Postural control deficits in people with fibromyalgia: a pilot study

Introduction  

Postural instability and falls are increasingly recognized problems in patients with fibromyalgia (FM). The purpose of this study was to determine whether FM patients, compared to age-matched healthy controls (HCs), have differences in dynamic posturography, including sensory, motor, and limits of stability. We further sought to determine whether postural instability is associated with strength, proprioception and lower-extremity myofascial trigger points (MTPs); FM symptoms and physical function; dyscognition; balance confidence; and medication use. Last, we evaluated self-reported of falls over the past six months.     

Fibromyalgia,myofascial pain,tender points and trigger points: splitting or lumping?

Myofascial trigger points (MTPs) have long been a contentious issue in relation to fibromyalgia, and poorly defined pain complaints in general. Can MTPs be reproducibly identified? Do MTPs have valid objective findings, such as spontaneous electromyographic activity, muscle microdialysis evidence for an inflammatory milieu or visualization with newer ultrasound techniques? Is fibromyalgia a syndrome of multiple MTPs, or is focal muscle tenderness a manifestation of central sensitization? These issues are discussed with relevance to a recent paper reporting that manual palpation of active MTPs elicits the spontaneous pain experienced by fibromyalgia patients.     

Bioprocess Control in Microscale: Scalable Fermentations in Disposable and User-Friendly Microfluidic Systems

Background  

The efficiency of biotechnological production processes depends on selecting the best performing microbial strain and the optimal cultivation conditions. Thus, many experiments have to be conducted, which conflicts with the demand to speed up drug development processes. Consequently, there is a great need for high-throughput devices that allow rapid and reliable bioprocess development. This need is addressed, for example, by the fiber-optic online-monitoring system BioLector which utilizes the wells of shaken microtiter plates (MTPs) as small-scale fermenters. To further improve the application of MTPs as microbioreactors, in this paper, the BioLector technology is combined with microfluidic bioprocess control in MTPs. To realize a user-friendly system for routine laboratory work, disposable microfluidic MTPs are utilized which are actuated by a user-friendly pneumatic hardware.     

Effects of lifestyle physical activity on perceived symptoms and physical function in adults with fibromyalgia: results of a randomized trial

Introduction  

Although exercise is therapeutic for adults with fibromyalgia (FM), its symptoms often create obstacles that discourage exercise. We evaluated the effects of accumulating at least 30 minutes of self-selected lifestyle physical activity (LPA) on perceived physical function, pain, fatigue, body mass index, depression, tenderness, and the six-minute walk test in adults with FM.     

Profile of Cerebrospinal microRNAs in Fibromyalgia

Introduction

Fibromyalgia (FM) is characterized by chronic pain and reduced pain threshold. The pathophysiology involves disturbed neuroendocrine function, including impaired function of the growth hormone/insulin-like growth factor-1 axis. Recently, microRNAs have been shown to be important regulatory factors in a number of diseases.The aim of this study was to try to identify cerebrospinal microRNAs with expression specific for FM and to determine their correlation to pain and fatigue.

Methods

The genome-wide profile of microRNAs in cerebrospinal fluid was assessed in ten women with FM and eight healthy controls using real-time quantitative PCR. Pain thresholds were examined by algometry. Levels of pain (FIQ pain) were rated on a 0-100 mm scale (fibromyalgia impact questionnaire, FIQ). Levels of fatigue (FIQ fatigue) were rated on a 0-100 mm scale using FIQ and by multidimensional fatigue inventory (MFI-20) general fatigue (MFIGF).

Results

Expression levels of nine microRNAs were significantly lower in patients with FM patients compared to healthy controls. The microRNAs identified were miR-21-5p, miR-145-5p, miR-29a-3p, miR-99b-5p, miR-125b-5p, miR-23a-3p, 23b-3p, miR-195-5p, miR-223-3p.The identified microRNAs with significantly lower expression in FM were assessed with regard to pain and fatigue. miR-145-5p correlated positively with FIQ pain (r=0.709, p=0.022, n=10) and with FIQ fatigue (r=0.687, p=0.028, n=10).

Conclusion

To our knowledge, this is the first study to show a disease-specific pattern of cerebrospinal microRNAs in FM.We have identified nine microRNAs in cerebrospinal fluid that differed between FM patients and healthy controls. One of the identified microRNAs, miR-145 was associated with the cardinal symptoms of FM, pain and fatigue.     

Does moderate-to-high intensity Nordic walking improve functional capacity and pain in fibromyalgia? A prospective randomized controlled trial

Introduction  

The objective of this study was to investigate the effects of moderate-to-high intensity Nordic walking (NW) on functional capacity and pain in fibromyalgia (FM).     

Cannabis use in patients with fibromyalgia: effect on symptoms relief and health-related quality of life

Background

The aim of this study was to describe the patterns of cannabis use and the associated benefits reported by patients with fibromyalgia (FM) who were consumers of this drug. In addition, the quality of life of FM patients who consumed cannabis was compared with FM subjects who were not cannabis users.

Methods

Information on medicinal cannabis use was recorded on a specific questionnaire as well as perceived benefits of cannabis on a range of symptoms using standard 100-mm visual analogue scales (VAS). Cannabis users and non-users completed the Fibromyalgia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index (PSQI) and the Short Form 36 Health Survey (SF-36).

Results

Twenty-eight FM patients who were cannabis users and 28 non-users were included in the study. Demographics and clinical variables were similar in both groups. Cannabis users referred different duration of drug consumption; the route of administration was smoking (54%), oral (46%) and combined (43%). The amount and frequency of cannabis use were also different among patients. After 2 hours of cannabis use, VAS scores showed a statistically significant (p<0.001) reduction of pain and stiffness, enhancement of relaxation, and an increase in somnolence and feeling of well being. The mental health component summary score of the SF-36 was significantly higher (p<0.05) in cannabis users than in non-users. No significant differences were found in the other SF-36 domains, in the FIQ and the PSQI.

Conclusions

The use of cannabis was associated with beneficial effects on some FM symptoms. Further studies on the usefulness of cannabinoids in FM patients as well as cannabinoid system involvement in the pathophysiology of this condition are warranted.     

Distinguishing fibromyalgia from rheumatoid arthritis and systemic lupus in clinical questionnaires: an analysis of the revised Fibromyalgia Impact Questionnaire (FIQR) and its variant, the Symptom Impact Questionnaire (SIQR), along with pain locations

Introduction

The purpose of this study was to explore a data set of patients with fibromyalgia (FM), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) who completed the Revised Fibromyalgia Impact Questionnaire (FIQR) and its variant, the Symptom Impact Questionnaire (SIQR), for discriminating features that could be used to differentiate FM from RA and SLE in clinical surveys.

Methods

The frequency and means of comparing FM, RA and SLE patients on all pain sites and SIQR variables were calculated. Multiple regression analysis was then conducted to identify the significant pain sites and SIQR predictors of group membership. Thereafter stepwise multiple regression analysis was performed to identify the order of variables in predicting their maximal statistical contribution to group membership. Partial correlations assessed their unique contribution, and, last, two-group discriminant analysis provided a classification table.

Results

The data set contained information on the SIQR and also pain locations in 202 FM, 31 RA and 20 SLE patients. As the SIQR and pain locations did not differ much between the RA and SLE patients, they were grouped together (RA/SLE) to provide a more robust analysis. The combination of eight SIQR items and seven pain sites correctly classified 99% of FM and 90% of RA/SLE patients in a two-group discriminant analysis. The largest reported SIQR differences (FM minus RA/SLE) were seen for the parameters "tenderness to touch," "difficulty cleaning floors" and "discomfort on sitting for 45 minutes." Combining the SIQR and pain locations in a stepwise multiple regression analysis revealed that the seven most important predictors of group membership were mid-lower back pain (29%; 79% vs. 16%), tenderness to touch (11.5%; 6.86 vs. 3.02), neck pain (6.8%; 91% vs. 39%), hand pain (5%; 64% vs. 77%), arm pain (3%; 69% vs. 18%), outer lower back pain (1.7%; 80% vs. 22%) and sitting for 45 minutes (1.4%; 5.56 vs. 1.49).

Conclusions

A combination of two SIQR questions ("tenderness to touch" and "difficulty sitting for 45 minutes") plus pain in the lower back, neck, hands and arms may be useful in the construction of clinical questionnaires designed for patients with musculoskeletal pain. This combination provided the correct diagnosis in 97% of patients, with only 7 of 253 patients misclassified.     

Development and validation of the self-administered Fibromyalgia Assessment Status: a disease-specific composite measure for evaluating treatment effect

Introduction  

The Fibromyalgia Impact Questionnaire (FIQ) is a composite disease-specific measure validated for fibromyalgia (FM), but it is rarely used in clinical practice. The objective was to develop and analyse the psychometric properties of a new composite disease-specific index (Fibromyalgia Assessment Status, FAS), a simple self-administered index that combines a patient's assessment of fatigue, sleep disturbances and pain evaluated on the basis of the 16 non-articular sites listed on the Self-Assessment Pain Scale (SAPS) in a single measure (range 0 to 10).     

Identification of a MicroRNA Signature for the Diagnosis of Fibromyalgia

Background

Diagnosis of fibromyalgia (FM), a chronic musculoskeletal pain syndrome characterized by generalized body pain, hyperalgesia and other functional and emotional comorbidities, is a challenging process hindered by symptom heterogeneity and clinical overlap with other disorders. No objective diagnostic method exists at present. The aim of this study was to identify changes in miRNA expression profiles (miRNome) of these patients for the development of a quantitative diagnostic method of FM. In addition, knowledge of FM patient miRNomes should lead to a deeper understanding of the etiology and/or symptom severity of this complex disease.

Methods

Genome-wide expression profiling of miRNAs was assessed in Peripheral Blood Mononuclear Cells (PBMCs) of FM patients (N=11) and population-age-matched controls (N=10) using human v16-miRbase 3D-Gene microarrays (Toray Industries, Japan). Selected miRNAs from the screen were further validated by RT-qPCR. Participating patients were long term sufferers (over 10 years) diagnosed by more than one specialist under 1990 American College of Rheumatology criteria.

Results

Microarray analysis of FM patient PBMCs evidenced a marked downregulation of hsa-miR223-3p, hsa-miR451a, hsa-miR338-3p, hsa-miR143-3p, hsa-miR145-5p and hsa-miR-21-5p (4-fold or more). All but the mildest inhibited miRNA, hsa-miR-21-5p, were validated by RT-qPCR. Globally, 20% of the miRNAs analyzed (233/1212) showed downregulation of at least 2-fold in patients. This might indicate a general de-regulation of the miRNA synthetic pathway in FM. No significant correlations between miRNA inhibition and FM cardinal symptoms could be identified. However, the patient with the lowest score for mental fatigue coincided with the mildest inhibition in four of the five miRNAs associated with the FM-group.

Conclusions

We propose a signature of five strikingly downregulated miRNAs (hsa-miR223-3p, hsa-miR451a, hsa-miR338-3p, hsa-miR143-3p and hsa-miR145-5p) to be used as biomarkers of FM. Validation in larger study groups is required before the results can be transferred to the clinic.     

LTC: a novel algorithm to improve the efficiency of contig assembly for physical mapping in complex genomes

Background  

Physical maps are the substrate of genome sequencing and map-based cloning and their construction relies on the accurate assembly of BAC clones into large contigs that are then anchored to genetic maps with molecular markers. High Information Content Fingerprinting has become the method of choice for large and repetitive genomes such as those of maize, barley, and wheat. However, the high level of repeated DNA present in these genomes requires the application of very stringent criteria to ensure a reliable assembly with the FingerPrinted Contig (FPC) software, which often results in short contig lengths (of 3-5 clones before merging) as well as an unreliable assembly in some difficult regions. Difficulties can originate from a non-linear topological structure of clone overlaps, low power of clone ordering algorithms, and the absence of tools to identify sources of gaps in Minimal Tiling Paths (MTPs).     

Nocturnal heart rate variability parameters as potential fibromyalgia biomarker: correlation with symptoms severity

Introduction  

At present, there is neither a laboratory test nor an imaging technique able to differentiate people with fibromyalgia (FM) from healthy controls. This lack of an objective biomarker has hampered FM recognition and research. Heart rate variability (HRV) analyses provide a quantitative marker of autonomic nervous system activity. Nighttime is a stable period in which most people are resting. Sleep is modulated by autonomic activity. Sleeping problems are prominent in FM. The objectives of this study are: 1) to explore different nocturnal HRV parameters as potential FM biomarkers and 2) to seek correlation between such HRV parameters and diverse FM symptoms.     

Cardiac autonomic impairment and chronotropic incompetence in fibromyalgia

Introduction  

We aimed to gather knowledge on the cardiac autonomic modulation in patients with fibromyalgia (FM) in response to exercise and to investigate whether this population suffers from chronotropic incompetence (CI).     

Involvement of Nav 1.8 sodium ion channels in the transduction of mechanical pain in a rodent model of osteoarthritis

Introduction  

A subgroup of voltage gated sodium channels including Nav1.8 are exclusively expressed on small diameter primary afferent neurons and are therefore believed to be integral to the neurotransmission of nociceptive pain. The present study examined whether local application of A-803467, a selective blocker of the Nav 1.8 sodium channel, can reduce nociceptive transmission from the joint in a rodent model of osteoarthritis (OA).     

A comparative study of recombinant and native frutalin binding to human prostate tissues

Background  

Numerous studies indicate that cancer cells present an aberrant glycosylation pattern that can be detected by lectin histochemistry. Lectins have shown the ability to recognise these modifications in several carcinomas, namely in the prostate carcinoma, one of the most lethal diseases in man. Thus, the aim of this work was to investigate if the α-D-galactose-binding plant lectin frutalin is able to detect such changes in the referred carcinoma. Frutalin was obtained from different sources namely, its natural source (plant origin) and a recombinant source (Pichia expression system). Finally, the results obtained with the two lectins were compared and their potential use as prostate tumour biomarkers was discussed.     

Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia

Introduction

The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM.

Methods

This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) < 40 kg/m², and had a score ≥ 50 on a 100-mm pain visual analog scale (VAS) at baseline. All patients began treatment in the extension study with SXB 4.5 g/night (administered in 2 equally divided doses) for at least 1 week, followed by possible serial 1.5 g/night dose increases to 9 g/night (maximum) or reductions to 4.5 g/night (minimum).

Results

Of the 560 FM patients enrolled in this extension study, 319 (57.0%) completed the study. The main reason for early discontinuation was adverse events (AEs; 23.0% of patients). Patients were primarily middle-aged (mean 46.9 ± 10.8 years), female (91.1%), white (91.4%), with a mean duration of FM symptoms of 9.9 ± 8.7 years. Serious AEs were experienced by 3.6% of patients. The most frequently reported AEs (incidence ≥ 5% at any dose or overall) were nausea, headache, dizziness, nasopharyngitis, vomiting, sinusitis, diarrhea, anxiety, insomnia, influenza, somnolence, upper respiratory tract infection, muscle spasms, urinary tract infection, and gastroenteritis viral. Maintenance of SXB therapeutic response was demonstrated with continued improvement from controlled-study baseline in pain VAS, Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint.

Conclusions

The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00423605","term_id":"NCT00423605"}}NCT00423605.     

Theory of Mind and Emotional Functioning in Fibromyalgia Syndrome: An Investigation of the Relationship between Social Cognition and Executive Function

Background

Fibromyalgia (FM) is a syndrome primarily characterised by chronic, widespread musculoskeletal pain. In the aetiology of this syndrome a crucial role is played by complex interactions among biological, genetic, psychological, and socio-cultural factors. Recently, researchers have started to explore emotional functioning in FM, with their attention focused on alexithymia, a personality construct that affects the regulation of a person’s own emotions. On the other hand, the detection and experience of emotional signals from other people have only been sparsely investigated in FM syndrome and no studies have investigated the ability to represent other people’s mental states (i.e. Theory of Mind, ToM) in these patients. Here we present the first study investigating a large set of social-cognitive abilities, and the possible relationships between these abilities and the performance on executive-function tasks, in a homogenous sample of patients with FM.

Methodology

Forty women with FM and forty-one healthy women matched for education and age were involved in the study. Social cognition was assessed with a set of validated experimental tasks. Measures of executive function were used to test the correlations between this dimension and the social-cognitive profile of patients with FM. Relationships between social-cognitive abilities and demographic, clinical and psychological variables were also investigated.

Principal Findings

Patients with FM have impairments both in the regulation of their own affect and in the recognition of other’s emotions, as well as in representing other people’s mental states. No significant correlations were found between social cognition tasks and the subcomponents of the executive function that were analysed.

Conclusions

The results show the presence of several impairments in social cognition skills in patients with FM, which are largely independent of both executive function deficits and symptoms of psychological distress. The impairments reported highlight the importance of adequately assessing ToM and emotional functioning in clinical practice.     

Oxidative stress correlates with headache symptoms in fibromyalgia: coenzyme Q₁₀ effect on clinical improvement

Background

Fibromyalgia (FM) is a chronic pain syndrome with unknown etiology and a wide spectrum of symptoms such as allodynia, debilitating fatigue, joint stiffness and migraine. Recent studies have shown some evidences demonstrating that oxidative stress is associated to clinical symptoms in FM of fibromyalgia. We examined oxidative stress and bioenergetic status in blood mononuclear cells (BMCs) and its association to headache symptoms in FM patients. The effects of oral coenzyme Q₁₀ (CoQ₁₀) supplementation on biochemical markers and clinical improvement were also evaluated.

Methods

We studied 20 FM patients and 15 healthy controls. Clinical parameters were evaluated using the Fibromyalgia Impact Questionnaire (FIQ), visual analogues scales (VAS), and the Headache Impact Test (HIT-6). Oxidative stress was determined by measuring CoQ₁₀, catalase and lipid peroxidation (LPO) levels in BMCs. Bioenergetic status was assessed by measuring ATP levels in BMCs.

Results

We found decreased CoQ₁₀, catalase and ATP levels in BMCs from FM patients as compared to normal control (P<0.05 and P<0.001, respectively) We also found increased level of LPO in BMCs from FM patients as compared to normal control (P<0.001). Significant negative correlations between CoQ₁₀ or catalase levels in BMCs and headache parameters were observed (r = −0.59, P<0.05; r = −0.68, P<0.05, respectively). Furthermore, LPO levels showed a significant positive correlation with HIT-6 (r = 0.33, P<0.05). Oral CoQ₁₀ supplementation restored biochemical parameters and induced a significant improvement in clinical and headache symptoms (P<0.001).

Discussion

The results of this study suggest a role for mitochondrial dysfunction and oxidative stress in the headache symptoms associated with FM. CoQ10 supplementation should be examined in a larger placebo controlled trial as a possible treatment in FM.     

A cardiorespiratory classifier of voluntary and involuntary electrodermal activity

Background  

Electrodermal reactions (EDRs) can be attributed to many origins, including spontaneous fluctuations of electrodermal activity (EDA) and stimuli such as deep inspirations, voluntary mental activity and startling events. In fields that use EDA as a measure of psychophysiological state, the fact that EDRs may be elicited from many different stimuli is often ignored. This study attempts to classify observed EDRs as voluntary (i.e., generated from intentional respiratory or mental activity) or involuntary (i.e., generated from startling events or spontaneous electrodermal fluctuations).     

Life cycle assessment of aquafeed ingredients

Purpose

This study performs an exploratory comparative evaluation of various animal and vegetable protein and lipid sources, used as feed in the aquaculture industry. The ingredients studied include fishmeal (FM) and fish oil (FO) from fisheries by-products, meal and fat by-products from poultry slaughter, FM and FO from Peruvian anchovy capture, and soybean meal and oil. The boundaries studied include the production or capture, the ingredient processing unit and the transport to the unit that processes the ingredients into aquafeeds in Portugal.

Methods

The LCA impact assessment method is the CML-IA baseline V3.04/EU25 and the results were obtained for the characterisation step. Some of the inventory data were collected from a Portuguese company (Savinor) that processes both by-products from local fisheries and by-products from poultry production. Savinor provided data specifically associated with the ingredients’ production. Obtained data were complemented with literature data from: fish capture and poultry production. Inventory data for the production of ingredients from Peruvian anchovy and soybeans were retrieved from literature. It was assumed that the transport of the ingredients produced from Peruvian anchovy, between Lima and Rotterdam, is made in a transoceanic vessel, and it is considered a transport by truck between Rotterdam and Ovar, for soybean ingredients and FM/FO produced from Peruvian anchovy.

Results and discussion

This paper shows that poultry meal and poultry fat from poultry slaughter by-products have the larger contribution to all environmental impact categories evaluated, being the production of poultry the life cycle stage that contributes most to the overall categories. On the other hand, FM and FO from Peruvian anchovy were the ingredients with a lower contribution to all impact categories, except for abiotic depletion category, for FM from Peruvian anchovy, and abiotic depletion, abiotic depletion (fossil fuels) and ozone layer depletion for FO from Peruvian anchovy. For these categories, soybean meal and oil had lower impacts, respectively. The ingredients were compared by classes (protein and lipid sources).

Conclusions

A general conclusion is that soybean meal and oil and FM/FO from Peruvian anchovy appear to be very interesting options for aquafeeds from an LCA perspective. However, some limitations identified for this study, as, for instance, that it does not account for the environmental benefits associated with the use of the mentioned by-products, that would otherwise be considered wastes (i.e. by-products from the fish canning sector and poultry slaughter) shall be evaluated in future studies.