Isolation and propagation of an Egyptian Theileria annulata infected cell line and evaluation of its use as a vaccine to protect cattle against field challenge.

Tropical theileriosis is an important protozoan tick-borne disease in cattle. Vaccination using attenuated schizont-infected cell lines is one of the methods used for controlling the disease. This study describes the production of attenuated schizont-infected cell lines from Egypt and an evaluation of its use as a vaccine to protect calves against clinical disease upon field challenge. Two groups of exotic and crossbred male calves were divided into vaccinated and control groups. The vaccinated groups were inoculated with 4 ml (1 × 106 cells/ml) of the attenuated cell line. Three weeks after vaccination, calves of both groups were transported to the New Valley Governorate (Egyptian oasis) where they were kept under field conditions and exposed to the natural Theileria annulata challenge. All animals in the control group showed severe clinical signs and died despite treatment with buparvaquone, which was administered after two days of persistent fever due to a severe drop in packed cell volume (PCV). Animals in the vaccinated group became seropositive without developing severe clinical signs other than transient fever. Post-mortem examinations revealed enlarged and fragile lymph nodes, spleen, and liver with necrosis and hemorrhages. These findings indicate that the Egyptian attenuated cell line was successful in protecting both exotic and crossbred animals against tropical theileriosis under field conditions.

Tunable Self-Referenced Molecular Thermometers via Manipulation of Dual Emission in Platinum(II) Pyridinedipyrrolide Complexes.

Optical temperature sensors based on self-referenced readout schemes such as the emission ratio and the decay time are crucial for a wide range of applications, with the former often preferred due to simplicity of instrumentation. This work describes a new group of dually emitting dyes, platinum(II) pincer complexes, that can be used directly for ratiometric temperature sensing without an additional reference material. They consist of Pt(II) metal center surrounded by a pyridinedipyrrolide ligand (PDP) and a terminal ligand (benzonitrile, pyridine, 1-butylimidazol or carbon monoxide). Upon excitation with blue light, these complexes exhibit green to orange emission, with quantum yields in anoxic toluene at 25 °C ranging from 13% to 86% and decay times spanning from 8.5 to 97 µs. The emission is attributed to simultaneous thermally activated delayed fluorescence (TADF) and phosphorescence processes on the basis of photophysical investigations and DFT calculations. Rather uniquely, simple manipulations in substituents of the PDP ligand and alteration of the terminal ligand allow fine-tuning of the ratio between TADF and phosphorescence from almost 100% TADF emission (Pt(MesPDPC6F5(BN)) to over 80% of phosphorescence (Pt(PhPDPPh(BuIm)). Apart from ratiometric capabilities, the complexes also are useful as decay time-based temperature indicators with temperature coefficients exceeding 1.5% K-1 in most cases. Immobilization of the dyes into oxygen-impermeable polyacrylonitrile produces temperature sensing materials that can be read out with an ordinary RGB camera or a smartphone. In addition, Pt(PhPDPPh)Py can be incorporated into biocompatible RL100 nanoparticles suitable for cellular nanothermometry, as we demonstrate with temperature measurements in multicellular colon cancer spheroids.

Early life stress in women with autoimmune thyroid disorders.

Autoimmune thyroid disorders (AITD) represent the most frequent of all autoimmune disorders. Their aetiopathogenesis is incompletely understood, but most likely multifactorial. Early life stress can have long-lasting effects on the immune system. The aim of the present study was to investigate, for the first time, whether patients with AITD are more frequently affected by early life stress. A total of N = 208 women were recruited into a case-control study. Of these, n = 78 (median age: 53, interquartile range: 15) were patients recruited from a thyroid outpatient clinic with confirmed Hashimoto's thyroiditis, Graves' disease, or AITD not otherwise specified. The remaining n = 130 age- and BMI-matched women (median age: 53, interquartile range: 12) were recruited from the general population. Early life stress was measured with the Childhood Trauma Questionnaire. Patients with AITD did not differ from controls regarding sexual abuse, physical abuse, and physical neglect. However, a greater number of patients reported emotional neglect (29.7% vs. 19.5%) and emotional abuse (41.3% vs. 32%). This study provides initial evidence for emotional neglect and abuse as potential risk factors for the development of AITD. Prospective confirmation of these findings could pave the way for the development of interventions to prevent AITD in predisposed individuals.

DNA Methylation Signatures of Functional Somatic Syndromes: Systematic Review.

OBJECTIVE: Functional somatic syndromes (FSS) are highly prevalent across all levels of health care. The fact that they are characterized by medically unexplained symptoms, such as fatigue and pain, raises the important question of their underlying pathophysiology. Psychosocial stress represents a significant factor in the development of FSS and can induce long-term modifications at the epigenetic level. The aim of this review was to systematically review, for the first time, whether individuals with FSS are characterized by specific alterations in DNA methylation. METHODS: MEDLINE and PsycINFO were searched from the first available date to September 2022. The inclusion criteria were as follows: a) adults fulfilling the research diagnostic criteria for chronic fatigue syndrome, fibromyalgia syndrome, and/or irritable bowel syndrome; b) healthy control group; and c) candidate-gene or genome-wide study of DNA methylation. RESULTS: Sixteen studies ( N = 957) were included. In candidate-gene studies, specific sites within NR3C1 were identified, which were hypomethylated in individuals with chronic fatigue syndrome compared with healthy controls. In genome-wide studies in chronic fatigue syndrome, a hypomethylated site located to LY86 and hypermethylated sites within HLA-DQB1 were found. In genome-wide studies in fibromyalgia syndrome, differential methylation in sites related to HDAC4 , TMEM44 , KCNQ1 , SLC17A9 , PRKG1 , ALPK3 , TFAP2A , and LY6G5C was found. CONCLUSIONS: Individuals with chronic fatigue syndrome and fibromyalgia syndrome seem to be characterized by altered DNA methylation of genes regulating cellular signaling and immune functioning. In chronic fatigue syndrome, there is preliminary evidence for these to be implicated in key pathophysiological alterations, such as hypocortisolism and low-grade inflammation, and to contribute to the debilitating symptoms these individuals experience. PREREGISTRATION: PROSPERO identifier: CRD42022364720.

Associations between indices of 24-hour heart rate variability and inflammation in individuals with major depressive disorder.

Biological cardiac risk factors, including reduced heart rate variability (HRV) and inflammation, are already prominent in patients with major depressive disorder (MDD) without existing cardiovascular disease. Although inverse relations between HRV and inflammation have been found across several populations, little work has been done concerning MDD. The present work thus intended to examine whether measures of HRV indices based on 24-h electrocardiograph recordings (24-h, daytime, nighttime) relate to levels of circulating inflammatory markers such as C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-α in eighty antidepressant-free individuals with MDD. A sample of 40 age- and sex-matched non-clinical controls was also involved to verify biological alterations in MDD. Individuals with MDD exhibited reduced total 24-h HRV (i.e., triangular index) and reduced daytime HRV (i.e., triangular index, HF-HRV, LF-HRV, RMSSD), as well as increased levels of all inflammatory markers. Multivariate analyses adjusted for age, sex, body mass index, and smoking revealed robust inverse associations of total 24-h HRV (i.e., triangular index) and daytime HRV (i.e., Triangular index, HF-HRV, LF-HRV, RMSSD) with IL-6. An attenuated daytime HRV may relate to higher circulating levels of IL-6 in the context of MDD. These findings show that biological cardiac risk factors may act in concert in MDD.

Does psychological treatment of major depression reduce cardiac risk biomarkers? An exploratory randomized controlled trial.

BACKGROUND: Depression is associated with an increased risk for cardiovascular disease (CVD). Biological cardiac risk factors are already elevated in depressed patients without existing CVD. The purpose of this exploratory trial was to examine whether treating Major Depression (MD) with cognitive behavioral therapy (CBT) is associated with improvements in cardiac risk biomarkers and whether depressive symptom severity at baseline moderates treatment effects. METHODS: Eighty antidepressant-free patients with MD were randomly assigned to CBT or waiting list (WL). Biological outcomes included long-term recordings (24-h, daytime, nighttime) of heart rate, heart rate variability (HRV), and blood pressure, as well as inflammatory markers such as C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-α. A sample of 40 age- and sex-matched non-clinical controls was also involved to verify biological alterations in MD at study entry. RESULTS: Compared to WL, CBT was associated with a significant increase in overall HRV, as indexed by the 24-h and daytime HRV triangular index, as well as trend improvements in 24-h low-frequency HRV and daytime systolic blood pressure. Self-rated depressive symptom severity moderated (or tended to moderate) improvements in CBT for 24-h and daytime heart rate and several indices of HRV (especially daytime measures). Inflammatory treatment effects were not observed. CONCLUSIONS: CBT increased overall HRV in patients with MD. Initially more depressed patients showed the most pronounced cardiovascular improvements through CBT. These exploratory findings may provide new insights into the biological effects of psychological treatment against depression and must be confirmed through future research.

Does childhood trauma impact daily psychobiological stress in somatic symptom disorder? An ambulatory assessment study.

Objectives: Somatic symptom disorder is characterized by excessive thoughts, feelings, and behaviors dedicated to bodily symptoms, which are often medically unexplained. Although 13% of the population are affected by this disorder, its aetiopathogenesis is not fully understood. Research in medically unexplained conditions (e.g., fibromyalgia) points to increased psychosocial stress and alterations in stress-responsive bodily systems as a potential contributing factor. This pattern has often been hypothesized to originate from early life stress, such as childhood trauma. The aim of this study was to examine, for the first time, whether individuals with somatic symptom disorder exhibit elevated levels of self-reported daily stress and alterations in the autonomic nervous system and hypothalamic-pituitary-adrenal axis, both in comparison to healthy controls and individuals with depressive disorders, and whether reports of childhood trauma influence these alterations. Methods: A total of N = 78 individuals were recruited into this study. Of these, n = 27 had a somatic symptom disorder, n = 23 were healthy controls, and n = 28 had a depressive disorder. All individuals underwent a 14-day measurement period at home, with five assessments of self-reported stress, salivary alpha-amylase, and cortisol per day. Childhood trauma was assessed by the Childhood Trauma Questionnaire. Results: Individuals with somatic symptom disorder exhibited higher daily stress levels (p = 0.063) as well as a less pronounced alpha-amylase awakening response (p = 0.050), compared to healthy controls (statistical trends). Moreover, they were characterized by significantly attenuated diurnal cortisol concentrations (p < 0.001). A nearly identical pattern was observed in individuals with depression. In individuals with somatic symptom disorder and depressive disorders, childhood trauma was, by trend, associated with a more pronounced alpha-amylase awakening response (b = -0.27, p = 0.077). Conclusions: This study provides preliminary evidence for elevated daily stress and blunted sympathetic and hypothalamic-pituitary-adrenal axis activity in individuals with somatic symptom disorder and depressive disorders. Further studies will help to uncover the conditions under which these dysregulations develop into medically unexplained vs. depressive symptoms.

Endogenous oestradiol and progesterone as predictors of oncogenic human papillomavirus (HPV) persistence.

BACKGROUND: High-risk human papillomavirus (HR-HPV) is the main aetiological factor for the development of cervical cancer. While nearly 70% of HR-HPV infections are cleared within 12 months, in the remainder of women they persist and can progress into cervical cancer. Oestradiol and progesterone have been shown to be involved in the development and progression of cervical cancer. The objective of this study was to investigate, for the first time, whether diurnal oestradiol and progesterone are also involved in HR-HPV persistence - before cervical cancer develops. METHODS: A total of N = 39 women between 18 and 31 years of age were investigated. All were nulliparous and regular users of combined oral contraceptives. Presence of HR-HPV was determined by cervical swabs. Salivary oestradiol and progesterone were measured upon awakening and at 11 am, 2 pm, and 5 pm. All HR-HPV positive women were re-tested in terms of HR-HPV status 12 months later. RESULTS: HR-HPV positive women had significantly higher morning (p = .007, partial eta2 = .221) and daily oestradiol levels (p < .001, partial eta2 = .442) when compared to HR-HPV negative women. In addition, those with persistent HR-HPV 12 months later had significantly elevated morning (p = .005, partial eta2 = .534) and daily (p = .027, partial eta2 = .346) oestradiol. Progesterone was found to be unrelated to HR-HPV. CONCLUSIONS: Oestradiol was positively linked to HR-HPV presence and persistence. Provided that these findings are replicated, regular monitoring of oestradiol levels may prove useful in identifying women who are at risk of developing cervical cancer.

Hair cortisol levels in women with medically unexplained symptoms.

Stress has been demonstrated to be involved in the development of medically unexplained symptoms. A key underlying mechanism could be lower levels of cortisol, which can contribute to symptoms such as fatigue or pain. However, the literature is highly equivocal, which may be due to methodological limitations inherent in short-term cortisol assessment. The aim of this case-control study was to investigate, for the first time, whether individuals with different forms of medically unexplained symptoms show altered hair cortisol concentrations, a long-term marker of hypothalamic-pituitary-adrenal functioning. Two groups of women with medically unexplained symptoms were recruited. The first had a functional somatic syndrome, characterised by specific medically unexplained symptoms (i.e., chronic fatigue syndrome, fibromyalgia, or irritable bowel syndrome, n = 33). The second had somatic symptom disorder, characterised by excessive thoughts, feelings, and behaviours devoted to various medically unexplained symptoms (n = 23). These groups were contrasted with healthy controls (n = 30), and women with depression (n = 27). Cortisol representing the previous three months was extracted from hair. Chronic stress and childhood trauma were assessed (retrospectively). Women with somatic symptom disorder had lower hair cortisol than healthy controls and women with functional somatic syndromes. No differences in hair cortisol were found between healthy controls, functional somatic syndromes, and depression. Neither childhood trauma nor chronic stress was correlated with hair cortisol. Provided that our findings are replicated, they may suggest that hypocortisolism is found in a specific subgroup of individuals with medically unexplained symptoms, and potentially in those characterised by excessive thoughts, feelings, and behaviours about symptoms.

Is stress related to the presence and persistence of oncogenic human papillomavirus infection in young women?

BACKGROUND: Persistent infection with high-risk human papillomavirus (HR-HPV) is the most important risk factor for the development of cervical cancer, but factors contributing to HR-HPV persistence are incompletely understood. The objective of this study was to test for associations of chronic stress and two aspects of diurnal cortisol secretion (i.e., the cortisol awakening response [CAR] and total cortisol output over the day [AUCgday]) with HR-HPV status at baseline and 12 months later (follow-up). METHODS: We evaluated 188 women (25 ± 3 years) at baseline. Follow-up investigation was restricted to HR-HPV infected women at baseline. Of the initial 48 HR-HPV positive participants, 42 completed the follow-up (16 HR-HPV positive and 26 HR-HPV negative). At baseline and follow-up, we determined HR-HPV status in cervical smears, assessed chronic stress, and repeatedly measured salivary cortisol over the day. At baseline, we analyzed salivary cortisol only in a subgroup of 90 participants (45 HR-HPV negative and 45 HR-HPV positive). RESULTS: At baseline, higher chronic stress (excessive demands at work: p = .022, chronic worrying: p = .032), and a higher CAR (p = .014) were related to baseline HR-HPV positivity. At follow-up, there was a statistical trend for a positive association between the CAR and HR-HPV positivity (p = .062). Neither the CAR nor the AUCgday mediated the associations between chronic stress and HR-HPV status. CONCLUSIONS: Our findings suggest that both chronic stress and diurnal cortisol are related to the presence of HR-HPV infection and may thus play a role in HPV-associated cervical carcinogenesis.

Hormones of the hypothalamic-pituitary-gonadal (HPG) axis in male depressive disorders - A systematic review and meta-analysis.

Sexual dysfunctions are common in men with depression. As the hypothalamic-pituitary-gonadal (HPG) axis is a crucial regulator of sexual function, and also affects mood and cognition, the following question arises: Is the HPG axis altered in depressed men when compared to healthy controls? To answer this question, PubMed and PsycINFO were searched. Inclusion criteria for the systematic review and meta-analysis were: (1) case-control study including male patients with a depressive disorder and (2) assessment of follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol, or testosterone. Seventeen studies were identified. Follicle-stimulating hormone and LH did not differ between patients and controls. By contrast, in patients, oestradiol was marginally increased (g = 0.52, 95% CI [-0.01, 1.04]; Z = 1.92, p = .055) and testosterone was significantly decreased (g = -0.45, 95% CI [-0.80, -0.10]; Z = -2.53, p = .012). Depressed men may be characterised by diminished testosterone and potentially elevated oestradiol, which beyond contributing to sexual dysfunction, could impact mood and cognition.

The Drosophila fussel gene is required for bitter gustatory neuron differentiation acting within an Rpd3 dependent chromatin modifying complex.

Members of the Ski/Sno protein family are classified as proto-oncogenes and act as negative regulators of the TGF-ß/BMP-pathways in vertebrates and invertebrates. A newly identified member of this protein family is fussel (fuss), the Drosophila homologue of the human functional Smad suppressing elements (fussel-15 and fussel-18). We and others have shown that Fuss interacts with SMAD4 and that overexpression leads to a strong inhibition of Dpp signaling. However, to be able to characterize the endogenous Fuss function in Drosophila melanogaster, we have generated a number of state of the art tools including anti-Fuss antibodies, specific fuss-Gal4 lines and fuss mutant fly lines via the CRISPR/Cas9 system. Fuss is a predominantly nuclear, postmitotic protein, mainly expressed in interneurons and fuss mutants are fully viable without any obvious developmental phenotype. To identify potential target genes or cells affected in fuss mutants, we conducted targeted DamID experiments in adult flies, which revealed the function of fuss in bitter gustatory neurons. We fully characterized fuss expression in the adult proboscis and by using food choice assays we were able to show that fuss mutants display defects in detecting bitter compounds. This correlated with a reduction of gustatory receptor gene expression (Gr33a, Gr66a, Gr93a) providing a molecular link to the behavioral phenotype. In addition, Fuss interacts with Rpd3, and downregulation of rpd3 in gustatory neurons phenocopies the loss of Fuss expression. Surprisingly, there is no colocalization of Fuss with phosphorylated Mad in the larval central nervous system, excluding a direct involvement of Fuss in Dpp/BMP signaling. Here we provide a first and exciting link of Fuss function in gustatory bitter neurons. Although gustatory receptors have been well characterized, little is known regarding the differentiation and maturation of gustatory neurons. This work therefore reveals Fuss as a pivotal element for the proper differentiation of bitter gustatory neurons acting within a chromatin modifying complex.

Thyroid Functioning and Fatigue in Women With Functional Somatic Syndromes - Role of Early Life Adversity.

Objective: Fatigue is a core feature of functional somatic syndromes (FSS). Fatigue is also prominent in patients with thyroid diseases, which is unsurprising given the role of the hypothalamic-pituitary-thyroid (HPT) axis in regulating physiological energy demands. Research in healthy women has shown that early life adversity is linked with alterations in the HPT axis. In view of the substantial prevalence of early life adversity in patients with FSS, our aim was to investigate whether HPT functioning is related to (a) fatigue, and (b) early life adversity in these patients. Methods:N = 33 female patients with FSS and n = 30 age-matched controls were recruited. Fasting morning blood samples were taken to determine thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and thyroxine (fT4). General, physical, and mental fatigue were measured via the multidimensional fatigue inventory (MFI). Early life adversity was measured using the childhood trauma questionnaire (CTQ). Results: Patients with FSS did not differ from controls in any thyroid parameters (all p > 0.672). However, the lower the patients' TSH and the higher their fT4, the greater was their general (ß = -0.32, p = 0.064; ß = 0.35, p = 0.038) and physical (ß = -0.47, p = 0.007; ß = 0.32, p = 0.077) fatigue. In addition, emotional neglect (ß = -0.32, p = 0.057), physical neglect (ß = -0.60, p = 0.001), physical abuse (ß = -0.47, p = 0.015), and sexual abuse (ß = -0.40, p = 0.026) were linked with lower TSH. Conclusion: The lower TSH and the higher fT4, the more fatigue was reported by patients with FSS. In addition, lower TSH was linked with more early life adversity. Larger, prospective studies are warranted to determine whether HPT functioning may be a mediating pathway between early life adversity and fatigue in FSS.

Hypothalamic-pituitary-thyroid (HPT) axis functioning in anxiety disorders. A systematic review.

Depression has repeatedly been linked to subclinical hypothyroidism, and thyroid hormones have successfully been used to augment antidepressant treatment. By contrast, the extent of thyroid dysfunction in anxiety disorders remains less clear. This is surprising, given that anxiety-related symptoms (e.g., nervousness, palpitations, increased perspiration) are highly prevalent in hyperthyroidism. The present study was undertaken to synthesize the literature on hypothalamic-pituitary-thyroid (HPT) axis functioning in anxiety disorders. The PubMed and PsycINFO databases were systematically searched. Three types of studies were included: (1) "comorbidity studies" assessing the prevalence of thyroid disorders in individuals with anxiety disorders, (2) "case-control studies" comparing HPT parameters between patients and controls, and (3) "correlational studies" assessing self-reported anxiety levels and HPT parameters. Risk of bias was assessed via a standardized quality rating. Twenty studies were eligible. Nearly all found the comorbidity between anxiety and thyroid disorders was significant. Half of the studies additionally supported the notion of subtle thyroid dysfunction in that thyroid-stimulating hormone (TSH) responses to the administration of thyrotropin-releasing hormone (TRH) were blunted and an inverse relationship was observed between self-reported anxiety levels and TSH. Overall, HPT assessments were well conducted, but several studies failed to adjust their analyses for smoking, body mass index (BMI), and depression. The findings resonate well with clinical recommendations to routinely screen for thyroid disorders in patients with anxiety disorders, and with what is known from basic research about thyroid-brain interactions. The results of the risk of bias assessment underscore the importance of further high-quality experimental and longitudinal epidemiological research.

Influence of stress systems and physical activity on different dimensions of fatigue in female fibromyalgia patients.

OBJECTIVE: Fatigue is a defining characteristic and one of the most debilitating features of fibromyalgia syndrome (FMS). The mechanisms underlying different dimensions of fatigue in FMS remain unclear. The aim of the current study was to test whether stress-related biological processes and physical activity modulate fatigue experience. METHODS: Using an ambulatory assessment design, 26 female FMS patients reported general, mental, and physical fatigue levels at six time points per day for 14 consecutive days. Salivary cortisol and alpha-amylase were analyzed as markers of neuroendocrine functioning. Participants wore wrist actigraphs for the assessment of physical activity. RESULTS: Lower increases in cortisol after awakening predicted higher mean daily general and physical fatigue levels. Additionally, mean daily physical activity positively predicted next-day mean general fatigue. Levels of physical fatigue at a specific time point were positively associated with momentary cortisol levels. The increase in cortisol after awakening did not mediate the physical activity - fatigue relationship. There were no associations between alpha-amylase and fatigue. CONCLUSION: Our findings imply that both changes in hypothalamic-pituitary-adrenal axis activity and physical activity contribute to variance in fatigue in the daily lives of patients with FMS. This study helps to paint a clearer picture of the biological and behavioral underpinnings of fatigue in FMS and highlight the necessity of interdisciplinary treatment approaches targeting biological, behavioral and psychological aspects of FMS.

Sociodemographic, lifestyle, and psychosocial determinants of hair cortisol in a South London community sample.

OBJECTIVE: Hypothalamic-pituitary-adrenal (HPA) measures are crucial for research into stress and stress-related disorders. Most HPA measures fluctuate depending on diurnal rhythms and state confounders. Hair cortisol concentrations (HCC) are less susceptible to such fluctuations, but less is known about trait-like confounders. Using a community sample, we tested the relationship between HCC and a range of variables including demographic variables, hair treatment, and medication, as well as psychosocial variables, namely childhood trauma, critical life events, and depressive symptoms. METHODS: Hair samples were collected from 144 individuals from the South East London Community Health (SELCoH) study. Childhood trauma, life events, and depressive symptoms were measured, together with age, sex, ethnicity, relationship status, educational attainment, employment status, occupational social class, hair washing frequency, hair treatments, season reflected in the hair sample, hazardous drinking, smoking, medication intake, and body mass index. Hair samples reflecting the past 3 months were collected and analysed using immunoassays. First, correlations (continuous variables) and simple linear regressions (dichotomous variables) were conducted to identify sociodemographic, hair-related, and lifestyle determinants of HCC. Next, multiple linear regressions were conducted to test the relationship between psychosocial variables and HCC when controlling for the identified confounders. RESULTS: Age (r=-0.17, p=0.050), White British ethnicity (ß=-0.19, p=0.023), heat-based treatments (ß=-0.22, p=0.010), and winter season (ß=-0.18, p=0.024) were associated with lower HCC, whereas summer season (ß=0.24, p=0.024), painkillers (ß=0.25, p=0.003), anxiolytics/antidepressants (ß=0.21, p=0.014), and hormonal contraceptives (ß=0.27, p=0.006) were associated with higher HCC. Controlling for these confounders, physical neglect during childhood (ß=-0.17, p=0.057), war-related experiences (ß=0.20, p=0.027), separation (ß=0.18, p=0.054), and being the victim of a serious crime (ß=-0.17, p=0.062) were linked with altered HCC. CONCLUSION: Our findings suggest that variation in HCC occurs according to sociodemographic, hair-related, and lifestyle variables, and that certain associations between stress and altered HCC can only be revealed when accounting for these confounders.

Classifying Fibromyalgia Syndrome as a Mental Disorder?-An Ambulatory Assessment Study.

PURPOSE: Fibromyalgia syndrome (FMS) is associated with psychological distress. The recent revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) raises the question of whether FMS is classifiable as "somatic symptom disorder" (SSD) and consequently as a mental disorder. To address this, the present ambulatory assessment study focuses on the everyday life occurrence of SSD symptoms in FMS and their predictive value concerning severity indicators of widespread pain. METHOD: Ambulatory data were assessed six times daily on 14 consecutive days via iPod. Twenty-eight women suffering from FMS indicated symptoms associated with SSD (somatic illness beliefs, health anxiety, time/energy devoted to pain, or health concerns) and momentary pain levels. Questionnaires regarding potential covariates (such as somatization, depression, health status) were completed at two additional sessions in the research laboratory. RESULTS: On average, SSD symptoms occurred three to four times daily and were mild to moderate in severity. Furthermore, these symptoms were both concurrently and prospectively associated with momentary pain intensity and subjective impairment by pain. Twenty percent of the variance in pain intensity and 28 % of the variance in subjective impairment were explained by momentary variables (SSD symptoms and intake of pain medication). Eighty-two percent of persons with FMS fulfilled the psychological SSD criterion when considering everyday occurring symptoms with at least mild severity. CONCLUSION: FMS might be diagnosed as a mental disorder according to DSM-5 in many cases. SSD symptoms proved to have predictive value for FMS severity and may thus have clinical relevance for diagnostic, prognostic, and intervention purposes.

Stress exacerbates pain in the everyday lives of women with fibromyalgia syndrome--The role of cortisol and alpha-amylase.

OBJECTIVE: Although fibromyalgia syndrome (FMS) is a chronic condition, its cardinal symptom pain is known to fluctuate over the day. Stress has often been claimed to exacerbate pain; however, there is barely any evidence on whether or not this is true on a day-to-day basis (and, alternatively, on whether pain leads to increased stress levels). Using an ecologically valid measurement design, we tested whether and how stress and pain are intertwined in participants with FMS. We additionally examined the role of the two major stress-responsive systems, the hypothalamic-pituitary-adrenal axis and the autonomic nervous system, as potential mediators of this relationship. METHODS: An ambulatory assessment study was conducted over the course of 14 days. On each day, 32 females with FMS provided six diary entries on momentary stress and pain levels. Saliva samples were collected at the same time points to determine cortisol and alpha-amylase as indicators of stress-responsive systems. RESULTS: Higher stress at a given measurement time point was associated with higher reported pain levels at the subsequent time point (UC=1.47, p<0.001), but not vice versa (UC<0.01, p=0.179). The stress-pain relationship was neither mediated by momentary cortisol nor by alpha-amylase; however, momentary cortisol was independently associated with momentary pain (UC=0.27, p=0.009). CONCLUSION: Stress seems to be a powerful exacerbating factor for pain as experienced by patients with FMS in their everyday lives. Cortisol may be involved in the diurnal fluctuation of pain levels in patients with FMS. Future studies should identify relevant daily stressors in persons with FMS and scrutinize the mechanisms underlying the cortisol-pain relationship.

The effects of music listening on pain and stress in the daily life of patients with fibromyalgia syndrome.

Music listening is associated with both pain- and stress-reducing effects. However, the effects of music listening in daily life remain understudied, and the psycho-biological mechanisms underlying the health-beneficial effect of music listening remain unknown. We examined the effects of music listening on pain and stress in daily life in a sample of women with fibromyalgia syndrome (FMS; i.e., a condition characterized by chronic pain) and investigated whether a potentially pain-reducing effect of music listening was mediated by biological stress-responsive systems. Thirty women (mean age: 50.7 ± 9.9 years) with FMS were examined using an ecological momentary assessment design. Participants rated their current pain intensity, perceived control over pain, perceived stress level, and music listening behavior five times per day for 14 consecutive days. At each assessment, participants provided a saliva sample for the later analysis of cortisol and alpha-amylase as biomarkers of stress-responsive systems. Hierarchical linear modeling revealed that music listening increased perceived control over pain, especially when the music was positive in valence and when it was listened to for the reason of 'activation' or 'relaxation'. In contrast, no effects on perceived pain intensity were observed. The effects of music listening on perceived control over pain were not mediated by biomarkers of stress-responsive systems. Music listening in daily life improved perceived control over pain in female FMS patients. Clinicians using music therapy should become aware of the potential adjuvant role of music listening in daily life, which has the potential to improve symptom control in chronic pain patients. In order to study the role of underlying biological mechanisms, it might be necessary to use more intensive engagement with music (i.e., collective singing or music-making) rather than mere music listening.

Functional somatic syndromes: asking about exclusionary medical conditions results in decreased prevalence and overlap rates.

BACKGROUND: The diagnosis of functional somatic syndromes (FSS) requires 1) presence of somatic symptoms, and 2) absence of medical conditions potentially accounting for these symptoms. Due to the limited feasibility of medical examinations, epidemiological research on FSS has neglected to assess the second criterion. Our objective was therefore to evaluate the implications of considering information on exclusionary medical conditions in epidemiological research on FSS. METHODS: A survey among 3'054 students was conducted. We compared prevalence rates and overlap of 17 FSS obtained by: 1) a symptom-based strategy and 2) a symptom-and-exclusion-based strategy including information on exclusionary medical conditions. RESULTS: The symptom-and-exclusion-based strategy led to a marked decrease in prevalence rates compared to the symptom-based strategy. Furthermore, it resulted in fewer individuals who were affected by multiple FSS. CONCLUSIONS: Adding self-reported information on exclusionary medical conditions leads to a significant decrease in the prevalence and overlap of FSS. More rigorous approaches to studying FSS should be adopted.