The Role of the Lipid Profile and Oxidative Stress in Fatigue, Sleep Disorders and Cognitive Impairment in Patients with Multiple Sclerosis.

The aim of this study is to investigate the relationship of the lipid profile, dysfunctional high-density lipoprotein, ischaemia-modified albumin and thiol-disulfide homeostasis with cognitive impairment, fatigue and sleep disorders in patients with multiple sclerosis. The cognitive functions of patients were evaluated with the Brief International Cognitive Assessment for Multiple Sclerosis battery. Fatigue was evaluated with the Fatigue Severity Scale and the Fatigue Impact Scale. The Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale were used to assess patients' sleep disturbance. Peripheral blood samples were collected, and lipid levels and myeloperoxidase and paraoxonase activity were measured. The myeloperoxidase/paraoxonase ratio, which indicates dysfunctional high-density lipoprotein, was calculated. Thiol-disulfide homeostasis and ischaemia-modified albumin were measured.
We did not identify any relationship between dysfunctional high-density lipoprotein and the physical disability, cognitive decline, fatigue and sleep problems of multiple sclerosis. Thiol-disulfide homeostasis was associated with cognitive scores. The shift of the balance towards disulfide was accompanied by a decrease in cognitive scores. On the other hand, we did not detect any relationship between fatigue and sleep disorders and thiol-disulfide homeostasis. Our findings revealed a possible correlation between cognitive dysfunction and thiol-disulfide homeostasis in multiple sclerosis patients.

Exploring levels of TSH and FT4 in patients with chronic fatigue syndrome (CFS), fibromyalgia (FM) and healthy controls did not reveal any associations between fatigue score and level of thyroid hormones.

AIM: The diagnoses of Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM) are highly associated with fatigue and pain, respectively. Physiologically and clinically an effect of thyroid status on fatigue and pain is expected. There may be clinically relevant differences in thyroid hormone axes though within values of reference in both patients with normal thyroid hormones, or in patients with well-regulated thyroid disease. These potential differences are explored in this study. MATERIALS AND METHODS: In the present study, female patients with CFS (n = 49) and FM (n = 58) as well as female healthy controls (n = 53) were included. We explored plasma levels of TSH and FT4 between the groups using Kruskall-Wallis, and the relation between fatigue score and levels of TSH and FT4 by means of Spearman's rho. RESULTS: There were no group differences between CFS patients, FM patients, and healthy controls in levels of TSH and FT4. CONCLUSION: As one might clinically and physiologically expect an association between thyroid function and fatigue, which may be associated with clinical disorders such as CFS and FM, we suggest future studies to examine the field further by exploring the influence of thyroid receptors and responses of the thyroid hormone cascade.

The Effect of Anti-fatigue Decoction on the Behaviors and Serological Indicators in a Central Fatigue Rat Model.

This study aimed to assess the effects of Anti-fatigue Decoction (AFD) against central fatigue by observing the behaviors and serological indicators of rats modeled by the modified multiple platform method (MMPM) after drug intervention. Grip strength measurements were used to evaluate the muscle strength of rats. The open field test was utilized to assess anxiety-like behavior, while the Morris water maze test was conducted to evaluate the memory function of the rats. Following the behavioral assessments, rat serum samples were collected to measure the concentrations of corticosterone (CORT) and lactic acid (LAC). The concentration of LAC was determined using the colorimetric method, while the concentration of CORT was measured using the enzyme-linked immunosorbent assay (ELISA) method. Compared to the blank control group, following MMPM modeling, rats exhibited significant reductions in grip strength and impaired ability to memory. The serum analysis revealed increased levels of LAC and CORT in the model group rats. AFD can noticeably reverse these adverse changes to a certain extent. These findings highlight the positive effects of AFD and coenzymeQ10 on physical and cognitive abilities and alterations in serum biomarker levels of central fatigue rats.

Metabolites Associated With Uremic Symptoms in Patients With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: The toxins that contribute to uremic symptoms in patients with chronic kidney disease (CKD) are unknown. We sought to apply complementary statistical modeling approaches to data from untargeted plasma metabolomic profiling to identify solutes associated with uremic symptoms in patients with CKD. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: 1,761 Chronic Renal Insufficiency Cohort (CRIC) participants with CKD not treated with dialysis. PREDICTORS: Measurement of 448 known plasma metabolites. OUTCOMES: The uremic symptoms of fatigue, anorexia, pruritus, nausea, paresthesia, and pain were assessed by single items on the Kidney Disease Quality of Life-36 instrument. ANALYTICAL APPROACH: Multivariable adjusted linear regression, least absolute shrinkage and selection operator linear regression, and random forest models were used to identify metabolites associated with symptom severity. After adjustment for multiple comparisons, metabolites selected in at least 2 of the 3 modeling approaches were deemed "overall significant." RESULTS: Participant mean estimated glomerular filtration rate was 43mL/min/1.73m2, with 44% self-identifying as female and 41% as non-Hispanic Black. The prevalence of uremic symptoms ranged from 22% to 55%. We identified 17 metabolites for which a higher level was associated with greater severity of at least one uremic symptom and 9 metabolites inversely associated with uremic symptom severity. Many of these metabolites exhibited at least a moderate correlation with estimated glomerular filtration rate (Pearson's r≥0.5), and some were also associated with the risk of developing kidney failure or death in multivariable adjusted Cox regression models. LIMITATIONS: Lack of a second independent cohort for external validation of our findings. CONCLUSIONS: Metabolomic profiling was used to identify multiple solutes associated with uremic symptoms in adults with CKD, but future validation and mechanistic studies are needed. PLAIN-LANGUAGE SUMMARY: Individuals living with chronic kidney disease (CKD) often experience symptoms related to CKD, traditionally called uremic symptoms. It is likely that CKD results in alterations in the levels of numerous circulating substances that, in turn, cause uremic symptoms; however, the identity of these solutes is not known. In this study, we used metabolomic profiling in patients with CKD to gain insights into the pathophysiology of uremic symptoms. We identified 26 metabolites whose levels were significantly associated with at least one of the symptoms of fatigue, anorexia, itchiness, nausea, paresthesia, and pain. The results of this study lay the groundwork for future research into the biological causes of symptoms in patients with CKD.

Immunoglobulin signature predicts risk of post-acute COVID-19 syndrome.

Following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a significant proportion of individuals develop prolonged symptoms, a serious condition termed post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) or long COVID. Predictors of PACS are needed. In a prospective multicentric cohort study of 215 individuals, we study COVID-19 patients during primary infection and up to one year later, compared to healthy subjects. We discover an immunoglobulin (Ig) signature, based on total IgM and IgG3 levels, which - combined with age, history of asthma bronchiale, and five symptoms during primary infection - is able to predict the risk of PACS independently of timepoint of blood sampling. We validate the score in an independent cohort of 395 individuals with COVID-19. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which facilitates the study of targeted treatment and pathomechanisms of PACS.

Iron deficiency and fatigue among adolescents with bleeding disorders.

Iron deficiency anemia is associated with heavy menstrual bleeding (HMB) and, by extension, a bleeding disorder (BD). It is unknown if iron deficiency without anemia is associated with a BD in adolescents. Moreover, the threshold of ferritin associated with fatigue in adolescents with HMB is unclear. In this multicenter study, we enrolled adolescents with HMB without BD. Participants underwent BD and anemia work-up in Young Women's Hematology Clinics and completed the Peds QL™ fatigue scale. BDs were defined as von Willebrand Disease, platelet function defect, clotting factor deficiencies, and hypermobility syndrome. Two hundred and fifty consecutive adolescents were enrolled, of whom 196 met eligibility criteria. Overall, 43% (95% confidence interval: 36%-50%) were diagnosed with BD. A total of 61% (n = 119) had serum ferritin levels < 15 ng/mL, 23.5% (n = 46) had iron deficiency only, and 37% (n = 73) had iron deficiency anemia. Low ferritin or ferritin dichotomized as < 15 or ≥ 15 ng/mL was not associated with BD on univariable analysis (p = .24) or when accounting for age, race, ethnicity, body mass index, and hemoglobin (p = .35). A total of 85% had total fatigue score below the population mean of 80.5, and 52% (n = 102) were > 2 SD (or < 54) below the mean, the cut-off associated with severe fatigue. A ferritin threshold of < 6 ng/mL had a specificity of 79.8% but a sensitivity of 36% for severe fatigue. In conclusion, iron deficiency without anemia is not a predictor of BD in adolescents with HMB in a specialty setting. Severe fatigue, especially sleep fatigue, is prevalent in adolescents with BD. Ferritin of < 6 ng/mL has ~80% specificity for severe fatigue in adolescents with HMB.

Multisystem Involvement in Post-Acute Sequelae of Coronavirus Disease 19.

OBJECTIVE: The purpose of this study was to describe cerebrovascular, neuropathic, and autonomic features of post-acute sequelae of coronavirus disease 2019 ((COVID-19) PASC). METHODS: This retrospective study evaluated consecutive patients with chronic fatigue, brain fog, and orthostatic intolerance consistent with PASC. Controls included patients with postural tachycardia syndrome (POTS) and healthy participants. Analyzed data included surveys and autonomic (Valsalva maneuver, deep breathing, sudomotor, and tilt tests), cerebrovascular (cerebral blood flow velocity [CBFv] monitoring in middle cerebral artery), respiratory (capnography monitoring), and neuropathic (skin biopsies for assessment of small fiber neuropathy) testing and inflammatory/autoimmune markers. RESULTS: Nine patients with PASC were evaluated 0.8 ± 0.3 years after a mild COVID-19 infection, and were treated as home observations. Autonomic, pain, brain fog, fatigue, and dyspnea surveys were abnormal in PASC and POTS (n = 10), compared with controls (n = 15). Tilt table test reproduced the majority of PASC symptoms. Orthostatic CBFv declined in PASC (-20.0 ± 13.4%) and POTS (-20.3 ± 15.1%), compared with controls (-3.0 ± 7.5%, p = 0.001) and was independent of end-tidal carbon dioxide in PASC, but caused by hyperventilation in POTS. Reduced orthostatic CBFv in PASC included both subjects without (n = 6) and with (n = 3) orthostatic tachycardia. Dysautonomia was frequent (100% in both PASC and POTS) but was milder in PASC (p = 0.002). PASC and POTS cohorts diverged in frequency of small fiber neuropathy (89% vs 60%) but not in inflammatory markers (67% vs 70%). Supine and orthostatic hypocapnia was observed in PASC. INTERPRETATION: PASC following mild COVID-19 infection is associated with multisystem involvement including: (1) cerebrovascular dysregulation with persistent cerebral arteriolar vasoconstriction; (2) small fiber neuropathy and related dysautonomia; (3) respiratory dysregulation; and (4) chronic inflammation. ANN NEUROL 2022;91:367-379.

Lactate Threshold Training Program on Patients with Multiple Sclerosis: A Multidisciplinary Approach.

Physical activity could play a key role in improving the quality of life, particularly in patients with nervous system diseases such as multiple sclerosis (MS). Through lactacid anaerobic training, this study aims to investigate the effects at a bio-psycho-physical level to counteract the chronic fatigue associated with the pathology, and to improve mental health at a psychological and neurotrophic level. Eight subjects (age: 34.88 ± 4.45 years) affected by multiple sclerosis were involved. A lactate threshold training program was administered biweekly for 12 weeks at the beginning of the study (T0), at the end of the study (T1) and at 9 months after the end of the study (T2), with physical, psychological and hematochemicals parameters, and dietary habits being tested. The results obtained confirmed that lactacid exercise can influence brain-derived neurotrophic factor (BDNF) levels as well as dehydroepiandrosterone sulfate (DHEAS) levels. In addition, levels of baseline lactate, which could be best used as an energy substrate, showed a decrease after the protocol training. Self-efficacy regarding worries and concerns management significantly increased from T0 to T1. The eating attitudes test (EAT-26) did not highlight any eating disease in the patients with a normal diet enrolled in our study. Physical exercise also greatly influenced the patients psychologically and emotionally, increasing their self-esteem. Lactate threshold training, together with dietary habits, appears to exert synergic positive effects on inflammation, neural plasticity and neuroprotection, producing preventive effects on MS symptoms and progression.

Effect of Lactobacillus fermentum HFY03 on the Antifatigue and Antioxidation Ability of Running Exhausted Mice.

Yak yogurt is mainly produced in Qinghai-Tibet Plateau. It is a kind of naturally fermented dairy product. It contains abundant microorganisms. Lactobacillus fermentum (LF) HFY03 is a lactic acid bacteria derived from it. Our main research content is to study the influence of LF-HFY03 on the antifatigue and antioxidation ability of running exhausted mice. We gave different doses of LF-HFY03 to mice by gavage for 4 weeks. We selected vitamin C as the positive control group, mainly to study the relationship between antioxidant capacity and fatigue resistance and LF-HFY03 in mice with running exhaustion. The results showed that LF-HFY03 and vitamin C could significantly improve the running time of mice. And with the increase in LF-HFY03 concentration, the exhaustion time of mice was also extended. LF-HFY03 can reduce the content of urea nitrogen and lactic acid and also can increase the content of free fatty acids and liver glycogen. The levels of alanine aminotransferase, serum creatine kinase, and aspartate aminotransferase in mice decreased gradually as the antioxidant peptide level of walnut albumin increased. LF-HFY03 can reduce malondialdehyde (MDA) levels in a quantification-dependent manner and can also increase catalase (CAT) and superoxide dismutase (SOD) levels. LF-HFY03 can also increase the expressions of CAT mRNA, Cu/Zn-SOD, and Mn-SOD in the liver of mice. At the same time, LF-HFY03 can also increase the expression of protein of threonine transporter 1 (AST1)/alanine/cysteine/serine, mRNA, nNOS, and eNOS. At the same time, the solution could reduce the expression of TNF-α, syncytin-1, and inducible nitric oxide synthase (iNOS). The results showed that LF-HFY03 has a high development and application prospect as an antifatigue probiotic nutritional supplement.

Investigating the Relationship between Vitamin D and Persistent Symptoms Following SARS-CoV-2 Infection.

The emergence of persistent symptoms following SARS-CoV-2 infection, known as long COVID, is providing a new challenge to healthcare systems. The cardinal features are fatigue and reduced exercise tolerance. Vitamin D is known to have pleotropic effects far beyond bone health and is associated with immune modulation and autoimmunity. We hypothesize that vitamin D levels are associated with persistent symptoms following COVID-19. Herein, we investigate the relationship between vitamin D and fatigue and reduced exercise tolerance, assessed by the Chalder Fatigue Score, six-minute walk test and modified Borg scale. Multivariable linear and logistic regression models were used to evaluate the relationships. A total of 149 patients were recruited at a median of 79 days after COVID-19 illness. The median vitamin D level was 62 nmol/L, with n = 36 (24%) having levels 30-49 nmol/L and n = 14 (9%) with levels <30 nmol/L. Fatigue was common, with n = 86 (58%) meeting the case definition. The median Borg score was 3, while the median distance covered for the walk test was 450 m. No relationship between vitamin D and the measures of ongoing ill-health assessed in the study was found following multivariable regression analysis. These results suggest that persistent fatigue and reduced exercise tolerance following COVID-19 are independent of vitamin D.

Oral Resveratrol supplementation attenuates exercise-induced Interleukin-6 but not Oxidative Stress after a high intensity cycling challenge in adults.

Previous studies demonstrated that resveratrol (RES) is able to enhance antioxidant, anti-inflammatory and insulin actions in humans. It is unclear whether RES can be used as ergogenic aids to enhance high-intensity cycling exercise performance and attenuate the high-intensity exercise-induced oxidative stress and inflammation. This study investigated the effect of RES supplementation on oxidative stress, inflammation, exercise-induced fatigue, and endurance performance. Eight male athletes participated in this single-blind crossover designed study and randomly instructed to receive four days of either oral RES (480 mg per day, totally 1920mg) or placebo supplementation. The cycling exercise challenge at 80% maximal oxygen consumption with 60 rpm was performed following 4 days of either RES or placebo supplementation. The total cycling performance time was recorded. In addition, blood samples were obtained to analyze the changes in blood glucose, plasma non-esterified fatty acid, serum lactate dehydrogenase, creatine kinase, uric acid, total antioxidant capacity, malondialdehyde, tumor necrosis factor-α, and interleukin-6. The exhausting time of cycling exercise challenge was not significantly increased in RES compared to that in placebo. However, IL-6 response was significantly decreased during exercise challenge in RES trial, and there were no differences in blood biomarkers, fatigue factors, and antioxidative response. Oral RES supplementation can attenuate exercise-induced IL-6 response but not fatigue and oxidative stress, inflammation response. However, we infer that 4-day oral RES supplementation has no ergogenic property on enhancing the high-intensity cycling exercise performance.

Tired of feeling tired - The role of circulating inflammatory biomarkers and long-term cancer related fatigue in breast cancer survivors.

BACKGROUND: Low-grade inflammation has been associated with cancer related fatigue (CRF). However, most studies focused on CRF during or shortly after treatment. Longitudinal studies are rare with inconsistent results. We assessed the association of inflammatory biomarkers with total CRF and all subdomains (physical, cognitive, affective) in long-term breast cancer survivors. METHOD: Patients recruited between 2002 and 2005 provided information on CRF at first follow-up (FU1) (N = 1292) and second follow-up (FU2) (N = 1205), after a median of 6.2 years and 11.7 years, respectively. Associations of 11 inflammatory biomarkers with CRF at FU1 and at FU2 were assessed using linear regression models. Logistic regression models were used to compare patients fatigued at both time-points and those never fatigued (N = 932). RESULTS: C-reactive protein (CRP) was significantly associated with total CRF at FU1 (ß = 1.47, 95%CI = 0.62-2.31, p = 0.0007), at FU2 (ß = 1.98, 95 %CI = 0.96-2.99, p = 0.0001) and with persistent CRF (OR = 1.29, 95%CI = 1.13-1.47, p < 0.0001). IL-6 levels were associated with total CRF at FU1 (ß = 1.01, 95%CI = 0.43-1.59, p = 0.0006), but not with CRF at FU2 or persistent CRF. No association remained significant after adjustment for relevant covariates. DISCUSSION: CRP and Il-6 were associated with risk of CRF in long-term breast cancer survivors, but were not independent of other known risk factors, suggesting that currently studied inflammatory markers are not suitable to identify patients at risk of long-term CRF.

Plasma metabolomic profile associated with fatigue in cancer patients.

BACKGROUND: Metabolomics is the newest -omics methodology and allows for a functional snapshot of the biochemical activity and cellular state. The goal of this study is to characterize metabolomic profiles associated with cancer-related fatigue, a debilitating symptom commonly reported by oncology patients. METHODS: Untargeted ultrahigh performance liquid chromatography/mass spectrometry metabolomics approach was used to identify metabolites in plasma samples collected from a total of 197 participants with or without cancer. Partial least squares-discriminant analysis (PLS-DA) was used to identify discriminant metabolite features, and diagnostic performance of selected classifiers was quantified using area under the receiver operating characteristics (AUROC) curve analysis. Pathway enrichment analysis was performed using Fisher's exact test and the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway database. FINDINGS: The global metabolomics approach yielded a total of 1120 compounds of known identity. Significant metabolic pathways unique to fatigued cancer versus control groups included sphingolipid metabolism, histidine metabolism, and cysteine and methionine metabolism. Significant pathways unique to non-fatigued cancer versus control groups included inositol phosphate metabolism, primary bile acid biosynthesis, ascorbate and aldarate metabolism, starch and sucrose metabolism, and pentose and glucuronate interconversions. Pathways shared between the two comparisons included caffeine metabolism, tyrosine metabolism, steroid hormone biosynthesis, sulfur metabolism, and phenylalanine metabolism. CONCLUSIONS: We found significant metabolomic profile differences associated with cancer-related fatigue. By comparing metabolic signatures unique to fatigued cancer patients with metabolites associated with, but not unique to, fatigued cancer individuals (overlap pathways) and metabolites associated with cancer but not fatigue, we provided a broad view of the metabolic phenotype of cancer-related fatigue.

Changes in patient-reported outcomes in light chain amyloidosis in the first year after diagnosis and relationship to NT-proBNP change.

We conducted a prospective cohort study in newly diagnosed systemic light chain (AL) amyloidosis patients (N = 59) to study patient-reported outcomes (PROs) through the first year. The median age was 68 years with 42% female, 8% Black, and 78% lambda subtype. Organ involvement was cardiac in 66%, renal in 58%, with 25% having 3 or greater organs involved. Between baseline and 3 months, all PROMIS®-29 domain scores worsened by 0.4-4.1 points except anxiety which improved by 2.1 points. By 1 year, scores improved compared to the greatest decline at 3 months, most statistically significant for global physical health, physical function, and fatigue. On stage-adjusted survival analysis, in addition to baseline global physical and mental health, domains measuring physical function, fatigue, anxiety, depression, and social roles were associated with 1-year survival. At 1 year, PROMIS measures were associated with NT-proBNP changes and hematologic response. Among patients with an NT-proBNP response, the improvement was seen in physical function, social roles, global mental health, and anxiety. Among patients with an NT-proBNP progression, worsening was seen with anxiety, depression, sleep, and global mental health. Measuring and tracking PROs in patients with AL amyloidosis is important and these important outcomes can be used as correlative endpoints in clinical care/research.

Tired of Being Ignored: Fatigue as a Presenting Symptom in Primary Hyperparathyroidism.

BACKGROUND: Fatigue is a common presenting symptom in primary hyperparathyroidism (PHPT). Although fatigue alone is not currently an indication for parathyroidectomy, it can have a significant detrimental effect on quality of life. The purpose of this study was to determine if there are underlying differences in demographic or disease characteristics in patients with PHPT who present with fatigue compared with those who do not. METHODS: We reviewed a prospective database of 2197 patients undergoing parathyroidectomy for PHPT by three endocrine surgeons from 2001 to 2019. Patients were divided into two groups based on the presence or absence of fatigue as a presenting symptom. Objective measures of disease severity were then compared between groups. RESULTS: A total of 1379 (63%) patients presented with fatigue. Patients presenting with fatigue were more likely to be female and to have a prior fracture, lower preoperative serum calcium (Ca), and normocalcemic PHPT. There were no statistically significant differences between groups in age, body mass index, history of nephrolithiasis, or preoperative serum parathyroid hormone levels. Patients presenting with fatigue were also more likely to have smaller parathyroid glands and multiglandular disease. No statistically significant differences were detected in postoperative serum Ca and parathyroid hormone levels, or cure or recurrence rates. CONCLUSIONS: Patients with PHPT who report fatigue as a presenting symptom present with more complex disease as manifested by a higher incidence of multiglandular disease and normocalcemic PHPT. Despite this, surgical cure is equivalent to other patients. Therefore, fatigue should be a discrete indication for parathyroidectomy in PHPT.

The association between plasma metabolites and sleep quality in the Southall and Brent Revisited (SABRE) Study: A cross-sectional analysis.

We examined the association between plasma metabolites and abnormal sleep patterns using data from the Southall and Brent REvisited (SABRE) cohort. Nuclear magnetic resonance spectroscopy provided 146 circulating plasma metabolites. Sleep questionnaires identified the presence or absence of: difficulty falling asleep, early morning waking, waking up tired, and snoring. Metabolites were compared between the sleep quality categories using the t test, and then filtered using a false discovery rate of 0.05. Generalised linear models with logit-link assessed the associations between filtered metabolites and sleep phenotypes. Adjustment was made for important demographic and health-related covariates. In all, 2,718 participants were included in the analysis. After correcting for multiple testing, three metabolites remained for difficulty falling asleep, 59 for snoring, and none for early morning waking and waking up tired. After adjusting for sex, age, ethnicity and years of education, 1 standard deviation increase in serum histidine and valine associated with lower odds of difficulty falling asleep by 0.89-0.90 (95% confidence intervals [CIs] 0.80-0.99). Branched-chain and aromatic amino acids (odds ratios [ORs] 1.19-1.25, 95% CIs 1.09-1.36) were positively associated with snoring. Total cholesterol in low-density lipoprotein (OR 0.90, 95% CI 0.83-0.97) and high-density lipoprotein (OR 0.88, 95% CI 0.81-0.95) associated with lower odds of snoring. In the fully adjusted model, most associations persisted. To conclude, histidine and valine associated with lower odds of difficulty falling asleep, while docosahexaenoic acid and cholesterol in low-density lipoprotein and high-density lipoprotein subfractions associated with lower odds of snoring. Identified metabolites could provide guidance on the metabolic pathways associated with adverse sleep quality.

Interleukin-8 Predicts Fatigue at 12 Months Post-Injury in Children with Traumatic Brain Injury.

Despite many children experiencing fatigue after childhood brain injury, little is known about the predictors of this complaint. To date, traditional indices of traumatic brain injury (TBI) severity have not predicted reliably persisting fatigue (up to three years post-injury). This study aimed to establish whether persisting fatigue is predicted by serum biomarker concentrations in child TBI. We examined whether acute serum biomarker expression would improve prediction models of 12-month fatigue based on injury severity. Blood samples were collected from 87 children (1-17 years at injury) sustaining mild to severe TBI (Glasgow Coma Scale [GCS] range 3-15; mean 12.43; classified as mild TBI [n = 50, 57%] vs. moderate/severe TBI [n = 37, 43%]), and presenting to the emergency departments (ED) and pediatric intensive care units (PICU) at one of three tertiary pediatric hospitals (Royal Children's Hospital (RCH); Hospital for Sick Children (HSC), Toronto; St Justine Children's Hospital (SJH), Montreal). Six serum biomarker concentrations were measured within 24 h of injury (interleukin-6, interleukin-8 [IL-8], soluble vascular cell adhesion molecule [SVCAM], S100 calcium binding protein B [S100B], neuron specific enolase [NSE], and soluble neural cell adhesion molecule [sNCAM]). Fatigue at 12 months post-injury was measured using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (parent report), classified as present/absent using previously derived cut-points. At 12 months post-injury, 22% of participants experienced fatigue. A model including IL-8 was the best serum biomarker for estimating the probability of children experiencing fatigue at 12 months post-injury. The IL-8 also significantly improved predictive models of fatigue based on severity.

Inflammation Mediates Exercise Effects on Fatigue in Patients with Breast Cancer.

PURPOSE: The randomized controlled OptiTrain trial showed beneficial effects on fatigue after a 16-wk exercise intervention in patients with breast cancer undergoing adjuvant chemotherapy. We hypothesize that exercise alters systemic inflammation and that this partially mediates the beneficial effects of exercise on fatigue. METHODS: Two hundred and forty women scheduled for chemotherapy were randomized to 16 wk of resistance and high-intensity interval training (RT-HIIT), moderate-intensity aerobic and high-intensity interval training (AT-HIIT), or usual care (UC). In the current mechanistic analyses, we included all participants with >60% attendance and a random selection of controls (RT-HIIT = 30, AT-HIIT = 27, UC = 29). Fatigue (Piper Fatigue Scale) and 92 markers (e.g., interleukin-6 [IL-6] and tumor necrosis factor α [TNF-α]) were assessed at baseline and postintervention. Mediation analyses were conducted to explore whether changes in inflammation markers mediated the effect of exercise on fatigue. RESULTS: Overall, chemotherapy led to an increase in inflammation. The increases in IL-6 (pleiotropic cytokine) and CD8a (T-cell surface glycoprotein) were however significantly less pronounced after RT-HIIT compared with UC (-0.47, 95% confidence interval = -0.87 to -0.07, and -0.28, 95% confidence interval = -0.57 to 0.004, respectively). Changes in IL-6 and CD8a significantly mediated the exercise effects on both general and physical fatigue by 32.0% and 27.7%, and 31.2% and 26.4%, respectively. No significant between-group differences in inflammatory markers at 16 wk were found between AT-HIIT and UC. CONCLUSIONS: This study is the first showing that supervised RT-HIIT partially counteracted the increase in inflammation during chemotherapy, i.e., IL-6 and soluble CD8a, which resulted in lower fatigue levels postintervention. Exercise, including both resistance and high-intensity aerobic training, might be put forward as an effective treatment to reduce chemotherapy-induced inflammation and subsequent fatigue.

Anabolic-catabolic hormonal responses in youth soccer players during a half-season.

This study sought to evaluate the hormonal response (i.e. total testosterone, free testosterone, cortisol, and their ratios TT/C and FT/C) in the under-19 youth soccer team (n = 18) throughout a six-month period. All sport medical examinations were conducted four times: before the beginning of the preparation period (T1), just after preparation period (T2), in the middle of the competitive period (T3), and at the end of the season (T4). The cortisol concentration was decreased at the T3 (-16.9%; p = 0.014), then increased at the T2 (16.8%; p = 0.001) and at the T4 (12.7%; p = 0.062), respectively, compared to the initial value. The analyses for total and free testosterone demonstrated no differences between the measurements. Finally, values of the TT/C and FT/C ratios were increased during the T3 (25%; p = 0.017, 24.4%; p = 0.021) in comparison with the initial measurement and decreased at the T4 (-28.9%; p = 0.001, - 30.8%; p = 0.001) in comparison with the T3. The study results showed that the lowest level of peripheral fatigue was recorded in the T3, which may suggest that a correct selection of training loads does not affect the severity of catabolic processes in youth players.

The effects of modified anti-inflammatory diet on fatigue, quality of life, and inflammatory biomarkers in relapsing-remitting multiple sclerosis patients: a randomized clinical trial.

BACKGROUND: The role of dietary interventions in improving the symptoms of Multiple Sclerosis (MS) has always been considered, but few studies have been conducted in this area. This study aimed to investigate the effects of modified anti-inflammatory diet on fatigue, quality of life, and inflammatory markers among patients with Relapsing-Remitting Multiple Sclerosis (RRMS). METHODS: This randomized clinical trial was conducted on 100 patients with RRMS. The patients were randomly divided into the diet group (anti-inflammatory diet) or the control group (healthy diet recommendations) for 12 weeks. Fatigue and quality of life were assessed by Modified Fatigue Impact Scale (MFIS) and Multiple Sclerosis Quality of Life (MSQoL-54), respectively. Anthropometric measures and inflammatory biomarkers, including Interleukin 17 (IL-17), Interleukin 4 (IL-4), and high sensitivity C-Reactive Protein (hs-CRP), were assessed at baseline and end of the study. RESULTS: The results showed a significant improvement in MFIS as well as in physical and mental components of MSQoL-54 (p = 0.001, p = 0.015, and p = 0.003, respectively) in the diet group compared to the control group. The results also showed a significant increase in IL-4 level (p = 0.022). However, no significant changes were detected in IL-17 and hs-CRP levels (p = 0.091, 0.418, respectively). CONCLUSION: Modified anti-inflammatory diet could improve fatigue and quality of life and increase IL-4 level.