Corticospinal output during muscular fatigue differs in multiple sclerosis patients compared to healthy controls

In multiple sclerosis (MS), fatigue is a common and often disabling symptom. It has multiple causes with central motor fatigue playing an important role.

Assessment of post-stroke fatigue: the fatigue scale for motor and cognitive functions

Post-stroke fatigue (PSF) is an important but still controversial issue since knowledge on its nature is still humble. The aim of the present study was to characterize PSF beyond the subacute phase.

SNP array profiling of childhood adrenocortical tumors reveals distinct pathways of tumorigenesis and highlights candidate driver genes

Childhood adrenocortical tumors (ACT) are rare malignancies, except in southern Brazil, where a higher incidence rate is associated to a high frequency of the founder R337H TP53 mutation. To date, copy number alterations in these tumors have only been analyzed by low-resolution comparative genomic hybridization.

Cyclin D1 in non-small cell lung cancer: a key driver of malignant transformation

PURPOSE: To review the evidence implicating the deregulation of cyclin D1 in the pathogenesis of non-small cell lung cancer (NSCLC), and to discuss the opportunities for targeted clinical intervention. METHODS: Data published until June 2006 are summarized, and previously unpublished results from our own research are included. RESULTS: In normal cells, cyclin D1 complexes with and activates cyclin-dependent kinases (CDK) and acts as a transcriptional regulator. The protein is frequently overexpressed in a wide range of cancers, sometimes coincident with CCND1 (cyclin D1) gene amplification (5-20% of tumours). A low level of somatic mutations have been seen in certain tumours. CCND1 is amplified in NSCLC and cyclin D1 is frequently overexpressed in tumours and pre-invasive bronchial lesions, generally from one parental allele. Mutation analyses revealed a frequent CCND1 gene polymorphism (A870G) that modulates alternative splicing and allows expression of an alternative cyclin D1 transcript (transcript cyclin D1b). The encoded cyclin D1b protein lacks a specific phosphorylation site required for nuclear export. Genotype has been correlated with the risk and/or severity of disease or drug response across a range of malignancies, including lung cancer. Together, these findings suggest a strong pathological role for cyclin D1 deregulation in bronchial neoplasia. CONCLUSION: Current data indicate that cyclin D1 overexpression is not a consequence of, but rather a pivotal element in the process of malignant transformation in the lung and other tissues. This understanding may open new avenues for lung cancer diagnosis, treatment and prevention.

Corticospinal output and loss of force during motor fatigue

The objective of this study was to analyze central motor output changes in relation to contraction force during motor fatigue. The triple stimulation technique (TST, Magistris et al. in Brain 121(Pt 3):437-450, 1998) was used to quantify a central conduction index (CCI = amplitude ratio of central conduction response and peripheral nerve response, obtained simultaneously by the TST). The CCI removes effects of peripheral fatigue from the quantification. It allows a quantification of the percentage of the entire target muscle motor unit pool driven to discharge by a transcranial magnetic stimulus. Subjects (n = 23) performed repetitive maximal voluntary contractions (MVC) of abductor digiti minimi (duration 1 s, frequency 0.5 Hz) during 2 min. TST recordings were obtained every 15 s, using stimulation intensities sufficient to stimulate all cortical motor neurons (MNs) leading to the target muscle, and during voluntary contractions of 20% of the MVC to facilitate the responses. TST was also repetitively recorded during recovery. This basic exercise protocol was modified in a number of experiments to further characterize influences on CCI of motor fatigue (4 min exercise at 50% MVC; delayed fatigue recovery during local hemostasis, "stimulated exercise" by 20 Hz trains of 1 s duration at 0.5 Hz during 2 min). In addition, the cortical silent period was measured during the basic exercise protocol. Force fatigued to approximately 40% of MVC in all experiments and in all subjects. In all subjects, CCI decreased during exercise, but this decrease varied markedly between subjects. On average, CCI reductions preceded force reductions during exercise, and CCI recovery preceded force recovery. Exercising at 50% for 4 min reduced muscle force more markedly than CCI. Hemostasis induced by a cuff delayed muscle force recovery, but not CCI recovery. Stimulated exercise reduced force markedly, but CCI decreased only marginally. Summarized, force reduction and reduction of the CCI related poorly quantitatively and in time, and voluntary drive was particularly critical to reduce the CCI. The fatigue induced reduction of CCI may result from a central inhibitory phenomenon. Voluntary muscle activation is critical for the CCI reduction, suggesting a primarily supraspinal mechanism.

Association of fatigue and psychological distress with quality of life in patients with a previous venous thromboembolic event

Health-related quality of life (QoL) has been associated with several social and medical conditions in patients with deep vein thrombosis (DVT) and pulmonary embolism (PE). To the best of our knowledge, there is no study investigating the relationship of QoL with psychological variables in this patient population. We assumed as a hypothesis an association between heightened levels of fatigue and psychological distress, as well as decreased QoL in patients with an objectively diagnosed venous thromboembolic event. Study participants were 205 consecutively enrolled out-patients (47.4 years, 54.6% men) with DVT and/or PE. Approximately 10 days before blood collection for thrombophilia work-up, QoL, fatigue, and psychological distress were assessed using the Short Form Health Survey (SF-12), the Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) as well as the Hospitality Anxiety and Depression scale (HADS). After controlling for demographic and medical factors, fatigue (p < 0.01) but not psychological distress (p>0.05) was negatively associated with physical QoL, explaining 11.0% of the variance. Fatigue (p < 0.001) and psychological distress (p < 0.001) were significant predictors of mental QoL, explaining an additional 36.2% and 3.6% of the variance. Further analyses revealed that all subscales of the HADS (e.g. anxiety and depression) and of the MFSI-SF (e.g. general fatigue, physical fatigue, emotional fatigue, mental fatigue and vigor) were significant predictors of mental QoL. MFSI-SF subscales also predicted physical QoL. The findings suggest that fatigue and psychological distress substantially predict QoL in patients with a previous venous thromboembolic event above and beyond demographic factors.

Independent association of sleep quality, fatigue, and vital exhaustion with platelet count in patients with a previous venous thromboembolic event

Elevated platelet count might reflect increased inflammation as an etiological factor for venous thromboembolism (VTE). Poor sleep, fatigue, and exhaustion are all associated with inflammation and are also common sequelae of chronic psychological stress that previously predicted increased risk of VTE. We hypothesized that platelet count would be high in patients with VTE who sleep poorly and who are fatigued and exhausted. We investigated 205 patients scheduled for thrombophilia work-up > or =3 months after an objectively diagnosed venous thromboembolic event. They completed the Jenkins Sleep Questionnaire to rate subjective sleep quality and the short forms of the Multidimensional Fatigue Symptom Inventory and Maastricht Vital Exhaustion Questionnaire. Platelet count was determined by a mechanical Coulter counter. Analyses controlled for age, sex, body mass index, time since the index event, and medication. After taking into account these covariates, poorer sleep quality (p = 0.001; DeltaR(2)= 0.046), high fatigue (p = 0.008; DeltaR(2)= 0.032), and vital exhaustion (p = 0.050; DeltaR(2)= 0.017) were all associated with elevated platelet count. In addition, high level of fatigue mediated the relationship between poor sleep quality and elevated platelet count (p = 0.046). Poor sleep quality, high levels of fatigue, and vital exhaustion were identified as correlates of an elevated platelet count in patients with a previous episode of VTE. Given the emerging role of inflammatory processes in VTE, the findings suggest a mechanism through which behavioral and chronic psychological stressors might contribute to incident and recurrent venous thrombotic events.

The moderating role of personal mastery on the relationship between caregiving status and multiple dimensions of fatigue

OBJECTIVE: A substantial proportion of chronically-stressed spousal dementia caregivers report fatigue. The objective of this study was to examine whether personal mastery moderates the relationship between caregiving status (caregiver/non-caregiver) and multiple dimensions of fatigue. METHODS: Seventy-three elderly Alzheimer's caregivers and 41 elderly non-caregivers completed the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) and questionnaires assessing mastery. RESULTS: Regression analyses indicated that global fatigue was significantly higher for caregivers (M = 38.0 +/- 21.0) compared to non-caregivers (M = 18.2 +/- 10.4). However, personal mastery moderated the relation between caregiving status and global fatigue (t = -2.03, df = 107, p = 0.045), such that for those with low mastery, caregivers' fatigue scores were 18.1 points higher than non-caregivers, and for those with high mastery, this difference was only 7.5 points. For specific dimensions of fatigue, mastery moderated the relations between caregiving status and both emotional (t = -2.01, df = 107, p = 0.047) and physical (t = -2.51, df = 107, p = 0.014) fatigue. Specifically, association between caregiving status and emotional fatigue was greater when mastery was low than when mastery was high. Caregiving status was significantly associated with physical fatigue when mastery was low, but not when mastery was high. Significant main effects were found between mastery and general fatigue and vigor. CONCLUSION: Given the proportion of fatigued caregivers and the impact fatigue has on health; these findings provide important information regarding mastery's relationship with fatigue and may inform interventions aiming to alleviate fatigue in caregivers. Copyright (c) 2009 John Wiley ; Sons, Ltd.

Reading on LCD vs e-Ink displays: effects on fatigue and visual strain

Purpose:  Most recently light and mobile reading devices with high display resolutions have become popular and they may open new possibilities for reading applications in education, business and the private sector. The ability to adapt font size may also open new reading opportunities for people with impaired or low vision. Based on their display technology two major groups of reading devices can be distinguished. One type, predominantly found in dedicated e-book readers, uses electronic paper also known as e-Ink. Other devices, mostly multifunction tablet-PCs, are equipped with backlit LCD displays. While it has long been accepted that reading on electronic displays is slow and associated with visual fatigue, this new generation is explicitly promoted for reading. Since research has shown that, compared to reading on electronic displays, reading on paper is faster and requires fewer fixations per line, one would expect differential effects when comparing reading behaviour on e-Ink and LCD. In the present study we therefore compared experimentally how these two display types are suited for reading over an extended period of time. Methods:  Participants read for several hours on either e-Ink or LCD, and different measures of reading behaviour and visual strain were regularly recorded. These dependent measures included subjective (visual) fatigue, a letter search task, reading speed, oculomotor behaviour and the pupillary light reflex. Results:  Results suggested that reading on the two display types is very similar in terms of both subjective and objective measures. Conclusions:  It is not the technology itself, but rather the image quality that seems crucial for reading. Compared to the visual display units used in the previous few decades, these more recent electronic displays allow for good and comfortable reading, even for extended periods of time.

Quantitative analysis of benign paroxysmal positional vertigo fatigue under canalithiasis conditions

In our daily life, small flows in the semicircular canals (SCCs) of the inner ear displace a sensory structure called the cupula which mediates the transduction of head angular velocities to afferent signals. We consider a dysfunction of the SCCs known as canalithiasis. Under this condition, small debris particles disturb the flow in the SCCs and can cause benign paroxysmal positional vertigo (BPPV), arguably the most common form of vertigo in humans. The diagnosis of BPPV is mainly based on the analysis of typical eye movements (positional nystagmus) following provocative head maneuvers that are known to lead to vertigo in BPPV patients. These eye movements are triggered by the vestibulo-ocular reflex, and their velocity provides an indirect measurement of the cupula displacement. An attenuation of the vertigo and the nystagmus is often observed when the provocative maneuver is repeated. This attenuation is known as BPPV fatigue. It was not quantitatively described so far, and the mechanisms causing it remain unknown. We quantify fatigue by eye velocity measurements and propose a fluid dynamic interpretation of our results based on a computational model for the fluid–particle dynamics of a SCC with canalithiasis. Our model suggests that the particles may not go back to their initial position after a first head maneuver such that a second head maneuver leads to different particle trajectories causing smaller cupula displacements.