Red blood cell distribution width as a surrogate biomarker of damage and disease activity in patients with systemic lupus erythematosus.

OBJECTIVES: Red blood cell distribution width (RDW) is a measure of variability in mean corpuscular volume. Alterations in RDW can be observed in a variety of human disorders, including inflammatory, cardiovascular, and hepatic or renal diseases. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect virtually any organ in the body. In this work, our objective was to analyse how a complete characterisation of disease characteristics in a large series of patients with SLE is related to RDW values. METHODS: 284 patients with SLE and 181 age- and sex-matched healthy controls were recruited. Complete blood count including RDW was assessed. Multivariable analysis was performed to analyse the relationship between RDW and SLE disease characteristics, including composite scores of disease activity and damage. RESULTS: After multivariable adjustment, RDW was higher in patients with SLE compared to controls (beta coefficient 0.8 [95% confidence interval: 0.3-1] %, p=0.003). Several disease characteristics, such as the presence of extractable nuclear antibodies and antiphospholipid syndrome, and the use of prednisone and azathioprine, were significantly associated with higher levels of RDW after adjustment for confounders. Of note, cumulative disease damage and disease activity scores were associated with higher RDW values after controlling for covariates. CONCLUSIONS: RDW may serve as a surrogate biomarker of accrual disease damage and activity in patients with SLE.

Relationship of Hematological Profiles with the Serum Complement System in Patients with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder identified by hematological abnormalities including anemia, leukopenia, and thrombocytopenia. Complement system disturbance is implicated in the pathogenesis of SLE. In this work, we aim to study how a full assessment of the complement system, which includes the evaluation of its three pathways, relates to blood cell counts in a population of patients with SLE. New-generation functional assays of the classical, alternative, and lectin pathways of the complement system were conducted in 284 patients with SLE. Additionally, serum levels of inactive molecules (C1q, C2, C3, C4, factor D) and activated molecules (C3a), as well as regulators (C1-inhibitor and factor H), were evaluated. Complete blood cell counts were analyzed. Multivariable linear regression analysis was performed to study the relationship of hematological profiles with this full characterization of the complement system. After multivariable adjustments that included age, sex, SLICC-DI (damage), and SLEDAI (activity) scores, as well as the use of aspirin, prednisone, methotrexate, azathioprine, and mycophenolate mofetil, several relationships were observed between the C pathways and the individual products and blood cells profile. Lower values of C1q and C2 were associated with lower hemoglobin levels. Lower leukocyte counts showed significantly lower values of C4, C1 inhibitor, C3, factor D, and alternative pathway functional levels. Neutrophil counts showed significant negative relationships only with the alternative pathway and C1-inh. In the case of lymphocytes, associations were found, especially with functional tests of the classical and alternative pathways, as well as with C2, C4, C3, and C3a. On the contrary, for platelets, significance was only observed, after multivariable adjustment, with lower C2 concentrations. In conclusion, the serum complement system and hematological profile in SLE are independently linked, after adjustment for disease activity and damage. These relationships are basically negative and are predominantly found in lymphocytes.

CTNND1 is involved in germline predisposition to early-onset gastric cancer by affecting cell-to-cell interactions.

BACKGROUND: CDH1 and CTNNA1 remain as the main genes for hereditary gastric cancer. However, they only explain a small fraction of gastric cancer cases with suspected inherited basis. In this study, we aimed to identify new hereditary genes for early-onset gastric cancer patients (EOGC; < 50 years old). METHODS: After germline exome sequencing in 20 EOGC patients and replication of relevant findings by gene-panel sequencing in an independent cohort of 152 patients, CTNND1 stood out as an interesting candidate gene, since its protein product (p120ctn) directly interacts with E-cadherin. We proceeded with functional characterization by generating two knockout CTNND1 cellular models by gene editing and introducing the detected genetic variants using a lentiviral delivery system. We assessed ß-catenin and E-cadherin levels, cell detachment, as well as E-cadherin localization and cell-to-cell interaction by spheroid modeling. RESULTS: Three CTNND1 germline variants [c.28_29delinsCT, p.(Ala10Leu); c.1105C > T, p.(Pro369Ser); c.1537A > G, p.(Asn513Asp)] were identified in our EOGC cohorts. Cells encoding CTNND1 variants displayed altered E-cadherin levels and intercellular interactions. In addition, the p.(Pro369Ser) variant, located in a key region in the E-cadherin/p120ctn binding domain, showed E-cadherin mislocalization. CONCLUSIONS: Defects in CTNND1 could be involved in germline predisposition to gastric cancer by altering E-cadherin and, consequently, cell-to-cell interactions. In the present study, CTNND1 germline variants explained 2% (3/172) of the cases, although further studies in larger external cohorts are needed.

Mean Platelet Volume Is Related to Cumulative Disease Damage in Patients with Systemic Lupus Erythematosus.

Mean platelet volume (MPV), which represents the average platelet size in femtoliters, has emerged as a reliable biomarker in several systemic and chronic disorders. However, its relationship with disease characteristics in large series of patients with systemic lupus erythematosus (SLE) has not been exhaustively studied to date. In the present work, we aimed to analyze how disease characteristics, including disease activity and cumulative damage, relate to MPV in a well-characterized series of SLE patients. In total, 179 patients with SLE and 181 age- and sex-matched healthy controls were recruited. Complete blood counts including MPV were assessed. Linear multivariable analysis was performed to evaluate the relationship between MPV and SLE disease characteristics, including composite scores of disease activity and damage. MPV was significantly lower in patients with SLE compared to controls after multivariable analysis (beta coefficient, -0.7 [95% confidence interval, -1.1 to -0.3)] fL, p < 0.001). Although the SLEDAI disease activity index was not related to MPV, the SLICC score measuring cumulative disease damage was significantly associated with lower MPV values after adjustment for covariates. Elements of the SLICC score that were associated with lower MPV levels were those pertaining to the kidney, peripheral vascular, and musculoskeletal manifestations of the disease. In conclusion, MPV is lower in patients with SLE compared to matched controls. This MPV downregulation is primarily due to the renal, peripheral vascular and musculoskeletal manifestations of the disease. MPV may represent a biomarker of accrual disease damage in SLE.

The complement system is linked to insulin resistance in patients with systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) patients more commonly have insulin resistance (IR) than control subjects. Recent studies have revealed that the complement (C) system is not only a mediator of the immune system but is also related to the pathogenesis of atherosclerosis in the general population. Given that the C alteration is a characteristic of SLE, in the present work we set out to analyse if there is a relationship between the C system and IR in patients with SLE. METHODS: New generation functional assays of the three pathways of the C system were performed in 225 non-diabetic patients with SLE. In addition, the serum levels of inactive (C1q, C2, C3, C4, factor D), activated (C3a) and regulators (C1 inhibitor and factor H) molecules of the C system were evaluated. Insulin and C-peptide serum levels were measured, and insulin resistance and indices of beta cell function were calculated using the homeostatic model assessment (HOMA). Metabolic syndrome criteria fulfillments were applied. Multivariable linear regression analysis was performed to assess the relationship between C system and IR indices and the presence of metabolic syndrome. RESULTS: After adjusting for covariates that included traditional cardiovascular risk factors associated with IR and prednisone, serum C3a and factor H levels were positively related to higher levels of the HOMA2-IR index. Besides, in the multivariable analysis, after adjustment for covariates, serum levels of C1q and C3 associated with a higher odds ratio for the presence of metabolic syndrome. CONCLUSIONS: IR and metabolic syndrome are positively and independently related to higher serum levels of some serum C elements in patients with SLE with a predominant role of the alternative pathway elements.

Blood Composite Scores in Patients with Systemic Lupus Erythematosus.

Complete blood count-derived ratios have been described as inflammatory biomarkers in several diseases. These hematological scores include the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index ([SIRI]; neutrophils × monocytes/lymphocytes). Our aim was to study how these biomarkers are related to disease expression in a large and well-characterized series of patients with systemic lupus erythematosus (SLE). A total of 284 SLE patients and 181 age- and sex-matched healthy controls were recruited. The NLR, MLR, PLR, and SIRI were calculated, and activity (SLEDAI-2K), severity (Katz), and damage index (SLICC-DI) scores were assessed in patients with SLE. Multivariable linear regression analysis was performed to study whether these scores differ between patients and controls and how they are related to clinical and laboratory features of the disease. Crude cell counts of neutrophils, monocytes, lymphocytes, and platelets were lower in SLE patients compared to controls. Despite this, NLR, MLR, and PRL, but not SIRI, were higher in SLE patients than in controls after multivariable analysis. However, the relationship between the different scores and disease characteristics was limited. Only the Katz severity index revealed a significant positive relationship with SIRI, NLR, and MLR after adjustment for covariates. Similarly, alternative complement cascade activation and low C3 were significantly associated with higher NLR, MLR, and PLR. In conclusion, although cytopenias are a common feature of patients with SLE, hematologic composite scores are independently higher in this population compared to controls. However, the relationship of these scores with the characteristics of the disease is scarce, with the relationship with the complement system being the most consistent.

Relationship between Disease Characteristics and Circulating Interleukin 6 in a Well-Characterized Cohort of Patients with Systemic Lupus Erythematosus.

Interleukin-6 (IL-6) is a proinflammatory cytokine that mediates pleiotropic functions in immune responses and inflammatory diseases. The literature lacks studies, with a clinical perspective, on the relationship between IL-6 serum levels and the characteristics of the disease in patients with systemic lupus erythematosus (SLE). In the present work, we aimed to analyze the association between circulating IL-6 and disease manifestations in a well-characterized series of patients with SLE. Serum IL-6 levels and disease activity (SLEDAI-2K), severity (Katz) and damage index (SLICC-DI), complete lipid profile, and subclinical carotid atherosclerosis were evaluated in 284 patients with SLE. In addition, a complete characterization of the complement system was performed in samples from patients with SLE. A multivariate linear regression analysis was carried out to study the relationship between clinical and laboratory characteristics of the disease and IL-6 levels. Age (beta coef. 0.07 [95%CI 0.01-0.1] pg/mL, p = 0.014), C-reactive protein (beta coef. 0.21 [95%CI 0.16-0.25] pg/mL, p < 0.01), and male gender (beta coef. 2 [95%CI 0.3-0.5] pg/mL, p = 0.024), were positively associated with higher IL-6 levels in SLE patients. Most disease characteristics and damage and activity indices did not show significant relationships with IL-6. However, after multivariate analysis, IL-6 was associated with lower serum levels of HDL cholesterol (beta coef. -0.04 [95%CI -0.08-(-0.1)] pg/mL, p = 0.011), and apolipoprotein A1 (beta coef. -0.02 [95%CI -0.04-(-0.001)] pg/mL, p = 0.035). In contrast, the alternative complement cascade, C1inh, and C3a were all positively and independently associated with higher serum levels of IL-6. Moreover, stratification of the Systematic Coronary Risk Assessment 2 (SCORE2) results according to different categories of cardiovascular risk was associated with higher circulating serum IL-6 levels (beta coef. 0.2 [95%CI 0.02-0.4], pg/mL, p = 0.028). In conclusion, in a large series of SLE patients, IL-6 was not associated with disease-related features of SLE, including damage, severity, or activity indices. However, an association was found between serum IL-6 levels and circulating C3a and cardiovascular risk. Our study emphasizes the importance that IL-6 could have in cardiovascular disease and complement system disruption of SLE patients. Therapies targeting IL-6 could have a role in these two clinical manifestations of patients with SLE.

HDL Cholesterol Efflux and the Complement System Are Linked in Systemic Lupus Erythematosus.

Cholesterol efflux capacity (CEC), the ability of high-density lipoprotein (HDL) cholesterol to accept cholesterol from macrophages, has been linked to cardiovascular events. Systemic lupus erythematosus (SLE) is characterized by the consumption of complement (C) proteins and has been associated with an increased risk of cardiovascular disease. CEC is reduced in SLE patients compared to controls. In the present work, our objective was to analyze whether the disruption of C influences CEC in patients with SLE. New-generation functional assays of the three pathways of the C system were performed in 207 patients with SLE. Additionally, serum levels of inactive (C1q, C2, C3, C4, and factor D) and activated (C3a) molecules, and regulators (C1-inhibitor and factor H) of C system were measured. CEC, using an in vitro assay, and lipoprotein serum concentrations were assessed. Multivariable linear regression analysis was performed to assess the relationship between C system and CEC. After full multivariable analysis, the alternative C cascade functional test showed a significant and negative relationship with CEC. This was also the case for C2 and C3, in which the associations were found to be positive and statistically significant, after adjustment for covariates. In conclusion, C system and CEC are interconnected in patients with SLE.

Relationship of Fibroblast Growth Factor 23 Serum Levels with Disease Characteristics in Systemic Lupus Erythematosus Patients.

Fibroblast growth factor 23 (FGF23), a hormone secreted by osteocytes and osteoblasts, is a major regulator of vitamin D and phosphate homeostasis. FGF23 has been associated with the disturbance of mineral homeostasis, and with kidney and cardiovascular diseases. Systemic lupus erythematosus (SLE) is an autoimmune disorder that can affect virtually any organ. In the present work, we set out to analyze the relationship of FGF23 with the expression of SLE, including patterns of activity, damage, and severity. A total of 284 well-characterized patients with SLE were recruited. Activity (SLEDAI), severity (Katz), and damage index (SLICC-DI) scores were determined. The serum levels of FGF23 were also assessed. Multivariable linear regression analysis was performed to study the relationship between disease characteristics and FGF23. FGF23 and 25(OH) vitamin D were negatively correlated. Furthermore, prednisone use was associated with higher circulating FGF23 after an adjustment for confounding factors. SLICC-DI was related to higher serum levels of FGF23 after a multivariable analysis. However, when the SLICC-DI index items and domains were analyzed separately, apart from proteinuria ≥3.5 gm/24 h, only the musculoskeletal domain, encompassing arthritis and osteoporosis, was significantly associated with higher serum levels of FGF23. In conclusion, an association is observed between elevated serum FGF23 levels and disease damage, particularly related to musculoskeletal complications and proteinuria, in patients with SLE.

Relationship between Malondialdehyde Serum Levels and Disease Features in a Full Characterized Series of 284 Patients with Systemic Lupus Erythematosus.

Malondialdehyde (MDA) is a marker of oxidative stress and antioxidant status. Oxidative stress has been observed to be increased in systemic lupus erythematosus (SLE). Some studies have shown that MDA is upregulated in SLE compared to controls. However, the literature lacks reports regarding the relationship of MDA to disease manifestations. This is relevant since SLE is a multisystemic disease which may affect virtually any organ in the body. In this study, we set out to analyze how MDA serum levels are associated with disease expression in a large series of SLE patients who were fully characterized in clinical and laboratory terms. A total of 284 patients with SLE were recruited. Serum levels of MDA, and the activity (SLEDAI), severity (Katz) and damage index (SLICC-DI) scores, full lipid profile, and carotid subclinical atherosclerosis were assessed. In addition, a full characterization of the complement system was performed in SLE patients' samples. Multivariable linear regression analysis was executed to study the relationship between clinical and laboratory disease characteristics and MDA. A statistically significant negative relationship was found between disease duration and MDA. In contrast, the presence of anti-nucleosome antibodies was positively associated with MDA. Regarding the SLICC-DI areas, both the musculoskeletal domain and the cutaneous domain were significantly related to higher serum MDA values. Furthermore, after adjustment for confounding factors, lower levels of the classical complement pathway, which denotes activation, were associated with higher serum levels of MDA. In conclusion, cumulative musculoskeletal and skin damage in SLE patients is associated with superior serum levels of MDA. In addition, activation of the complement system is also related to higher circulating MDA levels.

Aortic Diameters and Calcifications in Former World-Class Cyclists.

PURPOSE: Concerns on whether athletes--particularly older ones--are at an increased risk of pathological aortic dilation exist, and the prevalence of aortic calcifications in these individuals is unknown. We aimed to compare the dimensions, distensibility, and prevalence of calcifications in the thoracic aorta between former male professional cyclists (cases) and sex/age-matched controls. METHODS: We used a retrospective cohort design, where cases were former finishers of at least one Grand Tour (Tour de France, Giro d' Italia or Vuelta a España) and controls were untrained individuals with no previous sports history and free of cardiovascular risk. All participants underwent magnetic resonance and computer tomography assessments for the measurement of aortic dimensions and calcifications, respectively. RESULTS: Cases showed larger ( P < 0.05) dimensions than controls for aortic annulus, sinus, and arch, as well as for ascending and descending aorta. However, none of the participants presented with pathological aortic dilation (all diameters <40 mm). A slightly higher prevalence of calcifications in the ascending aorta was observed in cases (13% vs 0% in controls, P = 0.020). Subanalyses confirmed that cases who were still competing (masters category, n = 8) had larger aortic diameters ( P < 0.05) and a greater presence of calcifications in the ascending/descending aorta (38% vs 0% for both segments, P = 0.032) than those who had become inactive ( n = 15). No between-group differences were found for aortic distensibility. CONCLUSIONS: Former professional cyclists, particularly those who are still competing after retirement, show enlarged aortic diameters (albeit without exceeding upper limits of normality). Former professional cyclists also showed a slightly higher prevalence of calcifications in the ascending aorta than controls, although aortic distensibility was not compromised. The clinical relevance of these findings should be the subject of future studies.

Full characterization of the three pathways of the complement system in patients with systemic lupus erythematosus.

Background: To date a complete characterization of the components of the complement (C) pathways (CLassical, LEctin and ALternative) in patients with systemic lupus erythematosus (SLE) has not been performed. We aimed to assess the function of these three C cascades through functional assays and the measurement of individual C proteins. We then studied how they relate to clinical characteristics. Methods: New generation functional assays of the three pathways of the C system were assessed in 284 patients with SLE. Linear regression analysis was performed to study the relationship between the activity, severity, and damage of the disease and C system. Results: Lower values of the functional tests AL and LE were more frequent than those of the CL pathway. Clinical activity was not related to inferior values of C routes functional assays. The presence of increased DNA binding was negatively linked to all three C pathways and products, except for C1-inh and C3a which were positively related. Disease damage revealed a consistent positive, rather than a negative, relationship with pathways and C elements. Anti-ribosomes and anti-nucleosomes were the autoantibodies that showed a greater relationship with C activation, mainly due to the LE and CL pathways. Regarding antiphospholipid antibodies, the most related with C activation were IgG anti-ß2GP, predominantly involving the AL pathway. Conclusion: Not only the CL route, but also the AL and LE are related to SLE features. C expression patterns are linked to disease profiles. While accrual damage was associated with higher functional tests of C pathways, anti-DNA, anti-ribosomes and anti-nucleosomes antibodies, were the ones that showed a higher relationship with C activation, mainly due to the LE and CL pathways.

Transforming growth factor beta 1 is associated with subclinical carotid atherosclerosis in patients with systemic lupus erythematosus.

BACKGROUND: Transforming growth factor beta (TGF-ß1) is a multifunctional cytokine that has anti-inflammatory and immunosuppressive effects. TGF-ß1 has been linked to cardiovascular disease in the general population. The immunosuppressive effect of TGF-ß1 is believed to be dysregulated in patients with systemic lupus erythematosus (SLE). In the present work, we aimed to study the relationship of serum levels of TGF-ß1 with subclinical carotid atherosclerosis in patients with SLE. METHODS: The study included 284 patients with SLE. Serum levels of TGF-ß1 and subclinical carotid atherosclerosis (by carotid ultrasonography) were evaluated. In addition, the complete lipid profile and insulin resistance were analyzed. Multivariable linear and logistic regression analysis was performed to establish the relationship of TGF-ß1 with carotid subclinical atherosclerosis adjusting for traditional cardiovascular risk factors that included lipid profile and insulin resistance. RESULTS: Circulating TGF-ß1 was positively and significantly associated with higher levels of LDL:HDL cholesterol ratio and atherogenic index. TGF-ß1 was also associated with significantly lower levels of HDL cholesterol and apolipoprotein A1. Remarkably, TGF-ß1 was associated with the presence of carotid plaque not only after adjustment for demographics (age, sex, body mass index, diabetes, hypertension, and aspirin use) but also after adjustment for relationships of TGF-ß1 with lipid profile molecules, insulin resistance, and SLEDAI disease score (odds ratio 1.14 [95% confidence interval 1.003-1.30], p = 0.045). CONCLUSION: TGF-ß1 serum levels are positively and independently associated with the presence of subclinical atherosclerosis disease in patients with SLE.

Awake and Sleep Bruxism Prevalence and Their Associated Psychological Factors in First-Year University Students: A Pre-Mid-Post COVID-19 Pandemic Comparison.

There is a broad consensus accepting that psychological variables such as stress, anxiety, or depression play an important role in bruxism. The COVID-19 pandemic has led to an increase in stress, anxiety, and depression levels. The purpose of this study was to evaluate the impact of the COVID-19 pandemic on possible awake and sleep bruxism prevalence and on the psychological factors associated with bruxism, comparing pre-pandemic, pandemic/lockdown, and post-pandemic samples of first-year students. A total of 274 dentistry students from the Complutense University of Madrid participated in the study: 92 from 2018/2019 (pre-pandemic), 90 from 2020/2021 (pandemic), and 92 students from 2021/2022 (post-pandemic) academic years. The participants filled out a thorough battery of validated questionnaires evaluating bruxism and different psychological characteristics, such as anxiety, depression, somatization, personality, and stress coping styles. While sleep bruxism prevalence was significantly higher for the pandemic group, awake bruxism was smaller in comparison to pre-pandemic and post-pandemic groups. The post-pandemic group also presented higher levels of neuroticism and agreeableness personality traits, and positive reappraisal than the pre-pandemic group, with the pandemic group somewhere in between. Additionally, both the pandemic and post-pandemic group showed higher levels of depression and acceptance/resignation coping styles than the pre-pandemic group. Thus, among the three groups of students, the post-pandemic group was the one that showed a larger effect of the pandemic situation in their psychological variables, presenting higher levels of anxiety (state and trait), depression, acceptation/resignation coping style, higher neuroticism (emotional instability trait), and lower agreeableness trait. Nonetheless, the increase of positive reappraisal in the post-pandemic group (an adaptive coping stress style) might be also a sign of recovery. The higher sleep bruxism for the pandemic group might be related to the pandemic situation and lockdown, passively suffered, possibly promoting feelings of impotency, increased levels of depression and acceptance/resignation (normally considered a passive/maladaptive coping style), while acute stressful situations derived from daily personal social interactions might have increased anxiety levels and induced higher levels of awake bruxism observed in both the pre-pandemic and post-pandemic groups. However, further research, including larger and more representative samples, is needed to confirm this possible relationship.

Antitumor effects of lactate transport inhibition on esophageal adenocarcinoma cells

As a consequence of altered glucose metabolism, cancer cell intake is increased, producing large amounts of lactate which is pumped out the cytosol by monocarboxylate transporters (MCTs). MCT 1 and MCT4 are frequently overexpressed in tumors, and recently, MCT inhibition has been reported to exert antineoplastic effects. In the present study, MCT1 and MCT4 levels were assessed in esophageal adenocarcinoma (EAC) cells and the effects of the MCT-1 selective inhibitor AZD3965, hypoxia, and a glucose overload were evaluated in vitro. Two EAC cell lines (OE33 and OACM5.1C) were treated with AZD3965 (10–100 nM) under different conditions (normoxia/hypoxia) and also different glucose concentrations, and parameters of cytotoxicity, oxidative stress, intracellular pH (pHi), and lactate levels were evaluated. MCT1 was present in both cell lines whereas MCT4 was expressed in OE33 cells and only in a small proportion of OACM5.1C cells. Glucose addition did not have any effect on apoptosis nor cell proliferation. AZD3965 increased apoptosis and reduced proliferation of OACM5.1C cells, effects which were abrogated when cells were growing in hypoxia. MCT1 inhibition increased intracellular lactate levels in all the cells evaluated, but this increase was higher in cells expressing only MCT1 and did not affect oxidative stress. AZD3965 induced a decrease in pHi of cells displaying low levels of MCT4 and also increased the sodium/hydrogen exchanger 1 (NHE-1) expression on these cells. These data provide in vitro evidence supporting the potential of MCT inhibitors as novel antineoplastic drugs for EAC and highlight the importance of achieving a complete MCT inhibition. (AU)

Psychological and Behavioral Factors Involved in Temporomandibular Myalgia and Migraine: Common but Differentiated Profiles.

BACKGROUND: Many studies have revealed high comorbidity and a clear association between temporomandibular disorders (TMD) and migraine. Furthermore, evidence points out that common psychological and behavioral factors might be related to the observed TMD and migraine association. However, this association and the underlying psychological factors are poorly understood. OBJECTIVE: The main goal of this study was to describe the psychological and behavioral factors involved in TMD myalgia and migraine. METHODS: A sample of 142 participants were recruited to form 4 groups: migraine patients (ICHD-III criteria), painful-TMD patients (Myalgia DC/TMD criteria), patients suffering from both pathologies according to the same criteria, and control patients. After a dental and neurological examination, the patients filled several psychological questionnaires validated for the Spanish population to assess anxiety (STAI), depression (DEP), stress coping (CRI), and somatic, anxiety, and depression symptoms (BSI-18). RESULTS: The TMD myalgia patients, in general, showed a state of elevated anxiety, somatization, and reduced coping strategies, while the patients with migraine presented greater anxiety symptoms, depression (dysthymia trait and state), and somatization. CONCLUSIONS: According to the data of the present study, situational anxiety (transient emotional state), together with the lack of coping strategies, could be more associated with TMD myalgia, while anxiety, as a more stable and long-lasting emotional state, together with depression, might be more related to migraine. Further longitudinal studies are needed to unravel whether these differentiated profiles are a consequence or possible risk factors for migraine and TMD.

Antitumor effects of lactate transport inhibition on esophageal adenocarcinoma cells.

As a consequence of altered glucose metabolism, cancer cell intake is increased, producing large amounts of lactate which is pumped out the cytosol by monocarboxylate transporters (MCTs). MCT 1 and MCT4 are frequently overexpressed in tumors, and recently, MCT inhibition has been reported to exert antineoplastic effects. In the present study, MCT1 and MCT4 levels were assessed in esophageal adenocarcinoma (EAC) cells and the effects of the MCT-1 selective inhibitor AZD3965, hypoxia, and a glucose overload were evaluated in vitro. Two EAC cell lines (OE33 and OACM5.1C) were treated with AZD3965 (10-100 nM) under different conditions (normoxia/hypoxia) and also different glucose concentrations, and parameters of cytotoxicity, oxidative stress, intracellular pH (pHi), and lactate levels were evaluated. MCT1 was present in both cell lines whereas MCT4 was expressed in OE33 cells and only in a small proportion of OACM5.1C cells. Glucose addition did not have any effect on apoptosis nor cell proliferation. AZD3965 increased apoptosis and reduced proliferation of OACM5.1C cells, effects which were abrogated when cells were growing in hypoxia. MCT1 inhibition increased intracellular lactate levels in all the cells evaluated, but this increase was higher in cells expressing only MCT1 and did not affect oxidative stress. AZD3965 induced a decrease in pHi of cells displaying low levels of MCT4 and also increased the sodium/hydrogen exchanger 1 (NHE-1) expression on these cells. These data provide in vitro evidence supporting the potential of MCT inhibitors as novel antineoplastic drugs for EAC and highlight the importance of achieving a complete MCT inhibition.

Myocardial Fibrosis and Coronary Calcifications Caused by Endurance Exercise? Insights from Former Professional Cyclists.

PURPOSE: This study aimed to compare the prevalence of myocardial fibrosis and coronary calcification in individuals who have performed very high levels of strenuous endurance exercise (SEE; former male professional cyclists) and sex/age-matched controls. METHODS: We used a retrospective cohort study design, where cases were former finishers of ≥1 Grand Tour (Tour de France, Giro d' Italia or Vuelta a España) and controls were untrained individuals free of cardiovascular risk. All participants underwent cardiac magnetic resonance and cardiac computer tomography in the same center during years 2020-2021 to detect myocardial fibrosis (late gadolinium enhancement) and to quantify coronary calcium, respectively. RESULTS: Twenty-three cases (age, 46 ± 6 yr) and 59 controls (47 ± 7 yr) were studied. Fibrotic patches were evidenced only in the left ventricle, with a higher prevalence in cases (23% vs 2% in controls, P = 0.006). However, fibrotic tissue was nonischemic and of low extension (0.6% ± 0.4% of left ventricle mass), and no significant differences were found between cases and controls for native T1 or T2 values. No between-group differences were found for coronary calcium indicators, including Agatston or density scores. Subanalyses revealed no differences attending to whether cases were still performing regular SEE ( n = 8) or not ( n = 15) after professional retirement. CONCLUSIONS: Although former professional cyclists seemed to show a greater prevalence of myocardial fibrosis, the extension of fibrotic tissue was minimal and no alterations were found in coronary calcification indicators. While keeping in mind the low sample size of the cases' group, our results do not support evidence for major cardiac maladaptations with long-term exposure to SEE, at least in middle-age adults.

Vascular Endothelial Growth Factor and Its Soluble Receptor in Systemic Lupus Erythematosus Patients.

Vascular endothelial growth factor (VEGF) is a major regulator of physiological and pathological angiogenesis. Its soluble receptor (sVEGFR) is a potent VEGF antagonist. Systemic lupus erythematosus (SLE) is an autoimmune disease with a diverse array of clinical manifestations that affect virtually any organ. We aimed to analyze the relationship of VEGF and sVEGFR with SLE disease-related features including disease activity, damage, and severity. Serum levels of VEGF165 isoform and sVEGFR (receptor 1) were assessed in 284 well-characterized patients with SLE. Linear regression analysis was performed to analyze the relationship of disease characteristics with both VEGF and sVEGFR. Patients with a disease damage index (SLICC score) equal to or greater than 1 had significantly elevated serum levels of VEGF and sVEGFR. Regarding disease-specific features, musculoskeletal manifestations were the disease feature most commonly associated with the upregulation of both VEGF and sVEGFR. SLE disease damage is associated with higher levels of VEGF and sVEGFR.