Corrigendum: Study protocol for FIBROKIT: a new tool for fibromyalgia diagnosis and patient follow-up.

[This corrects the article DOI: 10.3389/fneur.2023.1286539.].

Study protocol for FIBROKIT: a new tool for fibromyalgia diagnosis and patient follow-up.

Fibromyalgia (FM) is a complex disease that is characterized by chronic musculoskeletal pain and has great economic impact. FM prevalence is about 2% to 4% worldwide, affecting mainly middle-aged women, and its complex pathophysiology complicates diagnosis, treatment and the findings of solid biomarkers. Previous studies have suggested an association between the disease and oxidative stress, mitochondrial metabolism, intestinal microbiota and inflammation, providing sufficient data to support the multifactorial origin of FM. Hence, the objective of this randomized, prospective, low-interventional, double-blinded and placebo-controlled clinical trial is the development of a specific panel of FM biomarkers and the evaluation of their response to a six-month nutritional intervention based on the Mediterranean diet supplemented with extra virgin olive oil (EVOO). For this purpose, the experimental design implies the recruitment of a large cohort of female Spanish patients. Middle-aged women who meet the diagnostic criteria for FM according to the American College of Rheumatology (ACR) will be eligible, along with age-matched healthy women. Both groups will be randomly divided into placebo (olive oil, OO) and treatment groups (extra virgin olive oil, EVOO), and will provide samples at the beginning (T0), after 3 months of nutritional intervention (T1), at the end of the nutritional intervention in 6 months (T2), and 6 months after the end of nutritional intervention (TF), being enrolled for 1 year. Data will be collected through health questionnaires, and whole blood and stool samples will be taken and analyzed. Blood will be used for western-blotting and proteomic analysis of mitochondrial homeostasis and plasma proteome, while stool will undergo metagenomic analysis, respectively. This study represents the first low-interventional investigation with more than 200 participants focused on exploring the association of oxidative stress, mitochondrial metabolism, intestinal microbiota and related pathways with a nutritional intervention in the context of FM. As a result, the outcomes of this study will significantly contribute to the development of a comprehensive and robust panel of diagnostic biomarkers, and will shed some light on their modulation with non-pharmacological therapies such as nutrition. Clinical trial registration: https://clinicaltrials.gov/study/NCT05921409, identifier: NCT05921409.

Microbiota and Mitochondrial Sex-Dependent Imbalance in Fibromyalgia: A Pilot Descriptive Study.

Fibromyalgia is a widespread chronic condition characterized by pain and fatigue. Among the long list of physiological disturbances linked to this syndrome, mitochondrial imbalance and oxidative stress stand out. Recently, the crosstalk between mitochondria and intestinal microbiota has caught the attention of biomedical researchers, who have found connections between this axis and several inflammatory and pain-related conditions. Hence, this pilot descriptive study focused on characterizing the mitochondrial mass/mitophagy ratio and total antioxidant capacity in PBMCs, as well as some microbiota components in feces, from a Peruvian cohort of 19 females and 7 males with FM. Through Western blotting, electrochemical oxidation, ELISA, and real-time qPCR, we determined VDAC1 and MALPLC3B protein levels; total antioxidant capacity; secretory immunoglobulin A (sIgA) levels; and Firmicutes/Bacteroidetes, Bacteroides/Prevotella, and Roseburia/Eubacterium ratios; as well as Ruminococcus spp., Pseudomonas spp., and Akkermansia muciniphila levels, respectively. We found statistically significant differences in Ruminococcus spp. and Pseudomonas spp. levels between females and males, as well as a marked polarization in mitochondrial mass in both groups. Taken together, our results point to a mitochondrial imbalance in FM patients, as well as a sex-dependent difference in intestinal microbiota composition.

Accuracy between 2D Photography and Dual-Structured Light 3D Facial Scanner for Facial Anthropometry: A Clinical Study.

(1) Background: Facial scanners are used in different fields of dentistry to digitalize the soft tissues of the patient's face. The development of technology has allowed the patient to have a 3-dimensional virtual representation, facilitating facial integration in the diagnosis and treatment plan. However, the accuracy of the facial scanner and the obtaining of better results with respect to the manual or two-dimensional (2D) method are questionable. The objective of this clinical trial was to evaluate the usefulness and accuracy of the 3D method (a dual-structured light facial scanner) and compare it with the 2D method (photography) to obtain facial analysis in the maximum intercuspation position and smile position. (2) Methods: A total of 60 participants were included, and nine facial landmarks and five interlandmarks distances were determined by two independent calibrated operators for each participant. All measurements were made using three methods: the manual method (manual measurement), the 2D method (photography), and the 3D method (facial scanner). All clinical and lighting conditions, as well as the specific parameters of each method, were standardized and controlled. The facial interlandmark distances were made by using a digital caliper, a 2D software program (Adobe Photoshop, version 21.0.2), and a 3D software program (Meshlab, version 2020.12), respectively. The data were analyzed by SPSS statistical software. The Kolmogorov-Smirnov test revealed that trueness and precision values were normally distributed (p > 0.05), so a Student's t-test was employed. (3) Results: Statistically significant differences (p ≤ 0.01) were observed in all interlandmark measurements in the 2D group (photography) to compare with the manual group. The 2D method obtained a mean accuracy value of 2.09 (±3.38) and 2.494 (±3.67) in maximum intercuspation and smile, respectively. On the other hand, the 3D method (facial scanner) obtained a mean accuracy value of 0.61 (±1.65) and 0.28 (±2.03) in maximum intercuspation and smile, respectively. There were no statistically significant differences with the manual method. (4) Conclusions: The employed technique demonstrated that it influences the accuracy of facial records. The 3D method reported acceptable accuracy values, while the 2D method showed discrepancies over the clinically acceptable limits.

Synthetic RNA derived from the foot-and-mouth disease virus genome elicits antiviral responses in bovine and porcine cells through IRF3 activation.

Foot-and-mouth disease virus (FMDV) is the causative agent of a highly transmissible disease affecting wild and domestic animals including pigs, cattle and sheep. The ability of synthetic RNA transcripts mimicking distinct domains in the non-coding regions of the FMDV genome (ncRNAs) to induce a potent innate immune response in swine cultured cells and mice has been previously described, as well as their enhancing effect on conventional inactivated FMD vaccines. Here, we provide evidence of the activation of interferon regulatory factor 3 (IRF3), a key transcriptional regulator of type I interferon (IFN)-dependent immune responses after transfection of swine and bovine cells with transcripts corresponding to the FMDV 3´ non-coding region (3´NCR). Induction of IFN-ß and Mx1expression, concomitantly with antiviral activity and IRF3 activation was observed in bovine MDBK cells transfected with the 3´NCR. Our results link the stimulation of the innate immune response observed in 3´NCR-transfected cells to the intracellular type I IFN signaling pathway and suggest the potential use of these molecules for antiviral strategies in cattle.