immune phenotype with or without clinical impact?

    PubMed

    Söderberg-Nauclér, Cecilia; Fornara, Olesja; Rahbar, Afsar

    2016-09-01

    The continuous emerging increase in life span has led to vulnerability to a number of different diseases in the elderly. Some of these risks may be attributed to specific changes in the immune system referred to as immunoscenescence. This term aims to describe decreased immune functions among elderly individuals, and is characterized to be harmful age-associated changes in the immune system that lead to its gradual immune dysfunction. An impaired function of the immune system may increase susceptibility to various diseases in the elderly population such as infections, cardiovascular diseases and cancer. Although it is unclear how this immune phenotype develops, emerging evidence suggest that it may reflect an exhaustion of the immune system, possibly caused by one or several chronic infections. The main candidate is human cytomegalovirus (CMV), which can induce immune dysfunctions observed in immunoscenescence. Although the immune system is currently considered to be exhausted in CMV positive elderly individuals, it is not known whether such dysfunction of the immune system is a main reason for increased susceptibility to other diseases, or if direct effects of the virus in disease pathogenesis reflect the increased vulnerability to them. These aspects will be discussed in this review.

  9. Immunity and immunization in elderly.

    PubMed

    Bourée, Patrice

    2003-12-01

    As the average life expectancy increases, retired people want to travel. Five to 8% of travellers in tropical areas are old persons. Immune system suffers of old age as the other organs. The number and the functions of the T-lymphocytes decrease, but the B-lymphocytes are not altered. So, the response to the vaccinations is slower and lower in the elderly. Influenza is a great cause of death rate in old people. The seroconversion, after vaccine, is 50% from 60 to 70 years old, 31% from 70 to 80 years old, and only 11% after 80 years old. But in public health, the vaccination reduced the morbidity by 25%, admission to hospital by 20%, pneumonia by 50%, and mortality by 70%. Antipoliomyelitis vaccine is useful for travellers, as the vaccines against hepatitis and typhoid fever. Pneumococcal vaccine is effective in 60%. Tetanus is fatal in at last 32% of the people above 80 years, therefore this vaccine is very important.

  10. 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

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

    PubMed Central

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

    2003-01-01

    Background: Persistent fatigue among employees, burnout, and chronic fatigue syndrome (CFS) are three fatigue conditions that share some characteristics in theory. However, these conditions have not been compared in empirical research, despite conceptual similarities. Methods: This cross sectional study aimed to investigate relations between persistent fatigue, burnout, and CFS by describing the clinical features of a sample of 151 fatigued employees on sick leave. Using validated instruments, subgroups based on research criteria for CFS and burnout within the sample of fatigued employees and a reference group of 97 diagnosed CFS patients were compared. Analyses of covariance were performed. Results: A total of 66 (43.7%) fatigued employees met research criteria for CFS (except symptom criteria) and 76 (50.3%) met research criteria for burnout. "CFS-like employees" (fatigued employees who met CFS criteria) reported stronger somatic attributions than "non-CFS-like employees". Burnt out CFS-like employees were more depressed and distressed than CFS-like employees who were not burnt out. Burnout cases among the non-CFS-like employees had stronger psychological attributions than fatigued employees who were not burnt out. Compared to diagnosed CFS patients, CFS-like employees merely had a shorter duration of fatigue complaints. Burnt out CFS-like employees had stronger psychological attributions and were more distressed than CFS patients. Conclusions: Fatigued employees shared many important characteristics with CFS patients, regardless of burnout status, and many fatigued employees met CFS criteria and/or burnout criteria. Differences however concerned the causal attributions that were made. This raises questions about the role of causal attributions: are they modified by fatigue complaints or do they determine illness outcome? PMID:12782744

  12. Exercise, intestinal barrier dysfunction and probiotic supplementation.

    PubMed

    Lamprecht, Manfred; Frauwallner, Anita

    2012-01-01

    Athletes exposed to high-intensity exercise show an increased occurrence of gastrointestinal (GI) symptoms like cramps, diarrhea, bloating, nausea, and bleeding. These problems have been associated with alterations in intestinal permeability and decreased gut barrier function. The increased GI permeability, a so-called 'leaky gut', also leads to endotoxemia, and results in increased susceptibility to infectious and autoimmune diseases, due to absorption of pathogens/toxins into tissue and the bloodstream. Key components that determine intestinal barrier function and GI permeability are tight junctions, protein structures located in the paracellular channels between epithelial cells of the intestinal wall. The integrity of tight junctions depends on sophisticated interactions between the gut residents and their expressed substances, the intestinal epithelial cell metabolism and the activities of the gut-associated lymphoid tissue. Probiotic supplements are an upcoming group of nutraceuticals that could offer positive effects on athlete's gut and entire health. Some results demonstrate promising benefits for probiotic use on the athlete's immune system. There is also evidence that probiotic supplementation can beneficially influence intestinal barrier integrity in acute diseases. With regard to exercise-induced GI permeability problems, there is still a lack of studies with appropriate data and a gap to understand the underlying mechanisms to support such health beneficial statements implicitly. This article refers (i) to exercise-induced intestinal barrier dysfunction, (ii) provides suggestions to estimate increased gut barrier permeability in athletes, and (iii) discusses the potential of probiotic supplementation to counteract an exercise-induced leaky gut. PMID:23075554

  13. Immune System Involvement

    MedlinePlus

    ... Tips" to find out more! Email * Zipcode The Immune System and Psoriatic Disease What is an autoimmune disease? ... swollen and painful joints and tendons. Treating the immune system The immune system is not only the key ...

  14. Immunization and Pregnancy

    MedlinePlus

    Immunization & Pregnancy Vaccines help keep apregnant woman and her growing family healthy. Vaccine Before pregnancy Hepatitis A ... 232-4636) • English or Spanish National Center for Immunization and Respiratory Diseases Immunization Services Division CS238938B 03/ ...

  15. Childhood Immunization Schedule

    MedlinePlus

    ... Recommendations Why Immunize? Vaccines: The Basics Instant Childhood Immunization Schedule Recommend on Facebook Tweet Share Compartir Get ... date. See Disclaimer for additional details. Based on Immunization Schedule for Children 0 through 6 Years of ...

  16. 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.

  17. 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... Deficiencies § 4.88a Chronic fatigue syndrome. (a) For VA purposes, the diagnosis of chronic fatigue syndrome requires: (1) new onset of debilitating fatigue severe enough to reduce daily activity to less than...

  18. 38 CFR 4.88a - Chronic fatigue syndrome.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Chronic fatigue syndrome... Deficiencies § 4.88a Chronic fatigue syndrome. (a) For VA purposes, the diagnosis of chronic fatigue syndrome requires: (1) new onset of debilitating fatigue severe enough to reduce daily activity to less than...

  19. 38 CFR 4.88a - Chronic fatigue syndrome.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Chronic fatigue syndrome... Deficiencies § 4.88a Chronic fatigue syndrome. (a) For VA purposes, the diagnosis of chronic fatigue syndrome requires: (1) new onset of debilitating fatigue severe enough to reduce daily activity to less than...

  20. 38 CFR 4.88a - Chronic fatigue syndrome.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Chronic fatigue syndrome... Deficiencies § 4.88a Chronic fatigue syndrome. (a) For VA purposes, the diagnosis of chronic fatigue syndrome requires: (1) new onset of debilitating fatigue severe enough to reduce daily activity to less than...

  1. 38 CFR 4.88a - Chronic fatigue syndrome.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Chronic fatigue syndrome... Deficiencies § 4.88a Chronic fatigue syndrome. (a) For VA purposes, the diagnosis of chronic fatigue syndrome requires: (1) new onset of debilitating fatigue severe enough to reduce daily activity to less than...

  2. Managing fatigue: It really is about sleep.

    PubMed

    Darwent, David; Dawson, Drew; Paterson, Jessica L; Roach, Gregory D; Ferguson, Sally A

    2015-09-01

    Biomathematical models of fatigue can assist organisations to estimate the fatigue consequences of a roster before operations commence. These estimates do not account for the diversity of sleep behaviours exhibited by employees. The purpose of this study was to develop sleep transfer functions describing the likely distributions of sleep around fatigue level estimates produced by a commercial biomathematical model of fatigue. Participants included 347 (18 females, 329 males) train drivers working commercial railway operations in Australia. They provided detailed information about their sleep behaviours using sleep diaries and wrist activity monitors. On average, drivers slept for 7.7 (±1.7)h in the 24h before work and 15.1 (±2.5)h in the 48h before work. The amount of sleep obtained by drivers before shifts differed only marginally across morning, afternoon and night shifts. Shifts were also classified into one of seven ranked categories using estimated fatigue level scores. Higher fatigue score categories were associated with significant reductions in the amount of sleep obtained before shifts, but there was substantial within-category variation. The study findings demonstrate that biomathematical models of fatigue have utility for designing round-the-clock rosters that provide sufficient sleep opportunities for the average employee. Robust variability in the amount of sleep obtained by drivers indicate that models are relatively poor tools for ensuring that all employees obtain sufficient sleep. These findings demonstrate the importance of developing approaches for managing the sleep behaviour of individual employees. PMID:26026969

  3. Fatigue and cardiorespiratory function following abdominal surgery.

    PubMed

    Christensen, T; Bendix, T; Kehlet, H

    1982-07-01

    Subjective feelings of fatigue were assessed before operation and 10, 20 and 30 days after uncomplicated elective abdominal surgery in 16 otherwise healthy patients, using a constructed fatigue scale model. In addition, all patients had an orthostatic stress test performed at the same times. Six of the patients also underwent a bicycle ergometer test measuring heart rate and oxygen consumption. Subjective feelings of fatigue were increased (P less than 0.01) at all three postoperative observations, and only 5 of 16 patients returned to their preoperative level. The increased subjective feeling of fatigue correlated positively (RS = 0.53, P less than 0.001) with the increased pulse rate seen during orthostatic stress after operation. Heart rate was about 5 per cent higher (n.s.) after operation when bicycling at the same work loads, while oxygen consumption decreased by about 2 per cent (P less than 0.01) at all three postoperative bicycle tests. It is concluded that even electric uncomplicated abdominal surgery is followed by a pronounced feeling of fatigue, which may persist 1 month after surgery in about one-third of patients. The fatigue scale model seems applicable for future studies on the pathogenesis and treatment of the postoperative fatigue syndrome.

  4. Fatigue crack propagation analysis of plaque rupture.

    PubMed

    Pei, Xuan; Wu, Baijian; Li, Zhi-Yong

    2013-10-01

    Rupture of atheromatous plaque is the major cause of stroke or heart attack. Considering that the cardiovascular system is a classic fatigue environment, plaque rupture was treated as a chronic fatigue crack growth process in this study. Fracture mechanics theory was introduced to describe the stress status at the crack tip and Paris' law was used to calculate the crack growth rate. The effect of anatomical variation of an idealized plaque cross-section model was investigated. The crack initiation was considered to be either at the maximum circumferential stress location or at any other possible locations around the lumen. Although the crack automatically initialized at the maximum circumferential stress location usually propagated faster than others, it was not necessarily the most critical location where the fatigue life reached its minimum. We found that the fatigue life was minimum for cracks initialized in the following three regions: the midcap zone, the shoulder zone, and the backside zone. The anatomical variation has a significant influence on the fatigue life. Either a decrease in cap thickness or an increase in lipid pool size resulted in a significant decrease in fatigue life. Comparing to the previously used stress analysis, this fatigue model provides some possible explanations of plaque rupture at a low stress level in a pulsatile cardiovascular environment, and the method proposed here may be useful for further investigation of the mechanism of plaque rupture based on in vivo patient data.

  5. Fatigue performance of welded aluminum deck structures

    SciTech Connect

    Haagensen, P.J.; Ranes, M.; Kluken, A.O.; Kvale, I.

    1996-12-01

    Aluminum alloys are used increasingly in load carrying structures where low weight and low maintenance costs are at a premium. Helicopter decks, structures for living quarters and personnel transfer bridges between platforms are examples of offshore applications. While these structures are not usually subjected to high fatigue loads, the increasing use of aluminum in high speed ships, and more recently in highway bridge structures, makes the question of fatigue performance more important. In this paper the fatigue properties of small scale weldments in an AA6005 alloy are compared with the results of fatigue tests on full scale sections of welded extrusions in the same material, which were used in an aluminum bridge deck structure. The fatigue performance is also compared with the fatigue clauses in the new British design code BS8118 for aluminium structures and the proposed Eurocode 9. The prospects of using a new joining technique, friction stir welding (FSW), in the production of large scale panels for deck and ship hull structures is discussed. The FSW process is described briefly, and some fatigue test data are presented.

  6. Managing fatigue: It really is about sleep.

    PubMed

    Darwent, David; Dawson, Drew; Paterson, Jessica L; Roach, Gregory D; Ferguson, Sally A

    2015-09-01

    Biomathematical models of fatigue can assist organisations to estimate the fatigue consequences of a roster before operations commence. These estimates do not account for the diversity of sleep behaviours exhibited by employees. The purpose of this study was to develop sleep transfer functions describing the likely distributions of sleep around fatigue level estimates produced by a commercial biomathematical model of fatigue. Participants included 347 (18 females, 329 males) train drivers working commercial railway operations in Australia. They provided detailed information about their sleep behaviours using sleep diaries and wrist activity monitors. On average, drivers slept for 7.7 (±1.7)h in the 24h before work and 15.1 (±2.5)h in the 48h before work. The amount of sleep obtained by drivers before shifts differed only marginally across morning, afternoon and night shifts. Shifts were also classified into one of seven ranked categories using estimated fatigue level scores. Higher fatigue score categories were associated with significant reductions in the amount of sleep obtained before shifts, but there was substantial within-category variation. The study findings demonstrate that biomathematical models of fatigue have utility for designing round-the-clock rosters that provide sufficient sleep opportunities for the average employee. Robust variability in the amount of sleep obtained by drivers indicate that models are relatively poor tools for ensuring that all employees obtain sufficient sleep. These findings demonstrate the importance of developing approaches for managing the sleep behaviour of individual employees.

  7. Effects of human fatigue on speech signals

    NASA Astrophysics Data System (ADS)

    Stamoulis, Catherine

    2001-05-01

    Cognitive performance may be significantly affected by fatigue. In the case of critical personnel, such as pilots, monitoring human fatigue is essential to ensure safety and success of a given operation. One of the modalities that may be used for this purpose is speech, which is sensitive to respiratory changes and increased muscle tension of vocal cords, induced by fatigue. Age, gender, vocal tract length, physical and emotional state may significantly alter speech intensity, duration, rhythm, and spectral characteristics. In addition to changes in speech rhythm, fatigue may also affect the quality of speech, such as articulation. In a noisy environment, detecting fatigue-related changes in speech signals, particularly subtle changes at the onset of fatigue, may be difficult. Therefore, in a performance-monitoring system, speech parameters which are significantly affected by fatigue need to be identified and extracted from input signals. For this purpose, a series of experiments was performed under slowly varying cognitive load conditions and at different times of the day. The results of the data analysis are presented here.

  8. Fatigue during intermittent-sprint exercise.

    PubMed

    Bishop, David J

    2012-09-01

    1. There is a reversible decline in force production by muscles when they are contracting at or near their maximum capacity. The task-dependent nature of fatigue means that the mechanisms of fatigue may differ between different types of contractions. This paper examines how fatigue manifests during whole-body, intermittent-sprint exercise and discusses the potential muscular and neural mechanisms that underpin this fatigue. 2. Fatigue is defined as a reversible, exercise-induced reduction in maximal power output (e.g. during cycling exercise) or speed (e.g. during running exercise), even though the task can be continued. 3. The small changes in surface electromyogram (EMG), along with a lack of change in voluntary muscle activation (estimated from both percutaneous motor nerve stimulations and trans-cranial magnetic stimulation), indicate that there is little change in neural drive to the muscles following intermittent-sprint exercise. This, along with the observation that the decrease in EMG is much less than that which would be predicted from the decrease in power output, suggests that peripheral mechanisms are the predominant cause of fatigue during intermittent-sprint exercise. 4. At the muscle level, limitations in energy supply, including phosphocreatine hydrolysis and the degree of reliance on anaerobic glycolysis and oxidative metabolism, and the intramuscular accumulation of metabolic by-products, such as hydrogen ions, emerge as key factors responsible for fatigue.

  9. Fatigue Properties of Cast Magnesium Wheels

    NASA Astrophysics Data System (ADS)

    Li, Zhenming; Luo, Alan A.; Wang, Qigui; Peng, Liming; Zhang, Peng

    2016-08-01

    This paper investigates the fatigue properties and deformation behavior of a newly developed Mg-2.96Nd-0.21Zn-0.39Zr magnesium alloy wheel in both as-cast and T6 conditions. Compared with the as-cast alloy, the T6-treated alloy shows a significant increase in fatigue strength and cyclic stress amplitude. This is believed to be attributed to the change of defect type from porosity to oxides and the increased matrix strength in the T6 (peak-aged) condition. For the as-cast alloy wheel, fatigue failure mainly originated from the cast defects including porosity, oxide film, and inclusion at or near the sample surface. In the T6-treated alloy, however, oxides and inclusions or slip bands initiate the fatigue cracks. Solution treatment appears to reduce or eliminate the shrinkage porosity because of grain growth and dissolution of as-cast eutectic phases in the grain boundaries. The cyclic stress amplitude of the as-cast alloy increases with increasing the number of cycles, while the T6-treated alloy shows cyclic softening after the stress reaches a maximum value. The Coffin-Manson law and Basquin equation can be used to evaluate the life of low cycle fatigue. The developed long crack model and multi-scale fatigue (MSF) models can be used to predict high-cycle fatigue life of the Mg-2.96Nd-0.21Zn-0.39Zr alloys with or without casting defects.

  10. Mental fatigue impairs physical performance in humans.

    PubMed

    Marcora, Samuele M; Staiano, Walter; Manning, Victoria

    2009-03-01

    Mental fatigue is a psychobiological state caused by prolonged periods of demanding cognitive activity. Although the impact of mental fatigue on cognitive and skilled performance is well known, its effect on physical performance has not been thoroughly investigated. In this randomized crossover study, 16 subjects cycled to exhaustion at 80% of their peak power output after 90 min of a demanding cognitive task (mental fatigue) or 90 min of watching emotionally neutral documentaries (control). After experimental treatment, a mood questionnaire revealed a state of mental fatigue (P = 0.005) that significantly reduced time to exhaustion (640 +/- 316 s) compared with the control condition (754 +/- 339 s) (P = 0.003). This negative effect was not mediated by cardiorespiratory and musculoenergetic factors as physiological responses to intense exercise remained largely unaffected. Self-reported success and intrinsic motivation related to the physical task were also unaffected by prior cognitive activity. However, mentally fatigued subjects rated perception of effort during exercise to be significantly higher compared with the control condition (P = 0.007). As ratings of perceived exertion increased similarly over time in both conditions (P < 0.001), mentally fatigued subjects reached their maximal level of perceived exertion and disengaged from the physical task earlier than in the control condition. In conclusion, our study provides experimental evidence that mental fatigue limits exercise tolerance in humans through higher perception of effort rather than cardiorespiratory and musculoenergetic mechanisms. Future research in this area should investigate the common neurocognitive resources shared by physical and mental activity. PMID:19131473

  11. Stereoscopic visual fatigue assessment and modeling

    NASA Astrophysics Data System (ADS)

    Wang, Danli; Wang, Tingting; Gong, Yue

    2014-03-01

    Evaluation of stereoscopic visual fatigue is one of the focuses in the user experience research. It is measured in either subjective or objective methods. Objective measures are more preferred for their capability to quantify the degree of human visual fatigue without being affected by individual variation. However, little research has been conducted on the integration of objective indicators, or the sensibility of each objective indicator in reflecting subjective fatigue. The paper proposes a simply effective method to evaluate visual fatigue more objectively. The stereoscopic viewing process is divided into series of sessions, after each of which viewers rate their visual fatigue with subjective scores (SS) according to a five-grading scale, followed by tests of the punctum maximum accommodation (PMA) and visual reaction time (VRT). Throughout the entire viewing process, their eye movements are recorded by an infrared camera. The pupil size (PS) and percentage of eyelid closure over the pupil over time (PERCLOS) are extracted from the videos processed by the algorithm. Based on the method, an experiment with 14 subjects was conducted to assess visual fatigue induced by 3D images on polarized 3D display. The experiment consisted of 10 sessions (5min per session), each containing the same 75 images displayed randomly. The results show that PMA, VRT and PERCLOS are the most efficient indicators of subjective visual fatigue and finally a predictive model is derived from the stepwise multiple regressions.

  12. Cardiac dysfunction and prenatal exposure to venlafaxine.

    PubMed

    Araújo, Ana R; Marçal, Mónica; Tuna, Madalena; Anjos, Rui

    2016-04-01

    Venlofaxine, a widely used antidepressant, is known to cause a withdrawal syndrome. We present a case of neonatal transient ventricular dysfunction in a neonate exposed to venlafaxine in utero. Other causes of ventricular dysfunction were excluded. Neonatal ventricular dysfunction can be a possible side effect of maternal use of this drug. PMID:27099733

  13. Adult Children of Dysfunctional Families: Childhood Roles.

    ERIC Educational Resources Information Center

    Jenkins, Stephen J.; And Others

    1993-01-01

    Used retrospective accounts to compare adult children of alcoholics (ACOAs), adults who experienced stressful events in childhood not involving parental alcoholism (A-D+), and adults with no reported dysfunction in family of origin (A-D-) with regard to dysfunctional roles adopted as children. Dysfunctional role adoption was more frequent in ACOA…

  14. Immune aging, dysmetabolism, and inflammation in neurological diseases

    PubMed Central

    Deleidi, Michela; Jäggle, Madeline; Rubino, Graziella

    2015-01-01

    As we age, the immune system undergoes a process of senescence accompanied by the increased production of proinflammatory cytokines, a chronic subclinical condition named as “inflammaging”. Emerging evidence from human and experimental models suggest that immune senescence also affects the central nervous system and promotes neuronal dysfunction, especially within susceptible neuronal populations. In this review we discuss the potential role of immune aging, inflammation and metabolic derangement in neurological diseases. The discovery of novel therapeutic strategies targeting age-linked inflammation may promote healthy brain aging and the treatment of neurodegenerative as well as neuropsychiatric disorders. PMID:26089771

  15. Probabilistic fatigue methodology and wind turbine reliability

    SciTech Connect

    Lange, C.H.

    1996-05-01

    Wind turbines subjected to highly irregular loadings due to wind, gravity, and gyroscopic effects are especially vulnerable to fatigue damage. The objective of this study is to develop and illustrate methods for the probabilistic analysis and design of fatigue-sensitive wind turbine components. A computer program (CYCLES) that estimates fatigue reliability of structural and mechanical components has been developed. A FORM/SORM analysis is used to compute failure probabilities and importance factors of the random variables. The limit state equation includes uncertainty in environmental loading, gross structural response, and local fatigue properties. Several techniques are shown to better study fatigue loads data. Common one-parameter models, such as the Rayleigh and exponential models are shown to produce dramatically different estimates of load distributions and fatigue damage. Improved fits may be achieved with the two-parameter Weibull model. High b values require better modeling of relatively large stress ranges; this is effectively done by matching at least two moments (Weibull) and better by matching still higher moments. For this purpose, a new, four-moment {open_quotes}generalized Weibull{close_quotes} model is introduced. Load and resistance factor design (LRFD) methodology for design against fatigue is proposed and demonstrated using data from two horizontal-axis wind turbines. To estimate fatigue damage, wind turbine blade loads have been represented by their first three statistical moments across a range of wind conditions. Based on the moments {mu}{sub 1}{hor_ellipsis}{mu}{sub 3}, new {open_quotes}quadratic Weibull{close_quotes} load distribution models are introduced. The fatigue reliability is found to be notably affected by the choice of load distribution model.

  16. Chronic fatigue syndrome: aetiology, diagnosis and treatment.

    PubMed

    Avellaneda Fernández, Alfredo; Pérez Martín, Alvaro; Izquierdo Martínez, Maravillas; Arruti Bustillo, Mar; Barbado Hernández, Francisco Javier; de la Cruz Labrado, Javier; Díaz-Delgado Peñas, Rafael; Gutiérrez Rivas, Eduardo; Palacín Delgado, Cecilia; Rivera Redondo, Javier; Ramón Giménez, José Ramón

    2009-10-23

    Chronic fatigue syndrome is characterised by intense fatigue, with duration of over six months and associated to other related symptoms. The latter include asthenia and easily induced tiredness that is not recovered after a night's sleep. The fatigue becomes so severe that it forces a 50% reduction in daily activities. Given its unknown aetiology, different hypotheses have been considered to explain the origin of the condition (from immunological disorders to the presence of post-traumatic oxidative stress), although there are no conclusive diagnostic tests. Diagnosis is established through the exclusion of other diseases causing fatigue. This syndrome is rare in childhood and adolescence, although the fatigue symptom per se is quite common in paediatric patients. Currently, no curative treatment exists for patients with chronic fatigue syndrome. The therapeutic approach to this syndrome requires a combination of different therapeutic modalities. The specific characteristics of the symptomatology of patients with chronic fatigue require a rapid adaptation of the educational, healthcare and social systems to prevent the problems derived from current systems. Such patients require multidisciplinary management due to the multiple and different issues affecting them. This document was realized by one of the Interdisciplinary Work Groups from the Institute for Rare Diseases, and its aim is to point out the main social and care needs for people affected with Chronic Fatigue Syndrome. For this, it includes not only the view of representatives for different scientific societies, but also the patient associations view, because they know the true history of their social and sanitary needs. In an interdisciplinary approach, this work also reviews the principal scientific, medical, socio-sanitary and psychological aspects of Chronic Fatigue Syndrome.

  17. Biomarkers of peripheral muscle fatigue during exercise

    PubMed Central

    2012-01-01

    Background Biomarkers of peripheral muscle fatigue (BPMFs) are used to offer insights into mechanisms of exhaustion during exercise in order to detect abnormal fatigue or to detect defective metabolic pathways. This review aims at describing recent advances and future perspectives concerning the most important biomarkers of muscle fatigue during exercise. Results BPMFs are classified according to the mechanism of fatigue related to adenosine-triphosphate-metabolism, acidosis, or oxidative-metabolism. Muscle fatigue is also related to an immunological response. impaired calcium handling, disturbances in bioenergetic pathways, and genetic responses. The immunological and genetic response may make the muscle susceptible to fatigue but may not directly cause muscle fatigue. Production of BPMFs is predominantly dependent on the type of exercise. BPMFs need to change as a function of the process being monitored, be stable without appreciable diurnal variations, correlate well with exercise intensity, and be present in detectable amounts in easily accessible biological fluids. The most well-known BPMFs are serum lactate and interleukin-6. The most widely applied clinical application is screening for defective oxidative metabolism in mitochondrial disorders by means of the lactate stress test. The clinical relevance of most other BPMFs, however, is under debate, since they often depend on age, gender, physical fitness, the energy supply during exercise, the type of exercise needed to produce the BPMF, and whether healthy or diseased subjects are investigated. Conclusions Though the role of BPMFs during fatigue is poorly understood, measuring BPMFs under specific, standardised conditions appears to be helpful for assessing biological states or processes during exercise and fatigue. PMID:23136874

  18. Chronic fatigue syndrome: aetiology, diagnosis and treatment

    PubMed Central

    Avellaneda Fernández, Alfredo; Pérez Martín, Álvaro; Izquierdo Martínez, Maravillas; Arruti Bustillo, Mar; Barbado Hernández, Francisco Javier; de la Cruz Labrado, Javier; Díaz-Delgado Peñas, Rafael; Gutiérrez Rivas, Eduardo; Palacín Delgado, Cecilia; Rivera Redondo, Javier; Ramón Giménez, José Ramón

    2009-01-01

    Chronic fatigue syndrome is characterised by intense fatigue, with duration of over six months and associated to other related symptoms. The latter include asthenia and easily induced tiredness that is not recovered after a night's sleep. The fatigue becomes so severe that it forces a 50% reduction in daily activities. Given its unknown aetiology, different hypotheses have been considered to explain the origin of the condition (from immunological disorders to the presence of post-traumatic oxidative stress), although there are no conclusive diagnostic tests. Diagnosis is established through the exclusion of other diseases causing fatigue. This syndrome is rare in childhood and adolescence, although the fatigue symptom per se is quite common in paediatric patients. Currently, no curative treatment exists for patients with chronic fatigue syndrome. The therapeutic approach to this syndrome requires a combination of different therapeutic modalities. The specific characteristics of the symptomatology of patients with chronic fatigue require a rapid adaptation of the educational, healthcare and social systems to prevent the problems derived from current systems. Such patients require multidisciplinary management due to the multiple and different issues affecting them. This document was realized by one of the Interdisciplinary Work Groups from the Institute for Rare Diseases, and its aim is to point out the main social and care needs for people affected with Chronic Fatigue Syndrome. For this, it includes not only the view of representatives for different scientific societies, but also the patient associations view, because they know the true history of their social and sanitary needs. In an interdisciplinary approach, this work also reviews the principal scientific, medical, socio-sanitary and psychological aspects of Chronic Fatigue Syndrome. PMID:19857242

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

    PubMed Central

    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. PMID:26881048

  20. 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

  1. Interpretation of Hospital Nurse Fatigue Using Latent Profile Analysis.

    PubMed

    Drake, Diane Ash; Steege, Linsey M Barker

    2016-01-01

    There has been a lack of consensus in the literature related to the conceptualization, definition, and measurement of hospital nurse fatigue. Using latent profile analysis, the Hospital Nurse Force Theory provided a conceptual format to identify 3 profiles of nurse fatigue from subjective reports of hospital patient care nurses in a survey cohort. All fatigue and adaptation variables demonstrated significant inverse relationships. Describing nurse fatigue in profiles that include measures of acute, chronic, physical, and mental fatigue dimensions provided a new and expanded view of nurse fatigue to monitor trends comprehensively and evaluate fatigue risk management strategies. PMID:27490883

  2. The relationship between observed fatigue damage and life estimation models

    NASA Technical Reports Server (NTRS)

    Kurath, Peter; Socie, Darrell F.

    1988-01-01

    Observations of the surface of laboratory specimens subjected to axial and torsional fatigue loadings has resulted in the identification of three damage fatigue phenomena: crack nucleation, shear crack growth, and tensile crack growth. Material, microstructure, state of stress/strain, and loading amplitude all influence which of the three types of fatigue damage occurs during a dominant fatigue life fraction. Fatigue damage maps are employed to summarize the experimental observations. Appropriate bulk stress/strain damage parameters are suggested to model fatigue damage for the dominant fatigue life fraction. Extension of the damage map concept to more complex loadings is presented.

  3. 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

  4. Fatigue fracture behavior of PEEK

    SciTech Connect

    Brillhart, M.; Botsis, J. )

    1993-09-01

    Experimental results on fatigue crack propagation in PEEK under different load levels, specimen thickness, and environmental temperatures (Brillhart, 1991; Brillhart and Botsis, 1992) are analyzed. When the kinetic data are plotted against J1 = sigma sub y delta (where sigma sub y is the yield stress of the material and delta is the crack tip opening displacement), the crack speed is practically independent of the load level, specimen thickness, and environmental temperatures up to 75 C. The experimental data is confronted with a power type kinetic equation and the kinetic equation of the crack layer model. The analysis indicates that both kinetic equations describe well the data under a wide spectrum of loading conditions. 7 refs.

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

    PubMed

    Arnett, S V; Clark, I A

    2012-12-10

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

  6. Composite materials: Fatigue and fracture. Vol. 3

    NASA Technical Reports Server (NTRS)

    O'Brien, T. K. (Editor)

    1991-01-01

    The present volume discusses topics in the fields of matrix cracking and delamination, interlaminar fracture toughness, delamination analysis, strength and impact characteristics, and fatigue and fracture behavior. Attention is given to cooling rate effects in carbon-reinforced PEEK, the effect of porosity on flange-web corner strength, mode II delamination in toughened composites, the combined effect of matrix cracking and free edge delamination, and a 3D stress analysis of plain weave composites. Also discussed are the compression behavior of composites, damage-based notched-strength modeling, fatigue failure processes in aligned carbon-epoxy laminates, and the thermomechanical fatigue of a quasi-isotropic metal-matrix composite.

  7. Acoustically induced structural fatigue of piping systems

    SciTech Connect

    Eisinger, F.L.; Francis, J.T.

    1999-11-01

    Piping systems handling high-pressure and high-velocity steam and various process and hydrocarbon gases through a pressure-reducing device can produce severe acoustic vibration and metal fatigue in the system. It has been previously shown that the acoustic fatigue of the piping system is governed by the relationship between fluid pressure drop and downstream Mach number, and the dimensionless pipe diameter/wall thickness geometry parameter. In this paper, the devised relationship is extended to cover acoustic fatigue considerations of medium and smaller-diameter piping systems.

  8. Sonic fatigue of launch vehicle components

    SciTech Connect

    Wentz, K.R.; Camden, M.P.

    1997-01-01

    Wright Laboratory has long been a leader in the technologies required for aerospace structures. One of these driving technology areas is that of the dynamic environments of acoustics and vibration to which structures are exposed and required to survive. This paper presents an overview of sonic fatigue of launch vehicle components. An experimental program to develop sonic fatigue design criteria for a proposed thermal protection system is reviewed. Wright Laboratory{close_quote}s experimental facilities utilized to subject structures to simulated launch vehicle environments which are necessary to generate the experimental data required to provide sonic fatigue design criteria are described. {copyright} {ital 1997 American Institute of Physics.}

  9. Fatigue of continuous fiber reinforced metallic materials

    NASA Technical Reports Server (NTRS)

    Johnson, W. S.; Mirdamadi, M.; Bakuckas, J. G., Jr.

    1993-01-01

    The complex damage mechanisms that occur in fiber reinforced advanced metallic materials are discussed. As examples, results for several layups of SCS-6/Ti-15-3 composites are presented. Fatigue tests were conducted and analyzed for both notched and unnotched specimens at room and elevated temperatures. Test conditions included isothermal, non-isothermal, and simulated mission profile thermomechanical fatigue. Test results indicated that the stress in the 0 degree fibers is the controlling factor for fatigue life for a given test condition. An effective strain approach is presented for predicting crack initiation at notches. Fiber bridging models were applied to crack growth behavior.

  10. Histopathology of meibomian gland dysfunction.

    PubMed

    Gutgesell, V J; Stern, G A; Hood, C I

    1982-09-01

    We conducted a histopathologic study of he meibomian glands of seven patients (all men, ranging in age from 58 to 83 years) who had severe or moderately severe meibomian dysfunction and who were undergoing ectropion or entropion repair. Abnormal features included signs of obstruction and dilatation of ducts, enlargement of acini with cystic degeneration and squamous metaplasia, foreign-body reaction and granuloma formation, a mild increase in inflammatory cells, and abnormal keratinization. Demodex organisms were found in both acini and ducts of one patient. These findings were similar to those reported in other entities involving meibomian duct obstruction, probably related to abnormalities of keratinization, plays an important role in the pathogenesis of meibomian gland dysfunction.

  11. Shift work and employee fatigue: implications for occupational health nursing.

    PubMed

    Yumang-Ross, Doreen J; Burns, Candace

    2014-06-01

    Long work hours and irregular shifts are part of the nation's 24-hour society and contribute to employee fatigue. Factors affecting employee fatigue are circadian rhythm, sleep quality and quantity, individual health, the environment, and work tasks. Employee fatigue contributes to accidents and injuries, and affects occupational performance, safety, and health. These findings should be used by occupational health nurses to address fatigue management and develop comprehensive fatigue management programs.

  12. Gonadal dysfunction in systemic diseases.

    PubMed

    Karagiannis, Asterios; Harsoulis, Faidon

    2005-04-01

    Gonadal function is significantly affected in many acute and chronic systemic diseases. As the function of the testes and the ovaries is determined by the integrity of the hypothalamic-pituitary-gonadal axis, it is obvious that a systemic disease may affect one or more levels of the axis in such a manner that the gonadal dysfunction may have various clinical and laboratory manifestations. In this brief review, the most common disturbances seen in the main systemic diseases will be discussed.

  13. Insulin dysfunction and Tau pathology

    PubMed Central

    El Khoury, Noura B.; Gratuze, Maud; Papon, Marie-Amélie; Bretteville, Alexis; Planel, Emmanuel

    2013-01-01

    The neuropathological hallmarks of Alzheimer's disease (AD) include senile plaques of β-amyloid (Aβ) peptides (a cleavage product of the Amyloid Precursor Protein, or APP) and neurofibrillary tangles (NFT) of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF). NFT pathology is important since it correlates with the degree of cognitive impairment in AD. Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99%) is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease. Insulin dysfunction, manifested by diabetes mellitus (DM) might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM) and type 2 diabetes (T2DM) are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since Tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment. Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia. PMID:24574966

  14. Hypnotic metaphor and sexual dysfunction.

    PubMed

    Gilmore, L G

    1987-01-01

    Although hypnosis can be very effective in alleviating sexual problems, few sex therapists use hypnotic methods. This paper seeks to encourage a greater use of hypnosis among clinicians by presenting: a description of the new hypnosis exemplified in the work of Milton H. Erickson; an explanation of one of Erickson's most important and innovative methods, the use of multiple embedded metaphors; and case histories illustrating the application of hypnotic approaches to sexual dysfunction.

  15. Mitochondrial dysfunction and organophosphorus compounds

    SciTech Connect

    Karami-Mohajeri, Somayyeh; Abdollahi, Mohammad

    2013-07-01

    Organophosphorous (OPs) pesticides are the most widely used pesticides in the agriculture and home. However, many acute or chronic poisoning reports about OPs have been published in the recent years. Mitochondria as a site of cellular oxygen consumption and energy production can be a target for OPs poisoning as a non-cholinergic mechanism of toxicity of OPs. In the present review, we have reviewed and criticized all the evidences about the mitochondrial dysfunctions as a mechanism of toxicity of OPs. For this purpose, all biochemical, molecular, and morphological data were retrieved from various studies. Some toxicities of OPs are arisen from dysfunction of mitochondrial oxidative phosphorylation through alteration of complexes I, II, III, IV and V activities and disruption of mitochondrial membrane. Reductions of adenosine triphosphate (ATP) synthesis or induction of its hydrolysis can impair the cellular energy. The OPs disrupt cellular and mitochondrial antioxidant defense, reactive oxygen species generation, and calcium uptake and promote oxidative and genotoxic damage triggering cell death via cytochrome C released from mitochondria and consequent activation of caspases. The mitochondrial dysfunction induced by OPs can be restored by use of antioxidants such as vitamin E and C, alpha-tocopherol, electron donors, and through increasing the cytosolic ATP level. However, to elucidate many aspect of mitochondrial toxicity of Ops, further studies should be performed. - Highlights: • As a non-cholinergic mechanism of toxicity, mitochondria is a target for OPs. • OPs affect action of complexes I, II, III, IV and V in the mitochondria. • OPs reduce mitochondrial ATP. • OPs promote oxidative and genotoxic damage via release of cytochrome C from mitochondria. • OP-induced mitochondrial dysfunction can be restored by increasing the cytosolic ATP.

  16. 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.

  17. Cardiac Function and Dysfunction in Sepsis.

    PubMed

    Fenton, Kimberly E; Parker, Margaret M

    2016-06-01

    Cardiac function and dysfunction are important in the clinical outcomes of sepsis and septic shock. Cardiac dysfunction is not a single entity, but is a broad spectrum of syndromes that result in biventricular cardiac dysfunction manifested by both systolic and diastolic dysfunction and is influenced by cardiac loading conditions (ie, preload and afterload). Elucidating the underlying pathophysiology has proved to be complex. This article emphasizes the underlying pathophysiology of cardiac dysfunction and explores recent evidence related to diagnosis, including the utility of biomarkers, the role of echocardiography, and management goals and treatment. PMID:27229645

  18. Gut dysfunction in Parkinson's disease.

    PubMed

    Mukherjee, Adreesh; Biswas, Atanu; Das, Shyamal Kumar

    2016-07-01

    Early involvement of gut is observed in Parkinson's disease (PD) and symptoms such as constipation may precede motor symptoms. α-Synuclein pathology is extensively evident in the gut and appears to follow a rostrocaudal gradient. The gut may act as the starting point of PD pathology with spread toward the central nervous system. This spread of the synuclein pathology raises the possibility of prion-like propagation in PD pathogenesis. Recently, the role of gut microbiota in PD pathogenesis has received attention and some phenotypic correlation has also been shown. The extensive involvement of the gut in PD even in its early stages has led to the evaluation of enteric α-synuclein as a possible biomarker of early PD. The clinical manifestations of gastrointestinal dysfunction in PD include malnutrition, oral and dental disorders, sialorrhea, dysphagia, gastroparesis, constipation, and defecatory dysfunction. These conditions are quite distressing for the patients and require relevant investigations and adequate management. Treatment usually involves both pharmacological and non-pharmacological measures. One important aspect of gut dysfunction is its contribution to the clinical fluctuations in PD. Dysphagia and gastroparesis lead to inadequate absorption of oral anti-PD medications. These lead to response fluctuations, particularly delayed-on and no-on, and there is significant relationship between levodopa pharmacokinetics and gastric emptying in patients with PD. Therefore, in such cases, alternative routes of administration or drug delivery systems may be required. PMID:27433087

  19. Gut dysfunction in Parkinson's disease

    PubMed Central

    Mukherjee, Adreesh; Biswas, Atanu; Das, Shyamal Kumar

    2016-01-01

    Early involvement of gut is observed in Parkinson’s disease (PD) and symptoms such as constipation may precede motor symptoms. α-Synuclein pathology is extensively evident in the gut and appears to follow a rostrocaudal gradient. The gut may act as the starting point of PD pathology with spread toward the central nervous system. This spread of the synuclein pathology raises the possibility of prion-like propagation in PD pathogenesis. Recently, the role of gut microbiota in PD pathogenesis has received attention and some phenotypic correlation has also been shown. The extensive involvement of the gut in PD even in its early stages has led to the evaluation of enteric α-synuclein as a possible biomarker of early PD. The clinical manifestations of gastrointestinal dysfunction in PD include malnutrition, oral and dental disorders, sialorrhea, dysphagia, gastroparesis, constipation, and defecatory dysfunction. These conditions are quite distressing for the patients and require relevant investigations and adequate management. Treatment usually involves both pharmacological and non-pharmacological measures. One important aspect of gut dysfunction is its contribution to the clinical fluctuations in PD. Dysphagia and gastroparesis lead to inadequate absorption of oral anti-PD medications. These lead to response fluctuations, particularly delayed-on and no-on, and there is significant relationship between levodopa pharmacokinetics and gastric emptying in patients with PD. Therefore, in such cases, alternative routes of administration or drug delivery systems may be required. PMID:27433087

  20. Neural effect of mental fatigue on physical fatigue: a magnetoencephalography study.

    PubMed

    Tanaka, Masaaki; Ishii, Akira; Watanabe, Yasuyoshi

    2014-01-13

    We sought to clarify the neural effect of mental fatigue on physical fatigue using magnetoencephalography (MEG) and classical conditioning techniques. Eleven right-handed volunteers participated in this study. On the first day, participants performed fatigue-inducing maximum handgrip trials for 10 min; metronome sounds were started 5 min after the beginning of the trials. We used metronome sounds as conditioned stimuli and maximum handgrip trials as unconditioned stimuli to cause physical fatigue. On the next day, MEG recordings during the imagery of maximum grips of the right hand guided by the metronome sounds were performed for 10 min just before (control session) and after (mental fatigue session) a 30-min fatigue-inducing mental task session. In the right anterior cingulate cortex (Brodmann's area 23), the alpha-band event-related synchronization of the mental fatigue session relative to the control session within the time window of 500–600 ms after the onset of handgrip cue sounds was identified. We demonstrated that mental fatigue suppresses activities in the right anterior cingulate cortex during physical fatigue.