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In recent years there has been an increasing interest in expanded hemodialysis (HDx), an emerging renal replacement therapy based on the use of medium cut-off membranes (MCO). Thanks to the internal architecture of these types of membranes, with a higher pore size and smaller fiber inner diameter to favor internal filtration rate, they can increase the removal of larger middle molecules in conventional hemodialysis. Secondarily, several reports suggest that this therapy potentially improve the outcomes for end-stage renal disease patients. However, HDx has not been defined yet and the characteristics of MCO membranes are not well stablished. The aim of this narrative review is to define HDx and summarize the dialyzers that have been used so far to perform this therapy, collect the evidence available on its efficacy and clinical outcomes compared with other hemodialysis techniques and settle the bases for its optimal prescription.

SUMMARYThe generation of organs from stem cells by blastocyst complementation is a promising approach to cover the clinical need for transplants. In order to generate rejection-free organs, complementation of both parenchymal and vascular cells must be achieved, as endothelial cells play a key role in graft rejection. Here we used a lineage-specific cell ablation system to produce mouse embryos unable to form both the cardiac and vascular systems. By mouse intraspecies blastocyst complementation we rescued heart and vascular development separately and in combination, obtaining complemented hearts with cardiomyocytes and endothelial cells of exogenous origin. Complemented chimeras were viable and reached adult stage, showing normal cardiac function and no signs of histopathological defects in the heart. Furthermore, we implemented the cell ablation system for rat-to-mouse blastocyst complementation, obtaining xenogeneic hearts whose cardiomyocytes were completely of rat origin. These results represent an advance in the experimentation towards the in vivo generation of transplantable organs.

Healthcare workers, clinicians and/or researchers require information on the consequences of illness on their patients, as well as on the effects associated with treatments, when making decisions on recommended treatments and for follow-up evaluations of the same. Identifying health indicators which provide necessary and appropriate data for the evaluation of clinical outcomes in terms of Health-Related Quality of Life (HRQoL), as established by the WHO Biopsychosocial Model, and which provide appropriate and pertinent information on physical, mental and social factors in patients, can improve decision-making in relation to a comprehensive and global perspective of clinical outcomes of the various treatments and procedures given to patients. This chapter aims to provide an overview of the various tools for assessing Health-Related Quality of Life, as a growing number of clinicians, researchers and patient groups wish for comprehensive and not merely biological measures of health. This may be explained by the growing number of self-administered or interview questionnaires which have the aim of measuring changes in health as well as the consequences of the various treatments used mainly on chronicity and chronic health conditions. During recent decades, numerous tools have been developed and applied to the measurement of the effects of Health-Related Quality of Life in patients based on biological or physical aspects, psychological or mental aspects, and social aspects. This chapter will review the most frequently-used tools for the measurement of Health-Related Quality of Life, and recommendations are made for their use in medical care according to psychometric characteristics and quality criteria, as a guide for use in the field of healthcare, in public health, or in outcomes research.

Morbid obesity represents the most severe form of obesity and surgical intervention would be its only successful treatment. Bariatric surgery could generate modifications in carbohydrate metabolism and in lipid profile plus lipoprotein-associated proteins and enzymes, such as lipoprotein-associated phoslipase A2 (Lp-PLA2), cholesteryl ester transfer protein (CETP), and paraoxonase (PON) 1. The aim of the present study was to analyze changes in inflammation markers, carbohydrate metabolism, and lipid parameters in patients who underwent bariatric surgery. Thirty-seven patients with morbid obesity were recruited. Evaluations were performed before (T0) and 1 (T1) and 6 (T2) months after surgery. Glucose, insulin, high-sensitivity C-reactive protein (hsCRP), triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, apolipoproteins (apo) A-I, and B plus Interleukin 1β and 6 levels in addition to CETP, Lp-PLA2, and PON 1 activities were determined. Body mass index decreased at T1 and T2 (p

Dopaminergic denervation in patients with Parkinson's disease is associated with changes in brain metabolism. Cerebral in-vivo mapping of glucose metabolism has been studied in severe stable parkinsonian monkeys, but data on brain metabolic changes in early stages of dopaminergic depletion of this model is lacking. Here, we report cerebral metabolic changes associated with progressive nigrostriatal lesion in the pre-symptomatic and symptomatic stages of the progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model of Parkinson's Disease. Monkeys (Macaca fascicularis) received MPTP injections biweekly to induce progressive grades of dopamine depletion. Monkeys were sorted according to motor scale assessments in control, asymptomatic, recovered, mild, and severe parkinsonian groups. Dopaminergic depletion in the striatum and cerebral metabolic patterns across groups were studied in vivo by positron emission tomography (PET) using monoaminergic ([11C]-dihydrotetrabenazine; 11C-DTBZ) and metabolic (2-[18F]-fluoro-2-deoxy-d-glucose; 18F-FDG) radiotracers. 11C-DTBZ-PET analysis showed progressive decrease of binding potential values in the striatum of monkeys throughout MPTP administration and the development of parkinsonian signs. 18F-FDG analysis in asymptomatic and recovered animals showed significant hypometabolism in temporal and parietal areas of the cerebral cortex in association with moderate dopaminergic nigrostriatal depletion. Cortical hypometabolism extended to involve a larger area in mild parkinsonian monkeys, which also exhibited hypermetabolism in the globus pallidum pars interna and cerebellum. In severe parkinsonian monkeys, cortical hypometabolism extended further to lateral-frontal cortices and hypermetabolism also ensued in the thalamus and cerebellum. Unbiased histological quantification of neurons in Brodmann's area 7 in the parietal cortex did not reveal neuron loss in parkinsonian monkeys versus controls. Early dopaminergic nigrostriatal depletion is associated with cortical, mainly temporo-parietal hypometabolism unrelated to neuron loss. These findings, together with recent evidence from Parkinson's Disease patients, suggest that early cortical hypometabolism may be associated and driven by subcortical changes that need to be evaluated appropriately. Altogether, these findings could be relevant when potential disease modifying therapies become available.

BackgroundPolycystic Ovary Syndrome (PCOS) often present metabolic disorders and hyperandrogenism (HA), facts that may influence the telomere length (TL).AimsTo compare the absolute TL (aTL) between women with PCOS and control women, and their association with the presence of obesity and HA parameters.Materials and methodsThe PCOS group included 170 unrelated women outpatients and the control group, 64 unrelated donor women. Anthropometric, biochemical-clinical parameters and androgen profile were determined. The PCOS patients were divided accordingly to the presence of obesity and androgenic condition. The aTL was determined from peripheral blood leukocytes by Real Time quantitative PCR.ResultsWomen with PCOS exhibited a significantly longer aTL than controls after age adjustment (p=0.001). A stepwise multivariate linear regression in PCOS women, showed that WC (waist circumference) contributed negatively (b=-0.17) while testosterone levels contributed positively (b=7.24) to aTL. The non-Obese PCOS (noOB-PCOS) presented the longest aTL when compared to controls (p=0.001). Meanwhile, the aTL was significantly higher in the hyperandrogenic PCOS phenotype (HA-PCOS) than in the controls (p=0.001) and non hyperandrogenic PCOS phenotype (NHA-PCOS) (p=0.04). Interestingly, when considering obesity and HA parameters in PCOS, HA exerts the major effect over the aTL as non-obese HA exhibited the lengthiest aTL (23.9 ± 13.13 Kbp). Conversely, the obese NHA patients showed the shortest aTL (16.5 ± 10.59 Kbp).ConclusionsWhilst a shorter aTL could be related to the presence of obesity, a longer aTL would be associated with HA phenotype. These findings suggest a balance between the effect produced by the different metabolic and hormonal components, in PCOS women.

Background: the management of postoperative esophageal leaks is a huge therapeutic challenge. Thanks to the advances in endoscopy, treatment with esophageal stents has been proposed as a valid option. Aims: the main objective of the study was to evaluate the effectiveness and safety of the use of fully covered esophageal metal stents in the treatment of postoperative esophageal leaks. Methods: a retrospective observational study was performed in patients with postoperative esophageal leaks, treated with fully covered self-expandable metal stents between June 2011 and May 2018. Results: twenty-five patients were evaluated and 34 stents were placed. The closure of the leak was observed in 21 patients after removal of the stent, with an overall technical success rate of 84 %. The mean time with a stent placed for closure of the fistula was 55.7 ± 27.11 days/patient (mean of 39 ± 24.30 days/stent). The most frequent complication was a partial distal stent migration (7/34 stents), followed by five cases of complete migration into the stomach. Conclusions: endoscopic treatment with fully covered self-expandable metal stents seems to be an effective and safe first-line treatment for postoperative esophageal leaks, according to the experience in our center.

Se propone una metodología docente alternativa para la realización de proyectos arquitectónicos, en el primer curso de esta asignatura en la Escuela Técnica Superior de Arquitectura de Madrid. Se utiliza una caja de juegos creada por el equipo docente, formada por cuatro barajas diferentes, en la que la elección fortuita de sus cartas sirve como desencadenante del proceso creativo del alumno. Se toma como referencia principal el proyecto realizado en 1975 por el músico Brian Eno y el artista Peter Schmidt, titulado “Oblique Strategies. Over One Hundred Worthwhile Dilemmas”, consistente en un conjunto de tarjetas con mensajes evocadores capaces de fomentar el pensamiento lateral en situaciones en la que el artista se ve bloqueado. A partir de provocaciones controladas, diferentes estrategias o trucos, contenidos en una serie de cartas que cada alumno debe ir descubriendo de forma a aleatoria a lo largo del curso, se plantean analogías, comparando ideas desvinculadas de lo racional, con ánimo de alejarse de los estereotipos, e indagar en la posibilidad de diferentes opciones. Se ensaya la inversión de conceptos y procesos, alterando su sentido para reconocer su contrario y experimentar el problema de manera diferente, descubriendo nuevos órdenes y modelos de entendimiento. La negación de las características obvias permite generar nuevas situaciones posibles. Maniobras todas fruto del acierto y la intensidad, las cartas se convertirán en la herramienta desde la que comenzar estas acciones. El desarrollo del juego incluye tres ejercicios con una duración de cuatro semanas cada uno de ellos, en los que deben proponer un espacio de juegos, un conjunto de espacios habitables y una estructura identificada como espacio comunitario. De cada uno de ellos realizarán los planos y las maquetas necesarias para su comprensión. Organizada en cuatro grandes grupos, Programa, Material, Acción y Sugerencia, las cartas de cada uno de estos apartados marcan el devenir de la partida. El movimiento de inicio obliga a cada alumno a coger una de cada mazo, configurando así la posición de partida de su curso. Tras la finalización del primer ejercicio, y habiendo realizado una encuesta a los alumnos sobre la pertinencia de la metodología empleada, algo más de la mitad consideran las cartas como una herramienta que facilita el desarrollo del proyecto mientras que el resto ha tenido dificultades al interpretar las instrucciones derivadas de su uso. Sin embargo, la gran mayoría de ellos, cerca del 80%, admiten que los resultados obtenidos son buenos, tanto por innovadores como por inesperados. El uso de esta nueva baraja permite afirmar que la combinación del azar y el rigor en la docencia de proyectos arquitectónicos lleva al alumno a generar soluciones alejadas de las ideas preconcebidas con las que afronta sus primeros cursos. La primera variable, como componente capaz de desbloquear y desencadenar proceso creativos, y la segunda, como confirmación y materialización de unas intuiciones desde las herramientas específicas del arquitecto. Las posibilidades de combinación, intercambio y adición de cartas a partir de las iniciales, ofrece un recorrido ilimitado en el desarrollo individual de los proyectos en el aula, derivado de la interpretación personal de los mensajes descubiertos en las cartas. Dentro del marco de la enseñanza de los primeros cursos de la asignatura de proyectos arquitectónicos, la herramienta permite acelerar el proceso creativo, concediendo al azar y a la intuición un papel principal que más tarde debe ser refrendado por la razón en el desarrollo completo de los ejercicios propuestos. No existe una única respuesta correcta al problema sino que dependiendo de la capacidad de cada alumno de modificar sus propuestas, lo que permite alcanzar una solución válida como parte de un proceso creativo evolutivo.

To evaluate Interleukin 1-beta (IL-1β) serum and mononuclear leucocyte mRNA levels, also rs16944 (−511C/T) genotype, in relation to hyperglycemic normalization in Type 2 diabetes (T2D) patients, we recruited 30 individuals recently T2D diagnosed with hyperglycemia studied at basal time and after 6 and 12 months of the normalization treatment. At basal time, the T polymorphic allele of the rs16944 was associated with lower IL-1β mRNA expression (p = 0.006); and higher glucose level was positive correlated to IL-1β protein levels (p = 0.015). After treatment, the individuals showed a significant decrease in glucose level (p = 0.003), but they did not express significant changes in the IL-1β serum levels. Surprisingly, we observed that the greater decreases in glucose level were associated to increased IL-1β serum levels (p = 0.040). This is the first follow-up study evaluating IL-1β mRNA expression and serum levels in hyperglycemic T2D individuals and after glycemic normalization treatment. The current results contribute to the knowledge of the relationship between inflammation and glucose metabolism in T2D. Fil: Iglesias Molli, Andrea Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Bergonzi, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Spalvieri, Mónica Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Linari, María Amelia. Union Obrera Metalurgica.; Argentina Fil: Frechtel, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina Fil: Cerrone, Gloria Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina

Introduccion: la calprotectina fecal es un parametro util a la hora de decidir si un paciente se puede beneficiar de la realizacion de estudios endoscopicos. No obstante, cierto numero de individuos sintomaticos y con cifras elevadas de este marcador no tendran lesiones endoscopicas. El objetivo de este estudio es determinar que factores se asocian a cifras alteradas de calprotectina fecal en pacientes con estudios endoscopicos de intestino delgado y colon normales. Metodos: estudio prospectivo y observacional de pacientes con sintomas digestivos. Se ha analizado la asociacion de diferentes variables con cifras alteradas de calprotectina y estudios endoscopicos (capsula de intestino delgado y colonoscopia) negativos. Resultados: se incluyen 143 pacientes (98 mujeres – 68,5 %), con una edad media 40,06 ± 16,42 (15-82) anos. El consumo de tabaco y la toma de antiinflamatorios no esteroideos se asocio a la presencia de cifras alteradas de calprotectina y estudios endoscopicos negativos (p: 0,029 y p: 0,006). Los valores medios de calprotectina fecal fueron significativamente mayores entre los fumadores, consumidores de antiinflamatorios y pacientes con test positivo de sobrecrecimiento bacteriano de intestino delgado. El tabaquismo (OR: 3,505; p: 0,028), la toma de antiinflamatorios (OR: 3,473; p: 0,021) y el sobrecrecimiento bacteriano (OR: 3,172; p: 0,013) son factores de riesgo independientes para presentar una calprotectina alterada sin lesiones endoscopicas. No se obtuvo asociacion con ninguna otra variable. Conclusiones: el consumo de tabaco y de antiinflamatorios no esteroideos tiene una fuerte asociacion con la presencia de valores elevados de calprotectina en ausencia de lesiones endoscopicas. Se ha observado tambien asociacion con el sobrecrecimiento bacteriano de intestino delgado.

Resumen Introduccion el uso de la enteroscopia con videocapsula fue aprobado por la FDA en 2001. La hemorragia digestiva y la enfermedad inflamatoria intestinal son sus principales indicaciones. En nuestro centro se realiza desde 2004. Material y metodos Hemos recogido de forma retrospectiva los pacientes tratados mediante capsula de intestino delgado desde octubre de 2004 hasta abril de 2015. Las indicaciones se han dividido en grupos: hemorragia digestiva de origen oscuro, tanto oculta como manifiesta; enfermedad inflamatoria intestinal; otras indicaciones. Los hallazgos se han dividido: lesiones vasculares; lesiones inflamatorias; otras lesiones; estudios normales; estudios no concluyentes. Resultados De un total de 1.291 estudios se ha incluido 1.027 en el analisis. La edad media es 56,45 anos, con 471 hombres y 556 mujeres. La enfermedad mas frecuentemente observada fueron las lesiones vasculares, asociadas o no a otras lesiones. Cuando la indicacion era una hemorragia digestiva, el impacto diagnostico fue del 80%. En la enfermedad inflamatoria esta cifra solo alcanza el 50%. El rendimiento diagnostico es mucho menor en el grupo de «otras indicaciones». No se han registrado complicaciones mayores. Discusion La capsula de intestino delgado tiene un alto rendimiento diagnostico en los casos de hemorragia digestiva; el numero de estudios con hallazgos positivos es menor en los de enfermedad inflamatoria intestinal. Conclusiones Se trata de una modalidad diagnostica segura y de gran utilidad para el diagnostico de enfermedad del intestino delgado, aunque se precisa mejorar el indice de sospecha en la enfermedad inflamatoria intestinal.

Introducción: la hiperglucemia es uno de los más importantes factores que determinan la producción de estrés oxidativo e inflamación, procesos que pueden acelerar el acortamiento de los telómeros.Objetivos: analizar la longitud telomérica absoluta (LTa) en individuos con niveles de glucosa en ayunas alterada (GAA) en comparación con individuos que presentan niveles normales de glucosa (GAN). Estudiar a partir de un estudio prospectivo controlado, la variación en la LTa en pacientes con DM2 descompensada antes y después del tratamiento.Materiales y métodos: se estudió una población de 246 individuos de ambos sexos, conformada por individuos con obesidad, individuos con DM2 o MODY e individuos controles sanos. Se dividieron en individuos con niveles de glucemia =110 mg/dl y 50Y). Se estudió un subgrupo de 30 pacientes con DM2 de reciente diagnóstico, al inicio (T0) y a los 6 meses (T6) de un tratamiento farmacológico y medidas higiénico-dietéticas, con el objetivo de lograr la compensación metabólica. En ambos estudios se determinaron las variables bioquímico-clínicas de todos los individuos y la LTa por PCR cuantitativa en tiempo real. Los análisis estadísticos se realizaron utilizando el software GraphPad Prism y SPSS.

ResumenLa obesidad es el principal componente del síndrome metabólico (SM) y determina la progresión de la enfermedad a las complicaciones metabólicas. Los individuos obesos metabólicamente sanos (OMS) parecen estar protegidos contra esas complicaciones. La longitud de los telómeros (LT) es un nuevo marcador del envejecimiento celular, que tiene una relación compleja con el SM. El objetivo principal de este estudio fue investigar por primera vez la LT en OMS y estudiar la asociación entre LT y el número de componentes del SM.Se estudió a 398 mujeres con una edad media de 46,76±15,47 años (rango: 18-86 años), que se agruparon en: individuos con normopeso sin ningún componente del SM (NP0), obesos sin SM (OMS) y de acuerdo con el número de componentes de SM en los grupos sin ningún componentes de SM (0), con uno o 2 componentes (1+2) y con SM por la presencia de 3 o más componentes (SM).La LT de los OMS no se diferenció de la de los NP0, pero fue significativamente mayor que la de los individuos con SM (p=0,032). Se observó una disminución de la LT con el aumento progresivo del número de componentes del SM (p=0,004), en donde el grupo 0 presentó una LT significativamente mayor que los grupos 1+2 (p=0,027) y SM (p=0,003).Demostramos por primera vez que las mujeres OMS presentan una LT similar a las mujeres NP0 y más larga que aquellas mujeres con SM. Además, confirmamos que la LT se acorta con el aumento en el número de alteraciones del SM.AbstractObesity is the principal component in Metabolic Syndrome (MetS) and determines the progression of metabolic complications. Metabolically healthy obese individuals (MHO) seem to be protected against those complications. Telomere length (TL), as a novel marker of cellular aging, has a complex relationship with MetS. The principal aim of this study was to investigate TL in MHO, and to study the association between TL and the number of MetS components.A study was conducted on 398 women (mean age: 46.76±15.47 years; range: 18 - 86 years), grouped according to the number of MetS components (0, 1+2, MetS), a group of normal-weight individuals with 0 MetS components (NW0), and a group of obese without MetS (MHO).No differences were found in the TL of the MHO group compared to the NW0, but it was significantly higher than that of individuals with MetS (P=.032). A decrease in TL was observed with a progressive increase in the number of MetS components (P=.004), whereas the group of individuals without MetS components had significantly longer TL than the groups with 1 and 2 components (P=.027), and MetS (P=.003).Shorter TL is not associated with MHO, but is related to MetS and with an increased number of metabolic abnormalities.

Background: Even before the onset of age-related diseases, obesity might be a contributing factor to the cumulative burden of oxidative stress and chronic inflammation throughout the life course. Obesity may therefore contribute to accelerated shortening of telomeres. Consequently, obese persons are more likely to have shorter telomeres, but the association between body mass index (BMI) and leukocyte telomere length (TL) might differ across the life span and between ethnicities and sexes. Objective: A collaborative cross-sectionalmeta-analysis of observational studies was conducted to investigate the associations between BMI and TL across the life span. Design: Eighty-seven distinct study samples were included in the meta-analysis capturing data from 146,114 individuals. Studyspecific age- and sex-adjusted regression coefficients were combined by using a random-effects model in which absolute [base pairs (bp)] and relative telomere to single-copy gene ratio (T/S ratio) TLs were regressed against BMI. Stratified analysis was performed by 3 age categories ("young": 18-60 y; "middle": 61-75 y; and "old": >75 y), sex, and ethnicity. Results: Each unit increase in BMI corresponded to a-3.99 bp (95% CI: -5.17, -2.81 bp) difference in TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -7.67 bp (95% CI:-10.03,-5.31 bp) difference. Each unit increase in BMI corresponded to a -1.58 × 10-3 unit T/S ratio (0.16% decrease; 95% CI: -2.14 × 10-3, -1.01 × 10-3) difference in ageand sex-adjusted relative TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -2.58 × 10-3 unit T/S ratio (0.26% decrease; 95% CI: -3.92 × 10-3, -1.25 × 10-3). The associations were predominantly for the white pooled population. No sex differences were observed. Conclusions: A higher BMI is associated with shorter telomeres, especially in younger individuals. The presently observed difference is not negligible. Meta-analyses of longitudinal studies evaluating change in body weight alongside change in TL arewarranted.

Splenorenal shunts are a rare cause of hyperammonemia and hepatic encephalopathy in the absence of cirrhosis. We report the case of a woman, who presented hepatic encephalopathy, with a normal functioning graft, after 14 years of liver transplantation, confirmed by liver biopsy.

Brucella abortus induces an inflammatory response that stimulates the endocrine system resulting in the secretion of cortisol and dehydroepiandrosterone (DHEA). Osteoarticular brucellosis is the most common presentation of the active disease in humans, and we have previously demonstrated that B. abortus infection inhibits osteoblast function. We aimed to evaluate the role of cortisol and DHEA on osteoblast during B. abortus infection. B. abortus infection induces apoptosis and inhibits osteoblast function. DHEA treatment reversed the effect of B. abortus infection on osteoblast by increasing their proliferation, inhibiting osteoblast apoptosis, and reversing the inhibitory effect of B. abortus on osteoblast differentiation and function. By contrast, cortisol increased the effect of B. abortus infection. Cortisol regulates target genes by binding to the glucocorticoid receptor (GR). B. abortus infection inhibited GRa expression. Cell responses to cortisol not only depend on GR expression but also on its intracellular bioavailability, that is, dependent on the activity of the isoenzymes 11β-hydroxysteroid dehydrogenase (HSD) type-1, 11β-HSD2 (which convert cortisone to cortisol and vice versa, respectively). Alterations in the expression of these isoenzymes in bone cells are associated with bone loss. B. abortus infection increased 11β-HSD1 expression but had no effect on 11β-HSD2. DHEA reversed the inhibitory effect induced by B. abortus infection on osteoblast matrix deposition in an estrogen receptor- and ERK1/2-dependent manner. We conclude that DHEA intervention improves osteoblast function during B. abortus infection making it a potential candidate to ameliorate the osteoarticular symptoms of brucellosis. Fil: Gentilini, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Pesce Viglietti, Ayelén Ivana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Arriola Benitez, Paula Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Iglesias Molli, Andrea Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Cerrone, Gloria Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Delpino, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina

TANK-binding kinase 1 (TBK1) loss-of-function (LoF) mutations are known to cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), often combined with memory deficits early in the disease course. We performed targeted resequencing of TBK1 in 1253 early onset Alzheimer's disease (EOAD) patients from 8 European countries to investigate whether pathogenic TBK1 mutations are enriched among patients with clinical diagnosis of EOAD. Variant frequencies were compared against 2117 origin-matched controls. We identified only 1 LoF mutation (p.Thr79del) in a patient clinically diagnosed with Alzheimer's disease and a positive family history of ALS. We did not observe enrichment of rare variants in EOAD patients compared to controls, nor of rare variants affecting NFκB induction. Of 3 common coding variants, rs7486100 showed evidence of association (OR 1.46 [95% CI 1.13-1.9]; p-value 0.01). Homozygous carriers of the risk allele showed reduced expression of TBK1 (p-value 0.03). Our findings are not indicative of a significant role for TBK1 mutations in EOAD. The association between common variants in TBK1, disease risk and reduced TBK1 expression warrants follow-up in FTD/ALS cohorts. ispartof: Neurobiology of Aging vol:62 pages:245- ispartof: location:United States status: published

The Metabolic Syndrome (MetS) is a cluster of cardiometabolic risk factors, usually accompanied by the presence of insulin resistance (IR) and a systemic subclinical inflammation state. Metabolically healthy obese (MHO) individuals seem to be protected against cardiometabolic complications. The aim of this work was to characterize phenotypically the low-grade inflammation and the IR in MHO individuals in comparison to obese individuals with MetS and control non obese. We studied two different populations: 940 individuals from the general population of Buenos Aires and 518 individuals from the general population of Venado Tuerto; grouped in three groups: metabolically healthy non-obese individuals (MHNO), MHO and obese individuals with MetS (MSO). Inflammation was measured by the levels of hs-CRP (high-sensitivity C reactive protein), and we found that MHO presented an increase in inflammation when compared with MHNO (Buenos Aires: p

Brucella abortus induces an inflammatory response that stimulates the endocrine system resulting in the secretion of cortisol and dehydroepiandrosterone (DHEA). Osteoarticular brucellosis is the most common presentation of the active disease in humans, and we have previously demonstrated that B. abortus infection inhibits osteoblast function. We aimed to evaluate the role of cortisol and DHEA on osteoblast during B. abortus infection. B. abortus infection induces apoptosis and inhibits osteoblast function. DHEA treatment reversed the effect of B. abortus infection on osteoblast by increasing their proliferation, inhibiting osteoblast apoptosis, and reversing the inhibitory effect of B. abortus on osteoblast differentiation and function. By contrast, cortisol increased the effect of B. abortus infection. Cortisol regulates target genes by binding to the glucocorticoid receptor (GR). B. abortus infection inhibited GRα expression. Cell responses to cortisol not only depend on GR expression but also on its intracellular bioavailability, that is, dependent on the activity of the isoenzymes 11β-hydroxysteroid dehydrogenase (HSD) type-1, 11β-HSD2 (which convert cortisone to cortisol and vice versa, respectively). Alterations in the expression of these isoenzymes in bone cells are associated with bone loss. B. abortus infection increased 11β-HSD1 expression but had no effect on 11β-HSD2. DHEA reversed the inhibitory effect induced by B. abortus infection on osteoblast matrix deposition in an estrogen receptor- and ERK1/2-dependent manner. We conclude that DHEA intervention improves osteoblast function during B. abortus infection making it a potential candidate to ameliorate the osteoarticular symptoms of brucellosis.

Background Patients with difficult-to-treat idiopathic nephrotic syndrome (INS), steroid-dependent nephrotic syndrome (SDNS), or frequently relapsing nephrotic syndrome (FRNS) require long-term immunosuppressive therapy. Rituximab offers an alternative treatment for patients with disease that has not responded to multiple therapies. Objective Our objective was to determine the efficacy and safety of rituximab in adult patients with difficult-to-treat (SDNS or FRNS) INS. Methods We performed a retrospective multicenter study that included 50 adults with difficult-to-treat INS in six Spanish centers. All patients were treated with steroids in combination with another immunosuppressant: 28 patients received rituximab as the additional treatment (rituximab group), and the other 22 patients not treated with rituximab served as the control group. Results Of the patients treated with rituximab, 23 (82%) experienced complete remission, 20 (71%) had no relapses after receiving rituximab, and 13 (46%) did not receive any immunosuppressant. Of those in the control group, 14 (63%) experienced complete remission, including eight without immunosuppressants (29%). The rituximab group experienced highly significant reductions in total number of relapses per year (p < 0.001), proteinuria (p = 0.03), steroid doses (p = 0.002), and tacrolimus doses (p = 0.001). Mean follow-up after rituximab was 31 +/- 26 months (range 8-86). The need for steroids and other immunosuppressants to achieve sustained remission was lower in the rituximab group than in the control group. Conclusions Rituximab treatment was safe and well tolerated. It effectively reduced the incidence of relapses and need for maintenance immunosuppressive therapy in adults with difficult-to-treat INS.