Scoliosis induced by costotransversectomy in minipigs model.

Aim To validate surgical costotransversectomy as a technique for creating a scoliosis model in minipigs and to assess whether differences in approach (posterior medial approach, posterior paramedial approach and anterior approach by video-assisted thoracoscopy) lead to differences in the production of spinal deformity. Creation of disease models in experimental animals, specifically in minipigs, is controversial, as no appropriate technique has been reported. Methods Surgical costotransversectomy was performed in 11 minipigs using 3 different approaches: posterior medial approach (4 animals, group I), posterior paramedial approach (3 animals, group II) and anterior approach by videothoracoscopy (4 animals, group III). A conventional x-ray study was performed in the immediate postoperative period. Follow-up lasted for 4 months. Specimens were humanely killed according to current protocols, and a second x-ray study was performed. A deformation was measured using the Cobb angle and direct observation of the rotational component. Results Data from group I revealed a scoliosis deformation of 27º-41º (mean 34.5º) with a macroscopic rotational component. No deformity (<10º) or rotational component was observed in groups II and III. Only a posterior medial costotransversectomy produced a significant deformity in minipigs and established a valid model for studying scoliosis in these animals. Conclusion Only a posterior medial costotransversectomy produces a significant deformity in minipigs and establish a valid model for studying scoliosis in these animals. A tensegrity model would elucidate such results and harmonize disparate conclusions. Further investigation is needed to demonstrate the reliability of tensegrity principles for spinal biomechanics.

Fiabilidad de la técnica del cálculo del nivel aceptable de resultados en pruebas de preguntas de elección múltiple / Reliability of the calculation technique of acceptable level of results in multiple choice tests

Se presenta la experiencia de once años de evaluación de los conocimientos teóricos de la asignatura Fisiopatología Quirúrgica en el grupo docente del Hospital General Universitario Gregorio Marañón dependiente del Departamento de Cirugía de la Universidad Complutense. Las pruebas durante este tiempo han sido homogéneas y han consistido en un test de 100 preguntas de elección múltiple (PEM) con 5 respuestas posibles y solo una correcta extraídas de nuestra base de datos de preguntas. En el curso 2015-16 se ha aplicado el mismo proceso de evaluación a los alumnos de Patología Quirúrgica de Digestivo de 4. ° curso. Este mismo grupo de alumnos se evaluó el año anterior en la asignatura de Fisiopatología Quirúrgica de 3. er curso y se observa una alta concordancia de los resultados demostrando la robustez del sistema de evaluación. En este trabajo se atiende únicamente a la evaluación de los conocimientos teóricos de los alumnos. La evaluación de las aptitudes y de las actitudes se realiza de forma diferente y no son motivo de este trabajo

The experience of eleven years of evaluation of theoretical knowledge of the subject Surgical Pathophysiology in the teaching Group of the Hospital General Universitario Gregorio Marañón belonging to the Department of Surgery of the Complutense University of Madrid is presented. Tests during this time have been homogeneous and consisted of 100 multiple choice questions with 5 possible answers and only one correct taken from our database of questions. During academic year 2015-16 the same evaluation process was applied to the students of Digestive Surgical Pathology (4th grade). This same group of students was assessed last year in the course of Surgical Pathophysiology of 3rd grade and high concordance of the results is observed demonstrating the robustness of the evaluation system. This paper take care only to the evaluation of theoretical knowledge of students. Assessing skills and attitudes is performed in a different way and are not the aim for this work

Uso de toxina botulínica paravertebral para detener la progresión de escoliosis en pollos pinealectomizados: la columna vertebral como sistema de tensegridad / Use of paravertebral injection of botulinum toxin to control scoliosis progression in pinealectomized chicken: the spine as a tensegrity system

Antecedentes y Objetivos. La escoliosis idiopática infantil no tiene un tratamiento satisfactorio que permita reducir la importante morbilidad y mortalidad asociada a los casos más severos y progresivos de la enfermedad. El desarrollo de procedimientos que puedan ralentizar la progresión de la enfermedad durante el desarrollo del niño puede influir favorablemente en el crecimiento y retrasar el tratamiento definitivo de la deformidad al momento de la madurez músculoesquelética. Presentamos un estudio sobre la influencia de la toxina botulínica en el desarrollo de deformidad en un modelo animal de escoliosis progresiva. Material y Método. Utilizamos 52 pollos Broiler hembra, en los que se practicó pinealectomía para producir escoliosis. Comparamos la evolución de la deformidad entre un grupo control y un grupo intervención asignado a recibir toxina botulínica paravertebral en la concavidad de la curva, bajo control electromiográfico. Realizamos estudios radiográficos y anatomopatológicos de los animales para evaluar los resultados. El grado de escoliosis se midió utilizando el método del ángulo de Cobb. Resultados. Cinco animales no sobrevivieron al estudio (1 en el grupo control y 4 en el de intervención). En el grupo control observamos una deformidad media de 32.9º (n= 25) y en el grupo intervención de 18.8º (n=22), encontrando diferencias estadísticamente significativas (p<0.05). Por tanto, la aplicación de toxina botulínica en la concavidad de la deformidad de pollos pinealectomizados frena la progresión de escoliosis. Conclusiones. La consideración de la columna vertebral y sus tejidos blandos asociados como una estructura de tensegridad puede explicar el fenómeno mediante el desequilibrio generado entre los componentes de tensión (músculos y ligamentos) y compresión (vértebras) que conforman el sistema. Estos resultados justifican nuevos estudios en investigación clínica para explorar una nueva alternativa para el tratamiento de la escoliosis idiopática infantil (AU)

Background and Objectives. Severe and progressive adolescent idiopathic scoliosis has no satisfactory treatment since high rates of morbidity and mortality are associated. Development of procedures that might slow down the progression of the deformity in the growing children may postpone definitive surgery to the end of musculoskeletal maturity period. A study about the influence of botulinum toxin in the development of deformity in a progressive scoliosis animal model is reported. Methods. Surgical pinealectomy was performed in 52 Broiler chickens to induce progressive scoliosis. Scoliosis progression among a control group and an intervention group assigned to paravertebral injection of botulinum toxin in curve´s concavity electromyographycally assisted is compared. Conventional x-ray and anatomopathologic studies were conducted to evaluate results. Cobb angle method was used to measure spine deformation. Results. Five animals died (1 in the control group and 4 in the intervention group). Mean scoliosis values observed were 32.9 degrees (n= 25) and 18.8 degrees (n= 22) for control and intervention groups respectively (p<0.05). Therefore, the use of botulinum toxin in the deformity´s concavity restrains scoliosis progression in pinealectomized chickens. Conclusions. The assumption of the spine and its associated soft tissues as a tensegrity structure may explain these results, through the induced imbalance between the tension (muscles and ligaments) and compression (vertebrae) components that shape the system. Further studies are necessary to determine clinical applications of this therapy in adolescent idiopathic scoliosis (AU)

Genetic variations of HSPA1A, the heat shock protein levels, and risk of atherosclerosis.

HSPA1A is a serum and intracellular heat shock protein with antiapoptotic and antithrombotic properties. The present study examines the hypothesis that a decrease in the synthesis of this protein in relation to certain polymorphisms of the regulatory region of the HSPA1A gene can define a vascular disease risk phenotype. A randomly selected population was studied and stratified into groups according to the degree of vascular risk. After applying the Task Force Chart to 452 people, the subjects were divided into three groups: group 0 (no vascular risk factor or risk < 5%), n = 239; group 1 (moderate (10-20%) risk, with no clinical cardiovascular disease), n = 161; and group 2 (overt atherosclerosis), n = 52. Serum and intragranulocytic HSPA1A was quantified, and direct Sanger sequencing was performed in all subjects. An analysis was made of the association of two single nucleotide polymorphisms (db rs1008438 -110A/C and db rs1043618 +190 G/C) with circulating and intragranulocytic HSPA1A and the risk of atherosclerosis. The atherosclerotic subjects showed significantly lower circulating HSPA1A levels than the other groups, regardless of the genotype. The patients with CC genotype for both polymorphisms showed significantly lower intragranulocytic HSPA1A levels than the other genotypes. Serum HSPA1A concentrations could be proposed as a biomarker of cardiovascular disease. CC homozygosis for polymorphisms db rs1008438 and db rs1043618 is associated with a decrease in the intragranulocytic production of HSPA1A. Given the antiatherogenic functions of intracellular HSPA1A, the -110A and +190 G alleles could constitute potential genetic biomarkers of a less severe clinical phenotype for the risk of developing atherosclerosis.

Mathematically gifted adolescents use more extensive and more bilateral areas of the fronto-parietal network than controls during executive functioning and fluid reasoning tasks.

The main goal of this study was to investigate the neural substrates of fluid reasoning and visuospatial working memory in adolescents with precocious mathematical ability. The study population comprised two groups of adolescents: 13 math-gifted adolescents and 14 controls with average mathematical skills. Patterns of activation specific to reasoning tasks in math-gifted subjects were examined using functional magnetic resonance images acquired while the subjects were performing Raven's Advanced Progressive Matrices (RAPM) and the Tower of London (TOL) tasks. During the tasks, both groups showed significant activations in the frontoparietal network. In the math-gifted group, clusters of activation were always bilateral and more regions were recruited, especially in the right hemisphere. In the TOL task, math-gifted adolescents showed significant hyper-activations relative to controls in the precuneus, superior occipital lobe (BA 19), and medial temporal lobe (BA 39). The maximum differences between the groups were detected during RAPM tasks at the highest level of difficulty, where math-gifted subjects showed significant activations relative to controls in the right inferior parietal lobule (BA 40), anterior cingulated gyrus (BA 32), and frontal (BA 9, and BA 6) areas. Our results support the hypothesis that greater ability for complex mathematical reasoning may be related to more bilateral patterns of activation and that increased activation in the parietal and frontal regions of math-gifted adolescents is associated with enhanced skills in visuospatial processing and logical reasoning.

Extracellular heat shock protein 70 (HSPA1A) and classical vascular risk factors in a general population.

Atherosclerosis is a chronic inflammatory and autoimmune disease. Candidate molecules/autoantigens include heat shock proteins (HSPs); Hsp70 (HSPA1A) is one of the best studied HSPs. Various studies have shown a correlation between extracellular Hsp70 (eHsp70) and anti-Hsp70/anti-Hsp60 antibody concentration and development of atherosclerosis. A random sample of 456 people aged 40-60 (218 males, 234 females) was studied to investigate the prevalence of traditional vascular risk factors and eHsp70 and anti-Hsp70/anti-Hsp60 antibodies levels, according to the risk of vascular disease. Task Force Chart was applied for classification. Subjects were divided into three groups: G0 (with no vascular risk factor or a risk lower than 5%), n = 239; G1 (moderated 10-20% risk, who do not have established disease) n = 161; and G2 (established atherosclerosis disease) n = 52. eHsp70 and anti-Hsp70 were significantly lower in the atherosclerosis group (group 2) with respect to the other groups. Disease-free people showed the highest anti-Hsp60 concentration compared with the other two groups. A correlation has not been demonstrated between the concentrations of circulating Hsp70 (HSPA1A), anti-Hsp70, and anti-Hsp60 and classical vascular risk factors and C-reactive protein. Low levels of eHsp70 and anti-Hsp70 antibodies should be considered as candidate FRV. Simultaneous decrease of eHsp70 and anti-Hsp70 antibodies would be explained by circulating immune complex formation, and both could be proposed as biomarkers for the progression of atherosclerotic disease. Levels of circulating anti-Hsp60 antibodies may constitute a marker of inflammation in atherosclerosis.

Reduction of heat shock protein antibody levels by statin therapy.

Atherosclerosis is a disease whose pathogenesis involves inflammatory and immunological mechanisms, including an autoimmune reaction against heat shock proteins (Hsps). The purpose of this study was to analyze whether the antiatherogenic effect of statin therapy was not limited to its lipid lowering effect, but also included anti-inflammatory and immunomodulatory effects, paying special attention to the measurement of circulating concentrations of anti-Hsp70 and anti-Hsp60 antibodies previously related to vascular disease. Two-hundred and seventy-five subjects aged 40-60 years, randomly selected in an epidemiological study on the incidence of vascular risk factors, were studied. Laboratory tests included a complete lipid profile after a 12-h fast and measurements of glucose, C-reactive-protein, anti-Hsp70 and anti-Hsp60 antibodies. Subjects with hypercholesterolemia had significantly higher concentrations of anti-Hsp70 antibodies as compared to subjects with normal cholesterol concentrations. Statin therapy was associated with 11.63 and 15.3% reductions in total and LDL-cholesterol (P = 0.005 and 0.017, respectively) as compared to untreated subjects, and with lower concentrations of circulating anti-Hsp70 (P = 0.016) antibodies. No differences were found in C-reactive-protein values. Since statin therapy not only reduces lipid profile, but also anti-Hsp70 and anti-Hsp60 antibody concentrations, without changing C-reactive-protein values, it is suggested that such an effect could not be accounted for by the anti-inflammatory properties of statins, but by their direct immunomodulatory properties through their effects on lymphocyte function.

1H MR spectroscopy in the assessment of gliomatosis cerebri.

OBJECTIVE: Gliomatosis cerebri is a rare brain tumor with a short survival time; for this reason, it is difficult to establish the degree of aggressivity in vivo. The MR spectroscopic findings on this tumor often do not agree with choline level. The purpose of this study was to evaluate whether MR spectroscopy can be used to measure tumor choline levels and whether the findings give useful information about tumor growth rate and patient survival time. SUBJECTS AND METHODS: We performed MRI and 1H MR spectroscopic studies on seven treatment-naive patients with gliomatosis cerebri and on 16 healthy volunteers. We then analyzed the association between survival time and levels of choline (Cho) and N-acetyl aspartate (NAA) normalized to creatine (Cr). RESULTS: The results showed a statistically significant (p = 0.05) inverse relation between Cho/Cr ratio and survival time. In addition, NAA/Cr ratio was significantly lower in the patient group than in the control group (p = 0.001). CONCLUSION: Cho/Cr ratio measured with MR spectroscopy seems to be related to survival time, possibly explaining the inconsistent findings previously reported for this parameter.

Heat shock proteins, end effectors of myocardium ischemic preconditioning?

The purpose of this study was to investigate (1) whether ischemia-reperfusion increased the content of heat shock protein 72 (Hsp72) transcripts and (2) whether myocardial content of Hsp72 is increased by ischemic preconditioning so that they can be considered as end effectors of preconditioning. Twelve male minipigs (8 protocol, 4 sham) were used, with the following ischemic preconditioning protocol: 3 ischemia and reperfusion 5-minute alternative cycles and last reperfusion cycle of 3 hours. Initial and final transmural biopsies (both in healthy and ischemic areas) were taken in all animals. Heat shock protein 72 messenger ribonucleic acid (mRNA) expression was measured by a semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method using complementary DNA normalized against the housekeeping gene cyclophilin. The identification of heat shock protein 72 was performed by immunoblot. In our "classic" preconditioning model, we found no changes in mRNA hsp72 levels or heat shock protein 72 content in the myocardium after 3 hours of reperfusion. Our experimental model is valid and the experimental techniques are appropriate, but the induction of heat shock proteins 72 as end effectors of cardioprotection in ischemic preconditioning does not occur in the first hours after ischemia, but probably at least 24 hours after it, in the so-called "second protection window."

ROC evaluation of statistical wavelet-based analysis of brain activation in [15O]-H2O PET scans.

This paper presents and evaluates a wavelet-based statistical analysis of PET images for the detection of brain activation areas. Brain regions showing significant activations were obtained by performing Student's t tests in the wavelet domain, reconstructing the final image from only those wavelet coefficients that passed the statistical test at a given significance level, and discarding artifacts introduced during the reconstruction process. Using Receiver Operating Characteristic (ROC) curves, we have compared this statistical analysis in the wavelet domain to the conventional image-domain Statistical Parametric Mapping (SPM) method. For obtaining an accurate assessment of sensitivity and specificity, we have simulated realistic single subject [15O]-H2O PET studies with different hyperactivation levels of the thalamic region. The results obtained from an ROC analysis show that the wavelet approach outperforms conventional SPM in identifying brain activation patterns. Using the wavelet method, activation areas detected were closer in size and shape to the region actually activated in the reference image.

Proteínas de choque térmico en el estrés quirúrgico: toracotomía frente a herniorrafia / Heat shock proteins in surgical stress: thoracotomy vs herniorrhaphy

Introducción. El estrés quirúrgico y anestésico libera citocinas y especies reactivas de oxígeno capaces de inducir la síntesis de las proteínas de choque térmico (HSP), proteínas con propiedades inmunomoduladoras y potentes autoantígenos. Se pretende estudiar la biología de las HSP70 intraleucocitarias y la posible respuesta autoinmunitaria desencadenada por 2 tipos diferentes de agresión quirúrgica. Pacientes y método. Grupo I: grupo control con 3 pacientes. Grupo II: grupo de toracotomía, cirugía radical y anestesia general, con 6 pacientes. Grupo III: grupo de cirugía poco radical, herniorrafia y raquianestesia, con 4 pacientes. Se analizaron HSP70 intraleucocitarias y anticuerpos anti-HSP70i, antes (T0) y 24 h después de la intervención (T1).Resultados. El 50 por ciento de los pacientes expuestos a toracotomía presentó un significativo descenso del contenido de HSP intracelulares en el postoperatorio, simultáneo al incremento de los valores de autoanticuerpos anti-HSP70i. El grupo de pacientes expuestos a herniorrafia con anestesia locorregional no desarrolló respuesta autoinmunitaria. Conclusiones. En el limitado número de pacientes estudiados, la enfermedad neoplásica y la mayor agresividad de la toracotomía parecen asociarse con una reducción de las HSP en comparación con lo que sucede en los pacientes más sanos a los que se les realizó una herniorrafia. La disminución de las HSP fue simultánea a la presencia de autoanticuerpos circulantes. No se observó relación entre el estado inmunitario previo y la respuesta autoinmunitaria en el postoperatorio inmediato (AU)

Method for bias field correction of brain T1-weighted magnetic resonance images minimizing segmentation error.

This work presents a new algorithm (nonuniform intensity correction; NIC) for correction of intensity inhomogeneities in T1-weighted magnetic resonance (MR) images. The bias field and a bias-free image are obtained through an iterative process that uses brain tissue segmentation. The algorithm was validated by means of realistic phantom images and a set of 24 real images. The first evaluation phase was based on a public domain phantom dataset, used previously to assess bias field correction algorithms. NIC performed similar to previously described methods in removing the bias field from phantom images, without introduction of degradation in the absence of intensity inhomogeneity. The real image dataset was used to compare the performance of this new algorithm to that of other widely used methods (N3, SPM'99, and SPM2). This dataset included both low and high bias field images from two different MR scanners of low (0.5 T) and medium (1.5 T) static fields. Using standard quality criteria for determining the goodness of the different methods, NIC achieved the best results, correcting the images of the real MR dataset, enabling its systematic use in images from both low and medium static field MR scanners. A limitation of our method is that it might fail if the bias field is so high that the initial histogram does not show bimodal distribution for white and gray matter.

Resolution recovery in Turbo Spin Echo using segmented Half Fourier acquisition.

Turbo Spin Echo (TSE) is a sequence of choice for obtaining T(2)-weighted images. TSE reduces acquisition time by acquiring several echoes within each TR, at the cost of introducing an exponential weighting in the k-space that leads to a certain image blurring. This is particularly important for short-T(2) structures, which can even disappear if their size in the phase encoding direction is comparable to the degree of blurring. This article suggests the use of a combination of Half Fourier (HF) and segmented (multishot) TSE (sHF-TSE) to recover the original resolution of the SE images. The improved symmetry of the dataset achieved by HF reconstruction is used to increase the resolution of the TSE images. The proposed combination, available in most clinical scanners, reduces the blurring artifact inherent to the TSE sequence without increasing the scan time or the number of acquisitions, but at the cost of a slight reduction of the signal-to-noise ratios (SNR). Qualitative and quantitative results are presented using both numerical simulation and imaging. Significant edge enhancement has been achieved for structures with short T(2), (narrowing of the full width at half maximum [FWHM] up to 45%). The proposed sequence is more sensitive to movement artifacts but has proven to be superior to the conventional TSE for imaging static structures.

Bioquímica y fisiopatología del envejecimiento: genes viejos / Biochemistry and phisiopathology of ageing: old genes

"Diversas plumas han explicado lo que significa envejecer. Pero sólo ahora podemos iniciar la conversación sobre la biología del envejecimiento. Porqué y cómo envejecemos. Los investigadores se han planteado estas cuestiones y, por fin, algunas respuestas están al alcance de la mano". La historia de la evolución ha determinado que los individuos se desarrollan el tiempo suficiente para producir y criar su prole. Por ello, el proceso de envejecimiento comprende un lento declive del vigor fisiológico y un incremento progresivo de la susceptibilidad a enfermedades que prevalecen con la edad. Se han identificado un número de genes humanos en los que ciertas mutaciones pueden conducir a la aparición acelerada de rasgos de senescencia. Los estudios de estos genes y de las funciones de sus productos proteicos pueden ayudar a comprender la naturaleza de la senescencia, y podrían orientar los mecanismos por los que pudiera retrasarse el envejecimiento.Los síndromes progeroides son condiciones que producen un envejecimiento prematuro y un acortamiento de la esperanza de vida. El rasgo más destacable de estas raras afecciones es el envejecimiento extremadamente acelerado. Los niños afectados desarrollan todos los signos externos de la edad avanzada. A diferencia del envejecimiento normal, los síndromes progeroides incluyen también signos tales como la falta de actividad ovárica o testicular (incluyendo esterilidad y ausencia de periodos menstruales) y una excepcional talla baja. Por tanto, la progeria no es exactamente un modelo de envejecimiento acelerado. La inestabilidad genómica ha sido propuesta insistentemente como el principal factor del proceso de envejecimiento. La contribución de la inestabilidad del genoma al envejecimiento se subraya por el hallazgo de que varios síndromes progeroides parciales, que se caracterizan por la rápida instauración de condiciones normalmente asociadas con el envejecimiento, se asocian con inestabilidad genómica. Dos de estos procesos, el síndrome de Werner y el síndrome de Rothmund-Thompson, están producidos por mutaciones en genes que codifican proteínas relacionadas con RecQ. RecQ es una ADN-helicasa; una enzima que utiliza la energía de la hidrólisis de los trifosfatos nucleotíficos para romper el emparejamiento de bases entre las hebras de los ácidos nucleicos, convirtiendo los ácidos nucleicos de doble hebra en monocatenarios. Las helicasas son esenciales en prácticamente todos los aspectos del metabolismo de los ácidos nucleicos -replicación, transcripción, traducción, reparación y recombinación-.Podría suponerse que los beneficiarios más inmediatos de la investigación en curso deberían ser los pacientes geriátricos. Sin embargo, el trabajo debería dirigirse a un nuevo médico que confeccione estategias para prolongar la vida de forma individualizada a sus pacientes: los pediatras. El mejor medio para asegurar la salud de los ancianos puede estar en mejorar el bienestar de nuestros niños (AU)

Biological dosimetry of magnetic resonance imaging.

PURPOSE: To check the bioeffects of the components of magnetic resonance imaging (MRI). MRI is based on an assumed harmless interaction between certain nuclei in the body when placed in a strong magnetic field and radio wave fields. There are three key factors actuating on the examining body: a powerful static magnetic field (SMF), magnetic gradient fields (MGFs), and pulsed radiofrequency (RF) radiation. MATERIALS AND METHODS: In vitro cells (L-132 cells) were used as biosensors, and different cellular compounds were used as biomarkers (heat shock proteins [HSPs] and their messenger ribonucleic acids [mRNAs], calcium, and adenosine-3',5'-cyclic monophosphate [cAMP]). The biosensors were placed in the bore of a 1.5-T MRI machine and the different electromagnetic fields were operated. RESULTS: HSPs and their mRNAs and cAMP did not respond to SMF, MGFs, or RF radiation. RF radiation increased cytosolic calcium concentration (18%, P < 0.05). CONCLUSION: Although MRI procedures do not induce any cellular stress response, it may cause an unfathomable calcium increase in vitro. Although the in vitro experimental conditions are not totally comparable to clinical situations, the usefulness of the in vivo biological dosimetry, circulating leukocytes as biosensors, and HSPs and/or calcium as biomarkers is suggested.