Artificial intelligence to predict clinical disability in patients with multiple sclerosis using FLAIR MRI.

PURPOSE: The purpose of this study was to create an algorithm that combines multiple machine-learning techniques to predict the expanded disability status scale (EDSS) score of patients with multiple sclerosis at two years solely based on age, sex and fluid attenuated inversion recovery (FLAIR) MRI data. MATERIALS AND METHODS: Our algorithm combined several complementary predictors: a pure deep learning predictor based on a convolutional neural network (CNN) that learns from the images, as well as classical machine-learning predictors based on random forest regressors and manifold learning trained using the location of lesion load with respect to white matter tracts. The aggregation of the predictors was done through a weighted average taking into account prediction errors for different EDSS ranges. The training dataset consisted of 971 multiple sclerosis patients from the "Observatoire français de la sclérose en plaques" (OFSEP) cohort with initial FLAIR MRI and corresponding EDSS score at two years. A test dataset (475 subjects) was provided without an EDSS score. Ten percent of the training dataset was used for validation. RESULTS: Our algorithm predicted EDSS score in patients with multiple sclerosis and achieved a MSE=2.2 with the validation dataset and a MSE=3 (mean EDSS error=1.7) with the test dataset. CONCLUSION: Our method predicts two-year clinical disability in patients with multiple sclerosis with a mean EDSS score error of 1.7, using FLAIR sequence and basic patient demographics. This supports the use of our model to predict EDSS score progression. These promising results should be further validated on an external validation cohort.

The impact of the invasive species Vespa velutina on honeybees: A new approach based on oxidative stress.

Honeybees have an essential role in ecosystems pollinating wild flowers and cultivated crops, representing an important cultural and economic benefit for humans. Honeybee populations are decreasing over the last decade, due to multifactorial causes. The aim of this field study was to investigate the effects of the presence of the invasive species Vespa velutina, a bee predator, in oxidative stress parameters of honeybee workers. To achieve this objective, positive or negative apiaries for the presence of the V. velutina were selected. Five honeybees from six hives of each apiary were sampled in spring, summer and autumn, analysing a total of 233 samples. Analysis of mRNA expression of oxidative stress-related genes, catalase enzymatic activity and lipid peroxidation were performed. An increase in sod2, tpx3, trxR1, gtpx1, gstS1, coxI, cytC and if2mt genes expression, as well as a raise in catalase activity and lipid peroxidation were observed in V. velutina positive samples. Thus, here we present a new methodology to analyze the impact of the predation pressure of the invasive species V. velutina on honeybees under field conditions. In conclusion, the results obtained in this study indicate the negative impact of the presence of the yellow-legged hornet on honeybees' health and the activation of their antioxidant system to protect them against this biotic stressor. Moreover, the redox status they present could increase the susceptibility of honeybees, essential insects that currently receive many inputs of different stresses, to another stressor.

Metástasis cutánea de carcinoma de mama primario / Cutaneous metastasis of primary breast carcinoma

RESUMEN: Se consideran metástasis cutáneas aquellas neoplasias que se extienden a la piel por diseminación linfática, hemática o por contigüidad, originadas generalmente de un tumor extracutáneo, casi siempre diseminado y agresivo. Las metástasis en la piel suelen constituir un evento tardío en el curso de la enfermedad neoplásica, pero también pueden presentarse como el primer signo de un tumor desconocido.1 El carcinoma de mama es la neoplasia maligna interna más frecuente en las mujeres y se manifiesta con mayor frecuencia entre la quinta y sexta década de la vida. El 45% de las metástasis en la piel de cáncer de mama se presentan entre 6 meses y 4 años después del diagnóstico del tumor primario, aunque pueden observarse lesiones metastásicas al cabo de 10 años, por lo que el riesgo de metástasis quedaría latente durante el resto de la vida.2 Constituye un factor pronóstico desfavorable de la enfermedad asociándose a la morbi-mortalidad de la paciente, ya que generalmente se encuentran metástasis concomitantes en órganos internos.

SUMMARY: Cutaneous metastases are considered to be those neoplasms that extend to the skin due to lymphatic and hematic dissemination, generally originating from an extra cutaneous tumor, almost always disseminated and aggressive. Metastases in the skin are usually a late event in the course of neoplastic disease, but they can also present as the first sign of an unknown tumor.1 Breast carcinoma is the most frequent internal malignant neoplasm in women, manifesting most frequently between the fifth and sixth decade of life. 45% of skin metastases of breast cancer occur between 6 months and 4 years after diagnosis of the primary tumor, although metastatic lesions can be observed after 10 years, so the risk of metastasis would remain latent during the rest of life.2 It is a prognostic factor of the disease associated with the morbidity and mortality of the patient, since concomitant metastases are usually found in distant organs.

Sarcoma de kaposi en pacientes vih: a proposito de dos casos / Kaposi´s sarcoma in hiv patients: regarding two case report

RESUMEN: El Sarcoma de Kaposi es unaneoplasia de origen vascular,asociado obligadamente al virus Herpes Humano tipo 8. Presenta manifestaciones cutáneas en primer lugar, mucosas, ganglionares y viscerales. Puede evolucionar de forma leve con lesiones cutáneas, hasta casos fulminantes con compromiso sistémico, en caso de no realizar tratamiento. Existen múltiples opciones terapéuticas, las cuales se definen según el compromiso de la enfermedad y la afectación del paciente por su patología de base.El diagnóstico se basa en la sospecha clínica y se confirma con una biopsia histopatológica. El sarcoma de Kaposi corresponde a la neoplasia más frecuente en los pacientes con VIHse encuentraprincipalmente en hombres homosexuales. En este artículo se presentan dos pacientes con VIH con diagnóstico de Sarcoma de Kaposi y se realiza una breve revisión de la bibliografía.

ABSTRACT: Kaposi´s sarcoma is a vascular origin neoplasm, obligatory associated with Human Herpes Virus 8. It presents cutaneous manifestations at a first place, mucous, ganglionic and viscerals. It may present a mild presentation with cutaneous manifestations, up to fulminant cases with systemicinvolvement,in case of not being treated. There are a number of therapeutic options, defined by the state of the illness and the involvement of the patient due to the primary pathology. The diagnosis is based on the clinical suspicion and it is confirmed by a histopathological biopsy. Kaposi´s sarcomais the most frequent neoplasm in patients with HIV, being more frequently in homosexual men. In this article two HIV patients with Kaposi´s sarcoma diagnosis are exposed and a brief revision of the literature is done.

[Randomised controlled study of inter-hemispheric electroencephalographic coherence following assisted therapy with dolphins in children with autism spectrum disorders]. / Estudio aleatorizado controlado de la coherencia interhemisferica del electroencefalograma tras terapia asistida con delfines en niños con trastorno del espectro autista.

INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impairments in executive function, language, emotional function, and social function. Its anatomofunctional substrate is related to a disorganization of the brain's functional connections. The aim is to investigate the cerebral connections in subjects with ASD through the analysis of the interhemispheric coherence (IHC) of the quantified electroencephalogram and its changes after dolphin assisted therapy (DAT) versus therapeutical intervention without dolphins (TIWD). PATIENTS AND METHODS: The IHC was determined in 44 subjects with ASD before randomly assigning them to two therapeutic groups: DAT (n = 22) and TIWD (n = 22). The results were statistically analyzed through the multi-measure ANOVA test for within-subject (time) and between-subject (DAT vs TIWD) factors. RESULTS: The IHC showed a significant reduction (p < 0.05) for both groups in the delta, theta, beta, and alpha frequencies (p < 0.001) in the anterior frontal region (F3-F4), alpha in the central region (C3-C4) (p < 0.05), and alpha (p < 0.05) and beta (p < 0.001) in the temporal region (T3-T4). In the intersection with the specific treatment (DAT), the coherence in the alpha band increased in Fp1-Fp2 (p < 0.05), and the delta did not decline in F3-F4 (p < 0.05). CONCLUSION: In 5-year-old children with ASD, DAT increases the IHC in the anterior frontal region and stabilizes the tendency to reduce the delta band in the posterior frontal region.

TITLE: Estudio aleatorizado controlado de la coherencia interhemisferica del electroencefalograma tras terapia asistida con delfines en niños con trastorno del espectro autista.Introduccion. El trastorno del espectro autista (TEA) es un trastorno del neurodesarrollo asociado con trastornos de la funcion ejecutiva, el lenguaje, la funcion emocional y la funcion social, cuyo sustrato anatomofuncional se relaciona con una desorganizacion de las conexiones funcionales cerebrales. El objetivo es investigar las conexiones cerebrales en sujetos con TEA mediante analisis de la coherencia interhemisferica (CIH) del electroencefalograma cuantificado y sus cambios tras la terapia asistida con delfines (TAD) frente a la intervencion terapeutica sin delfines (ITSD). Pacientes y metodos. Se determino la CIH en 44 sujetos con TEA antes de asignarse aleatoriamente a dos grupos de tratamiento: TAD (n = 22) e ITSD (n = 22). Los resultados se analizaron estadisticamente mediante el test de la ANOVA multimedida para los factores intrasujeto (tiempo) e intersujeto (TAD frente a ITSD). Resultados. La CIH mostro una reduccion significativa (p < 0,05) para ambos grupos en las frecuencias delta, theta, beta y alfa (p < 0,001) en la region frontal anterior (F3-F4). Se hallo tambien una reduccion en la frecuencia alfa en la region central (C3-C4) (p < 0,05), y alfa (p < 0,05) y beta (p < 0,001) en la region temporal (T3-T4). En la interseccion con el tratamiento especifico (TAD), la coherencia en la banda alfa aumento en Fp1-Fp2 (p < 0,05) y no descendio la delta en F3-F4 (p < 0,05). Conclusion. En niños de 5 años con TEA, la TAD aumenta la CIH en la region frontal anterior y estabiliza la tendencia a la reduccion de la banda delta en la region frontal posterior.

[Concordances between autism spectrum disorders and attention deficit hyperactivity disorder]. / Concordancias entre los trastornos del espectro del autismo y el trastorno por deficit de atencion/hiperactividad.

INTRODUCTION: The current literature acknowledges an overlap of genetic, clinical and neuropsychological aspects between autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), suggesting that there may be a common pattern that covers features ranging from the common genetic and structural aetiology to shared patterns of symptoms. AIM: To review the current advances in these common aspects. DEVELOPMENT: Several studies have pointed out preschool attentional difficulties as the basis of both disorders. From the genetic perspective, it is estimated that 50-72% of the genetic factors overlap between the two disorders. They also share a decrease in the volume of the corpus callosum and left frontal grey matter, as well as functional alterations such as dorsolateral prefrontal, striato-thalamic and superior parietal hypoactivation. Results are also found regarding executive functioning, with differential profiles for the two conditions, and also concerning the relationship between the repetitive and impulsive behaviours in the early stages of ASD and ensuing problems of hyperactivity. CONCLUSIONS: This new conception of the ASD-ADHD continuum, with a common neurodevelopmental basis and associated clinical features, could be of great use in clinical practice. It is suggested that this association should be taken into account when it comes to deciding on the treatment.

TITLE: Concordancias entre los trastornos del espectro del autismo y el trastorno por deficit de atencion/hiperactividad.Introduccion. La bibliografia actual reconoce un solapamiento de aspectos geneticos, clinicos y neuropsicologicos entre el trastorno del espectro del autismo (TEA) y el trastorno por deficit de atencion/hiperactividad (TDAH), sugiriendo que podria existir un patron comun que abarca desde la etiologia genetica y estructural comun hasta patrones sintomatologicos compartidos. Objetivo. Revisar los avances actuales en estos aspectos comunes. Desarrollo. Se han encontrado trabajos que apuntan a dificultades atencionales preescolares en la base de ambos trastornos. Desde la perspectiva genetica, se estima que un 50-72% de factores geneticos se solapan entre ambos trastornos. Tambien comparten una disminucion del volumen del cuerpo calloso y la sustancia gris frontal izquierda, y alteraciones funcionales como la hipoactivacion prefrontal dorsolateral, estriadotalamica y parietal superior. Se encuentran resultados en cuanto al funcionamiento ejecutivo, con perfiles diferenciales para ambas condiciones, y tambien sobre la relacion de los comportamientos repetitivos e impulsivos en las primeras etapas en TEA, con los problemas hiperactivos posteriores. Conclusiones. Esta nueva concepcion del continuo TEA-TDAH, con una base neuroevolutiva comun y caracteristicas clinicas asociadas, podria ser de gran utilidad para la practica clinica y se sugiere considerar la asociacion a la hora de plantear el tratamiento.

Liquen plano hipertrófico: A propósito de un caso / Lichen planus hypertrophic: Regarding a case report

El liquen plano hipertrófico es la segunda variante más común del liquen plano. Las lesiones clásicamente se localizan en: cara anterior de piernas y tobillos simétricamente y tienden a ser crónicas. Es una patología de importante diagnóstico, por la posibilidad de dar lugar al desarrollo de carcinoma espinocelular, con una frecuencia del 0,4% de los casos. En el siguiente artículo, presentamos el caso de un paciente con liquen hipertrófico en miembros inferiores. Además realizamos una breve reseña de la literatura.

Hypertrophic lichen planus is the second most common lichen planus variant. The lesions are classically located on: the anterior face of the legs and ankles symmetrically and tend to be chronic. It is a pathology of important diagnosis for the possibility of giving rise, to the development of squamous cell carcinoma. In the following article, we present the case of a patient with hypertrophic lichen in lower limbs. In addition we make a brief review of the current literature.

Perioperative functional neuroimaging of gliomas in eloquent brain areas.

Surgical resection of gliomas involving eloquent brain areas must be maximal in order to improve patients' survival, and safe to prevent postoperative impairments. Therefore, the precise spatial relationship between the lesion and eloquent brain areas needs to be established. Functional magnetic resonance imaging and diffusion tensor imaging are robust methods with increasing indications in neurosurgery for past decade. The aim of this review article is not only to pinpoint the major limitations of these methods in order to avoid erroneous conclusions, but also to detail practical aspects associated with the main paradigms routinely used in functional magnetic resonance imaging, and to discuss recent validation of functional magnetic resonance imaging and diffusion tensor imaging results with direct electrical stimulation during awake surgery.

Design, construction, and performance of a device for directional recrystallization of metallic alloys.

A device was designed to apply the directional recrystallization method to Fe-based alloys in order to obtain bamboo-like microstructures. This microstructure is suitable for improving creep properties and resistance to fatigue in some alloys and for enhancing pseudoelastic properties in shape memory alloys. The design and construction of a flat coil are described in detail. In addition, we developed an electromechanical system to control the movement of a wire within the flat coil. The construction details and system performance are presented. Furthermore, metallographic studies taken from the directionally recrystallized low-carbon steel samples are shown. Nearly monocrystalline and bamboo-like microstructures were achieved in the steel wires.

Spatial normalization of brain images and beyond.

The deformable atlas paradigm has been at the core of computational anatomy during the last two decades. Spatial normalization is the variant endowing the atlas with a coordinate system used for voxel-based aggregation of images across subjects and studies. This framework has largely contributed to the success of brain mapping. Brain spatial normalization, however, is still ill-posed because of the complexity of the human brain architecture and the lack of architectural landmarks in standard morphological MRI. Multi-atlas strategies have been developed during the last decade to overcome some difficulties in the context of segmentation. A new generation of registration algorithms embedding architectural features inferred for instance from diffusion or functional MRI is on the verge to improve the architectural value of spatial normalization. A better understanding of the architectural meaning of the cortical folding pattern will lead to use some sulci as complementary constraints. Improving the architectural compliance of spatial normalization may impose to relax the diffeomorphic constraint usually underlying atlas warping. A two-level strategy could be designed: in each region, a dictionary of templates of incompatible folding patterns would be collected and matched in a way or another using rare architectural information, while individual subjects would be aligned using diffeomorphisms to the closest template. Manifold learning could help to aggregate subjects according to their morphology. Connectivity-based strategies could emerge as an alternative to deformation-based alignment leading to match the connectomes of the subjects rather than images.

CYP3A5 Genotype and Time to Reach Tacrolimus Therapeutic Levels in Renal Transplant Children.

BACKGROUND: CYP3A5 gene polymorphism rs776746 has been associated with lower tacrolimus dose requirements and bioavailability in both adults and children. This variant causes a loss of CYP3A5 activity owing to a splice site variant leading to a truncated inactive enzyme. The aim of this study was to determine if the rs776746 gene polymorphism is related to the time to reach tacrolimus therapeutic levels in renal transplant children. METHODS: A prospective study was performed in renal transplant children receiving tacrolimus as part of their immunosuppressive regime. CYP3A5 genotype was determined by direct sequencing. Tacrolimus trough levels and serum creatinine at 1 week and 1 month after renal transplantation was obtained from clinical chart. RESULTS: A total of 42 patients were included; 19 (45.2%) were female, 23 (54.8%) received living-donor transplants, and 21 patients expressed CYP3A5*1/*1 or CYP3A5*1/*3. Tacrolimus dose was higher in expressers at week 1 (0.13 vs 0.10 mg/kg/d; P = .011), and week 4 after transplantation (0.17 vs 0.09 mg/kg/d; P < .0001). At 4 weeks after renal transplantation, only 9 patients from the expressers group (42.8%) had levels ≥7 ng/mL, in contrast to 18 in the nonexpressers group (85.7%; Fisher exact P = .008). CONCLUSIONS: Tacrolimus dose was significant higher in functional CYP3A5 expressers. Only 42.8% of such expressers had tacrolimus trough levels ≥7 ng/mL at 1 month after transplantation despite dose adjustments. Long-term follow up is needed to address the consequences of early post-transplantation bioavailability differences due to CYP3A5 genotype.

Fast contrast-enhanced 4D MRA and 4D flow MRI using constrained reconstruction (HYPRFlow): potential applications for brain arteriovenous malformations.

BACKGROUND AND PURPOSE: HYPRFlow is a novel imaging strategy that provides fast, high-resolution contrast-enhanced time-resolved images and measurement of the velocity of the entire cerebrovascular system. Our hypothesis was that the images obtained with this strategy are of adequate diagnostic image quality to delineate the major components of AVMs. MATERIALS AND METHODS: HYPRFlow and 3D TOF scans were obtained in 21 patients with AVMs with correlative DSA examinations in 14 patients. The examinations were scored for image quality and graded by using the Spetzler-Martin criteria. Mean arterial transit time and overlap integrals were calculated from the dynamic image data. Volume flow rates in normal arteries and AVM feeding arteries were measured from the phase contrast data. RESULTS: HYPRFlow was equivalent to 3D-TOF in delineating normal arterial anatomy, arterial feeders, and nidus size and was concordant with DSA for AVM grading and venous drainage in 13 of the 14 examinations. Mean arterial transit time on the AVM side was 0.49 seconds, and on the normal contralateral side, 2.53 seconds with P < .001. Across all 21 subjects, the mean arterial volume flow rate in the M1 segment ipsilateral to the AVM was 4.07 ± 3.04 mL/s; on the contralateral M1 segment, it was 2.09 ± 0.64 mL/s. The mean volume flow rate in the largest feeding artery to the AVM was 3.86 ± 2.74 mL/s. CONCLUSIONS: HYPRFlow provides an alternative approach to the MRA evaluation of AVMs, with the advantages of increased coverage, 0.75-second temporal resolution, 0.68-mm isotropic spatial resolution, and quantitative measurement of flow in 6 minutes.

[Epidemiological characteristics of out-of-hospital cardiorespiratory arrest recorded by the 061 emergencies system (SAMU) in the Balearic Islands (Spain), 2009-2012]. / Características epidemiológicas de las paradas cardiorrespiratorias extrahospitalarias registradas por el sistema de emergencias 061 (SAMU) de la Comunidad Autónoma de las Islas Baleares (2009-2012).

OBJECTIVE: To describe the epidemiology of out-of-hospital cardiorespiratory arrest (OHCA) and identify factors associated with recovery of spontaneous circulation (ROSC). DESIGN: Observational study of OHCA registered on a continuous basis in the Emergency Medical Services (EMS) database during 2009-2012. SETTING: The islands of Mallorca, Ibiza, Menorca and Formentera (Balearic Islands, Spain). PATIENTS: OHCA in patients ≥ 18 years of age. The main variables were: Patient sex, age, probable cause, place of arrest, bystander, witnessed, basic life support (BLS), shockable rhythm, intervention time, semi-automatic defibrillator (AED), duration of cardiopulmonary arrest (CA), and ROSC. Independent variables were defined according to the Utstein protocol, and the dependent variable was defined as ROSC. RESULTS: The EMS treated 1170 OHCAs (28/100,000 persons-year). We included 1130 CA. The mean age was 61.4 years (73.4% males). Most CA (72.3%) were of cardiac etiology, and 84.7% were witnessed. A total of 840 (74.3%) received BLS and 400 (47.6%) did so before arrival of the EMS (45 by bystander relatives). AED was available in 330 cases CA (29.2%) (96 with shockable rhythm). The interval between emergency call and BLS and between emergency call and advanced life support was 8.4 and 15.8min, respectively. Shockable rhythm was monitored in 257 CAs (22.7%). ROSC occurred in 261 (23.1%). Factors associated with ROSC were age, shockable rhythm, BLS before EMS arrival, and CA duration less than 30min. CONCLUSION: The incidence rate of the OHCA is low. The proportion of patients receiving BLS from relatives was low. Age, shockable rhythm and BSL before EMS arrival were associated with ROSC.

Advanced technologies applied to physiopathological analysis of central nervous system aneurysms and vascular malformations.

While depiction and definition of morphological and architectural characteristics of CNS vascular disorders remains the first step of an MR analysis, emerging imaging techniques offer new functional information that might help to characterize rupture risk of CNS vascular disorders. Two main orientations are suggested by recent studies: inflammation of the vessel wall and analysis of physical constraints of blood flow using 4D flow imaging (shear parietal). This paper will focus on radiological application of 4D flow imaging and inflammation imaging, in the characterization of potential prognostic markers of CNS vascular disorders. We will review the basic technical considerations of 4D flow MRA, inflammation imaging and discuss their applications in CNS vascular disorders: aneurysms, arteriovenous malformation, dural arteriovenous fistulas. We will illustrate their potential in the development of individual rupture risk criteria in brain vascular disorders.

3D fast spin-echo T1 black-blood imaging for the diagnosis of cervical artery dissection.

SUMMARY: We performed non-contrast-enhanced 3D fast spin-echo T1 imaging with variable flip angles (CUBE T1) at 3T in 11 patients with CAD. CUBE T1 allowed easy diagnosis of CAD, owing to its comprehensive neck coverage, high spatial resolution enabling multiplanar reformations, fat saturation, and BB effect, the latter also allowing lumen patency to be studied. This sequence may replace 2D axial T1WI for the diagnosis of CAD.

Serum soluble interleukin 2 receptor (sIL-2R) as a marker of acute rejection in renal transplant children.

The aim of the study was to evaluate whether or not serum levels of soluble interleukin 2 receptor (sIL-2R) predict acute rejection in pediatric recipients. We studied 51 pediatric renal transplant recipients divided into three groups: Group 1) Biopsy-proven cellular acute rejection (n = 19), Group 2) Graft dysfunction with histological diagnosis other than acute rejection (n = 8) and Group 3) Patients with stable graft function, no biopsy (n = 24). Serum samples for sIL-2R measurement by sandwich ELISA were obtained at the time of renal transplant and at the time of renal biopsy due to graft dysfunction (Groups 1 and 2) or at six months post-transplant in the case of Group 3. The mean ± s.e. serum values of sIL-2R were higher in patients during acute rejection (6539 ± 1802 pg/mL) compared to patients with other causes of graft dysfunction (2217 ± 256 pg/mL) or stable graft function at six months (2183 ± 283 pg/mL) (Kruskal-Wallis p = 0.004). When the sIL2-R levels at the time of transplant were compared to those at the time of biopsy (Groups 1 and 2) or at six months post-transplant in Group 3, there was no significant difference between baseline and biopsy in the acute rejection group (paired t-test = 0.07), whereas there was a significant reduction in Groups 2 and 3.

Proteomic analysis of MCF-7 breast cancer cell line exposed to leptin.

BACKGROUND: Obesity is a well-known factor risk for breast cancer in postmenopausal women. Circulating leptin levels are increased in obese and it has been suggested to play an important role in mammary tumor formation and progression. To contribute to the understanding of the molecular mechanisms underlying leptin action in breast cancer, our aim was to identify proteins regulated by leptin in MCF-7 human breast cancer cells. METHODS: We used two-dimensional gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) to identify proteins affected by leptin. RESULTS: Thirty proteins were found differentially expressed in MCF-7 cells after 48 h leptin exposure. Proteins regulated by leptin included proteins previously implicated in breast cancer such as catechol-o-methyltransferase, cathepsin D, hsp27, serine/threonine-protein phosphatase and regulatory proteins of the Ras signaling pathway. Proteins involved in other cellular functions such as stress response, cytosqueleton remodeling and proteins belonging to ubiquitin-proteasome system, were also identified. Furthermore, leptin-treated cells showed a substantial uptake of the serum carrier proteins albumin and alpha-2-HS-glycoprotein. CONCLUSIONS: This screening reveals that leptin influences the levels of key proteins involved in breast cancer which opens new avenues for the study of the molecular mechanisms linking obesity to breast cancer.

Apathy is related to cortex morphology in CADASIL. A sulcal-based morphometry study.

OBJECTIVES: Apathy is a debilitating symptom in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the pathophysiology of which remains poorly understood. The aim of this study was to evaluate the neuroanatomic correlates of apathy, using new MRI postprocessing methods based on the identification of cortical sulci, in a large cohort of patients with CADASIL. METHODS: A total of 132 patients with genetically confirmed diagnosis were included in this prospective cohort study. Global cognitive performances were assessed by the Mattis Dementia Rating Scale (MDRS) and disability by the modified Rankin score (mRS). Apathy was defined according to standard criteria. Depth, width, and cortical thickness of 10 large sulci of the frontal lobe in each hemisphere were measured. Logistic regression modeling was used to evaluate the links between apathy and cortical thickness, depth, or width of the different sulci. All models were adjusted for age, gender, level of education, MDRS, mRS, depression, and global brain volume. RESULTS: Complete MRI datasets of high quality were available in 119 patients. Depth of the posterior cingulate sulcus exhibited the strongest association with apathy in fully adjusted models (right: p value = 0.0006; left: p value = 0.004). Depth and width of cortical sulci in mediofrontal and orbitofrontal areas were independently associated with apathy. By contrast, cortical thickness was not. CONCLUSIONS: Cortical morphology in mediofrontal and orbitofrontal areas, by contrast to cortical thickness, is strongly and independently associated with apathy. These results suggest that apathy is related to a reduction of cortical surface rather than of cortical thickness secondary to lesion accumulation in CADASIL.

Pre-transplant mycophenolate mofetil pharmacokinetics in Mexican children.

Mycophenolate mofetil is an immunosuppressive pro-drug frequently used to prevent renal graft rejection. It is hydrolyzed by esterases to obtain the active drug mycophenolic acid (MPA). There is high inter-patient variation in mycophenolic acid pharmacokinetics. Area under the concentration versus time curve (AUC) is used for therapeutic drug monitoring and recommended levels are 30-60 microg x hr/L. The aim of this study was to determine mycophenolic acid pharmacokinetics in children awaiting renal allograft in order to predict mycophenolate mofetil dose requirements. Children with end-stage renal disease on the waiting list for renal allograft transplantation were invited to participate in the study. A nine-point pharmacokinetic profile was performed. All patients received a single dose (600 mg/m2, subcutaneously) of mycophenolate mofetil at time zero. Mycophenolic acid was measured by HPLC. The AUC0-12h was estimated by the trapezoidal rule. Ten children were included in the study. Mean age was 13.5 +/- 3.5 years. The median AUC0-12h was 20.3 microg x hr/L, median Cmax = 0.7 microg/mL. Two children (20%) had no detectable levels of mycophenolic acid after a single mycophenolate mofetil dose, other two patients had AUC > 60 microg x hr/L. One patient had abdominal pain 1 hr after the mycophenolate mofetil dose. Twenty percent of our patients had AUC0-12h higher than the recommended value after a single mycophenolate mofetil dose, those patients should receive lower mycophenolate mofetil dose since the beginning of the transplant to avoid adverse events, and another 20% of patients had no detectable mycophenolic acid levels after a single mycophenolate mofetil dose. UGT1A9 gene polymorphisms remain to be studied in our patients, since they could explain the differences in bioavailability.

17ß-Estradiol regulates oxidative stress in prostate cancer cell lines according to ERalpha/ERbeta ratio.

Estrogen action is mediated by the two receptor isoforms: estrogen receptor alpha and beta. Both receptors are expressed in human prostate tissue and have different action profiles. ERalpha is positively correlated with the malignancy of prostate cancer, while ERbeta may protect against abnormal prostate cell growth. 17ß-Estradiol (E2), at least in part, induces cancerous transformations by causing deleterious mutations through the formation of reactive oxygen species (ROS). The aim was to study the effect of E2 on oxidative stress and the expression of uncoupling proteins (UCPs) and antioxidant enzymes in several prostate cancer cell lines with different ERalpha/ERbeta ratios. The cell prostate lines with a lower ERalpha/ERbeta ratio had lower oxidative stress, which could be partially explained by the increased expression of antioxidant enzymes and UCPs. Moreover, the action of E2 on the expression of antioxidant enzymes and UCPs was dual and dependent on the ERalpha/ERbeta ratio. Treatments with 0.1 nM E2 in cell lines with high ERalpha/ERbeta ratio produced a decrease in antioxidant enzymes and UCPs levels, with an increase in ROS production. These effects disappeared when the treatment was done in the presence of an ERalpha antagonist (MPP). In the cell lines with greatest levels of ERbeta and the lowest ERalpha/ERbeta ratio, E2 treatment caused the up-regulation of antioxidant enzymes and UCPs with a look-up decrease in ROS production. These effects were reversed when the cells were treated with E2 in the presence of an ERbeta antagonist (R,R-THC). On the whole, our results suggest a dual E2 effect; increasing or decreasing oxidative stress in part by modulation of UCPs and antioxidant enzymes according to the abundance ERbeta and ERalpha/ERbeta ratio in prostate cancer cell lines.