Biology and therapeutic targeting of vascular endothelial growth factor A.

The formation of new blood vessels, called angiogenesis, is an essential pathophysiological process in which several families of regulators have been implicated. Among these, vascular endothelial growth factor A (VEGFA; also known as VEGF) and its two tyrosine kinase receptors, VEGFR1 and VEGFR2, represent a key signalling pathway mediating physiological angiogenesis and are also major therapeutic targets. VEGFA is a member of the gene family that includes VEGFB, VEGFC, VEGFD and placental growth factor (PLGF). Three decades after its initial isolation and cloning, VEGFA is arguably the most extensively investigated signalling system in angiogenesis. Although many mediators of angiogenesis have been identified, including members of the FGF family, angiopoietins, TGFß and sphingosine 1-phosphate, all current FDA-approved anti-angiogenic drugs target the VEGF pathway. Anti-VEGF agents are widely used in oncology and, in combination with chemotherapy or immunotherapy, are now the standard of care in multiple malignancies. Anti-VEGF drugs have also revolutionized the treatment of neovascular eye disorders such as age-related macular degeneration and ischaemic retinal disorders. In this Review, we emphasize the molecular, structural and cellular basis of VEGFA action as well as recent findings illustrating unexpected interactions with other pathways and provocative reports on the role of VEGFA in regenerative medicine. We also discuss clinical and translational aspects of VEGFA. Given the crucial role that VEGFA plays in regulating angiogenesis in health and disease, this molecule is largely the focus of this Review.

Autophagy modulates endothelial junctions to restrain neutrophil diapedesis during inflammation.

The migration of neutrophils from the blood circulation to sites of infection or injury is a key immune response and requires the breaching of endothelial cells (ECs) that line the inner aspect of blood vessels. Unregulated neutrophil transendothelial cell migration (TEM) is pathogenic, but the molecular basis of its physiological termination remains unknown. Here, we demonstrated that ECs of venules in inflamed tissues exhibited a robust autophagic response that was aligned temporally with the peak of neutrophil trafficking and was strictly localized to EC contacts. Genetic ablation of EC autophagy led to excessive neutrophil TEM and uncontrolled leukocyte migration in murine inflammatory models, while pharmacological induction of autophagy suppressed neutrophil infiltration into tissues. Mechanistically, autophagy regulated the remodeling of EC junctions and expression of key EC adhesion molecules, facilitating their intracellular trafficking and degradation. Collectively, we have identified autophagy as a modulator of EC leukocyte trafficking machinery aimed at terminating physiological inflammation.

Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study.

BACKGROUND: The effect of alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, on coronary plaque burden in patients with familial hypercholesterolemia has not been addressed. Our aim was to assess changes in coronary plaque burden and its characteristics after treatment with alirocumab by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of a noninvasive analysis of coronary computed tomographic angiography in asymptomatic subjects with familial hypercholesterolemia receiving optimized and stable treatment with maximum tolerated statin dose with or without ezetimibe. METHODS: This study is a phase IV, open-label, multicenter, single-arm clinical trial to assess changes in coronary plaque burden and its characteristics after 78 weeks of treatment with alirocumab in patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent an initial coronary computed tomographic angiography at baseline and another at 78 weeks. Every patient received 150 mg of alirocumab subcutaneiously every 14 days in addition to high-intensity statin therapy. The main outcome was the change on coronary plaque burden and its characteristics by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of analysis of coronary computed tomographic angiography. RESULTS: The study was completed by 104 patients. The median age was 53.3 (46.2-59.4) years. Of these patients, 54 were women (51.9%). Median low-density lipoprotein cholesterol was 138.9 (117.5-175.3) mg/dL at entry and 45.0 (36.0-65.0) mg/dL at follow-up (P<0.001). Coronary plaque burden changed from 34.6% (32.5%-36.8%) at entry to 30.4% (27.4%-33.4%) at follow-up (P<0.001). A significant change in the characteristics of the coronary atherosclerosis was also found: an increase in the proportion of calcified (+0.3%; P<0.001) and mainly fibrous (+6.2%; P<0.001) plaque, accompanied by a decrease in the percentage of fibro-fatty (-3.9%; P<0.001) and necrotic plaque (-0.6%; P<0.001). CONCLUSIONS: Treatment with alirocumab in addition to high-intensity statin therapy resulted in significant regression of coronary plaque burden and plaque stabilization on coronary computed tomographic angiography over 78 weeks in these groups of patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. ARCHITECT (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) could link and explain ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) results. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05465278.

Preference for Hedonic Goals in Fibromyalgia; Is It Always an Avoidance Mechanism? Looking the Relationship with Pain Acceptance from a Positive Psychology Perspective.

The aim of this study was to analyze the effect of openness to experience on pain acceptance through positive affect (PA) considering the moderating role of preference for mood management goals in women with fibromyalgia (FM). A cross-sectional study (n = 231) was carried out. A simple mediation model and a moderate mediation model were conducted by SPSS macro-PROCESS. Results showed that PA mediated positively the effect of openness to experience on acceptance (B = 0.46, SE = 0.80, t = 5,59; 95% CI = [0.3016, 0.6298], p < .001) and that the contribution of openness to experience to PA varied at different values of mood management goals (medium: - .04; ß = .40, p < .001; high: .95; ß = .61, p<.001). Findings may serve as a foundation for tailored interventions to promote activity through acceptance focusing on PA and mood management goals among women with medium to high level of hedonic goals.

Development and internal validation of a multifactorial risk prediction model for gallbladder cancer in a high-incidence country.

Since 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on prophylactic cholecystectomy for gallstone patients aged 35 to 49 years. The effectiveness of this prevention program has not yet been comprehensively evaluated. We conducted a retrospective study of 473 Chilean GBC patients and 2137 population-based controls to develop and internally validate three GBC risk prediction models. The Baseline Model accounted for gallstones while adjusting for sex and birth year. Enhanced Model I also included the non-genetic risk factors: body mass index, educational level, Mapuche surnames, number of children and family history of GBC. Enhanced Model II further included Mapuche ancestry and the genotype for rs17209837. Multiple Cox regression was applied to assess the predictive performance, quantified by the area under the precision-recall curve (AUC-PRC) and the number of cholecystectomies needed (NCN) to prevent one case of GBC at age 70 years. The AUC-PRC for the Baseline Model (0.44%, 95%CI 0.42-0.46) increased by 0.22 (95%CI 0.15-0.29) when non-genetic factors were included, and by 0.25 (95%CI 0.20-0.30) when incorporating non-genetic and genetic factors. The overall NCN for Chileans with gallstones (115, 95%CI 104-131) decreased to 92 (95%CI 60-128) for Chileans with a higher risk than the median according to Enhanced Model I, and to 80 (95%CI 59-110) according to Enhanced Model II. In conclusion, age, sex and gallstones are strong risk factors for GBC, but consideration of other non-genetic factors and individual genotype data improves risk prediction and may optimize allocation of financial resources and surgical capacity.

Exploring the moderated role of two psychological programs on sexual pleasure from physical symptoms, body image distortion and emotional problems of Hispanic women with breast cancer.

Decreased sexual pleasure is a common problem in women with breast cancer. The aim of this study was to evaluate the effect of psychoeducation vs. acceptance and commitment therapy to improve sexual pleasure according to the predictive role of physical, cognitive and emotional factors. Results of 139 Hispanic women (Mexico and Spain) diagnosed with breast cancer reveal that only the emotional factor of depression predicts decreased sexual pleasure. Although women who participated in the psychoeducation program presented greater physical symptomatology, body image distortions and emotional distress, the results seem to indicate that psychoeducational guidelines are relevant to improve sexual pleasure in those women who manifest higher levels of previous depression. Future research is required to clarify these issues.

Apelin Enhances the Effects of Fusobacterium nucleatum on Periodontal Ligament Cells In Vitro.

This study aimed to explore effects of Fusobacterium nucleatum with or without apelin on periodontal ligament (PDL) cells to better understand pathomechanistic links between periodontitis and obesity. First, the actions of F. nucleatum on COX2, CCL2, and MMP1 expressions were assessed. Subsequently, PDL cells were incubated with F. nucleatum in the presence and absence of apelin to study the modulatory effects of this adipokine on molecules related to inflammation and hard and soft tissue turnover. Regulation of apelin and its receptor (APJ) by F. nucleatum was also studied. F. nucleatum resulted in elevated COX2, CCL2, and MMP1 expressions in a dose- and time-dependent manner. Combination of F. nucleatum and apelin led to the highest (p < 0.05) expression levels of COX2, CCL2, CXCL8, TNF-α, and MMP1 at 48 h. The effects of F. nucleatum and/or apelin on CCL2 and MMP1 were MEK1/2- and partially NF-κB-dependent. The combined effects of F. nucleatum and apelin on CCL2 and MMP1 were also observed at protein level. Moreover, F. nucleatum downregulated (p < 0.05) the apelin and APJ expressions. In conclusion, obesity could contribute to periodontitis through apelin. The local production of apelin/APJ in PDL cells also suggests a role of these molecules in the pathogenesis of periodontitis.

Gallstones, Body Mass Index, C-Reactive Protein, and Gallbladder Cancer: Mendelian Randomization Analysis of Chilean and European Genotype Data.

BACKGROUND AND AIMS: Gallbladder cancer (GBC) is a neglected disease with substantial geographical variability: Chile shows the highest incidence worldwide, while GBC is relatively rare in Europe. Here, we investigate the causal effects of risk factors considered in current GBC prevention programs as well as C-reactive protein (CRP) level as a marker of chronic inflammation. APPROACH AND RESULTS: We applied two-sample Mendelian randomization (MR) using publicly available data and our own data from a retrospective Chilean and a prospective European study. Causality was assessed by inverse variance weighted (IVW), MR-Egger regression, and weighted median estimates complemented with sensitivity analyses on potential heterogeneity and pleiotropy, two-step MR, and mediation analysis. We found evidence for a causal effect of gallstone disease on GBC risk in Chileans (P = 9 × 10-5 ) and Europeans (P = 9 × 10-5 ). A genetically elevated body mass index (BMI) increased GBC risk in Chileans (P = 0.03), while higher CRP concentrations increased GBC risk in Europeans (P = 4.1 × 10-6 ). European results suggest causal effects of BMI on gallstone disease (P = 0.008); public Chilean data were not, however, available to enable assessment of the mediation effects among causal GBC risk factors. CONCLUSIONS: Two risk factors considered in the current Chilean program for GBC prevention are causally linked to GBC risk: gallstones and BMI. For Europeans, BMI showed a causal effect on gallstone risk, which was itself causally linked to GBC risk.

Is Thought Management a Resource for Functioning in Women with Fibromyalgia Irrespective of Pain Levels?

OBJECTIVE: This study aimed to examine the relationship between cognitive factors (cognitive fusion and catastrophizing) and functional limitation experienced by patients with fibromyalgia across different levels of pain severity (i.e., moderation). METHODS: The sample comprised 226 women with fibromyalgia. Their mean age was 56.91 years (standard deviation = 8.94; range = 30 to 78 years). RESULTS: Pain severity, cognitive fusion, and all components of catastrophizing (i.e., rumination, magnification, and helplessness) contributed to greater fibromyalgia impact on functioning in the multivariate analyses (all P < 0.001). A moderation effect was also found in the relationship between cognitive fusion and fibromyalgia impact on functioning (B = -0.12, t = -2.42, P = 0.016, 95% confidence interval: -0.22 to -0.02) and between magnification and fibromyalgia impact (B = -0.37, t = -2.21, P = 0.028, 95% confidence interval: -0.69 to -0.04). This moderation was not observed for rumination and helplessness. CONCLUSIONS: The results suggest that in interventions to improve functioning in people with fibromyalgia, some maladaptive forms of thought management (i.e., cognitive fusion and magnification) preferably should be challenged at milder levels of pain severity. According to our findings, cognitive fusion and magnification might have less room to impact functioning at higher levels of pain severity; therefore, rumination and helplessness, which had comparable associations with functioning irrespective of pain levels, would be preferable targets in psychological interventions in patients with fibromyalgia experiencing more severe pain levels.

Determinants of therapy switch in multiple sclerosis treatment-naïve patients: A real-life study.

BACKGROUND: With many options now available, first therapy choice is challenging in multiple sclerosis (MS) and depends mainly on neurologist and patient preferences. OBJECTIVES: To identify prognostic factors for early switch after first therapy choice. METHODS: Newly diagnosed relapsing-remitting MS patients from 24 Italian centers were included. We evaluated the association of baseline demographics, clinical, and magnetic resonance imaging (MRI) data to the switch probability for lack of efficacy or intolerance/safety with a multivariate Cox analysis and estimated switch rates by competing risks models. RESULTS: We enrolled 3025 patients. The overall switch frequency was 48% after 3 years. Switch risk for lack of efficacy was lower with fingolimod (hazard ratio (HR) = 0.50; p = 0.009), natalizumab (HR = 0.13; p < 0.001), dimethyl-fumarate (HR = 0.60; p = 0.037), teriflunomide (HR = 0.21; p = 0.031) as compared to interferons. Younger age (HR = 0.96; p < 0.001), diagnosis delay (HR = 1.23; p = 0.021), higher baseline Expanded Disability Status Scale (HR = 1.17; p = 0.001), and spinal cord lesions (HR = 1.46; p = 0.001) were independently associated with higher inefficacy switch rates. We found lower switch for intolerance/safety with glatiramer acetate (HR = 0.61; p = 0.001), fingolimod (HR = 0.35; p = 0.002), and dimethyl-fumarate (HR = 0.57; p = 0.022) as compared to interferons, while it increased with natalizumab (HR = 1.43; p = 0.022). Comorbidities were associated with intolerance switch (HR = 1.28; p = 0.047). CONCLUSION: Several factors are associated with higher switch risk in patients starting a first-line therapy and could be integrated in the decision-making process of first treatment choice.

The Influence of Physical Activity and Positive Affect on the Relationship between Pain Severity and Cognitive Performance in Women with Fibromyalgia.

Fibromyalgia, characterized by chronic pain and cognitive impairments, significantly impacts patients' quality of life. Physical exercise has been shown to improve cognitive functions and reduce pain severity. Additionally, positive affect enhances cognitive flexibility and facilitates better adaptation to chronic pain, suggesting that combining physical activity and positive affect could mitigate cognitive deficits in fibromyalgia patients. Objectives: The objective of this work is to explore the relationship between pain severity and cognitive performance through time spent doing moderate physical activity while taking into account the role of positive affect in fibromyalgia. Methods: This prospective study was structured into two phases of evaluation. First, pain severity, positive affect, and time spent performing moderate physical activity were evaluated, and one week later cognitive performance (assessed through the Stroop test) was also evaluated. The final sample consisted of 231 women with fibromyalgia. Moderated mediation analyses were performed using PROCESS. Results: The moderated mediation model showed that the effect of moderate physical activity on the relationship between pain severity and cognitive performance was significant for low levels of positive affect but not for moderate or high levels. That is, the indirect effect of pain intensity on cognitive performance through time spent doing moderate physical activity only has an effect when patients with fibromyalgia present low levels of positive affect. However, there was no significant indirect effect in the simple mediation model. Conclusions: The findings of this study underscore the importance of considering the level of positive affect when examining the impact of moderate physical activity on cognitive performance in women with fibromyalgia.

How to Promote Walking in Women with Fibromyalgia: A Look at Catastrophizing, Goal Conflict, and Avoidance from a Self-Emotional Regulatory Perspective.

The aim of this study was twofold: to explore the concordance between two measures of physical activity (accelerometer and IPAQ) among female fibromyalgia (FM) patients, as well as to examine the impact of psychosocial variables (catastrophism, activity avoidance) on walking among these patients. Helplessness, activity avoidance, and commitment to physical activity were evaluated in 132 FM women. After the first assessment, an accelerometer was placed by a psychologist on each participant for seven consecutive days. Eight days later, accelerometers were collected, and participants were evaluated again using the IPAQ. Two models were tested to analyze mediation and a moderated mediation effect. The mediating role of activity avoidance between helplessness and minutes walked was corroborated regarding the objective measure of walking. The effect of helplessness on minutes walked during a week was mediated by activity avoidance and assessed by accelerometers. Cognitive variables played a contextual role when trying to promote exercise. Activity avoidance must be understood as a key variable in physical activity promotion, specifically in the promotion of walking with the aim to do exercise in individuals with FM.

E-learning module for cytopathology education based on virtual microscopy.

INTRODUCTION: In cytopathology education, Virtual Microscopy e-learning modules (VM-eLM) have achieved remarkable results in the improvement and personalization of learning. However, it remains to be determined whether these modules can significantly contribute to improving the accuracy of cytological diagnosis. The aim of this work was to create a VM-eLM for gynecologic cytopathology education designed to improve screening and interpretation skills in two groups of cytologists: experienced and nonexperienced. MATERIALS AND METHODS: The module was designed in Moodle with both Whole Slide Images and Static Images taken from Papanicolaou smears that were diagnosed as: negative for intraepithelial lesion, low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, squamous cell carcinoma, or adenocarcinoma. We assessed the effectiveness of the module using 1) clinical quality indicators to measure skill development and 2) a user survey. RESULTS: After training, participants significantly improved their cytological screening skills, decreasing their false negative diagnosis by 78% in the non-experienced group and eliminating them entirely in the experienced group. Nonexperienced participants also significantly increased their recognition of low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion by 31% and 50%, respectively. Participants positively evaluated the module, highlighting its novelty, the possibility to train remotely, the immediate feedback and the quality of the Whole Slide Images. CONCLUSIONS: We designed, implemented and tested a VM-eLM for Gynecologic Cytopathology Education that improved cytological screening skills for both non-experienced and experienced cytologists, also increasing the diagnostic accuracy of preinvasive lesions by less experienced cytologists. The module was positively evaluated by participants, who perceived an improvement in their interpretive skills.

Critical Issues for Patients and Caregivers in Neuro-Oncology during the COVID-19 Pandemic: What We Have Learnt from an Observational Study.

OBJECTIVE: The COVID-19 pandemic affected neuro-oncological patients and their caregivers regarding tumor care and emotional functioning, including Quality of Life (QoL). This study aimed to understand how COVID-19 affected their psychological state and the relations between patients and health personnel in neuro-oncology. METHODS: A cross-sectional study was conducted on neuro-oncological patients and their caregivers. RESULTS: A total of 162 patients and 66 caregivers completed the questionnaire. Altogether, 37.5% of patients perceived a greater risk of contracting COVID-19 compared to the general population. On a 0-10 scale, the patients' tumor-related anxiety score was 5.8, and their COVID-19-related score was 4.6. The caregivers reported 7.7 and 5.5, respectively. QoL was described as at least good in 75% of both patients and caregivers; the caregivers' care burden increased in 22.7% of cases during the pandemic, with no correlation with QoL. Future perception often changed, both in patients and caregivers. In 18% of cases, the cancer treatment schedule was changed, either by patient decision or by medical decision. However, 93.5% of patients were satisfied with their overall care. CONCLUSIONS: A considerable proportion of patients and caregivers still perceived the tumor disease as more burdensome than the pandemic, and their future as more uncertain. Such data suggest the need to build a productive alliance between patients and health professionals.

Protocol for volume correlative light X-ray and electron microscopy of endothelial cells in mouse tissue.

Correlative light and electron microscopy (CLEM) greatly facilitate capturing the ultrastructure of spatially and/or temporally rare events. Here, we present a protocol for targeting regions of interests (ROIs) in tissue endothelial cells (ECs) using X-ray micro-computed tomography (µCT). We describe steps for ROI targeting guided by vasculature patterns and positions of EC nuclei visualized by light and X-ray microscopy. The protocol is applicable to thin or translucent tissues that contain defined landmarks visible in both light and X-ray microscopy. For complete details on the use and execution of this protocol, please refer to Reglero-Real et al.1.

Characteristics of Coronary Atherosclerosis Related to Plaque Burden Regression During Treatment With Alirocumab: The ARCHITECT Study.

BACKGROUND: Intensive lipid-lowering therapy may induce coronary atherosclerosis regression. Nevertheless, the factors underlying the effect of lipid-lowering therapy on disease regression remain poorly characterized. Our aim was to determine which characteristics of atherosclerotic plaque are associated with a greater reduction in coronary plaque burden (PB) after treatment with alirocumab in patients with familial hypercholesterolemia. METHODS: The ARCHITECT study (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) is a phase IV, open-label, multicenter, single-arm clinical trial to assess the effect of the treatment with alirocumab for 78 weeks on the coronary atherosclerotic PB and its characteristics in subjects with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent a coronary computed tomographic angiography at baseline and a final one at 78 weeks. Every patient received alirocumab 150 mg subcutaneously every 14 days in addition to high-intensity statin therapy. RESULTS: One hundred and four patients were enrolled. Median age was 53.3 (46.2-59.4) years and 54 were women (51.9%). The global coronary PB changed from 34.6% (32.5%-36.8%) at entry to 30.4% (27.4%-33.4%) at follow-up, which is -4.6% (-7.7% to -1.9%; P<0.001) reduction. A decrease in the percentage of unstable core (fibro-fatty+necrotic plaque; from 14.1 [7.9-22.3] to 8.0 [6.4-10.6]; -6.6%; P<0.001) was found. A greater PB (ß, 0.36 [0.13-0.59]; P=0.002) and a higher proportion of unstable core (ß, 0.15 [0.08-0.22]; P<0.001) were significantly related to PB regression. CONCLUSIONS: Treatment with alirocumab in addition to high-intensity statin therapy might produce a greater PB regression in patients with familial hypercholesterolemia with higher baseline PB and in those with larger unstable core. Further studies are needed to corroborate the hypothesis raised by these results. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05465278.

Pathological Cycle between Pain, Insomnia, and Anxiety in Women with Fibromyalgia and its Association with Disease Impact.

BACKGROUND: Pain, sleep disturbances, and mood disorders are considered common symptoms of fibromyalgia (FM). However, the interactions that are established between them and the implication that this has in the disease are not clear. The main objective of this study is to clarify the relationships established between insomnia, pain intensity and anxiety in women with FM. Additionally, the effect that the indicated pathological cycle between pain, insomnia and anxiety may have on the impact of the disease in these patients is explored. METHODS: A total of 228 women diagnosed with FM participated in this study (mean age = 56.99 years, SD = 10.35). Measurements were conducted at two time points. Initially, the women completed self-report questionnaires about anxiety (The Hospital Anxiety and Depression Scale; HADS), sleep problems (The Insomnia Severity Index; ISI) and pain intensity (Brief Pain Inventory; BPI), and a week later, they answered questions about the impact of fibromyalgia (Fibromyalgia Impact Questionnaire- Revised; FIQ-R). For data analysis, models 4 and 6 of the Macro Process for SPSS were used. RESULTS: Insomnia predicts higher levels of pain, which in turn predicts higher levels of anxiety, which in turn predicts a higher impact of fibromyalgia (B = 2.76, SE = 1.10, 95% CI = [0.79,5.11]). No significant results were found for the other interactions between the variables. CONCLUSIONS: Due to the clinical and scientific relevance of the insomnia-pain-anxiety pathological cycle and given the impact it has on FM, it is especially relevant to develop programs for patients with fibromyalgia based mainly on improving sleep quality.

Sedentary Behavior and Pain after Physical Activity in Women with Fibromyalgia-The Influence of Pain-Avoidance Goals and Catastrophizing.

BACKGROUND: Fibromyalgia is characterized by chronic pain and fatigue that triggers a functional disability caused by the lack of activity. Pain catastrophizing may contribute to avoiding activity with the intention of managing pain levels. Based on the sedentary behavior with fibromyalgia, the present study assessed the preference of pain-avoidance goals and pain catastrophizing as mediator and moderator variables, respectively, that influence pain perception after a 6-min-walking test. METHODS: The sample was composed of 76 women with fibromyalgia (mean age = 55.05, SD = 7.70). Previous sedentary behavior, preference for pain-avoidance goals, and pain catastrophizing were evaluated before starting the walking-test. Subsequently, pain perception was evaluated. RESULTS: A significant moderated-mediation model was found in which pain-avoidance goals mediated the relationship between sedentarism and pain after a walking-test, and pain catastrophizing moderated the relationship between the preference for pain-avoidance goals and pain perception. Specifically, high levels of pain catastrophizing contributed to increased pain perceptions after completing the test (B = 0.570, p = 0.03, CI 95% (0.09, 0.11)]. CONCLUSIONS: The results suggest that motivational interventions can improve the symptoms because their objectives are focused on managing conflict goals. These interventions should focus on catastrophic cognitions considering that pain catastrophizing is deemed to be one of the major inhibitors of physical activity in fibromyalgia.

Does Pain Acceptance Contribute to Improved Functionality through Walking in Women with Fibromyalgia? Looking at Depressive Comorbidity.

In the last decade, research has pointed to physical exercise as an effective treatment in fibromyalgia patients. Some studies have highlighted the role of acceptance and commitment therapy in optimizing the benefits of exercise in patients. However, given the high comorbidity in fibromyalgia, it is necessary to value its possible influence on the effect of certain variables, such as acceptance, on the benefits of treatments, such as physical exercise. Our aim is to test the role of acceptance in the benefits of walking over functional limitation, further assessing whether this model is equally valid, considering depressive symptomatology as an additional differential diagnosis. A cross-sectional study with a convenience sample through contacting Spanish fibromyalgia associations was carried out. A total of 231 women with fibromyalgia (mean age 56.91 years) participated in the study. Data were analyzed with the Process program (Model 4, Model 58, Model 7). The results highlight the role of acceptance as a mediator between walking and functional limitation (B = -1.86, SE = 0.93, 95% CI = [-3.83, -0.15]). This model, when depression is incorporated as a moderator, is significant only in patients without depression, revealing the need for personalized treatments in fibromyalgia, considering their most prevalent comorbidity.