EValuating the Effect of periopeRaTIve empaGliflOzin on cardiac surgery associated acute kidney injury: rationale and design of the VERTIGO study.

Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a serious complication in patients undergoing cardiac surgery with extracorporeal circulation (ECC) that increases postoperative complications and mortality. CSA-AKI develops due to a combination of patient- and surgery-related risk factors that enhance renal ischemia-reperfusion injury. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) such as empagliflozin reduce renal glucose reabsorption, improving tubulo-glomerular feedback, reducing inflammation and decreasing intraglomerular pressure. Preclinical studies have observed that SGLT2i may provide significant protection against renal ischemia-reperfusion injury due to their effects on inadequate mitochondrial function, reactive oxygen species activity or renal peritubular capillary congestion, all hallmarks of CSA-AKI. The VERTIGO (EValuating the Effect of periopeRaTIve empaGliflOzin) trial is a Phase 3, investigator-initiated, randomized, double-blind, placebo-controlled, multicenter study that aims to explore whether empagliflozin can reduce the incidence of adverse renal outcomes in cardiac surgery patients. Methods: The VERTIGO study (EudraCT: 2021-004938-11) will enroll 608 patients that require elective cardiac surgery with ECC. Patients will be randomly assigned in a 1:1 ratio to receive either empagliflozin 10 mg orally daily or placebo. Study treatment will start 5 days before surgery and will continue during the first 7 days postoperatively. All participants will receive standard care according to local practice guidelines. The primary endpoint of the study will be the proportion of patients that develop major adverse kidney events during the first 90 days after surgery, defined as ≥25% renal function decline, renal replacement therapy initiation or death. Secondary, tertiary and safety endpoints will include rates of AKI during index hospitalization, postoperative complications and observed adverse events. Conclusions: The VERTIGO trial will describe the efficacy and safety of empagliflozin in preventing CSA-AKI. Patient recruitment is expected to start in May 2024.

Transformation of Graphite Recovered from Batteries into Functionalized Graphene-Based Sorbents and Application to Gas Desulfurization.

The recycling and recovery of value-added secondary raw materials such as spent Zn/C batteries is crucial to reduce the environmental impact of wastes and to achieve cost-effective and sustainable processing technologies. The aim of this work is to fabricate reduced graphene oxide (rGO)-based sorbents with a desulfurization capability using recycled graphite from spent Zn/C batteries as raw material. Recycled graphite was obtained from a black mass recovered from the dismantling of spent batteries by a hydrometallurgical process. Graphene oxide (GO) obtained by the Tour's method was comparable to that obtained from pure graphite. rGO-based sorbents were prepared by doping obtained GO with NiO and ZnO precursors by a hydrothermal route with a final annealing step. Recycled graphite along with the obtained GO, intermediate (rGO-NiO-ZnO) and final composites (rGO-NiO-ZnO-400) were characterized by Wavelength Dispersive X-ray Fluorescence (WDXRF) and X-ray diffraction (XRD) that corroborated the removal of metal impurities from the starting material as well as the presence of NiO- and ZnO-doped reduced graphene oxide. The performance of the prepared composites was evaluated by sulfidation tests under different conditions. The results revealed that the proposed rGO-NiO-ZnO composite present a desulfurization capability similar to that of commercial sorbents which constitutes a competitive alternative to syngas cleaning.

Major response of a peritoneal mesothelioma to nivolumab and ipilimumab: a case report, molecular analysis and review of literature.

Malignant peritoneal mesothelioma (MPM) is a rare tumor associated with a poor prognosis and a lack of consensus regarding treatment strategies. While the Checkmate 743 trial demonstrated the superiority of first-line nivolumab and ipilimumab over chemotherapy in malignant pleural mesothelioma (MPlM), few studies have assessed the effectiveness of immunotherapy against MPM, due to its rarity. Here, we report a major and sustained 12-month response in a 74-year-old female patient who received the anti-PD-1 nivolumab and the anti-CTLA4 ipilimumab as first-line therapy for diffuse MPM. PD-L1 was expressed and BAP1 expression was lost, as shown by immunohistochemistry, however the BAP1 gene was not mutated. Our findings suggest a role for ICI in non-resectable diffuse MPM exhibiting PD-L1 overexpression and loss of BAP1 expression, and instill new hope in their treatment. To our knowledge, this is the second reported case of dual immunotherapy used as first-line in MPM with a major clinical response. To investigate the clinical outcome, we conducted additional molecular analyses of the MPM tumor and we reviewed the literature on immunotherapy in MPM to discuss the role of PD-L1 and BAP1.

Effectiveness of Therapeutic Exercise for Children Undergoing Treatment for Cancer: A Systematic Review.

PURPOSE: To evaluate the effectiveness of therapeutic physical exercise (TPE) interventions on the physical functioning, psychosocial well-being, and quality of life (QoL) of children undergoing treatment for cancer. METHOD: Systematic review: databases were searched in April 2023. Selection criteria: children (<18 years old) undergoing treatment for cancer or a malignant neoplasm, randomized controlled trial design, utilization of TPE, and including physical and psychosocial outcomes. Internal validity was measured with Physiotherapy Evidence Database scale. RESULTS: Seven randomized controlled trials were included. Most studies showed that strength, fatigue, and QoL improved after the intervention. Cardiorespiratory capacity through 6-minute walk test and physical activity levels were better in the experimental groups. No changes were noted in other variables. CONCLUSIONS: This review supports the importance of a TPE program during cancer treatment, with the aim of maintaining physical capacities and counteracting physical inactivity.

"Cap polyposis", refractory to drug treatment, including infliximab.

Cap polyposis is a rare disease characterized by the presence of inflammatory polyps with an adherent fibrin sheath ("cap"), in variable number and size, in the rectum and sigmoid. It presents with tenesmus, mucous stools and rectorrhagia. There is currently no standardized treatment, having been treated empirically with aminosalicylates, oral or rectal steroids, metronidazole, H. pylori eradication therapy and infliximab with variable results. In refractory cases, endoscopic resection of polyps may be used and surgery may even be necessary. We present the case of a 36-year-old patient diagnosed in our center with cap polyposis, refractory to both pharmacological and endoscopic treatment, and therefore treatment with infliximab was decided out of indication. The case we present is the fourth case of cap polyposis treated with infliximab available in the current literature and highlights the difficulty of achieving a clinical response with pharmacological treatment, including biologic drugs such as infliximab.

Association of Moderate-to-Vigorous Physical Activity, Sedentary Time, Fat Percentage, and Physical Fitness with Gait Parameters in Women with Fibromyalgia: The Al-Ándalus Project.

Gait impairments have been found in women with fibromyalgia, reducing the physical activity possibilities in this population and leading to a negative correlation with fibromyalgia impact. The aim of this study was to analyze the individual and independent associations of moderate-to-vigorous physical activity (MVPA), sedentary time, fat percentage, and physical fitness with gait parameters in women with fibromyalgia. A total of 84 women with fibromyalgia were included. MVPA and sedentary time were assessed with accelerometry, fat percentage with bioimpedance analysis, and physical fitness with field-based fitness tests. Gait was assessed during a "6 min walk test" and categorized in velocity, cadence, step length, step cycle duration, unipedal stance phase, and bipedal stance phase. Individual relationships were analyzed by partial correlations and independent relationships by linear regressions, adjusting by age and height. MVPA, sedentary time, fat percentage, and physical fitness were correlated with most gait parameters (rpartial between |0.842| and |0.219|; p ≤ 0.05). Physical fitness was independently associated with all gait parameters (ß between |0.346| and |0.761|; p ≤ 0.002). In addition, MVPA was independently associated with velocity and step length (ß = 0.241 and 0.292; both p = 0.004), and fat percentage was associated with bipedal stance phase (ß = 0.242; p = 0.049). Good levels of MVPA, physical fitness, and adequate weight balance are associated with improved gait parameters in women with fibromyalgia.

Effectiveness of Mepolizumab in Patients with Severe Eosinophilic Asthma with/without Nasal Polyposis: A Real-Life Study.

INTRODUCTION: Asthma is one of the most common chronic diseases and affects around 334 million people worldwide. The estimated prevalence of severe asthma is 3-10% of the asthmatic population. Mepolizumab has demonstrated efficacy in reducing exacerbations, oral corticosteroid use, and improving quality of life, asthma control, and lung function in patients with severe eosinophilic asthma (SEA). Our study aimed to check the response to mepolizumab in a series of severe asthma patients regarding exacerbations, oral corticosteroid use, asthma control, quality of life, and lung function and to compare the response between patients with and without nasal polyps. METHOD: This is a retrospective, multicenter study of RE-ASGRAMUR (Register of Severe Asthma of the Region of Murcia) performed in eight hospitals of the Region of Murcia (Spain) under routine clinical practice conditions. We included patients diagnosed with SEA who completed at least 1 year of treatment with mepolizumab. We analyzed clinical characteristics, drug tolerance, and effectiveness: exacerbations, ACT, miniAQLQ, forced expiratory volume in 1 s (FEV1), and use of oral corticosteroids. We also compared the results between patients with and without nasal polyps. RESULTS: The median of exacerbations before treatment was 3 and decreased to 0 after treatment (mean decrease of 77.4%). The median diary oral prednisone intake was 15 mg before treatment and 5 mg after treatment (mean 56% reduction). We have obtained a significant improvement in other variables: ED visits and hospitalizations, asthma control (ACT), quality of life (miniAQLQ), and lung function (FEV1). Thirty-four out of 70 patients (48.57%) fulfilled the criteria of super-responder, and 17 out of 70 (24.29%) had a complete response. More patients in the group with nasal polyps fulfilled the criteria of super-responder and complete response to mepolizumab. CONCLUSIONS: Mepolizumab is a safe and effective treatment for SEA patients, improving exacerbations, oral corticosteroid intake, asthma control, quality of life, and lung function. In patients with associated nasal polyposis, there is a statistically significant higher proportion of super-responders and complete responders.

Validación de la escala de gravedad percibida de la violencia de pareja contra la mujer en población ecuatoriana

Introducción: La violencia de pareja contra la mujer (VPM) es un problema de salud pública a nivel global cuya prevalencia en Ecuador es de las más elevadas de Latinoamérica. La gravedad percibida de la VPM influye en las actitudes públicas hacia la VPM, como la aceptabilidad, el sentido de responsabilidad personal o la disposición a intervenir en casos de VPM. Método: En este estudio se presenta la adaptación de la escala española de gravedad percibida de la VPM (PS-IPVAW) al contexto cultural ecuatoriano, en una muestra de 652 participantes. Resultados: Los resultados mostraron que la escala PS-IPVAW tiene una buena consistencia interna, que sus ítems tienen una baja carga de deseabilidad social, que es invariante entre géneros y que se relaciona con la culpabilidad a la víctima, la aceptabilidad de la VPM y el sexismo hostil. Discusión: La escala PS-IPVAW es un instrumento con suficientes evidencias de fiabilidad y validez para evaluar la gravedad percibida de la VPM en Ecuador y representa un importante aporte para mejorar las estrategias de prevención, intervención y erradicación de este tipo de violencia en el contexto ecuatoriano.

Introduction: Intimate partner violence against women (IPVAW) is a global public health problem whose prevalence in Ecuador is among the highest in Latin America. The perceived severity of IPV influences public attitudes toward IPVAW, such as acceptability, sense of personal responsibility, or willingness to intervene in cases of IPV. Method: This study presents the adaptation of the Spanish scale of perceived severity of IPVAW (PS-IPVAW) to the Ecuadorian cultural context, in a sample of 652 participants. Results: Our results showed that the PS-IPVAW scale has good internal consistency, its items presented low loadings of social desirability, that it is invariant across genders and that it is related to victim blaming, acceptability of IPV and hostile sexism. Discussion: The PS-IPVAW scale showed adequate evidence.

Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial.

BACKGROUND: PD-1 inhibitors combined with chemotherapy have shown efficacy in gastric or gastro-esophageal junction cancer. We compared the efficacy and safety of pembrolizumab plus chemotherapy with placebo plus chemotherapy in participants with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma. METHODS: KEYNOTE-859 is a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial, done at 207 medical centres across 33 countries. Eligible participants were aged 18 years and older with previously untreated histologically or cytologically confirmed locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive pembrolizumab or placebo 200 mg, administered intravenously every 3 weeks for up to 35 cycles. All participants received investigator's choice of fluorouracil (intravenous, 800 mg/m2 per day) administered continuously on days 1-5 of each 3-week cycle plus cisplatin (intravenous, 80 mg/m2) administered on day 1 of each 3-week cycle or capecitabine (oral, 1000 mg/m2) administered twice daily on days 1-14 of each 3-week cycle plus oxaliplatin (intravenous, 130 mg/m2) administered on day 1 of each 3-week cycle. Randomisation was done using a central interactive voice-response system and stratified by geographical region, PD-L1 status, and chemotherapy in permuted block sizes of four. The primary endpoint was overall survival, assessed in the intention-to-treat (ITT) population, and the populations with a PD-L1 combined positive score (CPS) of 1 or higher, and PD-L1 CPS of 10 or higher. Safety was assessed in the as-treated population, which included all randomly assigned participants who received at least one dose of study intervention. Here, we report the results of the interim analysis. This study is registered with ClinicalTrials.gov, NCT03675737, and recruitment is complete. FINDINGS: Between Nov 8, 2018, and June 11, 2021, 1579 (66%) of 2409 screened participants were randomly assigned to receive pembrolizumab plus chemotherapy (pembrolizumab group; n=790) or placebo plus chemotherapy (placebo group; n=789). Most participants were male (527 [67%] of 790 participants in the pembrolizumab plus chemotherapy group; 544 [69%] of 789 participants in the placebo plus chemotherapy group) and White (426 [54%]; 435 [55%]). Median follow-up at the data cutoff was 31·0 months (IQR 23·0-38·3). Median overall survival was longer in the pembrolizumab group than in the placebo group in the ITT population (12·9 months [95% CI 11·9-14·0] vs 11·5 months [10·6-12·1]; hazard ratio [HR] 0·78 [95% CI 0·70-0·87]; p<0·0001), in participants with a PD-L1 CPS of 1 or higher (13·0 months [11·6-14·2] vs 11·4 months [10·5-12·0]; 0·74 [0·65-0·84]; p<0·0001), and in participants with a PD-L1 CPS of 10 or higher (15·7 months [13·8-19·3] vs 11·8 months [10·3-12·7]; 0·65 [0·53-0·79]; p<0·0001). The most common grade 3-5 adverse events of any cause were anaemia (95 [12%] of 785 participants in the pembrolizumab group vs 76 [10%] of 787 participants in the placebo group) and decreased neutrophil count (77 [10%] vs 64 [8%]). Serious treatment-related adverse events occurred in 184 (23%) participants in the pembrolizumab group and 146 (19%) participants in the placebo group. Treatment-related deaths occurred in eight (1%) participants in the pembrolizumab group and 16 (2%) participants in the placebo group. No new safety signals were identified. INTERPRETATION: Participants in the pembrolizumab plus chemotherapy group had a significant and clinically meaningful improvement in overall survival with manageable toxicity compared with participants in the placebo plus chemotherapy group. Therefore, pembrolizumab with chemotherapy might be a first-line treatment option for patients with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma. FUNDING: Merck Sharp and Dohme.

New Approaches to Targeted Therapy in Melanoma.

It was just slightly more than a decade ago when metastatic melanoma carried a dismal prognosis with few, if any, effective therapies. Since then, the evolution of cancer immunotherapy has led to new and effective treatment approaches for melanoma. However, despite these advances, a sizable portion of patients with advanced melanoma have de novo or acquired resistance to immune checkpoint inhibitors. At the same time, therapies (BRAF plus MEK inhibitors) targeting the BRAFV600 mutations found in 40-50% of cutaneous melanomas have also been critical for optimizing management and improving patient outcomes. Even though immunotherapy has been established as the initial therapy in most patients with cutaneous melanoma, subsequent effective therapy is limited to BRAFV600 melanoma. For all other melanoma patients, driver mutations have not been effectively targeted. Numerous efforts are underway to target melanomas with NRAS mutations, NF-1 LOF mutations, and other genetic alterations leading to activation of the MAP kinase pathway. In this era of personalized medicine, we will review the current genetic landscape, molecular classifications, emerging drug targets, and the potential for combination therapies for non-BRAFV600 melanoma.

Effectiveness of a gamified digital intervention based on lifestyle modification (iGAME) in secondary prevention: a protocol for a randomised controlled trial.

INTRODUCTION: Combating physical inactivity and reducing sitting time are one of the principal challenges proposed by public health systems. Gamification has been seen as an innovative, functional and motivating strategy to encourage patients to increase their physical activity (PA) and reduce sedentary lifestyles through behaviour change techniques (BCT). However, the effectiveness of these interventions is not usually studied before their use. The main objective of this study will be to analyse the effectiveness of a gamified mobile application (iGAME) developed in the context of promoting PA and reducing sitting time with the BCT approach, as an intervention of secondary prevention in sedentary patients. METHODS AND ANALYSIS: A randomised clinical trial will be conducted among sedentary patients with one of these conditions: non-specific low back pain, cancer survivors and mild depression. The experimental group will receive a 12-week intervention based on a gamified mobile health application using BCT to promote PA and reduce sedentarism. Participants in the control group will be educated about the benefits of PA. The International Physical Activity Questionnaire will be considered the primary outcome. International Sedentary Assessment Tool, EuroQoL-5D, MEDRISK Instruments and consumption of Health System resources will be evaluated as secondary outcomes. Specific questionnaires will be administered depending on the clinical population. Outcomes will be assessed at baseline, at 6 weeks, at the end of the intervention (12 weeks), at 26 weeks and at 52 weeks. ETHICS AND DISSEMINATION: The study has been approved by the Portal de Ética de la Investigación Biomédica de Andalucía Ethics Committee (RCT-iGAME 24092020). All participants will be informed about the purpose and content of the study and written informed consent will be completed. The results of this study will be published in a peer-reviewed journal and disseminated electronically and in print. TRIAL REGISTRATION NUMBER: NCT04019119.

Risk for recurrence of symptomatic upper-extremity deep vein thrombosis in patients without cancer: Analysis of three RIETE cohorts.

BACKGROUND: The natural history of patients with a pacemaker-related upper-extremity deep vein thrombosis (UEDVT) has not been consistently studied. METHODS: We used the RIETE registry data to compare the outcomes during anticoagulation and after its discontinuation in noncancer patients with symptomatic UEDVT associated with a pacemaker, other catheters, or no catheter. The major outcome was the composite of symptomatic pulmonary embolism or recurrent DVT. RESULTS: As of February 2022, 2578 patients with UEDVT were included: 156 had a pacemaker-related UEDVT, 557 had other catheters, and 1865 had no catheter. During anticoagulation, 61 patients (2.3%) developed recurrent VTE, 38 had major bleeding (1.4%), and 90 died (3.4%). After its discontinuation, 52 patients (4.4%) had recurrent acute venous thromboembolism (VTE) and six had major bleeding (0.5%). On multivariable analysis, there were no differences among subgroups in the rates of VTE recurrences or major bleeding during anticoagulation. After its discontinuation, patients with a pacemaker-related UEDVT had a higher risk for VTE recurrences than those with no catheter (adjusted OR: 4.59; 95% CI: 1.98-10.6). CONCLUSIONS: Patients with pacemaker-related UEDVT are at increased risk for VTE recurrences after discontinuing anticoagulation. If our findings are validated in adequately designed trials, this may justify changes in the current recommendations on the duration of anticoagulation.

Discriminant Model for Insulin Resistance in Type 2 Diabetic Patients.

Introduction: Patients with type 2 diabetes mellitus tend to have insulin resistance, a condition that is evaluated using expensive methods that are not easily accessible in routine clinical practice. Objective: To determine the anthropometric, clinical, and metabolic parameters that allow for the discrimination of type 2 diabetic patients who have insulin resistance from those who do not. Methods: A cross-sectional analytical observational study was carried out in 92 type 2 diabetic patients. A discriminant analysis was applied using the SPSS statistical package to establish the characteristics that differentiate type 2 diabetic patients with insulin resistance from those without it. Results: Most of the variables analyzed in this study have a statistically significant association with the HOMA-IR. However, only HDL-c, LDL-c, glycemia, BMI, and tobacco exposure time allow for the discrimination of type 2 diabetic patients who have insulin resistance from those who do not, considering the interaction between them. According to the absolute value of the structure matrix, the variable that contributes most to the discriminant model is HDL-c (-0.69). Conclusions: The association between HDL-c, LDL-c, glycemia, BMI, and tobacco exposure time allows for the discrimination of type 2 diabetic patients who have insulin resistance from those who do not. This constitutes a simple model that can be used in routine clinical practice.

Characterization of the water bodies of Extremadura (SW Spain).

Extremadura is the region that stores the greatest amount of fresh water in Spain. Such water is mainly used for power generation, irrigation in agriculture, biodiversity conservation, tourism, recreation, and human and livestock consumption. Nevertheless, crucial information on the total number of water bodies and their geometrical characteristics and spatial distribution patterns are still missing. Thus, our main goal was to characterize the Extremenian water bodies geometrically and spatially through different statistical techniques such as kernel density, Moran's index, the Getis-Ord Gi*, and principal component analysis (PCA). Firstly, all existing hydrological information was gathered, and using aerial aircraft imagery and satellite images, each water body (WB) was then carefully collected, checked, and corrected. We have inventoried 100,614 WBs (mean density: 2.45 WB km2), irregularly distributed on the territory. WBs with an area < 0.01 km2 (100 ha) represent 64.5% of the total. A multivariate statistical study was conducted, showing that livestock, aridity of the climate, and topography are the main factors controlling the density of water bodies (WBs) in this area. It can be concluded that monitoring of small bodies is crucial to understand their spatial distribution, since they are spread over areas in which extensive farming and commercial crops such as tobacco strongly influence the way of living of many families.

Longitudinal association of sedentary time and physical activity with pain and quality of life in fibromyalgia.

OBJECTIVE: To analyze changes over time and the predictive value of baseline and changes of sedentary time (ST) and physical activity (PA) on pain, disease impact, and health-related quality of life (HRQoL) at 2- and 5-year follow-up in women with fibromyalgia. METHODS: This is a longitudinal and exploratory study with three time points. A total of 427 women with fibromyalgia (51.4 ± 7.6 years) were followed after 2 (n = 172) and 5 years (n = 185). ST and PA (light and moderate-to-vigorous [MVPA]) were assessed using triaxial accelerometers. Pain, disease impact, and HRQoL were measured using: pressure pain threshold, the pain subscale of the revised fibromyalgia impact questionnaire (FIQR), the bodily pain subscale of the 36-item short-form health survey (SF-36), a visual analog scale (VAS), the FIQR, and the SF-36 physical and mental components. RESULTS: Over 5 years, pressure pain threshold, ST, light PA, and MVPA variables were worsened, while FIQR and SF-36 variables were improved (Cohen's d < 0.1-0.3). Baseline ST or light PA were not associated with future outcomes, whereas greater MVPA at baseline was associated with better SF-36 bodily pain at 5-year follow-up (ß = 0.13). Reducing ST and increasing light PA were associated with better bodily pain (ß = -0.16 and 0.17, respectively) and SF-36 physical component (ß = -0.20 and 0.17, respectively) at 5-year follow-up. Increasing MVPA was associated with less pain (pressure pain threshold, VAS, and FIQR-pain) and better SF-36 physical component at 2- and 5-year follow-up (ß's from -0.20 to 0.21). CONCLUSIONS: Objectively measured variables slightly worsened over years, while for self-reported outcomes there was a trend for improvement. Reductions in ST and increases in light PA and MVPA were associated with better HRQoL at 5-year follow-up, and increases in MVPA were additionally associated with better pain and HRQoL at 2-year follow-up.

Sedentary time is associated with depressive symptoms and state anxiety in women with fibromyalgia. Could physical activity and fitness modify this association? The al-Ándalus project.

PURPOSE: To analyze the associations of total and prolonged sedentary time (ST) with depressive symptoms and state anxiety in women with fibromyalgia and whether these associations are modified by moderate-to-vigorous physical activity (MVPA) and physical fitness. METHODS: This cross-sectional exploratory study included 386 women with fibromyalgia aged 51.2 ± 7.6 years. Total ST, time in prolonged bouts of ST (≥30- and ≥60-min) and MVPA were measured with triaxial accelerometry. Depressive symptoms were assessed with the "Beck Depression Inventory-second edition," state anxiety with the "State-Trait Anxiety Inventory," and physical fitness with the "Senior Fitness Test Battery." RESULTS: Total and prolonged ST were directly associated with depressive symptoms (total: ß = 0.19, ≥30-min bout: ß = 0.15, and ≥60-min bout: ß = 0.12) and odds of severe depressive symptoms (all, p < 0.001). These associations generally remained significant after adjustments for MVPA and physical fitness (all, p < 0.05). Total and prolonged ST were directly associated with state anxiety (total: ß = 0.11, ≥30-min bout: ß = 0.12, and ≥60-min bout: ß = 0.07; all, p < 0.001). These associations were generally independent of MVPA (p < 0.05) but vanished when considering physical fitness (p > 0.05). CONCLUSIONS: Higher levels of total and prolonged ST are associated with greater depressive symptoms and state anxiety in women with fibromyalgia. MVPA did not modify these associations, although physical fitness could play a protective role specially for state anxiety.IMPLICATIONS FOR REHABILITATIONReducing sedentary time and avoiding its accumulation in prolonged periods could potentially reduce depressive symptoms and state anxiety in fibromyalgia.Higher sedentary time is associated with more severe depressive symptoms even in patients who engage in moderate-to-vigorous physical activity.Higher levels of physical fitness could attenuate the negative associations of sedentary time with depressive symptoms and, specially, state anxiety."Sit less, move more and exercise to increase your fitness" could be a positive message for people with fibromyalgia in clinical settings.

Effect of Punicalagin and Ellagic Acid on Human Fibroblasts In Vitro: A Preliminary Evaluation of Their Therapeutic Potential.

BACKGROUND: Pomegranate is a fruit that contains various phenolic compounds, including punicalagin and ellagic acid, which have been attributed to anti-inflammatory, antioxidant, and anticarcinogenic properties, among others. OBJECTIVE: To evaluate the effect of punicalagin and ellagic acid on the viability, migration, cell cycle, and antigenic profile of cultured human fibroblasts (CCD-1064Sk). MTT spectrophotometry was carried out to determine cell viability, cell culture inserts were used for migration trials, and flow cytometry was performed for antigenic profile and cell cycle analyses. Cells were treated with each phenolic compound for 24 h at doses of 10-5 to 10-9 M. RESULTS: Cell viability was always significantly higher in treated versus control cells except for punicalagin at 10-9 M. Doses of punicalagin and ellagic acid in subsequent assays were 10-6 M or 10-7 M, which increased the cell migration capacity and upregulated fibronectin and α-actin expression without altering the cell cycle. CONCLUSIONS: These in vitro findings indicate that punicalagin and ellagic acid promote fibroblast functions that are involved in epithelial tissue healing.