Brief Coping Scale TCS-9: Optimising the Assessment of Coping Strategies. The case of Health Care Workers.

Background: The COVID-19 pandemic has intensified the focus on mental health, particularly on the coping strategies of healthcare workers who have faced unparalleled stress due to their pivotal role in addressing health disparities and determinants of health. Constantly operating in high-risk environments and managing the surge of critically ill patients, these professionals' psychological resilience has been sternly tested, necessitating robust assessment tools. Aim: This study aims to refine the extensive 54-item Toulouse Coping Scale into a more pragmatic and less time-consuming instrument while preserving its statistical integrity, to support the mental well-being of healthcare workers. Setting: The setting for this study was amongst healthcare workers in Greece, during the COVID-19 pandemic, a period marked by significant psychological demands on medical staff. Methods: We conducted an unbiased exploratory factor analysis on the Toulouse Coping Scale's 54 items, drawing from a sample of 144 healthcare workers, adhering to strict methodological criteria. Results: Data completeness was achieved across the sample, which comprised 40 (28%) males and 104 (72%) females, predominantly aged between 31 and 50 years. The final instrument, encapsulating two domains with a total of nine questions, demonstrated strong internal consistency, with an eigenvalue of 3.438 for the first domain and 1.478 for the second, validated by a scree plot. Conclusion: The streamlined TCS-9 scale facilitates a more rapid assessment of coping strategies while reducing redundancy. The two-domain structure ensures that the revised scale retains the original's thoroughness in a more concise form. Contribution: By enabling quicker and more efficient evaluations, the TCS-9 enhances the practicality of assessing coping mechanisms in healthcare settings, thereby contributing to the sustenance of health systems and the promotion of health equity.

Reaction Time in Fibromyalgia Patients.

BACKGROUND: Fibromyalgia has unknown aetiology and is associated with reduced information processing speed and therefore prolonged reaction time. However, the processes underlying this are unknown. OBJECTIVES: First, to compare the reaction time in a cohort of fibromyalgia patients and a matched group of normal controls. Second, to assess whether detailed symptoms of pain and autonomic function, as well as measures of tinnitus, fatigue, daytime sleepiness and Mycoplasma pneumoniae infection are predictors of reaction time in fibromyalgia. METHODS: The between-groups mean serial five-choice reaction time difference was assessed in a cohort of fibromyalgia patients and in a matched group of normal controls in an analytical case-- controlled study. With the mean serial five-choice reaction time as the dependent variable for the fibromyalgia group, a mixed stepwise multiple linear regression was performed with inputs relating to pain, dysautonomia, tinnitus, fatigue, daytime sleepiness and Mycoplasma pneumoniae infection. RESULTS: The mean (standard error) serial five-choice reaction time for the fibromyalgia group was 448.4 (23.0) ms, compared with 386.3 (8.3) ms for the control group (p = 0.007). The final multiple linear regression model (p < 0.001; adjusted R2 = 0.772) contained 13 predictors: eight sensory pain and three affective pain parameters, and Mycoplasma pneumoniae IgG and IgA assay results. CONCLUSION: Certain sensory and affective pain parameters, as well as Mycoplasma pneumoniae infection, appear to be predictors of reaction time in fibromyalgia. Further research into the pathophysiological mechanisms by which they affect information processing is warranted and may shed light on the aetiology of fibromyalgia.

T Lymphocyte Interferon-gamma Response to Anaplasmataceae-related Major Surface Proteins and Ankyrin A in Fibromyalgia.

BACKGROUND: The aetiology of fibromyalgia is unknown; its symptoms may be related to a T-lymphocyte-mediated response to infectious organisms. OBJECTIVES: First, to test the hypothesis that fibromyalgia is associated with increased interferon (IFN)-γ-secreting T-lymphocytes after stimulation with Anaplasmataceae-related major surface proteins (MSFs) and the macromolecular translocation type IV secretion system effector ankyrin repeat domain-containing protein A (AnkA). Second, to ascertain the relationship in fibromyalgia between (i) the IFN-γ-secreting T-lymphocyte response to stimulation with Anaplasmataceae-related MSFs and AnkA, and (ii) co-infection by Borrelia and Yersinia spp., and antinuclear antibodies. METHODS: Using a case-control design, patients fulfilling the American College of Rheumatology revised criteria for fibromyalgia, and controls, underwent the following blinded assessments: (i) enzyme- linked immune absorbent spot (ELISpot) IFN-γ release assay of T-lymphocyte reactivity to Anaplasmataceae-related MSFs and AnkA; (ii) ELISpot IFN-γ release assays of T-lymphocyte reactivity to three Borrelia antigens, namely Borrelia burgdorferi full antigen (B31); peptide mix (from Borrelia burgdorferi sensu stricto, Borrelia afzelii, Borrelia garinii); and Borrelia burgdorferi lymphocyte function-associated antigen-1; (iii) immunoglobulin (Ig) A assay by enzyme-linked immunosorbent assay (ELISA) of antibodies to Yersinia spp.; (iv) IgG (ELISA) antibodies to Yersinia spp.; (v) serum antinuclear antibodies (immunofluorescence). RESULTS: The groups were age- and sex-matched. The mean (standard error) value of IFN-γ release for the fibromyalgia group was 1.52 (0.26), compared with 1.00 (0.22) for the controls. Generalised linear modelling (p<0.001) of IFN-γ release in the fibromyalgia patients showed significant main effects of all three indices of Borrelia infection and of antinuclear antibodies. CONCLUSION: Anaplasmataceae may play an aetiological role in fibromyalgia.

The Role of Chlamydia pneumoniae in the Aetiology of Autoimmune Diseases.

Introduction The most prevalent chronic human autoimmune disorder worldwide is rheumatoid arthritis. Synovial samples from acute-phase patients are polymerase chain reaction-positive for Chlamydia pneumoniae (C. pneumoniae) DNA and express chlamydial hsp60. Furthermore, anti-cyclic citrullinated peptide (anti-CCP) antibodies promote apoptosis of mature human Saos-2 osteoblasts via cell surface binding to citrullinated heat shock protein 60 (HSP60). Hence, we hypothesised that C. pneumoniae infection is associated with anti-CCP antibodies. Methods C. pneumoniae IgA and anti-CCP antibody levels were determined in 26 healthy subjects in this cross-sectional study. Serum C. pneumoniae IgA antibody levels were assessed using an enzyme-linked immunosorbent assay. Serum anti-CCP antibody levels were assessed using fluoroenzymeimmunoassay. Results There was a highly significant positive correlation between the two sets of antibodies (rs = 0.621; P = 0.0007). Linear regression analysis showed that this correlation was not the result of age or sex. Discussion A biologically plausible mechanism is put forward for these results, involving HSP60 acting as an endogenous ligand for toll-like receptor 4 (TLR4) and the interaction of TLR4 with lipopolysaccharides, which occur in the outer membrane of the C. pneumoniae elementary body. Pronounced pro-inflammatory mediator secretion then takes place. The release of Ca2+ ions may then activate local peptidylarginine deiminases, leading to the formation of CCPs and thus the reported finding. Confirmation of these results may have potential clinical implications in terms of diagnosis, including pre-symptomatic diagnosis, and treatment.

A Novel and Accurate Method for Estimating Deaths and Cases During Outbreaks of Infectious Diseases Including COVID-19.

Introduction: Epidemiological modelling of infectious diseases plays an important role in driving public health policy. Commonly used models are described, including those based on exponential growth (Laplace and related distributions); susceptible-infected-removed; the Gompertz distribution; and the skew-reflected-Gompertz distribution. These are all sensitive to the timing of peak infection. The development of a novel method for forecasting the number of deaths occurring during epidemics of infectious diseases is described. Methods: The mathematical development of the authors' novel asymmetric difference model is detailed in this paper. Its predictions for mortality rates associated with the COVID-19 pandemic for 14 countries were compared with the corresponding published mortality data. Results: Forecasts by the asymmetric difference model of deaths from SARS-CoV-2 in different countries, actual recorded deaths to 30th June 2020, and corresponding errors included UK (42,700; 55,904; -24%); Poland (1490; 1444; +3%); Denmark (580; 605; -4%); Netherlands (6510; 6189; +5%); France (34,280; 29,836; +15%); Canada (1500; 8591; -78%); USA (44,540; 124,734; -64%); and Italy (22,020; 34,980; -37%). The model output was dependent upon forecast date accuracy for the peak of the disease outbreak. For Spain, the forecast date was one day early and for 10 (71%) countries the forecast peak occurred within seven days (inclusive) of the actual date. Discussion: Mortality prediction by the asymmetric difference model is relatively accurate. Furthermore, this new model does not appear to be as unduly sensitive to the timing of peak infection as other models. Indeed, its prediction of peak infection also appears to be relatively accurate.

Association between Cardiac Atrioventricular Conduction and Antibodies to Chlamydia Pneumoniae in Fibromyalgia Patients.

BACKGROUND: Fibromyalgia patients may complain of cardiovascular symptoms, including chest pain and palpitations. It has been proposed that infection by Chlamydia pneumoniae might be common in fibromyalgia. Chlamydia pneumoniae infection has also been hypothesized to be a causative factor in cardiac disease. OBJECTIVE: This study aims to test the hypothesis that there is an association between atrioventricular conduction and antibodies to Chlamydia pneumoniae in fibromyalgia. METHODS: Thirteen female fibromyalgia patients underwent serum Chlamydia pneumoniae IgG assays and 12-lead electrocardiography in a cross-sectional study. None of the patients was taking medication which might affect atrioventricular conduction, and none suffered from hypothyroidism, renal disease, hepatic disease, or carotid hypersensitivity. RESULTS: There was a significant positive correlation between the PR interval duration and the serum Chlamydia pneumoniae IgG level (r = 0.650; p = 0.016). CONCLUSION: This study supports the hypothesis of an association between atrioventricular conduction and antibodies to Chlamydia pneumoniae in fibromyalgia patients. It suggests that the higher the level of such antibodies, the greater the electrocardiographic PR interval, and therefore the slower the atrioventricular conduction. Potential pathophysiological mechanisms include a chronic inflammatory response to Chlamydia pneumoniae and the action of the bacterial lipopolysaccharide. The latter may involve stimulators of interferon genes, activation of the cardiac NOD-like receptor protein 3 inflammasomes, and downregulation of fibroblast growth factor 5 in the heart.

Salivary clearance of caffeine in children.

Background: Measurement of salivary caffeine (1,3,7-trimethylpurine-2,6-dione or 1,3,7-trimethylxanthine) clearance can, in principle, be used to assess hepatic function, diagnose chronic hepatic disease and conduct investigations of substrates of hepatic cytochrome P450 (CYP) isozymes in children, without recourse to venepuncture. However, little is known about childhood sexual dimorphism of hepatic CYP isoforms. Furthermore, the association, if any, between salivary caffeine clearance and age in children has not hitherto been established. The aims of this study were to assess whether salivary caffeine clearance differs between boys and girls and whether it varies with age during childhood. Methods: Following at least 24 h' abstinence from dietary caffeine, nine boys (mean (standard error) age 9.6 (1.1) y) and eight girls (mean age 11.0 (1.2) y), none of whom was a smoker or suffered from chronic hepatic disease, ingested an oral caffeine dose titrated by body mass, namely 3 mg kg-1. Salivary samples collected two and 14 h later underwent spectrophotometric caffeine analysis. Results: The boys and the girls were age matched. The mean caffeine clearance in the boys was 2.47 (0.33) mL min-1 kg-1, while that in the girls was 2.20 (0.31) mL min-1 kg-1 (p = 0.56). The salivary caffeine clearance was negatively correlated with age (r = -0.59, p = 0.01). Conclusion: Stratification by sex appears to be unnecessary when considering childhood salivary caffeine clearance or when conducting investigations in children of CYP1A2 and xanthine oxidase substrates. Furthermore, childhood salivary caffeine clearance is negatively correlated with age.

The Principal Components of Autonomic Dysfunction in Fibromyalgia Assessed by the Refined and Abbreviated Composite Autonomic Symptom Score.

BACKGROUND: We have recently confirmed that non-pain autonomic dysfunction symptoms occur in fibromyalgia and can be assessed with the 31-item Composite Autonomic Symptom Score (COMPASS 31) instrument. Fibromyalgia patients have been found to have higher scores than matched controls across all six domains of this instrument. OBJECTIVES: To analyse the principal components of the autonomic COMPASS 31 domain scores in fibromyalgia patients to understand better the fundamental dimensions of dysautonomia in this disorder. METHODS: A principal component analysis of fibromyalgia autonomic domain scores was carried out using a varimax orthogonal rotation with decomposition being based on the correlation matrix and setting a threshold of greater than one for the eigenvalues. RESULTS: Three mutually orthogonal principal components, accounting for over 80% of the total variance, were identified. The first was a function of the secretomotor, orthostatic intolerance and pupillomotor domains; the second was a function of the vasomotor and urinary bladder domains; and the third was a function of the gastrointestinal and orthostatic intolerance domains. There was a positive correlation between symptom domain scores of the Revised Fibromyalgia Impact Questionnaire and the first principal component scores (rs = 0.536, p = 0.006). CONCLUSION: This analysis has reduced the dimensionality of autonomic dysfunction in fibromyalgia patients from six to three. The internal structure of the fibromyalgia dysautonomia data reflected by these results may help in the elucidation of the aetiology of this complex and difficult-to-treat disorder.

Antinuclear Antibody Seropositivity in Fibromyalgia Associated with Borrelia-specific T Lymphocytes.

BACKGROUND: Our group have recently reported that there is no evidence of an association between fibromyalgia and Borrelia-specific T lymphocytes. However, a small number of case reports has suggested that infection by the bacterial genus Borrelia may be associated with the presence of antinuclear antibodies (ANAs). OBJECTIVE: To test the hypothesis that those fibromyalgia patients who are ANA seropositive are more likely to show evidence of Borrelia-specific T lymphocyte reactivity than those who are seronegative. METHODS: T lymphocyte reactivity to Borrelia burgdorferi sensu stricto (full antigen) was assessed using the enzyme-linked immunospot and serum ANA status was assessed using immunofluorescence in 27 fibromyalgia patients fulfilling the revised diagnostic criteria of the American College of Rheumatology. RESULTS: The ANA seropositive and seronegative groups were matched for age, sex and ethnicity; the T lymphocyte reactivity to Borrelia burgdorferi sensu stricto (full antigen) in the former group (mean 5.60) was significantly higher than that in the seronegative group (mean 1.77; p < 0.05). CONCLUSION: This novel study points to an association of ANA seropositivity in fibromyalgia with Borrelia-specific T lymphocytes.

The efficacy of psychoeducation in managing low back pain: A systematic review.

Low back pain is a relatively common health problem which afflicts many adults, and its prevalence increases with age. Several studies have indicated that psychosocial factors are of importance in low back pain. The aim of this study was to carry out a systematic review of the efficacy of psychoeducation in managing low back pain from evidence provided by randomised controlled trials. The inclusion criteria for studies included in this systematic review were randomised controlled trials; patients with low back pain, with or without sciatica; the inclusion of a psychoeducation (treatment) arm; and age of patients ≥ 17 years. Data extraction revealed the heterogeneous nature of the psychoeducational interventions. Accordingly, it was deemed inappropriate to carry out a formal meta-analysis. Ultimately, nine studies, corresponding to 10 publications, were included in the systematic review. When possible, group contrast mean difference effect sizes were calculated for the studies. Overall, favourable outcomes associated with personalised telephone coaching, while unfavourable outcomes were associated with both Transtheoretical Model-based counselling and motivational enhancement treatment. Other forms of one-to-one counselling were associated with intermediate outcomes. Psychoeducation via personalised telephone coaching was particularly associated with reduced low back pain, reduced daily living disability, improved function and improved recovery expectation. On the basis of this review, the following suggestions are made relating to the design and publication of future studies of the efficacy of psychoeducation in the management of low back pain. First, it would be good to use an experimental design which blinds both the patients and the assessors to group status. Second, it is recommended that all the relevant outcome data from a study are published, either in the corresponding paper or in an on-line supplement. Third, it is important to ensure that the intervention and control groups are matched at baseline. Clearly, baseline group differences can emerge following random allocation of patients into two groups. It may be useful, therefore, to carry out all baseline assessments immediately prior to the randomisation process; an independent assessor could then examine the degree of matching at baseline before the rest of the study proceeds. It is also important that sufficiently large sample sizes be recruited.

Predictors of poor psychological functioning of healthcare workers based in Greece during the COVID-19 pandemic.

Background: Poor psychological functioning during the COVID-19 pandemic has been reported in several studies of healthcare workers from around the world. Factors that might predict this have yet to be established. Objectives: First, to ascertain which factors were associated with poor psychological functioning in a cohort of healthcare workers during the COVID-19 pandemic. Second, to characterize key sociodemographic aspects of this cohort. Third, to determine the degree to which any predictors of poor psychological functioning were associated with each other. Methods: A questionnaire-based cross-sectional study was conducted of 144 healthcare workers in Patras, Greece, during the COVID-19 pandemic. The questionnaire consisted of: (1) demographic survey questions; (2) the Psychological Consequences Questionnaire scale; (3) the Kessler Psychological Distress scale; and (4) Toulouse's scale for coping strategies. The data were analyzed using general linear modeling. Results: The statistical model (p < 10-10) indicated that smoking or taking drugs to calm anxiety, feeling ashamed, and being overwhelmed by one's feelings were all predictors of poor psychological functioning. Conversely, income was a protective factor. A post hoc network analysis showed that smoking or taking drugs to calm anxiety was relatively strongly associated with feeling ashamed; the latter was also associated with feeling overwhelmed. There was a weak negative association between income and feeling ashamed. Conclusion: This study highlights the critical importance of psychological functioning in shaping the mental well-being of healthcare professionals during pandemics. Prioritizing the mental health of frontline workers is crucial for their well-being and for the overall functioning of healthcare systems.

Detection of 41-kDa bacterial flagellin protein by the lymphocyte transformation test-memory lymphocyte immunostimulation assay.

BACKGROUND/OBJECTIVES: Diagnosis of human infection by various species of the bacterial genus Borrelia is mainly reliant on serological testing, polymerase chain reaction (PCR) or culture but such serological tests have been reported to have heterogeneous sensitivities, while Borrelia PCR and culture have been reported as being of modest diagnostic value. It has been suggested that the adjunctive use of the lymphocyte transformation test-memory lymphocyte immunostimulation assay (LTT-MELISA) may be helpful in this regard; however, the clinical usefulness of this assay has been questioned. The Borrelia immunodominant 41-kDa flagellin protein almost always gives rise to a marked human antibody response following infection. It was therefore decided to determine whether the LTT-MELISA detects the human antibody response to this antigen. METHODS: Blood samples from consecutive patients with possible borreliosis attending a clinic were independently tested by both Western blots and LTT-MELISA. RESULTS: After omitting cases with indeterminate Western blot results and equivocal LTT-MELISA results, multiple linear regression modelling demonstrated that the 41-kDa flagellin immunoglobulin (Ig) M level was predictable from two LTT-MELISA variables (F 2,51 = 5.981, P = 0.005). Similarly, the corresponding 41-kDa IgG model also contained two LTT-MELISA variables (F 2,57 = 3.700, P = 0.031). CONCLUSION: It is concluded that the LTT-MELISA appears to be able to detect the response to this antigen.

Human enteroviral infection in fibromyalgia: a case-control blinded study.

OBJECTIVE: This study aimed to test the hypothesis that fibromyalgia is associated with a human enteroviral infection. METHODS: Venous peripheral blood samples from 27 patients fulfilling the American College of Rheumatology revised diagnostic criteria for fibromyalgia and from 26 age- and sex-matched controls, who underwent immunofluorescence assays for coxsackievirus A7 IgG, coxsackievirus B1 IgG, coxsackievirus A7 IgA, coxsackievirus B1 IgA, echovirus IgG, and echovirus IgA. These immunological tests were performed blind to group status. RESULTS: There were no significant differences between the patient and control groups in respect of positive results for coxsackievirus A7 IgG (p=0.467), coxsackievirus B1 IgG (p=0.491), coxsackievirus A7 IgA (p=0.586), coxsackievirus B1 IgA (p=0.467), echovirus IgG (p=0.236), and echovirus IgA (p=1). CONCLUSIONS: The results of this systematic study do not support the hypothesis that fibromyalgia is associated with infection by a human enterovirus.

Human enteroviral infection in fibromyalgia: a case-control blinded study

SUMMARY OBJECTIVE: This study aimed to test the hypothesis that fibromyalgia is associated with a human enteroviral infection. METHODS: Venous peripheral blood samples from 27 patients fulfilling the American College of Rheumatology revised diagnostic criteria for fibromyalgia and from 26 age- and sex-matched controls, who underwent immunofluorescence assays for coxsackievirus A7 IgG, coxsackievirus B1 IgG, coxsackievirus A7 IgA, coxsackievirus B1 IgA, echovirus IgG, and echovirus IgA. These immunological tests were performed blind to group status. RESULTS: There were no significant differences between the patient and control groups in respect of positive results for coxsackievirus A7 IgG (p=0.467), coxsackievirus B1 IgG (p=0.491), coxsackievirus A7 IgA (p=0.586), coxsackievirus B1 IgA (p=0.467), echovirus IgG (p=0.236), and echovirus IgA (p=1). CONCLUSIONS: The results of this systematic study do not support the hypothesis that fibromyalgia is associated with infection by a human enterovirus.

Major Histocompatibility Complex Class II HLA-DRB1 Allelic Epitopes in Fibromyalgia.

BACKGROUND: Preliminary evidence has pointed an association of the gene HLA-DRB1 with fibromyalgia. HLA-DRB1 alleles carrying the shared or susceptibility epitope encoding the five-amino acid motif QKRAA, QRRAA or RRRAA in positions 70 to 74 of the major histocompatibility complex class II DRß chain are associated with several autoimmune diseases. OBJECTIVE: The objective of this study was to test the hypothesis that susceptibility epitope-encoding HLA-DRB1 alleles are associated with fibromyalgia. METHODS: Using a case-control design, the prevalence of susceptibility epitope-encoding HLADRB1 alleles in 27 white Caucasian patients fulfilling the revised diagnostic criteria for fibromyalgia of the American College of Rheumatology was compared with that in 27 white Caucasian ageand sex-matched healthy controls. RESULTS: 13 (48%) of the fibromyalgia patients had susceptibility epitope-coding HLA-DRB1 alleles compared with 15 (56%) of the controls (P = 0.785). The DRB1*01 allele encoding the protective epitope 70-DERAA-74 motif was found in one of the control subjects; none of the fibromyalgia patients had such a protective epitope. CONCLUSION: While the present study does not provide evidence supporting the potential role of HLA-DRB1 in the etiology of fibromyalgia, it does not exclude the possibility that there is a polygenic component to a putative genetic causative role.

Inflammation and Nitro-oxidative Stress as Drivers of Endocannabinoid System Aberrations in Mood Disorders and Schizophrenia.

The endocannabinoid system (ECS) is composed of the endocannabinoid ligands anandamide (AEA) and 2-arachidonoylgycerol (2-AG), their target cannabinoid receptors (CB1 and CB2) and the enzymes involved in their synthesis and metabolism (N-acyltransferase and fatty acid amide hydrolase (FAAH) in the case of AEA and diacylglycerol lipase (DAGL) and monoacylglycerol lipase (MAGL) in the case of 2-AG). The origins of ECS dysfunction in major neuropsychiatric disorders remain to be determined, and this paper explores the possibility that they may be associated with chronically increased nitro-oxidative stress and activated immune-inflammatory pathways, and it examines the mechanisms which might be involved. Inflammation and nitro-oxidative stress are associated with both increased CB1 expression, via increased activity of the NADPH oxidases NOX4 and NOX1, and increased CNR1 expression and DNA methylation; and CB2 upregulation via increased pro-inflammatory cytokine levels, binding of the transcription factor Nrf2 to an antioxidant response element in the CNR2 promoter region and the action of miR-139. CB1 and CB2 have antagonistic effects on redox signalling, which may result from a miRNA-enabled negative feedback loop. The effects of inflammation and oxidative stress are detailed in respect of AEA and 2-AG levels, via effects on calcium homeostasis and phospholipase A2 activity; on FAAH activity, via nitrosylation/nitration of functional cysteine and/or tyrosine residues; and on 2-AG activity via effects on MGLL expression and MAGL. Finally, based on these detailed molecular neurobiological mechanisms, it is suggested that cannabidiol and dimethyl fumarate may have therapeutic potential for major depressive disorder, bipolar disorder and schizophrenia.

Is Fibromyalgia Associated with Borrelia-specific T Lymphocytes?

BACKGROUND: Although fibromyalgia is a common cause of chronic musculoskeletal pain, its aetiology and pathophysiology are uncertain. It has recently been suggested that fibromyalgia symptomatology represents a T lymphocyte-mediated immune response to pathogens, which are known risk factors for autoimmune diseases. One major suggested candidate pathogen is the bacterial genus Borrelia. However, to date, this hypothesis has not been tested. OBJECTIVE: The aim was to carry out the first test of this hypothesis by comparing Borrelia-specific T lymphocyte reactivity in fibromyalgia patients and matched controls. METHODS: The enzyme-linked immunospot assay was used to detect T-lymphocyte reactivity to Borrelia burgdorferi sensu stricto (full antigen), outer surface protein (Osp) A from Borrelia burgdorferi sensu stricto, Borrelia afzelii and Borrelia garinii, native OspC plus decorin binding protein A recombinant and lymphocyte function antigen-1 (shared epitope) in 27 patients who fulfilled the revised diagnostic criteria for fibromyalgia of the American College of Rheumatology and in 26 control subjects. The assays were carried out blind to the group status of the participants. RESULTS: The two groups did not differ by age, sex or ethnicity. They did not differ significantly in respect of T lymphocyte reactivity to Borrelia burgdorferi sensu stricto (full antigen) (p = 0.847), Osp mix (p = 0.709) or lymphocyte function antigen-1 (p = 0.367). CONCLUSION: This novel controlled study provides no evidence of an association between fibromyalgia and Borrelia-specific T lymphocytes.

Clinical Assessment of Autonomic Function in Fibromyalgia by the Refined and Abbreviated Composite Autonomic Symptom Score (COMPASS 31): A Case-Controlled Study.

BACKGROUND: It has been shown that autonomic dysfunction in fibromyalgia can be assessed by the Composite Autonomic Symptom Score (COMPASS) questionnaire. More recently, a refined and much abbreviated 31-item version of the questionnaire has been developed, the COMPASS 31. OBJECTIVES: First, to determine whether the COMPASS 31 can assess changes in autonomic function in fibromyalgia. Second, to assess whether the COMPASS 31 values in fibromyalgia patients are positively correlated with scores on the Revised Fibromyalgia Impact Questionnaire (FIQR). METHODS: A cross-sectional, case-controlled study was carried out with 25 fibromyalgia patients and 26 healthy controls. RESULTS: The two groups were matched for age, sex and ethnicity, but not for body mass index (BMI). The total mean (standard error) COMPASS 31 for the fibromyalgia patients, 37.2 (1.8), differentiated the patients from the controls (9.5 (1.4); p < 0.00000001). The scores were greater in the fibromyalgia patients across all COMPASS 31 autonomic domains, namely orthostatic intolerance (p < 0.00000001), and vasomotor (p < 0.0001), secretomotor (p < 0.000001), gastrointestinal (p < 0.000001), bladder (p < 0.00001) and pupillomotor functions (p < 0.00000001). The total COMPASS 31 values were positively correlated with FIQR scores (rs = 0.45, p < 0.05). General linear modelling of the COMPASS 31 scores showed that only group status (fibromyalgia or control) was significant (p = 3.4 × 10-16), with age, sex and BMI being non-significant. CONCLUSION: This study confirms that non-pain autonomic dysfunction symptoms occur in fibromyalgia and can be assessed with the COMPASS 31.

Intertwined associations between oxidative and nitrosative stress and endocannabinoid system pathways: Relevance for neuropsychiatric disorders.

The endocannabinoid system (ECS) appears to regulate metabolic, cardiovascular, immune, gastrointestinal, lung, and reproductive system functions, as well as the central nervous system. There is also evidence that neuropsychiatric disorders are associated with ECS abnormalities as well as oxidative and nitrosative stress pathways. The goal of this mechanistic review is to investigate the mechanisms underlying the ECS's regulation of redox signalling, as well as the mechanisms by which activated oxidative and nitrosative stress pathways may impair ECS-mediated signalling. Cannabinoid receptor (CB)1 activation and upregulation of brain CB2 receptors reduce oxidative stress in the brain, resulting in less tissue damage and less neuroinflammation. Chronically high levels of oxidative stress may impair CB1 and CB2 receptor activity. CB1 activation in peripheral cells increases nitrosative stress and inducible nitric oxide (iNOS) activity, reducing mitochondrial activity. Upregulation of CB2 in the peripheral and central nervous systems may reduce iNOS, nitrosative stress, and neuroinflammation. Nitrosative stress may have an impact on CB1 and CB2-mediated signalling. Peripheral immune activation, which frequently occurs in response to nitro-oxidative stress, may result in increased expression of CB2 receptors on T and B lymphocytes, dendritic cells, and macrophages, reducing the production of inflammatory products and limiting the duration and intensity of the immune and oxidative stress response. In conclusion, high levels of oxidative and nitrosative stress may compromise or even abolish ECS-mediated redox pathway regulation. Future research in neuropsychiatric disorders like mood disorders and deficit schizophrenia should explore abnormalities in these intertwined signalling pathways.

The endocannabinoidome in neuropsychiatry: Opportunities and potential risks.

The endocannabinoid system (ECS) comprises two cognate endocannabinoid receptors referred to as CB1R and CB2R. ECS dysregulation is apparent in neurodegenerative/neuro-psychiatric disorders including but not limited to schizophrenia, major depressive disorder and potentially bipolar disorder. The aim of this paper is to review mechanisms whereby both receptors may interact with neuro-immune and neuro-oxidative pathways, which play a pathophysiological role in these disorders. CB1R is located in the presynaptic terminals of GABAergic, glutamatergic, cholinergic, noradrenergic and serotonergic neurons where it regulates the retrograde suppression of neurotransmission. CB1R plays a key role in long-term depression, and, to a lesser extent, long-term potentiation, thereby modulating synaptic transmission and mediating learning and memory. Optimal CB1R activity plays an essential neuroprotective role by providing a defense against the development of glutamate-mediated excitotoxicity, which is achieved, at least in part, by impeding AMPA-mediated increase in intracellular calcium overload and oxidative stress. Moreover, CB1R activity enables optimal neuron-glial communication and the function of the neurovascular unit. CB2R receptors are detected in peripheral immune cells and also in central nervous system regions including the striatum, basal ganglia, frontal cortex, hippocampus, amygdala as well as the ventral tegmental area. CB2R upregulation inhibits the presynaptic release of glutamate in several brain regions. CB2R activation also decreases neuroinflammation partly by mediating the transition from a predominantly neurotoxic "M1" microglial phenotype to a more neuroprotective "M2" phenotype. CB1R and CB2R are thus novel drug targets for the treatment of neuro-immune and neuro-oxidative disorders including schizophrenia and affective disorders.