Basic Study and Clinical Implications of Left Ventricular False Tendon. Is it Associated With Innocent Murmur in Children or Heart Disease?

Introducción y objetivos: El falso tendón del ventrículo izquierdo es una estructura descrita anatómicamente por Turner. Se desconoce su función dentro de la fisiología cardiaca. Se ha postulado, sin alcanzar consenso, su relación con diversas alteraciones eléctricas funcionales. El objetivo es conocer cuando aparece, su prevalencia, su composición histológica y su asociación con el soplo inocente infantil o con enfermedad cardiaca. Métodos: La investigación básica se realizó por la disección anatómica en cadáveres de corazones humanos adultos para describir el falso tendón y su histología. La investigación clínica se realizó en población pediátrica mediante ecocardiografía y se analizó su relación con cardiopatía, el soplo inocente infantil u otras alteraciones. Prenatalmente se realizaron ecocardiografías fetales a diferentes edades gestacionales. Resultados: La presencia del falso tendón es la norma en la disección cardiaca, y está constituido por fibras de tejido muscular y conectivo. En la población pediátrica, la presencia ecocardiografía del falso tendón fue del 83%, y solo mostró relación estadísticamente significativa con el soplo inocente infantil y una menor aceleración de la aorta. Por ecocardiografía fetal, se objetivó su presencia desde al menos la semana 20 de gestación . Conclusiones: El falso tendón del ventrículo izquierdo es una normalidad clínica visible por ecocardiografía fetal ya desde la semana 20, con presencia hasta la edad adulta sin relación con enfermedad, únicamente con la presencia de soplo inocente en edad pediátrica; queda por determinar si es la causa del soplo y si es su ausencia o anomalías estructurales lo que se relaciona con enfermedad.Introduction and objectives: Left ventricular false tendon is a structure of unknown function in cardiac physiology that was first described anatomically by Turner. This condition may be related to various electrical or functional abnormalities, but no consensus has ever been reached. The purpose of this study was to determine the time of appearance, prevalence and histologic composition of false tendon, as well as its association with innocent murmur in children and with heart disease. Methods: The basic research was performed by anatomic dissection of hearts from adult human cadavers to describe false tendon and its histology. The clinical research consisted of echocardiographic study in a pediatric population to identify any relationship with heart disease, innocent murmur in children, or other abnormalities. Fetal echocardiography was performed prenatally at different gestational ages. Results: False tendon was a normal finding in cardiac dissection and was composed of muscle and connective tissue fibers. In the pediatric population, false tendon was present in 83% on echocardiography and showed a statistically significant association only with innocent murmur in children and slower aortic acceleration. The presence of false tendon was first observed on fetal echocardiography from week 20 of pregnancy

Relationship between Anthropometric Variables and Muscle Dysmorphia in Gymnasts in the Province of Alicante

Objetivo: Se muestra un estudio novedoso en el que se analiza si las medidas antropométricas pueden ser utilizadas para clasificar la dismorfia muscular (DM), en gimnastas que asisten a sala de musculación. Metodología: Se analizaron gimnastas de varias salas de musculación de Alicante (zona urbana del sureste español), donde se recogieron las medidas de 141 varones de edad comprendida entre 18-45 años, que persiguen el aumento de su masa muscular. Se tuvieron en cuenta el cálculo del IMC (kg/m2), el somatotipo (endomorfia, mesomorfia y ectomorfia) y se han clasificado los posibles casos de dismorfia muscular, mediante la Escala de satisfacción muscular. Resultados: La muestra está constituida por 68 normopeso; 66 sobrepeso y 7 obesos, clasificados como DM en un 25.0% los normopeso, 33.3% sobrepeso y 85.7% los obesos (p=0.004). En el somatotipo, el único componente que presenta diferencias entre no DM y DM es la mesomorfia (p=0.024). Conclusión: La Dismorfia muscular es un concepto claramente psicológico difícilmente diagnosticable mediante medidas antropométricas. Únicamente la mesomorfia, es la medida que aparece incrementada en la DM, pudiendo ser un parámetro de ayuda en el diagnóstico y seguimiento de la DM. Además, el riesgo de padecer DM aumenta con el grado de obesidad.Objective: It shows a new study that examines if the anthropometric measurements can be used to classify the muscle dysmorphia (MD), in gymnasts who attend fitness room. Methodology: Gymnasts were analyzed several weights rooms of Alicante (urban area of southeastern Spain), where the measurements were 141 males aged between 18-45 years, aiming to enhance their muscle mass. We had in mind the calculation of BMI (kg/m2), the somatotype (endomorphy, mesomorphy and ectomorphy) and have been classified potential cases of muscle dysmorphia, using the Muscle appareance satisfaction escale. Results: The sample was composed of 68 normoweight; 66 overweight and 7 obese, classified as MD in a 25.0% the normoweight, 33.3% overweight and 85.7% of the obese (p=0.004 ). On the somatotype, the only component that presents differences between non-MD and MD is mesomorphy (p=0.024). Conclusion: Muscle dysmorphia is a concept clearly difficult psychological diagnosable using anthropometric measures. Mesomorphy is the only measure that is increased in the MD, and may be a parameter to aid in the diagnosis and follow-up to the MD. In addition, the risk of developing MD is increase with the degree of obesity

NLRP3 Inflammasome in Vascular Disease: A Recurrent Villain to Combat Pharmacologically

Despite the great advances in medicine, mortality from cardiovascular diseases keeps on growing. This tendency is not likely to change considering the pandemic proportions of obesity and diabetes. Besides, the global population is more aged as life expectancy increases, and vascular aging plays a key role in the increased risk of vascular disease. In light of recent trials, namely the CANTOS study, showing the enormous potential of anti-inflammatory therapies and in particular those targeted to IL-1β, a change in therapeutical management of cardiovascular diseases is coming about. The NLRP3 inflammasome is a multiprotein complex that assembles to engage the innate immune defense by processing the maturation of pro-inflammatory cytokines IL-1β and IL-18. Substantial evidence has positioned the NLRP3 inflammasome at the center of vascular disease progression, with a particular significance in the context of aging and the low-grade chronic inflammation associated (inflammaging). Therefore, pharmacological blockade of the NLRP3 inflammasome and its end products has arisen as an extremely promising tool to battle vascular disease. In this review, we discuss the mechanisms by which the NLRP3 inflammasome contributes to vascular disease, with particular attention to the consequences of aging, and we enumerate the therapeutic options available to combat this recurrent villainWork revised coming from the manuscript’s co-authors has been supported by funding from Plan Nacional I+D [PID2020-115590RB-100/AEI/ 10.13039/501100011033] to C.P. and C.F.S-F and Talent Advanced Researchers’ Grant from Comunidad Autónoma de Madrid (2019-T1/IND13794) to F.C.; I.V. is supported by an FPU-MECD fellowship (FPU16/02612); L.S. is supported by an FPI-UAM fellowship (SFPI/2020-0053

Molecular and Clinical Implications of Somatostatin Receptor Profile and Somatostatin Analogues Treatment in Oral Cavity Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC) incidence has increased by 50% over the last decade. Unfortunately, surgery and adjuvant radiotherapy and chemotherapy are still the mainstream modality of treatment, underscoring the need for alternative therapies. Somatostatin-analogues (SSA) are efficacious and safe treatments for a variety of tumors, but the presence of somatostatin-receptors (SSTs) and pharmacological effects of SSA on OSCC are poorly known. In this study, we demonstrated that SST2 and SST3 levels were significantly higher in OSCC, compared to adjacent healthy control tissues. SST2 expression was associated with less regional metastasis and a lower recurrence rate. Moreover, SST2 was elevated in OSCC and associated with histopathological good prognosis factors, such as high peritumoral inflammation, smaller depth of invasion, and expansive vs. infiltrative front of tumor invasion. Importantly, treatment with different SSA (octreotide, lanreotide, and pasireotide) significantly reduced cell-proliferation in OSCC primary cell cultures. Altogether, this study demonstrated that SST2 is overexpressed in OSCC vs. healthy tissues and could represent a novel prognostic biomarker, since its expression is associated with tumors that show better prognostic factors and less recurrent rate. Moreover, our data unveil clear antitumoral effects of SSAs on OSCC, opening new avenues to explore their potential as targeting therapy to OSCC

Validity of Virtual Reality Body Exposure to Elicit Fear of Gaining Weight, Body Anxiety and Body-Related Attentional Bias in Patients with Anorexia Nervosa

Fear of gaining weight (FGW), body image disturbances, associated anxiety and body-related attentional bias are the core symptoms of anorexia nervosa (AN) and play critical roles in its development and maintenance. The aim of the current study is to evaluate the usefulness of virtual reality-based body exposure software for the assessment of important body-related cognitive and emotional responses in AN. Thirty female patients with AN, one of them subclinical, and 43 healthy college women, 25 with low body dissatisfaction (BD) and 18 with high BD, owned a virtual body that had their silhouette and body mass index. Full-body illusion (FBI) over the virtual body was induced using both visuo-motor and visuo-tactile stimulation. Once the FBI was induced, the FBI itself, FGW, body anxiety and body-related attentional bias toward weight-related and non-weight-related body areas were assessed. One-way analyses of covariance (ANCOVA), controlling for age, showed that AN patients reported higher FGW, body anxiety and body-related attentional bias than healthy controls. Unexpectedly, patients with AN reported significantly lower FBI levels than healthy participants. Finally, Pearson correlations showed significant relationships between visual analog scales and body-related attentional bias measures, compared to other eating disorder measures. These results provide evidence about the usefulness of virtual reality-based body exposure to elicit FGW and other body-related disturbances in AN patients. Thus, it may be a suitable intervention for reducing these emotional responses and for easing weight recovery

AN-VR-BE. A randomized controlled trial for reducing fear of gaining weight and other eating disorder symptoms in anorexia nervosa through virtual reality-based body exposure

In vivo body exposure therapy is considered an effective and suitable intervention to help patients with anorexia nervosa (AN) reduce their body image disturbances (BIDs). However, these interventions have notable limitations and cannot effectively reproduce certain fears usually found in AN, such as the fear of gaining weight (FGW). The latest developments in virtual reality (VR) technology and embodiment-based procedures could overcome these limitations and allow AN patients to confront their FGW and BIDs. This study aimed to provide further evidence of the efficacy of an enhanced (by means of embodiment) VR-based body exposure therapy for the treatment of AN. Thirty-five AN patients (16 in the experimental group, 19 in the control group) participated in the study. FGW, BIDs, and other body-related and ED measures were assessed before and after the intervention and three months later. The experimental group received treatment as usual (TAU) and five additional sessions of VR-based body exposure therapy, while the control group received only TAU. After the intervention, ED symptoms were clearly reduced in both groups, with most of the changes being more noticeable in the experimental group. Specifically, after the intervention and at follow-up, significant group differences were found in the FGW and BIDs, with the experimental group showing significantly lower values than the control group. The current study provides new insights and encouraging findings in the field of exposure-based therapies in AN. VR technology might improve research and clinical practice in AN by providing new tools to help patients confront their core fears (i.e., food- or weight-related cues) and improve their emotional, cognitive, and behavioral responses to their body image

Canagliflozin: A New Therapeutic Option in Patients That Present Postprandial Hyperinsulinemic Hypoglycemia after Roux-en-Y Gastric Bypass: A Pilot Study

Cirurgia bariàtrica; Teràpia farmacològica; Hipoglucèmia postprandialCirugía bariátrica; Terapia farmacológica; Hipoglucemia posprandialBariatric surgery; Pharmacological therapy; Postprandial hypoglycemiaIntroduction: Roux-en-Y gastric bypass (RYGB) is the most common surgical procedure for morbid obesity. However, it can present serious late complications, like postprandial hyperinsulinemic hypoglycemia (PHH). Recent data suggested an increase in intestinal SGLT-1 after RYGB. However, there is no data on the inhibition of SGLT-1 to prevent PHH in patients with prior RYBG. On this basis, we aimed to evaluate (a) the effect of canagliflozin 300 mg on the response to 100 g glucose overload (oral glucose tolerance test [OGTT]); (b) the pancreatic response after intra-arterial calcium stimulation in the context of PHH after RYGB. Materials and Methods: This is a prospective pilot study including patients (n = 21) with PHH after RYGB, matched by age and gender with healthy controls (n = 5). Basal OGTT and after 2 weeks of daily 300 mg of canagliflozin was performed in all cases. In addition, venous sampling after intra-arterial calcium stimulation of the pancreas was performed in 10 cases. Results: OGTT after canagliflozin showed a significant reduction of plasma glucose levels (minute 30: 161.5 ± 36.22 vs. 215.9 ± 58.11 mg/dL; minute 60: 187.46 ± 65.88 vs. 225.9 ± 85.60 mg/dL, p < 0.01) and insulinemia (minute 30: 95.6 ± 27.31 vs. 216.35 ± 94.86 mg/dL, p = 0.03; minute 60: 120.85 ± 94.86 vs. 342.64 ± 113.32 mIU/L, p < 0.001). At minute 180, a significant reduction (85.7%) of the rate of hypoglycemia was observed after treatment with canagliflozin (p < 0.00001). All cases presented normal pancreatic response after intra-arterial calcium administration. Conclusion: Canagliflozin (300 mg) significantly decreased glucose absorption and prevented PHH after 100 g OGTT in patients with RYGB. Our results suggest that canagliflozin could be a new therapeutic option for patients that present PHH after RYGB.There were no funding sources

Pharmacological Blockade of NLRP3 Inflammasome/IL1β-Positive Loop Mitigates Endothelial Cell Senescence and Dysfunction

The clinical relevance of IL-1β in chronic inflammation underlying atherosclerosis has been reinforced by recent evidence associating pharmacological inhibition of the cytokine with lower cardiovascular risk. Previously, we have demonstrated a direct involvement of IL-1β in endothelial senescence. Therefore, this can be a key mechanism contributing to the sterile inflammatory milieu associated with aging, termed inflammaging. In the present study, we have evaluated whether a positive feedback of IL-1β in the NLRP3 inflammasome via NF-κB could promote human endothelial senescence in vitro and murine endothelial dysfunction in vivo. Our results indicate that the NLRP3 inflammasome is pivotal in mediating the detrimental effects of IL-1β, showing that auto-activation is a crucial feature boosting endothelial cell senescence in vitro, which is paralleled by vascular dysfunction in vivo. Hence, the inhibitor of NLRP3 inflammasome assembly, MCC 950, was able to disrupt the aforementioned positive loop, thus alleviating inflammation, cell senescence and vascular dysfunction. Besides, we explored alternative NLRP3 inflammasome inhibitory agents such as the RAS heptapeptide Ang-(1-7) and the anti-aging protein klotho, both of which demonstrated protective effects in vitro and in vivo. Altogether, our results highlight a fundamental role for the hereby described NLRP3 inflammasome/IL-1β positive feedback loop in stress-induced inflammaging and the associated vascular dysfunction, additionally providing evidence of a potential therapeutic use of MCC 950, Ang-(1-7) and recombinant klotho to block this loop and its deleterious effectsThis work has been supported by funding from 1) Plan Nacional I+D (PID2020-115590RB100/AEI/ 10.13039/501100011033) to C.P. and C.F.S-F; 2) Talent Advanced Researchers' Grant from Comunidad Autónoma de Madrid (2019-T1/IND-13794) to F.C., and 3) FONDECYT 1130300 to G.D.A. P.D. is recipient of a European social fund and Comunidad Autónoma de Madrid fellowship (PEJ-2018-AI/SAL-9955). I.V. is supported by an FPU-MECD fellowship (FPU16/02612

Three-dimensional cardiac fibre disorganization as a novel parameter for ventricular arrhythmia stratification after myocardial infarction

Aims: Myocardial infarction (MI) alters cardiac fibre organization with unknown consequences on ventricular arrhythmia. We used diffusion tensor imaging (DTI) of three-dimensional (3D) cardiac fibres and scar reconstructions to identify the main parameters associated with ventricular arrhythmia inducibility and ventricular tachycardia (VT) features after MI. Methods and results: Twelve pigs with established MI and three controls underwent invasive electrophysiological characterization of ventricular arrhythmia inducibility and VT features. Animal-specific 3D scar and myocardial fibre distribution were obtained from ex vivo high-resolution contrast-enhanced T1 mapping and DTI sequences. Diffusion tensor imaging-derived parameters significantly different between healthy and scarring myocardium, scar volumes, and left ventricular ejection fraction (LVEF) were included for arrhythmia risk stratification and correlation analyses with VT features. Ventricular fibrillation (VF) was the only inducible arrhythmia in 4 out of 12 infarcted pigs and all controls. Ventricular tachycardia was also inducible in the remaining eight pigs during programmed ventricular stimulation. A DTI-based 3D fibre disorganization index (FDI) showed higher disorganization within dense scar regions of VF-only inducible pigs compared with VT inducible animals (FDI: 0.36; 0.36-0.37 vs. 0.32; 0.26-0.33, respectively, P = 0.0485). Ventricular fibrillation induction required lower programmed stimulation aggressiveness in VF-only inducible pigs than VT inducible and control animals. Neither LVEF nor scar volumes differentiated between VF and VT inducible animals. Re-entrant VT circuits were localized within areas of highly disorganized fibres. Moreover, the FDI within heterogeneous scar regions was associated with the median VT cycle length per animal (R2 = 0.5320). Conclusion: The amount of scar-related cardiac fibre disorganization in DTI sequences is a promising approach for ventricular arrhythmia stratification after MI.The CNIC (Madrid, Spain) is supported by the Ministry of Science, Innovation and Universities and the Pro CNIC Foundation. The CNIC and the BSC (Barcelona, Spain) are Severo Ochoa Centers of Excellence (SEV-2015-0505 and SEV-2011-0067, respectively). This study was supported by grants from Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (RD12/0042/0036, CB16/11/00458), Spanish Ministry of Science, Innovation and Universities (SAF2016-80324-R, PI16/02110, and DTS17/00136), and by the European Commission [ERA-CVD Joint Call (JTC2016/APCIN-ISCIII-2016), grant#AC16/00021]. The study was also partially supported by the Fundacion Interhospitalaria para la Investigacion Cardiovascular (FIC, Madrid, Spain), the Spanish Society of Cardiology (Dr. Pedro Zarco award) and the Heart Rhythm section of the Spanish Society of Cardiology (DFR). J.J. is supported by R01 Grant HL122352 from the National Heart Lung and Blood Institute, USA National Institutes of Health. J.A.S. is funded by the CompBioMed project, H2020-EU.1.4.1.3 European Union's Horizon 2020 research and innovation programme, grant#675451. D.G.L. has received financial support through the 'la Caixa' Fellowship Grant for Doctoral Studies, 'la Caixa' Banking Foundation, Barcelona, Spain.S