Introduction: Previous studies suggest personality, the multifaceted characteristics underlying a person’s affect, cognition, and behavior, may influence fibromyalgia. We examined associations among personality, fibromyalgia impact, and health-related outcomes in patients with fibromyalgia. We further tested whether anxiety and depression mediated the effect of personality on fibromyalgia impact. Methods: We performed a secondary analysis using baseline data from a randomized trial on fibromyalgia. Personality was assessed using the NEO-Five Factor Inventory 3. Fibromyalgia impact was evaluated using the revised Fibromyalgia Impact Questionnaire (FIQR). We also measured symptom severity, anxiety, depression, stress, quality of life, social support, self-efficacy, outcome expectations, and mindfulness. Multivariable linear regression was performed to evaluate each association. Mediation analysis assessed whether anxiety and depression mediated the relationship between personality and FIQR. Results: There were 92 participants, 95% female, mean age 52 years, body mass index (BMI) 30 kg/m2, 52% white, and mean duration of body pain 14 years. Higher neuroticism was significantly associated with higher FIQR (P = 0.002) and symptom severity (P = 0.008), as well as higher levels of anxiety, depression, and stress, worse mental component quality of life, and lower self-efficacy, mindfulness, and social support. Higher conscientiousness and extraversion were associated with better psychological health and health-related outcomes. The effect of neuroticism on fibromyalgia impact was mediated by anxiety and depression. Conclusions: Personality was associated with fibromyalgia impact and a variety of health outcomes. Identifying the factors that influence fibromyalgia will help us better understand the condition and provide insight for more effective treatment.

Immune checkpoint proteins, such as PD-L1 and PD-1, are important in several cancers; however, their role in osteosarcoma (OSA) and soft tissue sarcoma (STS) remains unclear. Our aims were to determine whether subsets of OSA/STS harbor tumor-infiltrating lymphocytes (TILs) and express PD-L1, and how PD-L1 expression is related to clinical outcome. Tissue sections of 25 cases each of untreated undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), liposarcoma (LPS) and 24 of leiomyosarcoma (LMS) were subjected to immunohistochemistry (IHC) for immune cells, PD-L1 and PD-1. RT-qPCR was utilized to quantify levels of PD-L1 mRNA from 33 UPS, 57 MFS and 79 OSA primary-untreated specimens. PD-L1 mRNA levels were tested for their correlation with overall survival in patients presenting without metastases. Transcriptome analysis evaluated biological pathway differences between high and low PD-L1 expressers. A subset of UPS and MFS contained TILs and expressed PD-L1 and PD-1; LMS and LPS did not. PD-L1 levels by IHC and RT-qPCR were positively correlated. PD-L1 over-expression was associated with better survival for UPS and OSA, but not MFS. The Th1 pathway was significantly activated in UPS with high levels of PD-L1 and improved survival. Some sarcoma subtypes harbor TILs and express PD-L1. Patients with UPS and OSA with high levels of PD-L1 had better overall survival than those with low expression levels. Important biological pathways distinguish PD-L1 high and low groups. The stratification of patients with OSA/STS with respect to potential immune therapies may be improved through investigation of the expression of immune cells and checkpoint proteins.

Protein disulfide isomerases (PDIs) catalyze disulfide bond formation between protein cysteine residues during protein folding in the endoplasmic reticulum (ER) lumen and are essential for maintaining ER homoeostasis. The life cycle of the hepatitis C virus (HCV) is closely associated with the ER. Synthesis and maturation of HCV proteins occur in the ER membrane and are mediated by multiple host cell factors that include also PDI. Here, we present a study investigating the effect of PDI inhibition on Huh7 human hepatoma cells harboring an HCV subgenomic replicon using the abscisic acid-derived PDI inhibitor origamicin. Transcriptional profiling shows that origamicin changed the expression levels of genes involved in the oxidative and ER stress responses and the unfolded protein response, as indicated by the upregulation of antioxidant enzymes and chaperone proteins, the downregulation of cell-cycle proteins, and induction of apoptosis-associated genes. Our data suggest that origamicin negatively impacts HCV replication by causing an imbalance in cellular homoeostasis and induction of stress responses. These insights suggest that inhibition of PDIs by low-molecular-weight inhibitors could be a promising approach to the discovery of novel antiviral compounds.