Light is a major environmental factor regulating circadian rhythms, sleep- wake cycles, and mood-related behaviors. Patients with Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often experience circadian disruption and poor sleep quality, which severely compromise their quality of life; however, the relationship between light exposure and illness severity remains largely unknown. An observational cross-sectional cohort secondary study used collected data from 100 ME/CFS patients and 56 healthy controls to explore the impact of spontaneous light exposure on multidimensional health status and circulating biochemical parameters. Demographic and clinical features were assessed using validated patient-reported outcome measures. Light intensity, wrist temperature, and physical activity were continuously monitored at home over one week using wrist-worn actigraphy. Light intensity during predefined intervals and rhythmic variables of light cycle were calculated. Principal component analysis (PCA) was applied to reduce dimensionality of light variables. Multivariable analysis was performed adjusting for age, sex, body mass index, and physical activity. Following PCA of the light patterns, two components emerged across groups with high consistency: PC1 (explaining 61.7% of the total variance) reflected higher daytime light and rhythm stability, and PC2 (explaining 16.1%) represented nocturnal/early-morning light and rhythm instability. In ME/CFS patients, light variables were more extensively associated with clinical outcomes measures (FIS-40, PSQI and SF-36) than in healthy controls (all p < 0.05). Furthermore, PC2 was associated with higher levels of VCAM-1 and triglycerides, and lower serotonin concentrations (all p < 0.05). Four distinct light patterns were identified based on PCA scores: nocturnal light, healthy, adverse, and low diurnal light. ME/CFS patients exhibiting the healthy light pattern showed significantly lower fatigue, fewer sleep complaints, reduced autonomic dysfunction, and higher quality of life compared to those with the adverse light pattern (all p < 0.05). No significant differences were observed among healthy controls. Light exposure patterns show distinct associations with symptom variability in ME/CFS compared to healthy controls. More stable daytime light appears to relate to better symptom profiles, whereas irregular exposure and nocturnal light are linked to poorer health outcomes. Although causality cannot be inferred, these findings highlight light exposure as a potentially modifiable, non-invasive target for behavioral interventions aimed at improving the quality of life in ME/CFS, representing a promising emerging for future translational research.
This study investigates the prevalence and underlying factors of fatigue in individuals with Marfan syndrome (MFS) and hypermobile Ehlers-Danlos syndromes (hEDS), highlighting the necessity for focused research on this symptom within these patient populations. Cross-sectional, multicentre study. Data were collected from participants diagnosed with MFS or hEDS across multiple healthcare centres. The study enrolled 282 participants (127 with MFS and 155 with hEDS). Fatigue was measured using the Fatigue Severity Scale (FSS). Additional assessments included the Patient Health Questionnaire-9 (PHQ-9) for depression and the Insomnia Severity Index (ISI) for sleep disturbances. Participants with hEDS exhibited significantly higher median fatigue scores (FSS median=5.9, IQR=5.00-6.44) compared with the MFS group (FSS median=4.0, IQR=2.88-5.00). Significant predictors of fatigue included being female, having hEDS, participating in psychotherapy, and elevated scores on depression and insomnia scales. In the overall sample, hEDS significantly predicted fatigue (B=0.430, p=0.022), with depression and insomnia as strong influencers (PHQ-9: B=0.12, p<0.001; ISI: B=0.092, p<0.001). Notably, 80% of the hEDS group reported clinically relevant fatigue levels, compared with 31.5% in the MFS group. Daily persistence of fatigue was especially pronounced in hEDS, with 72.2% reporting everyday fatigue versus 25.2% in MFS. Temporal fatigue patterns also differed, with a more evenly distributed pattern throughout the day in hEDS, correlating with higher insomnia scores. The results underscore the severe impact of fatigue on individuals with hEDS compared with those with MFS, suggesting the need for targeted, multidisciplinary management strategies to enhance quality of life. NCT05712564.
Fatigue affects approximately 80% of people with Multiple Sclerosis (PwMS) and can impact several domains of daily life. However, the neural underpinnings of fatigue in MS are still not completely clear. The aim of our study was to investigate the spontaneous large-scale networks functioning associated with fatigue in PwMS using the EEG microstate approach with a spectral decomposition. Forty-three relapsing-remitting MS patients and twenty-four healthy controls (HCs) were recruited. All participants underwent an administration of Modified Fatigue Impact scale (MFIS) and a 15-min resting-state high-density EEG recording. We compared the microstates of healthy subjects, fatigued (F-MS) and non-fatigued (nF-MS) patients with MS; correlations with clinical and behavioral fatigue scores were also analyzed. Microstates analysis showed six templates across groups and frequencies. We found that in the F-MS emerged a significant decrease of microstate F, associated to the salience network, in the broadband and in the beta band. Moreover, the microstate B, associated to the visual network, showed a significant increase in fatigued patients than healthy subjects in broadband and beta bands. The multiple linear regression showed that the high cognitive fatigue was predicted by both an increase and decrease, respectively, in delta band microstate B and beta band microstate F. On the other hand, higher physical fatigue was predicted with lower occurrence microstate F in beta band. The current findings suggest that in MS the higher level of fatigue might be related to a maladaptive functioning of the salience and visual network.
Fatigue is a common symptom of multiple sclerosis (MS) and impacts quality of life, yet the role of chrononutrition and sleep in MS management remains underexplored. We aimed to investigate the cross-sectional associations of meal and sleep timing with fatigue in persons with MS (pwMS). We implemented a chrononutrition questionnaire within the Swiss MS Registry to quantify the relationships between meal timing, sleep patterns and fatigue among pwMS. In unadjusted analyses of 958 participants (median age 49 years, 73% women), a longer interval between the first and last meals (eating window) was associated with less fatigue (OR per 1 SD change in predictor=0.84, 95% CI 0.75 to 0.94), while later wake-up (OR 1.26, 95% CI 1.12 to 1.43) and first meal (OR 1.28, 95% CI 1.14 to 1.44) were associated with more fatigue. Later weekend versus weekday patterns ('social jetlag') across meal and sleep timing were associated with less fatigue.Adjustment for lifestyle factors attenuated most of the relationships, with employment status being the most influential. After adjustment, a larger 'social jetlag' in first meal (OR 0.86, 95% CI 0.76 to 0.97) and going to bed later (OR 0.86, 95% CI 0.76 to 0.97) remained associated with less fatigue, while a longer time in bed (OR 1.28, 95% CI 1.12 to 1.46) remained associated with more fatigue. Associations of meal and sleep timing with fatigue in pwMS were influenced by lifestyle factors, particularly employment status. After adjustment, eating the first meal later during weekends compared with weekdays, going to bed later and a shorter time in bed were associated with less reported fatigue. The apparent benefits of 'social jetlag' on first meal times require confirmation from prospective and interventional studies.
Cancer survivors who do not engage in regular physical activity often experience persistent psychological distress and fatigue, which can significantly impact their quality of life. While handgrip strength (HGS) is recognized as an indicator of overall health and physical resilience, the combined role of HGS and physical inactivity in predicting psychological distress and fatigue in this population remains unclear. This study aimed to examine the relationships between self-reported physical inactivity, HGS, and psychological distress, specifically depressive symptoms, anxiety, and cancer-related fatigue (CRF), in physically inactive cancer survivors. This cross-sectional study included 42 physically inactive cancer survivors (mean age = 63.2 years, SD = 8.96) recruited from the Cancer Institute (IRCCS) in Bari, Italy. Physical inactivity was quantified based on self-reported weekly physical activity minutes, with all participants engaging in less than 150 min per week. The participants underwent HGS assessment and completed validated psychological measures, including the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI-Y1 and STAI-Y2), and the Fatigue Severity Scale (FSS). Bivariate correlations were examined via Spearman's rank correlation coefficients, and multiple linear regression analyses were performed to identify independent predictors of psychological distress and fatigue, adjusting for covariates such as age, sex, cancer type, and time since treatment completion. Both lower HGS and greater physical inactivity were significantly correlated with greater depressive symptoms (HGS: ρ = -0.524, p < 0.001; physical inactivity: ρ = -0.662, p < 0.001), greater fatigue severity (HGS: ρ = -0.599, p < 0.001; physical inactivity: ρ = -0.662, p < 0.001), and increased trait anxiety (HGS: ρ = -0.532, p < 0.001; physical inactivity: ρ = -0.701, p < 0.001). No significant associations were found between physical inactivity or HGS and state anxiety (p > 0.05). Multiple regression analyses confirmed that both HGS and physical inactivity independently predicted depressive symptoms (HGS: β = -0.435, p = 0.009; physical inactivity: β = -0.518, p = 0.002), trait anxiety (HGS: β = -0.313, p = 0.038; physical inactivity: β = -0.549, p < 0.001), and fatigue (HGS: β = -0.324, p = 0.033; physical inactivity: β = -0.565, p < 0.001), even after adjusting for covariates. Low physical activity and reduced muscle strength independently predict psychological distress and fatigue in cancer survivors. These findings highlight the potential exacerbating role of physical inactivity in both physical and psychological vulnerability, underscoring the need for interventions promoting regular exercise. Integrating strength assessments and structured physical activity programs may be key strategies in survivorship care to improve mental well-being and overall quality of life.
Binge Eating Disorder (BED) is a prevalent and under-recognized eating disorder associated with psychological distress and maladaptive coping. Healthcare professionals are frequently exposed to high levels of occupational stress, which may increase their vulnerability to disordered eating behaviors, including BED. This study aimed to explore the relationship between work-related stress, emotional exhaustion and the risk of developing binge eating symptoms among healthcare professionals in Italy. A cross-sectional online survey was conducted between May and July 2024 among 312 healthcare professionals. Participants completed a structured questionnaire comprising sociodemographic data, stress-related variables, the Emotional Exhaustion subscale of the Maslach Burnout Inventory (MBI) and the Binge Eating Scale (BES). The sample was predominantly female (81.7%) with a mean age of 37.6 years. Twenty percent reported a history of eating disorders and 60.3% reported stress or anxiety. Significant associations were found between BES scores and stress-related variables, including anxiety, emotional exhaustion, eating during work breaks and vending machine use (p< 0.005). Higher BES scores were correlated with burnout symptoms such as fatigue, emotional drain and inability to cope. A strong association also emerged between BES scores and the perceived impact of stress on eating habits. Work-related stress and burnout symptoms are significantly associated with binge eating tendencies among healthcare professionals. Preventive strategies - such as institutional stress management programs and access to healthy food - are essential to promote well-being and prevent maladaptive eating behaviors in high-stress healthcare environments.
Lung cancer screening with low-dose computed tomography (LDCT) among heavy smokers can decrease lung cancer mortality. Smoking cessation intervention is recommended within the screening program; however, the methods for smoking cessation in the LDCT screening context are not well established. We have previously shown that a novel smartphone app can increase the chance for smoking cessation along with lung cancer screening. The effects of lung cancer screening, smoking cessation, and the use of smartphone apps on health-related quality of life (HRQoL) are widely unknown. This study aims to investigate the effect of lung cancer screening, smoking cessation, and the use of smoking cessation app on HRQoL, an exploratory end point of the low-dose computed tomography screening for lung cancer combined to different smoking cessation methods in Finland (LDCT-SC-FI) study. This study was conducted as a part of the LDCT-SC-FI (NCT05630950), which was a randomized controlled trial investigating different smoking cessation methods in participants undergoing lung cancer screening with LDCT. The main inclusion criteria included an age of 50-74 years, a marked smoking history (smoked ≥15 cigarettes per day for ≥25 years or smoked ≥10 cigarettes per day for ≥30 years), an active smoking status, and access to a smartphone. The recruitment was carried out by newspaper and internet advertisements and informing relevant health care units at hospital districts. The study participants (n=200), all at Oulu University Hospital, were randomized in 1:1 fashion to a yearly LDCT with standard smoking cessation (written material) or a stand-alone smartphone app-based cessation. HRQoL, an exploratory study end point, was assessed at baseline and at 1 year with Quality of Life Questionnaire Core 30 (QLQ-C30) and EQ-5D. In total, 199 and 186 individuals had both questionnaires completed at baseline and at 1 year, respectively. We did not detect a change in HRQoL between the time points using QLQ-C30 global health status score or EQ-5D index score. Smoking cessation at 1-year time did not affect QLQ-C30 global health status or EQ-5D. We observed improved quality of life scores by EQ-5D at 1 year (control: mean 0.720, SD 0.197 vs app: mean 0.799, SD 0.197; improved in 17/93, 18% of controls vs 29/93, 31% in app arm), while there was no difference in means at baseline. Smartphone app arm reported reduced pain (EQ-5D effect size [ES] 0.049, 95% CI 0.006-0.12; P=.01; adjusted ES 0.026; P=.007; QLQ-C30 ES 0.076, 95% CI 0.02-0.16; P<.001; adjusted ES 0.05; P=.02) and increased mobility (EQ-5D ES 0.031, 95% CI 0.01-0.09; P=.02; adjusted ES 0.037; P=.008) at 1 year. The number of completed questionnaires in the app was associated with improved HRQoL by EQ-5D (ES 0.073, 95% CI 0.00-0.180; P=.04; adjusted ES 0.071; P=.04). This is the first study to test a smoking cessation smartphone app in the context of lung cancer screening. The use of the developed app correlated with improved HRQoL, mainly by decreased pain and fatigue. To conclude, the studied app provides a feasible and effective cessation intervention that is readily implementable in population-based lung cancer screening programs, with enhanced health benefits beyond smoking cessation.
Background: Cancer-related health outcomes are shaped by the interplay of aging, complex treatment exposures, and individual psychological characteristics. Mitochondrial dysfunction has been implicated as an underlying biological process affecting cancer-related outcomes. This secondary, exploratory pilot analysis aimed to examine age- and treatment-related differences in fatigue, coping self-efficacy, resilience, and skeletal muscle mitochondrial oxidative capacity, measured via phosphorus-31 magnetic resonance spectroscopy (31P-MRS). Methods: Eleven cancer survivors (mean age 53.3 ± 12.7 years) were recruited from a larger symptom management trial. Participants underwent 31P-MRS to assess mitochondrial function via phosphocreatine recovery time constant (τPCr). Patient-reported outcome measures and physical function assessments were collected. Group comparisons and correlation analyses were conducted to evaluate differences and associations based on age (<65 vs. ≥65 years) and treatment. Because treatment categories were not mutually exclusive and the time since last treatment was not collected, treatment-related comparisons are descriptive only. Given the small available sample size, we conducted this study as exploratory and hypothesis-generating. Results: Older survivors (≥65) had longer τPCr (59.5 vs. 50.1 s), weaker grip strength, higher fatigue, and lower physical performance compared to younger participants, although differences were not statistically significant. Treatment-related patterns were descriptive; participants receiving multiple treatments had shorter τPCr but lower muscular strength, while immunotherapy recipients reported higher fatigue and lower physical activity. Among younger participants, a negative correlation was observed between τPCr and fatigue (ρ = -0.71), and positive correlations were observed with resilience (ρ = 0.61) and coping self-efficacy (ρ = 0.74), reflecting a pattern that warrants cautious interpretation in this small sample. Conclusions: These preliminary results suggest age- and treatment-related differences in fatigue, physical performance, psychological factors, and skeletal muscle mitochondrial bioenergetics. These signals warrant further testing in larger, adequately powered cohorts to clarify mechanisms and inform the development of personalized survivorship care strategies.
In the traditional Chinese medicine (TCM) clinic, qi deficiency is a common syndrome pattern in major depressive disorder (MDD). Sijunzi decoction (SJZD), a classic muti-herbal formula to replenish qi and nourish blood, is widely used to treat qi deficiency syndrome. The symptoms of qi deficiency are very similar to fatigue. Currently the mainstream antidepressant treatment outcome for depression with fatigue remains unsatisfying. SJZD has potential for improvement in the treatment of depression with qi deficiency, which has not been scientifically characterized previously. The study aimed to test the effects of SJZD in a mouse model of depression with qi deficiency/fatigue and to investigate the associated mechanisms, focusing on inflammation in the hippocampus and muscles. Balb/c and 129S1/SvImJ (129/S1) strains of mice were compared for depression-like and qi deficiency-like behaviors following receiving the same procedure of chronic unpredictable mild stress (CUMS). Qi deficiency behavior was assessed using grip strength test (GST), exhaustive swimming test (EST) and degree of redness (DOR). Depressive behavior was assessed using sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST). SJZD was administrated for 1 week in CUMS-exposed mice in both strains. The conventional antidepressant fluoxetine (FLX), ineffective to fatigue/qi deficiency, was used to compared with SJZD, qPCR was used to detect gene expressions of inflammatory factors in the hippocampus and muscles in both strains. Balb/c and 129/S1 mice both showed depressive symptoms comparably after exposed to CUMS. However, qi deficiency symptoms were only shown in Balb/c mice, with decreased grip strength in GST, reduced swimming times in EST and decreased degree of redness in DOR. SJZD was able to reverse both depressive deficits and qi deficiency in Balb/c mice, without influencing 129/S1 mice. Consistent with the depression-phenotype, the expressions of the inflammatory factors including IL-1β, TNF-α, NF-kB and CD8 in the hippocampus were upregulated in both Balb/c and 129/S1 mice, which were reversed by SJZD only in Balb/c mice. Consistent with the qi deficiency-phenotype, the expressions of these inflammatory factors were up-regulated in the muscles only in Balb/c mice, which were reversed by SJZD. In contrast, FLX elicited antidepressant effects without changing qi deficiency in Balb/c mice, consistent with its improvement of inflammation in the hippocampus, but not muscles. Balb/c strain mice showed co-susceptibility to depression and qi deficiency/fatigue following CUMS, both of which were alleviated by SJZD. These effects were associated with the suppression of inflammation in the hippocampus and muscles respectively, suggesting that the anti-inflammation effects of SJZD on both brain and the peripheral systems may play a part in qi-replenishing and antidepressant functions. Our study provides the first scientific evidence, leveraging animal genetics, to demonstrate the necessity and efficacy of stratified treatment of depression, using TCM treatment based on syndrome differentiation.
A major challenge in diagnosing post COVID lies in differentiating symptoms following a confirmed SARS-CoV-2 infection from those that may also occur in uninfected individuals (post COVID mimics) and be associated with a broader impact of the pandemic. The WHO post COVID definition was applied to the Luxembourgish longitudinal CON-VINCE cohort, where SARS-CoV-2 infection was confirmed via either a positive RT-qPCR or a serology test. Risk factor analysis was conducted on 1,865 individuals. Female gender, lower resilience, greater loneliness, and a higher number of comorbidities were associated with symptoms persistence. The symptomatology and comorbidity profiles of 559 participants (including 50 post COVID and 66 post COVID mimics) were investigated. Two distinct clusters of persistent symptoms were identified: (1) depression with anxiety, present in both infected and non-infected groups, and (2) memory impairment with fatigue, unique to the post COVID group. Therefore, presence of both memory impairment and fatigue may help differentiate post COVID patients from post COVID mimics. Yet, verification that memory impairment was newly developed was not possible, as this symptom was not recorded at baseline. Our findings suggest that future studies should consider factors affecting development of persistent post COVID-like symptoms observed in individuals that were never infected.
Fatigue is a common comorbidity in patients with axial spondyloarthritis (axSpA), often reported also by those in clinical remission or with moderate disease activity. The aim of this study is to assess the prevalence of fatigue in patients with axSPA, and to investigate possible non-disease-related determinants, with a special focus on depression. Patients with axSpA were assessed using the Chalder's Fatigue Questionnaire (CFQ) for fatigue, and the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D) for depression. Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index (BASFI) and Health Assessment Questionnaire (HAQ) were also used to assess disease activities and disability. Univariate and multivariate linear regressions were performed to identify possible predictors of fatigue. Out of 119 patients, 53 (44.5%) had fatigue. Patients with fatigue had higher HADS-D, ASDAS, BASFI, HAQ scores. HADS-D was predictive of CFQ score in univariate and multivariate regressions for total CFQ, and for mental and physical subscales. The correlation between HADS-D and CFQ total score was statistically significant also when taking into consideration only patients in clinical remission and with moderate disease activity. Depressed patients had higher CFQ score compared to non-depressed ones, and did not show any difference in CFQ scores when stratified for disease activity or systemic inflammation. The study found correlation between fatigue and disease activity and depression in patients with axSpA. These findings suggest that depression could represent the major determinant of fatigue in patients with axSpA, independently of clinical activity.
Co-creation has emerged as a crucial strategy for addressing complex public health challenges, including promotion and prevention of mental health concerns. While the evidence base for effective interventions continues to grow, significant gaps remain in their implementation and integration into real-world settings. Co-creation offers a valuable tool for strengthening mental health promotion strategies, ensuring that interventions are evidence-based, contextually relevant, culturally sensitive, sustainable and acceptable to those directly affected. However, there is a paucity of studies examining the evaluation of co-creation research, particularly regarding how participatory methods foster adaptation and influence outcomes and long-term sustainability. This protocol outlines a study designed to implement, evaluate and strengthen co-creation methodologies through a participatory and formative evaluation approach. This study adopts a mixed-methods design within the ADVANCE project, a multi-country initiative focused on co-creating mental health promotion and prevention interventions with groups in vulnerable situations across seven European countries. End-users, healthcare professionals, and decision-makers will be engaged throughout the project in both intervention design and evaluation. Co-creation activities initiated with intervention scenario building and prioritization, drawing on desk reviews and online Delphi surveys co-developed with locally-set Society Advisory Groups (SAGs). The selection of intervention scenarios for implementation was performed using scenario-based workshops involving stakeholders in six partner countries. A second goal is to evaluate the co-creation process, which was co-designed in consultation with country teams and SAGs. A longitudinal qualitative study based on semistructured interviews with co-creators across two time points will be conducted, following the co-development of the interview guide through an online World Café. This study introduces an innovative approach by embedding participatory and formative evaluation into the co-creation process, enabling ongoing adaptation of co-creation activities. Through continuous stakeholder engagement, the project seeks to address barriers deriving from power imbalances, conflicting priorities, and resource limitations. Qualitative and participatory methods will be combined to elicit stakeholders' views, identify drawbacks and promote adjustments to ensure meaningful collaboration and reduce participation fatigue. Expected outcomes include actionable recommendations to inform policy, reduce stigma and foster the co-creation of more inclusive, effective, sustainable and scalable mental health promotion and prevention strategies across Europe.
The REBECCA project taps into the potential of using real-world data (RWD) for supporting groundbreaking clinical research on complex chronic conditions as a complement to Randomised Controlled Trials. REBECCA moves beyond the analysis of clinical data from Electronic health records, by combining it with detailed monitoring data from multiple wearables, online behaviour and self-reported data to monitor patients's quality of life in terms of their functional and emotional status. The project focuses on the detection of cancer-related fatigue, developed during breast cancer recovery, using digital biomarker profiles for early detection of the disease and assessing the value of detailed and longitudinal patient monitoring as a means of improving patient care. The project also demonstrates the extensibility of REBECCA monitoring to other forms of cancer, such as prostate cancer. We describe the three clinical trials being conducted in Norway and the use of the REBECCA platform, capable of detailed monitoring and privacy preserving federated cross-country data analysis. The RWD will be analyzed in the context of data from questionnaires (Patient Reported Outcome Measures) and results from analysis of biological samples. Through this approach we expect that the REBECCA project will produce new knowledge on clinical management of cancer patients and contribute to new biological knowledge on cancer-related fatigue. Status and perspectives: The REBECCA project is ongoing, and patient follow-up will be completed during February 2026. The initial analyses of RWD, PROMs and biological samples have started together with the partners in the REBECCA consortium. The REBECCA trials are approved by the Regional Ethics Committee of the Western Health Authority (REK Vest) under the IDs 225,855 (REBECCA-1), 242,088 (REBECCA-2) and 619,903 (REBECCA-3). All trials have also been registered at clinicaltrials.gov (NCT05587777, NCT06120595 and NCT06435091). Trial registration: NCT05587777, Retrospectively registered 19th of October 2022, https://clinicaltrials.gov/study/ NCT05587777; NCT05587777, Retrospectively registered 6th of November 2023, https://clinicaltrials.gov/study/ NCT06120595; NCT05587777, Retrospectively registered 23rd of May 2024, https://clinicaltrials.gov/study/ NCT06435091.
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation tool with potential for managing neuromuscular fatigue, possibly due to alterations in corticospinal excitability. However, inconsistencies in intra- and inter- individual variability responsiveness to tDCS limit its clinical use. Emerging evidence suggests harnessing homeostatic metaplasticity induced via tDCS may reduce variability and boost its outcomes, yet little is known regarding its influence on neuromuscular fatigue in healthy adults. We explored whether cathodal tDCS (ctDCS) prior to exercise combined with anodal tDCS (atDCS) could augment corticospinal excitability and attenuate neuromuscular fatigue. 15 young healthy adults (6 males, 22 ± 4 years) participated in four pseudo-randomised neuromodulation sessions: sham stimulation prior and during exercise, sham stimulation prior and atDCS during exercise, ctDCS prior and atDCS during exercise, ctDCS prior and sham stimulation during exercise. The exercise constituted an intermittent maximal voluntary contraction (MVC) of the right first dorsal interosseous (FDI) for 10 min. Neuromuscular fatigue was quantified as an attenuation in MVC force, while motor evoked potential (MEP) amplitude provided an assessment of corticospinal excitability. MEP amplitude increased during the fatiguing exercise, whilst across time, force decreased. There were no differences in MEP amplitudes or force between neuromodulation sessions. These outcomes highlight the ambiguity of harnessing metaplasticity to ameliorate neuromuscular fatigue in young healthy individuals.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystemic disorder mostly triggered by viral infections, with core symptoms including post-exertional malaise (PEM), fatigue, pain, and cognitive dysfunction. Its prevalence has increased significantly in the context of the coronavirus disease 2019 (COVID-19) pandemic. Despite its severity and impact on patients' quality of life, ME/CFS remains poorly understood. On May 12 and 13, 2025, the 3rd International Conference hosted by the Charité Fatigue Center brought together nearly 200 researchers from various disciplines on-site, and around 3,700 participants online to discuss recent advances in ME/CFS research, diagnostics, clinical care, and therapeutic trials. The program featured 33 lectures by international experts on key topics such as post-COVID syndrome (PCS), care structures, and pathophysiological mechanisms including cardiovascular dysregulation, immune dysregulation, autoimmune mechanisms, and metabolic dysfunction. In addition, results from clinical trials addressing disease mechanisms, including those specifically targeting autoantibodies, were presented. While public awareness and funding opportunities have increased in the wake of the pandemic and the emergence of PCS, ME/CFS remains severely underresearched. Sustained and adequately funded research efforts are urgently required to advance understanding, identify diagnostic markers, and develop targeted therapeutic interventions.
Physical and motor fatigue are debilitating symptoms common in multiple sclerosis (MS). Lifestyle interventions may be effective in managing MS-related fatigue. This scoping review aims to: (i) identify and summarise lifestyle interventions including those focused on diet, physical activity, and sleep, or multicomponent interventions for physical and motor fatigue management in MS; and (ii) provide recommendations for future research in this area. Database searches of MEDLINE (Ovid), Cochrane (Cochrane Library), Scopus (Elsevier), CINAHL (EBSCOhost), and Embase (Ovid) were conducted. To be included in this scoping review, studies were to be published in a peer reviewed scientific journal, focused on a non-pharmacological lifestyle intervention (physical activity, exercise, sleep, diet, or a combination), and written in English. Forty-one studies were included for analysis. Included participants were predominantly female, living with relapsing-remitting MS, with a median age of 48 years. The design of the studies comprised mainly of randomised control trials and pilot/feasibility studies. All included studies incorporated a physical activity intervention, with most examining aerobic/endurance exercise. Most studies reported an effect on improving physical/motor fatigue and a large proportion incorporated an endurance training program. To build on the current evidence and progress MS-fatigue related recommendations, further studies with larger sample sizes and a more inclusive range of MS types are required. Finally, with a gap of research investigating the role of diet and sleep on motor and physical fatigue in MS, research into this field is critically needed.
Exertional dyspnoea in post-COVID syndrome is a debilitating manifestation, requiring appropriate comprehensive management. However, limited-resources healthcare systems might be unable to expand their healthcare-providing capacity and are expected to be overwhelmed by increasing healthcare demand. Furthermore, since post-COVID exertional dyspnoea is regarded to represent an umbrella term, encompassing several clinical conditions, stratification of patients with post-COVID exertional dyspnoea, depending on risk factors and underlying aetiologies might provide useful for healthcare optimization and potentially help relieve healthcare service from overload. Hence, we aimed to investigate the frequency, functional characterization, and predictors of post-COVID exertional dyspnoea in a large cohort of post-COVID patients in Apulia, Italy, at 3-month post-acute SARS-CoV-2 infection. A cohort of laboratory-confirmed 318 patients, both domiciliary or hospitalized, was evaluated in a post-COVID Unit outpatient setting. Post-COVID exertional dyspnoea and other post-COVID syndrome manifestations were collected by medical history. Functional characterization of post-COVID exertional dyspnoea was performed through a 6-min walking test (6-mwt). The association of post-COVID exertional dyspnoea with possible risk factors was investigated through univariate and multivariate logistic regression analysis. At medical evaluation, post-COVID exertional dyspnoea was reported by as many as 190/318 patients (59.7%), showing relatively high prevalence also in domiciliary-course patients. However, functional characterization disclosed a 6-mwt-based desaturation walking drop in only 24.1% of instrumental post-COVID exertional dyspnoea patients. Multivariate analysis identified five independent predictors significantly contributing to PCED, namely post-COVID-fatigue, pre-existing respiratory co-morbidities, non-asthmatic allergy history, age, and acute-phase-dyspnoea. Sex-restricted multivariate analysis identified a differential risk pattern for males (pre-existing respiratory co-morbidities, age, acute-phase-dyspnoea) and females (post-COVID-fatigue and acute-phase-dyspnoea). Our findings revealed that post-COVID exertional dyspnoea is characterized by relevant clinical burden, with potential further strain on healthcare systems, already weakened by pandemic waves. Sex-based subgroup analysis reveals sex-specific dyspnoea-underlying risk profiles and pathogenic mechanisms. Knowledge of sex-specific risk-determining factors might help optimize personalized care management and healthcare resources.
This study aimed to investigate circadian rhythm manifestations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients (including a subpopulation of long-COVID patients) and matched healthy controls while also exploring their association with cardiovascular health variables. Thirty-one ME/CFS patients (75% females), 23 individuals diagnosed with post-COVID ME/CFS (56% females) and 31 matched healthy controls (68% females) were enrolled in this study. Demographic and clinical characteristics were assessed using validated self-reported outcome measures. Actigraphy data, collected over one week, were used to analyze the 24-h profiles of wrist temperature, motor activity, and sleep circadian variables in the study participants. Associations between lipid profile with endothelial dysfunction biomarkers (such as endothelin-1, ICAM-1 and VCAM-1) and with sleep and circadian variables were also studied. No differences were found in these variables between the two group of patients. Patients showed lower activity and worse sleep quality than matched healthy controls, together with a worse lipid profile than controls, that was associated with disturbances in the circadian temperature rhythm. ICAM-1 levels were associated with plasma lipids in healthy controls, but not in patients, who showed higher levels of endothelin-1 and VCAM-1. These findings suggest that lipid profiles in ME/CFS are linked to disrupted circadian rhythms and sleep patterns, likely due to endothelial dysfunction. Furthermore, they highlight the intricate relationship between sleep, circadian rhythms, and cardiovascular health in this condition.
Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID-19 syndrome (LC) show substantial clinical overlap, but direct comparative microbiome studies remain limited. Methods: In this cross-sectional study, we compared the fecal gut microbiome of patients with ME/CFS, LC, and healthy controls (HC) within a unified analytical framework using 16S rRNA profiling, differential abundance testing, and multivariate modeling. We also examined associations between microbiome variation and questionnaire-derived symptom-domain scores. Results: Alpha-diversity did not differ significantly among groups, whereas beta-diversity analyses showed small but significant disease-associated community differences with broad overlap between cohorts. Differential abundance analysis identified stronger signals in disease-versus-control contrasts than in the direct ME/CFS vs. LC contrast. Both ME/CFS and LC shared enrichment of Sutterella and depletion of Terrisporobacter and Lachnospiraceae relative to HC. Predicted functional profiling showed shared disease-versus-control changes in pathways related to anaerobic acetate/H2 carbon flow, inositol/polyol degradation, phosphonate/C1-related metabolism, and lysine-derived fermentation. Regression analyses showed the strongest microbiome associations with fatigue-related and physiosomatic domains, while affective, cognitive, and gastrointestinal outcomes showed weaker signals. Conclusions: Overall, these findings support the presence of overlapping but non-identical gut microbiome alterations in ME/CFS and LC. The results provide a basis for future longitudinal and multi-omics studies aimed at clarifying the stability, functional relevance, and clinical utility of these microbial patterns.
Impulsive-compulsive behaviors (ICBs) in Parkinson's disease are associated with psychiatric comorbidities, reduced quality of life, caregiver burden and serious psychosocial consequences. These behaviors greatly impact patients and their families, and pose a challenge for clinicians. To assess and compare the effects of pharmacological and non-pharmacological treatments for ICBs in people with Parkinson's disease, and to assess whether the effects differ according to ICB subtype. We searched the Cochrane Movement Disorders Group Specialized Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PEDro, and major trials registries, along with handsearching of abstracts, to 13 June 2025. We included parallel-group and cross-over randomized controlled trials (RCTs) in people with Parkinson's disease with ICBs comparing pharmacological or non-pharmacological treatment with placebo or no treatment. Our critical outcomes were change in the frequency and severity of ICBs from baseline, and adverse effects or events. Our important outcomes were change in: quality of life, neuropsychiatric symptoms (depression, anxiety, apathy, anhedonia), impulsivity, cognition, motor and non-motor symptoms associated with ICBs in Parkinson's disease. We used the revised Cochrane risk of bias tool for randomized trials (RoB 2) for outcomes reported in the summary of findings tables. We included four studies, each evaluating a different intervention. Due to this heterogeneity, we could not conduct a meta-analysis and instead provided a narrative summary of the studies and their findings. For continuous outcomes, we calculated mean differences (MDs), while for binary outcomes, we calculated risk ratios (RRs), both with 95% confidence intervals (CIs). We used the GRADE approach to assess the certainty of evidence for each outcome. We included four RCTs: three parallel-group and one cross-over design, with a total of 151 participants. Sample sizes ranged from 17 to 50 per study; participants' mean age ranged from 57.6 to 61.2 years. Women comprised 23.5% to 32% of participants. Three studies compared pharmacological interventions - amantadine, naltrexone, and clonidine (one study each) - to placebo. One study compared a non-pharmacological intervention (cognitive behavioral therapy, CBT) to a wait-list control. Non-profit organizations supported three studies; one did not report funding information. The studies were conducted in Europe and North America and were published between 2010 and 2023. Follow-up durations ranged from one to six months. All studies evaluated critical outcome measures of interest. Only one study assessed any of the review's important outcomes of interest. Amantadine versus placebo The evidence is very uncertain about the effect of amantadine versus placebo on adverse events (RR 4.50, 95% CI 0.25 to 81.76; 17 participants). The one study exploring this comparison did not assess any other review outcomes. Naltrexone versus placebo Compared to placebo, naltrexone may result in little to no difference in change in severity of ICBs (; low-certainty evidence). The evidence is very uncertain about the effect of naltrexone on adverse events, including dizziness (RR 4.00, 95% CI 0.48 to 33.22; 48 participants), nausea (RR 15.00, 95% CI 0.90 to 248.78; 48 participants), headache (RR 1.25, 95% CI 0.38 to 4.10; 48 participants), and blood pressure changes (RR 1.67, 95% CI 0.72 to 3.86; 48 participants). [Figure: see text] Clonidine versus placebo The evidence from one study (with 39 participants assessed for all outcomes) is very uncertain about the effect of clonidine on change in frequency of ICBs (RR 0.89, 95% CI 0.54 to 1.47), change in severity of ICBs (), and adverse events, including sleepiness (RR 0.53, 95% CI 0.05 to 5.34), falls (RR 3.15, 95% CI 0.14 to 72.88), nausea (RR 3.15, 95% CI 0.14 to 72.88), orthostatic hypotension (RR 1.58, 95% CI 0.30 to 8.43), restless legs syndrome (RR 3.15, 95% CI 0.14 to 72.88), fatigue (RR 0.70, 95% CI 0.13 to 3.75) and asymptomatic bradycardia (RR 3.15, 95% CI 0.14 to 72.88). The evidence is also very uncertain about the effect of clonidine versus placebo on any changes in participants' quality of life (), depression () and anxiety (). [Figure: see text] [Figure: see text] [Figure: see text] [Figure: see text] CBT versus wait-list control The evidence suggests that, compared to wait-list control, CBT may result in little to no difference in change in frequency (RR 0.79, 95% CI 0.50 to 1.26; 42 participants; low-certainty evidence) and severity of ICBs (; 31 participants; low-certainty evidence). [Figure: see text] The variety of interventions and the small sample sizes precluded data synthesis, including meta-analysis, as well as subgroup and sensitivity analyses. We judged all four studies to have 'some concerns' or a high risk of bias overall. The RCTs reviewed here provide only uncertain evidence regarding the effectiveness of both pharmacological and non-pharmacological treatments for ICBs. This uncertainty is due to limited evidence, small sample sizes, short follow-up periods, and an uncertain balance between side effects and efficacy. Future RCTs should include appropriate critical and important outcomes and explore different ICBs separately, with adequate sample sizes and follow-up durations. This Cochrane review had no dedicated funding. Protocol (2023): doi.org/10.1002/14651858.CD015046.