Isogeometric Analysis for Reduced Fluid-Structure Interaction Models in Haemodynamic Applications

Isogeometric analysis (IGA) is a computational methodology recently developed to numerically approximate Partial Differential Equation (PDEs). It is based on the isogeometric paradigm, for which the same basis functions used to represent the geometry are then used to approximate the unknown solution of the PDEs. In the case in which Non-Uniform Rational B-Splines (NURBS) are used as basis functions, their mathematical properties lead to appreciable benefits for the numerical approximation of PDEs, especially for high order PDEs in the standard Galerkin formulation. In this framework, we propose an a priori error estimate, extending existing results limited to second order PDEs. The improvements in both accuracy and efficiency of IGA compared to Finite Element Analysis (FEA), encourage the use of this methodology in the haemodynamic applications. In fact, the simulation of blood flow in arteries requires the numerical approximation of Fluid-Structure Interaction (FSI) problems. In order to account for the deformability of the vessel, the Navier-Stokes equations representing the blood flows, are coupled with structural models describing the mechanical response of the arterial wall. However, the FSI models are complex from both the mathematical and the numerical points of view, leading to high computational costs during the simulations. With the aim of reducing the complexity of the problem and the computational costs of the simulations, reduced FSI models can be considered. A first simplification, based on the assumption of a thin arterial wall structure, consists in considering shell models to describe the mechanical properties of the arterial walls. Moreover, by means of the additional kinematic condition (continuity of velocities) and dynamic condition (balance of contact forces), the structural problem can be rewritten as generalized boundary condition for the fluid problem. This results in a generalized Navier-Stokes problem which can be expressed only in terms of the primitive variables of the fluid equations (velocity and pressure) and in a fixed computational domain. As a consequence, the computational costs of the numerical simulations are significantly reduced. On the other side, the generalized boundary conditions associated to the reduced FSI model could involve high order derivatives, which need to be suitably approximated. With this respect, IGA allows an accurate, straightforward and efficient numerical approximation of the generalized Navier-Stokes equations characterizing the reduced FSI problem. In this work we consider the numerical approximation of reduced FSI models by means of IGA, for which we discuss the numerical results obtained in Haemodynamic applications

Differences between kinematic synergies and muscle synergies during two-digit grasping

International audienceThe large number of mechanical degrees of freedom of the hand is not fully exploited during actual movements such as grasping. Usually, angular movements in various joints tend to be coupled, and EMG activities in different hand muscles tend to be correlated. The occurrence of covariation in the former was termed kinematic synergies, in the latter muscle synergies. This study addresses two questions: (i) Whether kinematic and muscle synergies can simultaneously accommodate for kinematic and kinetic constraints. (ii) If so, whether there is an interrelation between kinematic and muscle synergies. We used a reach-grasp-and-pull paradigm and recorded the hand kinematics as well as eight surface EMGs. Subjects had to either perform a precision grip or side grip and had to modify their grip force in order to displace an object against a low or high load. The analysis was subdivided into three epochs: reach, grasp-and-pull, and static hold. Principal component analysis (PCA, temporal or static) was performed separately for all three epochs, in the kinematic and in the EMG domain. PCA revealed that (i) Kinematic-and muscle-synergies can simultaneously accommodate kinematic (grip type) and kinetic task constraints (load condition). (ii) Upcoming grip and load conditions of the grasp are represented in kinematic-and muscle-synergies already during reach. Phase plane plots of the principal muscle-synergy against the principal kinematic synergy revealed (iii) that the muscle-synergy is linked (correlated, and in phase advance) to the kinematic synergy during reach and during grasp-and-pull. Furthermore (iv), pair-wise correlations of EMGs during hold suggest that muscle-synergies are (in part) implemented by coactivation of muscles through common input. Together, these results suggest that kinematic synergies have (at least in part) their origin not just in muscular activation, but in synergistic muscle activation. In short: kinematic synergies may result from muscle synergies

High frequency of psychopathology in subjects wishing to lose weight: an observational study in Italian subjects.

AbstractObjectiveTo investigate the frequency of psychiatric disorders in subjects wishing to lose weight categorized according to BMI.DesignCross-sectional study.SettingAn academic outpatient clinical nutrition service in Italy.SubjectsA total of 207 subjects (thirty-nine men and 168 women; mean age: 38·7 (sd 14·1) years) consecutively attending the study centre for the first time between January 2003 and December 2006.ResultsIn the entire study group, eighty-three (40 %) subjects had a psychiatric disorder according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision. Eating disorders were the most prevalent psychiatric condition (thirty-six subjects, 17·4 %), followed by mood and anxiety disorders (9·7 % and 8·7 %, respectively). The frequency of psychiatric disorders among different BMI categories was as follows: 75·0 % in underweight, 50·0 % in normal weight, 33·3 % in overweight and 33·3 % in obese subjects.ConclusionsPsychiatric disorders may be frequently found in subjects wishing to lose weight. Our results highlight the importance of psychiatric assessment especially in underweight and normal-weight subjects

Is drop-out from obesity treatment a predictable and preventable event?

BACKGROUND: Attrition is an important but understudied issue that plays a vital role in the successful treatment of obesity. To date, most studies focusing on attrition rates and/or its predictors have been based on pretreatment data routinely collected for other purposes. Our study specifically aims at identifying the predictors of drop-out focusing on empirically or theoretically-based factors. METHODS: We conducted a retrospective observational study in an academic outpatient clinical nutrition service in Pavia, Italy. We examined a total of 98 adult obese patients (36 males, 62 females) who underwent a 6-month dietary behavioral weight-loss treatment at our Center. Pre-treatment and treatment-related variables were collected or calculated from clinical charts in order to discriminate those subjects who completed treatment from those who abandoned it before its completion. Multivariable regression analysis was used to identify the independent predictors of drop-out. RESULTS: The drop-out rates were 21% at 1 month and 57% at 6 months. Compared with completers, noncompleters were significantly younger in terms of age at first dieting attempt (24.0 ± 10.7 vs. 31.3 ± 11.2 years, P = 0.005), had lower diastolic blood pressure (87.8 ± 9.7 vs. 92.7 ± 11.4 mmHg, P = 0.022), had a lower baseline body fat percentage (38.5 ± 6.4 vs. 41.2 ± 4.4% weight, P = 0.015), and had a lower percentage of early weight loss (-1.8 ± 1.8% vs. -3.1 ± 2.1%, P = 0.035). Moreover, noncompleters significantly differed from completers with regard to type of referral (34.1% vs. 53.3% sent by a physician, P = 0.036) and SCL-90 anger-hostility subscale (0.83 ± 0.72 vs. 0.53 ± 0.51, P = 0.022). A multivariable logistic regression analysis including pre-treatment variables showed that body fat percentage (P = 0.030) and SCL-90 anger-hostility subscale (P = 0.021) were independently associated with attrition. In a multivariable model considering both pre-treatment and treatment-related factors, attrition was found to be independently related to the age at first dieting attempt (P = 0.016) and the achievement of early weight loss (P = 0.029). CONCLUSIONS: Our data confirm that psychopathological tracts, early dieting attempts, and a poor initial treatment response are key independent predictors of drop-out from obesity treatment

Oxygen consumption is depressed in patients with lactic acidosis due to biguanide intoxication

INTRODUCTION: Lactic acidosis can develop during biguanide (metformin and phenformin) intoxication, possibly as a consequence of mitochondrial dysfunction. To verify this hypothesis, we investigated whether body oxygen consumption (VO2), that primarily depends on mitochondrial respiration, is depressed in patients with biguanide intoxication. METHODS: Multicentre retrospective analysis of data collected from 24 patients with lactic acidosis (pH 6.93 +/- 0.20; lactate 18 +/- 6 mM at hospital admission) due to metformin (n = 23) or phenformin (n = 1) intoxication. In 11 patients, VO2 was computed as the product of simultaneously recorded arterio-venous difference in O2 content [C(a-v)O2] and cardiac index (CI). In 13 additional cases, C(a-v)O2, but not CI, was available. RESULTS: On day 1, VO2 was markedly depressed (67 +/- 28 ml/min/m2) despite a normal CI (3.4 +/- 1.2 L/min/m2). C(a-v)O2 was abnormally low in both patients either with (2.0 +/- 1.0 ml O2/100 ml) or without (2.5 +/- 1.1 ml O2/100 ml) CI (and VO2) monitoring. Clearance of the accumulated drug was associated with the resolution of lactic acidosis and a parallel increase in VO2 (P < 0.001) and C(a-v)O2 (P < 0.05). Plasma lactate and VO2 were inversely correlated (R2 0.43; P < 0.001, n = 32). CONCLUSIONS: VO2 is abnormally low in patients with lactic acidosis due to biguanide intoxication. This finding is in line with the hypothesis of inhibited mitochondrial respiration and consequent hyperlactatemia

Relationship between p53 and p27 expression following HER2 signaling

HER2, frequently associated with low p27 expression in breast tumors, when activated has been found to upmodulate p53 in tumor cells. The aim of this work was to investigate the role of p53 in the connection between HER2 and p27. Fifty-two breast tumor specimens, characterized for p53 mutations, were analyzed immunohistochemically (IHC) for HER2, p53 and p27 expression. p27, inversely associated with HER2, was found in 29% of tumors with IHC-negative mutated p53 versus 93% of tumors with accumulation of p53 protein and 59% with wild-type p53 (p=0.001), indicating a direct association between p53 and p27 expression. HER2-overexpressing cell lines carrying wild-type or null p53 protein, and treated with heregulin beta1 (HRG), were analyzed for expression and subcellular localization of p53 and p27. In HER2-overexpressing cells stimulated with HRG, p27 protein expression increased in parallel with p53 with no corresponding increase in p27 transcript. No p27 increase was observed in p53-null cells. Transfection with wild-type p53 restored p27 upmodulation in HRG-stimulated cells, indicating a crucial role of p53 in determining p27 upmodulation following HER2 activation. Together, our data demonstrate the crucial role of p53 in determining p27 upmodulation following HER2 activation. This could have implications in the response to Transtuzumab therapy

Characteristics of people living in Italy after a cancer diagnosis in 2010 and projections to 2020

BACKGROUND: Estimates of cancer prevalence are widely based on limited duration, often including patients living after a cancer diagnosis made in the previous 5 years and less frequently on complete prevalence (i.e., including all patients regardless of the time elapsed since diagnosis). This study aims to provide estimates of complete cancer prevalence in Italy by sex, age, and time since diagnosis for all cancers combined, and for selected cancer types. Projections were made up to 2020, overall and by time since diagnosis. METHODS: Data were from 27 Italian population-based cancer registries, covering 32% of the Italian population, able to provide at least 7 years of registration as of December 2009 and follow-up of vital status as of December 2013. The data were used to compute the limited-duration prevalence, in order to estimate the complete prevalence by means of the COMPREV software. RESULTS: In 2010, 2,637,975 persons were estimated to live in Italy after a cancer diagnosis, 1.2 million men and 1.4 million women, or 4.6% of the Italian population. A quarter of male prevalent cases had prostate cancer (n\u2009=\u2009305,044), while 42% of prevalent women had breast cancer (n\u2009=\u2009604,841). More than 1.5 million people (2.7% of Italians) were alive since 5 or more years after diagnosis and 20% since 6515 years. It is projected that, in 2020 in Italy, there will be 3.6 million prevalent cancer cases (+\u200937% vs 2010). The largest 10-year increases are foreseen for prostate (+\u200985%) and for thyroid cancers (+\u200979%), and for long-term survivors diagnosed since 20 or more years (+\u200945%). Among the population aged 6575 years, 22% will have had a previous cancer diagnosis. CONCLUSIONS: The number of persons living after a cancer diagnosis is estimated to rise of approximately 3% per year in Italy. The availability of detailed estimates and projections of the complete prevalence are intended to help the implementation of guidelines aimed to enhance the long-term follow-up of cancer survivors and to contribute their rehabilitation need

Transcranial, noninvasive evaluation of the potential misery perfusion during hyperventilation therapy of traumatic brain injury patients

Hyperventilation (HV) therapy uses vasoconstriction to reduce intracranial pressure (ICP) by reducing cerebral blood volume. However, as HV also lowers cerebral blood flow (CBF), it may provoke misery perfusion (MP) where the decrease in CBF is coupled with increased oxygen extraction fraction (OEF). MP may rapidly lead to the exhaustion of brain energy metabolites, making it vulnerable to ischemia. MP is difficult to detect at the bedside, which is where transcranial hybrid, near-infrared spectroscopies are promising since they noninvasively measure OEF and CBF.Peer ReviewedPostprint (author's final draft

Non-invasive estimation of intracranial pressure by diffuse optics: a proof-of-concept study

Intracranial pressure (ICP) is an important parameter to monitor in several neuropathologies. However, because current clinically accepted methods are invasive, its monitoring is limited to patients in critical conditions. On the other hand, there are other less critical conditions for which ICP monitoring could still be useful; therefore, there is a need to develop non-invasive methods. We propose a new method to estimate ICP based on the analysis of the non-invasive measurement of pulsatile, microvascular cerebral blood flow with diffuse correlation spectroscopy. This is achieved by training a recurrent neural network using only the cerebral blood flow as the input. The method is validated using a 50% split sample method using the data from a proof-of-concept study. The study involved a population of infants (n = 6) with external hydrocephalus (initially diagnosed as benign enlargement of subarachnoid spaces) as well as a population of adults (n = 6) with traumatic brain injury. The algorithm was applied to each cohort individually to obtain a model and an ICP estimate. In both diverse cohorts, the non-invasive estimation of ICP was achieved with an accuracy of 0.9) and good concordance (Lin's concordance correlation coefficient >0.9) in comparison with standard clinical, invasive ICP monitoring. This preliminary work paves the way for further investigations of this tool for the non-invasive, bedside assessment of ICP.This work leading to the results was funded by the European Union’s Horizon 2020 project “BitMap: Brain injury and trauma monitoring using advanced photonics” (No. 675332); Fundació CELLEX Barcelona; Ministerio de Economía y Competitividad /FEDER (PHOTODEMENTIA, DPI2015-64358-C2-1-R); Instituto de Salud Carlos III / FEDER (MEDPHOTAGE, DTS16/00087 and PI18/00468); the “Severo Ochoa” Programme for Centers of Excellence in R&D (SEV-2015-0522); the Obra social “laCaixa” Foundation (LlumMedBcn); Institució CERCA, AGAUR-Generalitat (2017 SGR 1380); LASERLAB-EUROPE IV; KidsBrainIT (ERA-NET NEURON) and la Fundació La Marató de TV3 (201709.31 and 201724.31).Peer ReviewedPostprint (author's final draft

MicroRNA-21/PDCD4 proapoptotic signaling from circulating CD34+ cells to vascular endothelial cells:a potential contributor to adverse cardiovascular outcomes in patients with critical limb ischemia

Dataset related to the article with title: MicroRNA-21/PDCD4 proapoptotic signaling from circulating CD34+ cells to vascular endothelial cells: a potential contributor to adverse cardiovascular outcomes in patients with critical limb ischemia By:Gaia Spinetti1, Elena Sangalli1, Elena Tagliabue1, Davide Maselli1, Ornella Colpani1, David Ferland-McCollough2, Franco Carnelli1, Patrizia Orlando1, Agostino Paccagnella3, Anna Furlan3, Piero Maria Stefani3, Luisa Sambado3, Maria Sambataro3, and Paolo Madeddu2. 1IRCCS MultiMedica, Milan, Italy; 2University of Bristol, Bristol, UK, 3Ca Foncello Hospital, Treviso, Italy. Diabetes Care. 2020 Jul;43(7):1520-1529. doi: 10.2337/dc19-2227. Epub 2020 May 1. Abstract Objective. In patients with type 2 diabetes (T2D) and critical limb ischemia (CLI), migration of circulating CD34+ cells predicted cardiovascular mortality at 18 months post-revascularization. This study aimed to provide long-term validation and mechanistic understanding of the biomarker. Research Design and Methods. The association between CD34+ cell migration and cardiovascular mortality was reassessed at 6 years post-revascularization. In a new series of T2D-CLI and control subjects, immuno-sorted bone marrow (BM)-CD34+ cells were profiled for microRNA expression and assessed for apoptosis and angiogenesis activity. The differentially regulated microRNA-21, and its pro-apoptotic target PDCD4, were titrated to verify their contribution in transferring damaging signals from CD34+ cells to endothelial cells. Results. Multivariable regression analysis confirmed CD34+ cell migration forecasts long-term cardiovascular mortality. CD34+ cells from T2D-CLI patients were more apoptotic and less proangiogenic than controls and featured microRNA-21 downregulation, modulation of several long non-coding RNAs acting as microRNA-21 sponges, and upregulation of the microRNA-21 proapoptotic target PDCD4. Silencing miR-21 in control CD34+ cells phenocopied the T2D-CLI cell behavior. In coculture, T2D-CLI CD34+ cells imprinted naïve endothelial cells, increasing apoptosis, reducing network formation, and modulating the TUG1 sponge/microRNA-21/PDCD4 axis. Silencing PDCD4 or scavenging ROS protected endothelial cells from the negative influence of T2D-CLI CD34+ cells Conclusions. Migration of CD34+ cells predicts long-term cardiovascular mortality in T2D-CLI patients. An altered paracrine signalling conveys anti-angiogenic and pro-apoptotic features from CD34+ cells to the endothelium. This damaging interaction may increase the risk for life-threatening complications