Community Health Workers Deliver Mental Health Intervention to Uninsured Latinx in Baltimore: Evaluation and Lessons Learned in a Pilot Program.

BACKGROUND: Implementation of evidence-based interventions to reduce depression among uninsured Latinx patients who are at high risk of depression are rare. OBJECTIVES: Our goal was to evaluate Strong Minds, a language and culturally tailored, evidence-based intervention adapted from cognitive behavioral therapy (CBT) for mild-moderate depression and anxiety, delivered by community health workers (CHWs) in Spanish to uninsured Latinx immigrants. METHODS: As part of the pilot, 35 participants, recruited from a free community primary care clinic, completed Strong Minds. Assessments and poststudy interviews were conducted. Paired t-tests were used to assess change of depressive symptoms at 3 and 6 months. LESSONS LEARNED: CHW delivery of depression care to this population was feasible and among those who completed the program, preliminary evidence of depression outcomes suggests potential benefit. CHWs had specific training and support needs related to mental health care delivery. CONCLUSIONS: Further implementation studies of depression care interventions using CHWs for underserved Latinx is needed.

Coupled mathematical modeling of cisplatin electroporation.

The use of electrochemotherapy (ECT) is a well-established technique to increase the cellular uptake of cytotoxic agents within certain cancer treatment strategies. The study of the mechanisms that take part in this complex process is of high interest to gain a deeper knowledge of it, enabling the improvement of these strategies. In this work, we present a coupled multi-physics electroporation model based on a related previous one, to describe the effect of a set of electric pulses on cisplatin transport across the plasma membrane. The model applies a system of partial differential equations that includes Poisson's equation for the electric field, Nernst-Planck's equation for species transport, Maxwell's tensor and mechanical equilibrium equation for membrane deformation and Smoluchowski's equation for pore creation dynamics. Our numerical results were compared with previous numerical and experimental published data with good qualitative and quantitative agreement. These results indicate that pore aperture is favored at the cell poles by the electric field and mechanical stress forces, giving support to the dominant hypothesis of hydrophilic pore creation as the main mechanism of drug entry during an ECT treatment.

Molecular similarity between the mechanisms of epithelial fusion and fetal wound healing during the closure of the caudal neural tube in mouse embryos.

BACKGROUND: Neural tube (NT) closure is a complex developmental process that takes place in the early stages of embryogenesis and that is a key step in neurulation. In mammals, the process by which the neural plate generates the NT requires organized cell movements and tissue folding, and it terminates with the fusion of the apposed ends of the neural folds. RESULTS: Here we describe how almost identical cellular and molecular machinery is used to fuse the spinal neural folds as that involved in the repair of epithelial injury in the same area of the embryo. For both natural and wound activated closure of caudal neural tissue, hyaluronic acid and platelet-derived growth factor signaling appear to be crucial for the final fusion step. CONCLUSIONS: There seems to be no general wound healing machinery for all tissues but rather, a tissue-specific epithelial fusion machinery that embryos activate when necessary after abnormal epithelial opening.

Enhanced Myeloid Leukocytes in Obese Children and Adolescents at Risk for Metabolic Impairment.

Objective: We aimed to examine if myeloid leukocyte profiles are associated with metabolic impairment in children and adolescents with obesity, and if sex, age, or race influence this relationship. Methods: 282 children ages 8-17 were evaluated. Predictor measures were absolute neutrophil counts (ANC), absolute monocyte count, monocyte subtypes and C reactive protein (CRP). Outcome variables were waist circumference, fasting glucose and insulin, HOMA-IR, HbA1c (%) and lipid profiles. Pearson correlation coefficients were used to determine associations between predictor and outcome variables. Wilcoxon two-sample tests were used to evaluate differences by sex. Results: CRP (p < 0.0001), ANC (p < 0.0018), and classical monocytes (p = 0.05) were significantly higher in children with obesity. CRP, ANC and classical monocytes showed positive correlations with waist circumference, insulin, HOMA-IR and triglycerides. CRP was positively associated with ANC overall (p = 0.05). ANC demonstrated positive correlation with monocytes (p < 0.001). The associations between predictor and outcome variables were influenced by sex, race, and age. Conclusions: CRP and myeloid leukocyte populations, specifically classical monocytes and neutrophils associate with both body composition and metabolic parameters in children with obesity suggesting that these cells may play a critical role in metabolic impairment. Race, gender and age interactions between monocytes and metabolic parameters were significant.

Herramienta para la detección automática de nódulos pulmonares solitarios en series de imágenes de tomografía computarizada multicorte / A tool for automated detection of solitary pulmonary nodules in series of multicut computerized tomography images

Introducción: el nódulo pulmonar solitario es uno de los problemas más frecuentes en la práctica del radiólogo, que constituye un hallazgo incidental habitual en los estudios torácicos realizados durante el ejercicio clínico diario. Objetivo: implementar un sistema de diagnóstico asistido por computadora que facilite la detección del nódulo pulmonar solitario en las series de imágenes de tomografía computarizada multicorte. Métodos: se utilizó Matlab para el desarrollo y evaluación de un conjunto de algoritmos que constituyen elementos necesarios de un sistema de diagnóstico asistido por computadora. En orden: un algoritmo para la extracción de las regiones de interés, algoritmo para la extracción de características y un algoritmo de detección de nódulo pulmonar solitario para el cual se probaron varios clasificadores. La evaluación de los algoritmos fue efectuada en base a las anotaciones realizada por especialistas a la colección de imágenes LIDC-IDRI (Lung Image Database Consortium). Resultados: el método de segmentación empleado para extracción de las regiones de interés permitió generar la adecuada división de las imágenes originales en regiones significativas. El algoritmo utilizado en la detección mostró para el conjunto de prueba además de buena exactitud (de 96,4 por ciento), un buen balance de sensibilidad (91,5 por ciento) para una tasa de 0,84 falsos positivos por imagen. Conclusiones: el trabajo de investigación y la implementación realizada se reflejan en la construcción de una interfaz gráfica en Matlab como prototipo del sistema de diagnóstico asistido por computadora, con el que se puede contribuir a detectar más fácilmente el NPS(AU)

Introduction: solitary pulmonary nodules are one of the most frequent problems in radiographic practice. They are a common incidental finding in chest studies conducted during routine clinical work. Objective: implement a computer-assisted diagnostic system facilitating detection of solitary pulmonary nodules in multicut computerized tomography image series. Methods: Matlab was used to develop and evaluate a set of algorithms constituting necessary components of a computer-assisted diagnostic system. The order was the following: an algorithm to extract regions of interest, another to extract characteristics, and another to detect solitary pulmonary nodules, for which several classifiers were tested. Evaluation of the algorithms was based on notes taken by specialists on the LIDC-IDRI (Lung Image Database Consortium) image collection. Results: the segmentation method used for extraction of regions of interest made it possible to create a suitable division of the original images into significant regions. The algorithm used for detection found that the test set exhibited good accuracy (96.4%), a good sensitivity balance (91.5%), and a 0.84 rate of false positives per image. Conclusions: the research and implementation work done is reflected in the construction of a Matlab graphic interface serving as a prototype for a computer-assisted diagnostic system which may facilitate detection of SPNs.

Outcomes and Resource Use Among Overweight and Obese Children With Sepsis in the Pediatric Intensive Care Unit.

OBJECTIVE: To evaluate the effect of overweight and obesity on outcomes and resource use among patients with sepsis in the pediatric intensive care unit (PICU). DESIGN: Retrospective analysis of clinical characteristics, resource use, and mortality among children 0 to 20 years of age admitted to the C.S. MottChildren's Hospital PICU (University of Michigan) between January 2009 and December 2015, with a diagnostic code for sepsis at admission (based on International Classification of Diseases, Ninth Revision-Clinical Modification codes) and with weight and height measurements at PICU admission. MEASUREMENTS AND MAIN RESULTS: A total of 454 participants met the inclusion criteria. Seventy-six were categorized as underweight (body mass index [BMI] percentile <5th) and were excluded, which left a final sample size of 378 participants. Children with a BMI >5th and <85th percentiles for age were categorized as normal weight and those with a BMI >85th percentile as overweight/obese. After descriptive and bivariate analyses, multivariate regression methods were used to assess the independent effect of obesity status on mortality and the use of PICU technology after adjustment for patient age and illness severity at admission. Of the 378 patients studied, 41.3% were overweight/obese. There was no difference in microbiologic etiology of sepsis (P = .36), median PICU length of stay in days (5.4 vs 5.6; P = .61), or PICU mortality (6.4% vs 7.2%; P = .76) by weight status. The use of specialized PICU technology including extracorporeal membrane oxygenation (odds ratio [OR]: 2.77, 95% confidence interval [CI]:1.13-6.79) and continuous renal replacement therapy (OR: 4.58, 95% CI: 1.16-18.0) was higher among overweight/obese patients, compared with normal weight patients. CONCLUSIONS: Although PICU mortality and length of stay were similar for obese-overweight patients and normal weight critically ill children with sepsis, there was significantly higher use of specialized organ-supportive technology among obese patients, likely indicating higher occurrence of multiple organ dysfunction.

Fascitis plantar. Criterios y experiencias sobre la infiltración con anestésicos locales y corticoesteroides / Plantar fasciitis Criteria and experiences on infiltration with local anesthetics and corticosteroids

Introducción: Dentro del grupo de las enfermedades del sistema osteomioarticular la fascitis plantar (FP) es una de las causas más frecuente de dolor crónico del pie. Objetivo: aportar criterios sobre el empleo de la infiltración de anestésicos locales y corticoesteroides para el tratamiento de la fascitis plantar. Desarrollo: se seleccionaron las infiltraciones de corticoesteroides y de anestésicos locales que se realizan con mayor frecuencia en la práctica clínica, se analizó su efectividad según la evidencia en la literatura internacional y a partir de ahí se contrastaron los resultados encontrados con los criterios y experiencias de los autores de este trabajo. Conclusiones: Las consideraciones realizadas en este estudio apuntan a que el uso de los corticoides mediante infiltraciones en patologías ortopédicas es un medio valioso para mejorar la inflamación de los tejidos y para el alivio de los dolores, tanto cuando se emplea en las articulaciones como en las partes blandas(AU)

Introduction: within the group of diseases of the osteomioarticular system, plantar fasciitis (FP) is one of the most frequent causes of chronic foot pain. Objective: to provide criteria on the use of infiltration of local anesthetics and corticosteroids for the treatment of plantar fasciitis. Development: the infiltrations of corticosteroids and local anesthetics that are performed more frequently in clinical practice were selected, their effectiveness was analyzed according to the evidence in the international literature and from there the results were contrasted with the criteria and experiences of the patients authors of this work. Conclusions: the considerations made in this study suggest that the use of corticosteroids through infiltrations in orthopedic pathologies is a valuable means to improve inflammation of the tissues and for the relief of pain, both when used in the joints and in the joints and soft parts(AU)

Cell membrane electroporation modeling: A multiphysics approach.

Electroporation-based techniques, i.e. techniques based on the perturbation of the cell membrane through the application of electric pulses, are widely used at present in medicine and biotechnology. However, the electric pulse - cell membrane interaction is not yet completely understood neither explicitly formalized. Here we introduce a Multiphysics (MP) model describing electric pulse - cell membrane interaction consisting on the Poisson equation for the electric field, the Nernst-Planck equations for ion transport (protons, hydroxides, sodium or calcium, and chloride), the Maxwell tensor and mechanical equilibrium equation for membrane deformations (with an explicit discretization of the cell membrane), and the Smoluchowski equation for membrane permeabilization. The MP model predicts that during the application of an electric pulse to a spherical cell an elastic deformation of its membrane takes place affecting the induced transmembrane potential, the pore creation dynamics and the ionic transport. Moreover, the coincidence among maximum membrane deformation, maximum pore aperture, and maximum ion uptake is predicted. Such behavior has been corroborated experimentally by previously published results in red blood and CHO cells as well as in supramolecular lipid vesicles.

Microenvironmental influence on microtumour infiltration patterns: 3D-mathematical modelling supported by in vitro studies.

Mathematical modelling approaches have become increasingly abundant in cancer research. Tumour infiltration extent and its spatial organization depend both on the tumour type and stage and on the bio-physicochemical characteristics of the microenvironment. This sets a complex scenario that often requires a multidisciplinary and individually adjusted approach. The ultimate goal of this work is to present an experimental/numerical combined method for the development of a three-dimensional mathematical model with the ability to reproduce the growth and infiltration patterns of a given avascular microtumour in response to different microenvironmental conditions. The model is based on a diffusion-convection reaction equation that considers logistic proliferation, volumetric growth, a rim of proliferative cells at the tumour surface, and invasion with diffusive and convective components. The parameter values of the model were fitted to experimental results while radial velocity and diffusion coefficients were made spatially variable in a case-specific way through the introduction of a shape function and a diffusion-limited-aggregation (DLA)-derived fractal matrix, respectively, according to the infiltration pattern observed. The in vitro model consists of multicellular tumour spheroids (MTSs) of an epithelial mammary tumour cell line (LM3) immersed in a collagen I gel matrix with a standard culture medium ("naive" matrix) or a conditioned medium from adipocytes or preadipocytes ("conditioned" matrix). It was experimentally determined that both adipocyte and preadipocyte conditioned media had the ability to change the MTS infiltration pattern from collective and laminar to an individual and atomized one. Numerical simulations were able to adequately reproduce qualitatively and quantitatively both kinds of infiltration patterns, which were determined by area quantification, analysis of fractal dimensions and lacunarity, and Bland-Altman analysis. These results suggest that the combined approach presented here could be established as a new framework with interesting potential applications at both the basic and clinical levels in the oncology area.

The relationship between adiposity and bone density in U.S. children and adolescents.

OBJECTIVE: In adults, obesity has been associated with several health outcomes including increased bone density. Our objective was to evaluate the association between percent body fat and fat mass with bone mineral density (BMD) in a nationally representative population of children and adolescents. STUDY DESIGN: A total of 8,348 participants 8-18 years of age from the National Health and Nutrition Examination Survey (NHANES) 1999-2006 had whole body DXA scans performed. We conducted linear regressions to examine the relationship between percent body fat and fat mass with outcome variables of total body, pelvic and lumbar spine areal BMD (aBMD), controlling for lean body mass and assessing for gender and race/ethnicity interactions. RESULTS: We found evidence of gender and race/ethnicity interactions with percent body fat and total fat mass for the different BMD areas. Generally, there were decreases in total body aBMD (p<0.001) and lumbar spine aBMD (p<0.001) with increasing percent body fat and total fat mass, with less consistent patterns for pelvic aBMD. CONCLUSION: Our findings of regional differences in the relationship of adiposity to aBMD in children and adolescents with significant interactions by gender and race/ethnicity emphasizes the need for further investigations to understand the impact of adiposity on bone health outcomes.

Mathematical modelling of microtumour infiltration based on in vitro experiments.

The present mathematical models of microtumours consider, in general, volumetric growth and spherical tumour invasion shapes. Nevertheless in many cases, such as in gliomas, a need for more accurate delineation of tumour infiltration areas in a patient-specific manner has arisen. The objective of this study was to build a mathematical model able to describe in a case-specific way as well as to predict in a probabilistic way the growth and the real invasion pattern of multicellular tumour spheroids (in vitro model of an avascular microtumour) immersed in a collagen matrix. The two-dimensional theoretical model was represented by a reaction-convection-diffusion equation that considers logistic proliferation, volumetric growth, a rim with proliferative cells at the tumour surface and invasion with diffusive and convective components. Population parameter values of the model were extracted from the experimental dataset and a shape function that describes the invasion area was derived from each experimental case by image processing. New possible and aleatory shape functions were generated by data mining and Monte Carlo tools by means of a satellite EGARCH model, which were fed with all the shape functions of the dataset. Then the main model is used in two different ways: to reproduce the growth and invasion of a given experimental tumour in a case-specific manner when fed with the corresponding shape function (descriptive simulations) or to generate new possible tumour cases that respond to the general population pattern when fed with an aleatory-generated shape function (predictive simulations). Both types of simulations are in good agreement with empirical data, as it was revealed by area quantification and Bland-Altman analysis. This kind of experimental-numerical interaction has wide application potential in designing new strategies able to predict as much as possible the invasive behaviour of a tumour based on its particular characteristics and microenvironment.

The role of additional pulses in electropermeabilization protocols.

Electropermeabilization (EP) based protocols such as those applied in medicine, food processing or environmental management, are well established and widely used. The applied voltage, as well as tissue electric conductivity, are of utmost importance for assessing final electropermeabilized area and thus EP effectiveness. Experimental results from literature report that, under certain EP protocols, consecutive pulses increase tissue electric conductivity and even the permeabilization amount. Here we introduce a theoretical model that takes into account this effect in the application of an EP-based protocol, and its validation with experimental measurements. The theoretical model describes the electric field distribution by a nonlinear Laplace equation with a variable conductivity coefficient depending on the electric field, the temperature and the quantity of pulses, and the Penne's Bioheat equation for temperature variations. In the experiments, a vegetable tissue model (potato slice) is used for measuring electric currents and tissue electropermeabilized area in different EP protocols. Experimental measurements show that, during sequential pulses and keeping constant the applied voltage, the electric current density and the blackened (electropermeabilized) area increase. This behavior can only be attributed to a rise in the electric conductivity due to a higher number of pulses. Accordingly, we present a theoretical modeling of an EP protocol that predicts correctly the increment in the electric current density observed experimentally during the addition of pulses. The model also demonstrates that the electric current increase is due to a rise in the electric conductivity, in turn induced by temperature and pulse number, with no significant changes in the electric field distribution. The EP model introduced, based on a novel formulation of the electric conductivity, leads to a more realistic description of the EP phenomenon, hopefully providing more accurate predictions of treatment outcomes.

Upper thoracic disc disease (T1-T9) in large-breed dogs.

The purpose of this study was to identify large-breed dogs with intervertebral disc disease (IVDD) in the upper thoracic region (thoracic vertebrae 1-9 [T1-T9]). Medical records of all dogs that were diagnosed with IVDD on MRI between February 2008 and September 2011 were reviewed. Of 723 dogs diagnosed with IVDD based on MRI, 527 (72.9%) were small-breed dogs. There were 21 (10.7%) large-breed dogs with IVDD in the T1-T9 region, whereas no small-breed dogs were identified with lesions in that region. The most common upper thoracic lesion sites were T2-T3 (33.3%) and T4-T5 (25.9%). The majority of dogs with T1-T9 lesions were German shepherd dogs (52.4%). Larger, older dogs were more likely to have T1-T9 lesions and more likely to have multiple regions with IVDD, in particular German shepherd dogs (35.1%). Dogs with T1-T9 IVDD were more likely to have IVDD in another region (66.7%). All large-breed dogs presenting with T3-L3 myelopathy should have diagnostic imaging performed of their entire thoracic and lumbar spine.

Caracterización y costes asociados al perfil del paciente con diabetes tipo 2 en tratamiento con metformina al que se le añade un segundo fármaco antidiabético oral: estudio de base poblacional / Characterization of and costs associated to the profile of patients with type 2 diabetes treated with metformin who are added a second oral antidiabetic drug: a population study

OBJETIVOS: Determinar el cumplimiento, control metabólico, complicaciones y costes sanitarios de los pacientes tratados con metformina que iniciaron un segundo fármaco antidiabético en pacientes con diabetes tipo 2 (DM2).Pacientes y métodos; Diseño observacional-multicéntrico de carácter retrospectivo. Se evaluaron pacientes de edad igual o superior a 30 años, en tratamiento con metformina y que iniciaron un segundo tratamiento antidiabético durante 2008-2009. Se establecieron 4 grupos de pacientes (metformina y otro antidiabético): a) inhibidores de la dipeptidil peptidasa 4 (IDPP4); b) sulfonilureas; c) glitazonas, y d) insulinas. Principales medidas: comorbilidad, control metabólico, cumplimiento y complicaciones. El seguimiento se realizó durante 2 años. El modelo de costes diferenció los costes sanitarios directos (atención primaria/especializada) e indirectos (productividad laboral). Análisis estadístico: modelos de regresión logística y ANCOVA, p < 0,05. RESULTADOS: Se seleccionaron 2.067 pacientes (edad media: 66,6 años; varones: 53,1%). Un 25,1% iniciaron un segundo tratamiento con IDPP4; 42,9% con sulfonilureas, 14,0% con glitazonas, y 18,0% con insulinas. A los 2 años de seguimiento, los pacientes tratados con IDPP4 mostraron un mayor cumplimiento terapéutico (70,3 vs. 59,9%, 60,3% y 58,4); mejor control de la DM2 (64,3 vs. 62,6%, 62,8 y 50,5%) y menor proporción de hipoglucemias (13,9 frente a 40,4%, 37,6% y 58,9%, respectivamente) (p < 0,001). El promedio/unitario de los costes totales fue de 2.321 € frente a 2.475 €, 2.724 €, y 3.164 €, respectivamente; p < 0,001. Las tasas de eventos cardiovasculares e insuficiencia renal fueron del 3,7; 6,4; 7,6, y 10,2%, respectivamente. CONCLUSIONES: Las sulfonilureas fueron los fármacos más utilizados. Los pacientes en tratamiento con IDPP4 presentaron mayor cumplimiento y control de la diabetes, con menores tasas de hipoglucemias y costes sanitarios

OBJECTIVES: To determine compliance, metabolic control, complications and healthcare costs of patients treated with metformin started a second antidiabetic drug in patients with type 2 diabetes (T2DM). PATIENTS AND METHODS: Design multicenter observational retrospective. Patients were evaluated ≥30 years (age), treated with metformin and started a second antidiabetic treatment during 2008-2009. There were 4 patient groups (metformin and another antidiabetic): a) dipeptidyl peptidase-4 inhibitors (IDPP4), b) sulfonylureas, c) glitazones and d) insulin. Main measures: comorbidity, metabolic control, compliance and complications. Patients were followed for 2 years. The cost model differed direct health costs (primary care / specialist) and indirect (labor productivity). Statistical analysis: logistic regression models and ANCOVA, p < 0.05. RESULTS: 2067 patients were included (mean age: 66.6 years male: 53.1%). 25.1% started a second treatment with IDPP4; 42.9% sulfonylureas, 14.0% glitazones and 18.0% insulin. At 2 years follow-up, patients treated with IDPP4 showed greater adherence vs. 70.3%. 59.9%, 60.3% and 58.4; better control of 64.3% vs. DM2. 62.6%, 62.8% and 50.5% and a decrease of 13.9% compared to hypoglycaemia 40.4%, 37.6% and 58.9% respectively (p < 0.001). The average / unit total costs was €2,321 vs. €2,475, €2,724 and €3,164, respectively, p < 0.001. Rates of cardiovascular events and renal failure were 3.7%, 6.4%, 7.6% and 10.2% respectively. CONCLUSIONS: Sulfonylureas were the most commonly used drugs. Patients treated with IDPP4 had higher compliance and control of diabetes, with lower rates of hypoglycaemia and healthcare costs

The role of pH fronts in tissue electroporation based treatments.

Treatments based on electroporation (EP) induce the formation of pores in cell membranes due to the application of pulsed electric fields. We present experimental evidence of the existence of pH fronts emerging from both electrodes during treatments based on tissue EP, for conditions found in many studies, and that these fronts are immediate and substantial. pH fronts are indirectly measured through the evanescence time (ET), defined as the time required for the tissue buffer to neutralize them. The ET was measured through a pH indicator imaged at a series of time intervals using a four-cluster hard fuzzy-c-means algorithm to segment pixels corresponding to the pH indicator at every frame. The ET was calculated as the time during which the number of pixels was 10% of those in the initial frame. While in EP-based treatments such as reversible (ECT) and irreversible electroporation (IRE) the ET is very short (though enough to cause minor injuries) due to electric pulse characteristics and biological buffers present in the tissue, in gene electrotransfer (GET), ET is much longer, enough to denaturate plasmids and produce cell damage. When any of the electric pulse parameters is doubled or tripled the ET grows and, remarkably, when any of the pulse parameters in GET is halved, the ET drops significantly. Reducing pH fronts has relevant implications for GET treatment efficiency, due to a substantial reduction of plasmid damage and cell loss.

[Characterization of and costs associated to the profile of patients with type 2 diabetes treated with metformin who are added a second oral antidiabetic drug: a population study]. / Caracterización y costes asociados al perfil del paciente con diabetes tipo 2 en tratamiento con metformina al que se le añade un segundo fármaco antidiabético oral: estudio de base poblacional.

OBJECTIVES: To determine compliance, metabolic control, complications and healthcare costs of patients treated with metformin started a second antidiabetic drug in patients with type 2 diabetes (T2DM). PATIENTS AND METHODS: Design multicenter observational retrospective. Patients were evaluated ≥30 years (age), treated with metformin and started a second antidiabetic treatment during 2008-2009. There were 4 patient groups (metformin and another antidiabetic): a) dipeptidyl peptidase-4 inhibitors (IDPP4), b) sulfonylureas, c) glitazones and d) insulin. MAIN MEASURES: comorbidity, metabolic control, compliance and complications. Patients were followed for 2 years. The cost model differed direct health costs (primary care / specialist) and indirect (labor productivity). STATISTICAL ANALYSIS: logistic regression models and ANCOVA, p<0.05. RESULTS: 2067 patients were included (mean age: 66.6 years male: 53.1%). 25.1% started a second treatment with IDPP4; 42.9% sulfonylureas, 14.0% glitazones and 18.0% insulin. At 2 years follow-up, patients treated with IDPP4 showed greater adherence vs. 70.3%. 59.9%, 60.3% and 58.4; better control of 64.3% vs. DM2. 62.6%, 62.8% and 50.5% and a decrease of 13.9% compared to hypoglycaemia 40.4%, 37.6% and 58.9% respectively (p<0.001). The average / unit total costs was €2,321 vs. €2,475, €2,724 and €3,164, respectively, p<0.001. Rates of cardiovascular events and renal failure were 3.7%, 6.4%, 7.6% and 10.2% respectively. CONCLUSIONS: Sulfonylureas were the most commonly used drugs. Patients treated with IDPP4 had higher compliance and control of diabetes, with lower rates of hypoglycaemia and healthcare costs.

Mathematical modeling of human glioma growth based on brain topological structures: study of two clinical cases.

Gliomas are the most common primary brain tumors and yet almost incurable due mainly to their great invasion capability. This represents a challenge to present clinical oncology. Here, we introduce a mathematical model aiming to improve tumor spreading capability definition. The model consists in a time dependent reaction-diffusion equation in a three-dimensional spatial domain that distinguishes between different brain topological structures. The model uses a series of digitized images from brain slices covering the whole human brain. The Talairach atlas included in the model describes brain structures at different levels. Also, the inclusion of the Brodmann areas allows prediction of the brain functions affected during tumor evolution and the estimation of correlated symptoms. The model is solved numerically using patient-specific parametrization and finite differences. Simulations consider an initial state with cellular proliferation alone (benign tumor), and an advanced state when infiltration starts (malign tumor). Survival time is estimated on the basis of tumor size and location. The model is used to predict tumor evolution in two clinical cases. In the first case, predictions show that real infiltrative areas are underestimated by current diagnostic imaging. In the second case, tumor spreading predictions were shown to be more accurate than those derived from previous models in the literature. Our results suggest that the inclusion of differential migration in glioma growth models constitutes another step towards a better prediction of tumor infiltration at the moment of surgical or radiosurgical target definition. Also, the addition of physiological/psychological considerations to classical anatomical models will provide a better and integral understanding of the patient disease at the moment of deciding therapeutic options, taking into account not only survival but also life quality.

The role of pH fronts in reversible electroporation.

We present experimental measurements and theoretical predictions of ion transport in agar gels during reversible electroporation (ECT) for conditions typical to many clinical studies found in the literature, revealing the presence of pH fronts emerging from both electrodes. These results suggest that pH fronts are immediate and substantial. Since they might give rise to tissue necrosis, an unwanted condition in clinical applications of ECT as well as in irreversible electroporation (IRE) and in electrogenetherapy (EGT), it is important to quantify their extent and evolution. Here, a tracking technique is used to follow the space-time evolution of these pH fronts. It is found that they scale in time as t(½), characteristic of a predominantly diffusive process. Comparing ECT pH fronts with those arising in electrotherapy (EChT), another treatment applying constant electric fields whose main goal is tissue necrosis, a striking result is observed: anodic acidification is larger in ECT than in EChT, suggesting that tissue necrosis could also be greater. Ways to minimize these adverse effects in ECT are suggested.