Mandibular advancement devices in the treatment of obstructive sleep apnea syndrome

La apnea del sueño es un trastorno respiratorio, con consecuencias no deseables para la salud, que ocurre durante el sueño cuando se obstruyen o colapsan las vías aéreas superiores. El fenómeno es bien conocido clínicamente, con diagnosis y tratamientos médicos contrastados, pero no existe una metodología sencilla ni los instrumentos y técnicas de análisis necesarias para conocer y valorar cualitativa y cuantitativamente la respuesta física y clínica de una actuación mandibular concreta. En este trabajo se muestra como las técnicas digitales de tratamiento de imágenes, la dinámica de fluidos y la implementación de criterios ingenieriles de diseño importados de otros campos de actividad permiten, a partir de unas imágenes médicas convencionales, establecer una metodología de análisis sencilla útil clínicamente para decidir las actuaciones, de presión o mecánicas, mandibulares más convenientes. La metodología se aplica a un paciente que sufre el síndrome y se estudia el efecto de un dispositivo mandibular (DAM® ), especialmente innovador, premiado científica y empresarialmente en varias ocasiones, que por medio de un avance de la mandíbula, variable y distinto para cada paciente según las necesidades clínicas, provoca una apertura significativa de las vías aéreas superiores.Obstructive sleep apnea syndrome (OSAS) consists in the occurrence of recurrent episodes of airflow limitation during sleep, with undesirable consequences for the health. The phenomenon is well known from a medical point of view (prognosis, diagnosis and treatment), but there is not a methodology or analysis tools for the quantification of the clinical response using Mandibular Advancement Devices (MAD). This paper shows how combining image processing, fluid dynamics and engineering design criteria, imported from other fields, allow to establish a simple analysis method clinically useful to decide the more convenient positioning of the MAD based on the pressure or mechanical movement of the jaw. This methodology is applied to a patient suffering OSAS which the objective to evaluate the changes provoked in the upper-airways due to an innovative mandibular device.Peer Reviewe

A multi-method approach towards understanding the pathophysiology of aortic dissections – the complementary role of in-silico, in-vitro and in-vivo information

Management and follow-up of chronic aortic dissections continues to be a clinical challenge due to progressive aortic dilatation. To predict dilatation, guidelines suggest follow-up of the aortic diameter. However, dilatation is triggered by haemodynamic parameters (pressure and wall shear stresses (WSS)), and geometry of false (FL) and true lumen (TL). We aimed at a better understanding of TL and FL haemodynamics by performing in-silico (CFD) and in-vitro studies on an idealized dissected aorta and compared this to a typical patient. We observed an increase in diastolic pressure and wall stress in the FL and the presence of diastolic retrograde flow. The inflow jet increased WSS at the proximal FL while a large variability in WSS was induced distally, all being risk factors for wall weakening. In-silico, in-vitro and in-vivo findings were very similar and complementary, showing that their combination can help in a more integrated and extensive assessment of aortic dissections, improving understanding of the haemodynamic conditions and related clinical evolution

An N-Terminal Extension to UBA5 Adenylation Domain Boosts UFM1 Activation: Isoform-Specific Differences in Ubiquitin-like Protein Activation

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.Modification of proteins by the ubiquitin-like protein, UFM1, requires activation of UFM1 by the E1-activating enzyme, UBA5. In humans, UBA5 possesses two isoforms, each comprising an adenylation domain, but only one containing an N-terminal extension. Currently, the role of the N-terminal extension in UFM1 activation is not clear. Here we provide structural and biochemical data on UBA5 N-terminal extension to understand its contribution to UFM1 activation. The crystal structures of the UBA5 long isoform bound to ATP with and without UFM1 show that the N-terminus not only is directly involved in ATP binding but also affects how the adenylation domain interacts with ATP. Surprisingly, in the presence of the N-terminus, UBA5 no longer retains the 1:2 ratio of ATP to UBA5, but rather this becomes a 1:1 ratio. Accordingly, the N-terminus significantly increases the affinity of ATP to UBA5. Finally, the N-terminus, although not directly involved in the E2 binding, stimulates transfer of UFM1 from UBA5 to the E2, UFC1.Marie Curie Career Integration GrantIsrael Science FoundationIsraeli Cancer Associatio

Mandibular advancement devices in the treatment of obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome (OSAS) consists in the occurrence of recurrent episodes of airflow limitation during sleep, with undesirable consequences for the health. The phenomenon is well known from a medical point of view (prognosis, diagnosis and treatment), but there is not a methodology or analysis tools for the quantification of the clinical response using Mandibular Advancement Devices (MAD). This paper shows how combining image processing, fluid dynamics and engineering design criteria, imported from other fields, allow to establish a simple analysis method clinically useful to decide the more convenient positioning of the MAD based on the pressure or mechanical movement of the jaw. This methodology is applied to a patient suffering OSAS which the objective to evaluate the changes provoked in the upper-airways due to an innovative mandibular device

Mandibular advancement devices in the treatment of obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome (OSAS) consists in the occurrence of recurrent episodes of airflow limitation during sleep, with undesirable consequences for the health. The phenomenon is well known from a medical point of view (prognosis, diagnosis and treatment), but there is not a methodology or analysis tools for the quantification of the clinical response using Mandibular Advancement Devices (MAD). This paper shows how combining image processing, fluid dynamics and engineering design criteria, imported from other fields, allow to establish a simple analysis method clinically useful to decide the more convenient positioning of the MAD based on the pressure or mechanical movement of the jaw. This methodology is applied to a patient suffering OSAS which the objective to evaluate the changes provoked in the upper-airways due to an innovative mandibular device

Statistical analysis for rupture risk prediction of abdominal aortic aneurysms (AAA) based on its morphometry

The morphometry of the abdominal aortic aneurysms (AAA) it has been recognized as one of the main factors that may predispose its rupture. The variation of the AAA morphometry, over time, induces modifications in hemodynamic behavior which, in turn, alters the spatial and temporal distribution of hemodynamic stress on the aneurismatic wall, establishing a bidirectional process that can influence the rupture phenomenon. In order to evaluate potential correlations between the main geometric parameters characterizing the AAA and hemodynamic stresses, 13 unrupture AAA patient-specific models were created. To AAA geometric characterization, twelve indices based on lumen center line were defined and determined. The computing of temporal and spatial distributions of hemodynamic stresses was conducted through Computational Fluid Dynamics. Statistical techniques were used to assess the relationships between the hemodynamic parameters and the different geometrical indices of the AAA. Regression analyses were conducted to obtain linear predictor models for hemodynamic stresses using the different indices defined in this paper as predictor variables. The statistical analysis confirmed that the length L, the asymmetry and the saccular index significantly influenced the hemodynamic stresses. The results obtained show the potential of the use of statistical techniques in predicting the rupture risk of patient-specific AAA

Modelización computacional cardiaca

Cardiovascular diseases currently have a major social and economic impact, constituting one of the leading causes of mortality and morbidity. Personalized computational models of the heart are demonstrating their usefulness both to help understand the mechanisms underlying cardiac disease, and to optimize their treatment and predict the patient''s response. Within this framework, the Spanish Research Network for Cardiac Computational Modelling (VHeart-SN) has been launched. The general objective of the VHeart-SN network is the development of an integrated, modular and multiscale multiphysical computational model of the heart. This general objective is addressed through the following specific objectives: a) to integrate the different numerical methods and models taking into account the specificity of patients; b) to assist in advancing knowledge of the mechanisms associated with cardiac and vascular diseases; and c) to support the application of different personalized therapies. This article presents the current state of cardiac computational modelling and different scientific works conducted by the members of the network to gain greater understanding of the characteristics and usefulness of these models