588 research outputs found
Ad infinitum
Treballs Finals de Grau de Belles Arts. Facultat de Belles Arts. Universitat de Barcelona, Curs: 2015-16, Tutora: Eulàlia Grau Costa[cat] Ad Infinitum és un treball que pretén ser un “Estudi del buit” entenent-lo com espai amb capacitat d’expansió indefinida, un espai obert i infinit que vull capturar i fer sensible a l’espectador mitjançant línies i formes geomètriques que el defineixen i el modelen. A través de l’estudi dels treballs anteriors, faig un repàs de com s’ha anat generant la concepció que tinc del buit i quins conceptes s’han anat esclarint a mida que descobria nous referents artístics per tal d’apropar-me més a les sensacions que vull reflectir. Així doncs, la instal·lació que es presenta en aquest treball és la continuació de tot l’estudi realitzat durant els darrers anys,
i que pretén generar en l’espectador una nova experiència de la percepció de l’espai i del buit, entenent-lo com a quelcom incommensurable, que inevitablement relaciono amb la foscor i l’espai còsmic.[eng] Ad Infinitum is a work which wants to be a “Study about vacuum” understanding it as a space which can be expanded undefined, an opened and infinite space that I want to capture and make it perceptible to the observer by lines and geometric forms which reveals and configure it. By the previous works, I make a review about how my idea of the vacuum has been generated and which concepts have become clearer while I was discovering new artistic models to be closer to the sense I want to show. So the installation of this work wants to produce to the observer a new experience of perception of the space and the vacuum, understanding it as a something incommensurable that I relate with the darkness and the cosmic space inevitably
Metabolic Profiling in Maturity-Onset Diabetes of the Young (MODY) and Young Onset Type 2 Diabetes Fails to Detect Robust Urinary Biomarkers
It is important to identify patients with Maturity-onset diabetes of the young (MODY) as a molecular diagnosis determines both treatment and prognosis. Genetic testing is currently expensive and many patients are therefore not assessed and are misclassified as having either type 1 or type 2 diabetes. Biomarkers could facilitate the prioritisation of patients for genetic testing. We hypothesised that patients with different underlying genetic aetiologies for their diabetes could have distinct metabolic profiles which may uncover novel biomarkers. The aim of this study was to perform metabolic profiling in urine from patients with MODY due to mutations in the genes encoding glucokinase (GCK) or hepatocyte nuclear factor 1 alpha (HNF1A), type 2 diabetes (T2D) and normoglycaemic control subjects. Urinary metabolic profiling by Nuclear Magnetic Resonance (NMR) and ultra performance liquid chromatography hyphenated to Q-TOF mass spectrometry (UPLC-MS) was performed in a Discovery set of subjects with HNF1A-MODY (n = 14), GCK-MODY (n = 17), T2D (n = 14) and normoglycaemic controls (n = 34). Data were used to build a valid partial least squares discriminate analysis (PLS-DA) model where HNF1A-MODY subjects could be separated from the other diabetes subtypes. No single metabolite contributed significantly to the separation of the patient groups. However, betaine, valine, glycine and glucose were elevated in the urine of HNF1A-MODY subjects compared to the other subgroups. Direct measurements of urinary amino acids and betaine in an extended dataset did not support differences between patients groups. Elevated urinary glucose in HNF1A-MODY is consistent with the previously reported low renal threshold for glucose in this genetic subtype. In conclusion, we report the first metabolic profiling study in monogenic diabetes and show that, despite the distinct biochemical pathways affected, there are unlikely to be robust urinary biomarkers which distinguish monogenic subtypes from T2D. Our results have implications for studies investigating metabolic profiles in complex traits including T2D.publishedVersio
Assessment of High-Sensitivity C-Reactive Protein Levels as Diagnostic Discriminator of Maturity-Onset Diabetes of the Young Due to HNF1A Mutations
OBJECTIVE: Despite the clinical importance of an accurate diagnosis in individuals with monogenic forms of diabetes, restricted access to genetic testing leaves many patients with undiagnosed diabetes. Recently, common variation near the HNF1 homeobox A (HNF1A) gene was shown to influence C-reactive protein levels in healthy adults. We hypothesized that serum levels of high-sensitivity C-reactive protein (hs-CRP) could represent a clinically useful biomarker for the identification of HNF1A mutations causing maturity-onset diabetes of the young (MODY). RESEARCH DESIGN AND METHODS: Serum hs-CRP was measured in subjects with HNF1A-MODY (n = 31), autoimmune diabetes (n = 316), type 2 diabetes (n = 240), and glucokinase (GCK) MODY (n = 24) and in nondiabetic individuals (n = 198). The discriminative accuracy of hs-CRP was evaluated through receiver operating characteristic (ROC) curve analysis, and performance was compared with standard diagnostic criteria. Our primary analyses excluded approximately 11% of subjects in whom the single available hs-CRP measurement was >10 mg/l. RESULTS: Geometric mean (SD range) hs-CRP levels were significantly lower (
Utilización de recursos de atención primaria por parte de inmigrantes y autóctonos que han contactado con los servicios asistenciales de la ciudad de Lleida
ObjetivoEvaluar y comparar la utilización de recursos en los distintos servicios de atención primaria (AP) entre inmigrantes y autóctonos.DiseñoEstudio observacional transversal en población visitada en AP.EmplazamientoPersonas atendidas por 15 médicos de AP en 5 áreas básicas de salud (ABS) de la ciudad de Lleida de marzo a agosto de 2005.ParticipantesSe incluyó a todos los inmigrantes atendidos durante el período de estudio (1.599 pacientes de origen inmigrante). Se realizó un muestreo aleatorio de 300 pacientes en cada una de las 15 consultas participantes (4.156 pacientes de origen autóctono). Se consideró población autóctona aquella cuyo país de origen es España y población inmigrante aquella que proviene de los países de renta baja y media, independientemente del tiempo de asistencia al ABS.Mediciones principalesEdad, sexo, tipo de visitas realizadas y las derivaciones efectuadas. Se utilizaron modelos de regresión multinomial para estimar el riesgo relativo (RR) de haber realizado las visitas.ResultadosLos inmigrantes tienen una probabilidad superior a los autóctonos de realizar más de 3 visitas, frente a 1 o 2 visitas (RR = 1,23; intervalo de confianza [IC] del 95%, 1,04-1,91%). La estimación del RR de haber realizado visitas es superior en los inmigrantes para todas las categorías, excepto en enfermería (RR = 0,59; IC del 95%, 0,5-0,71%).ConclusionesLos inmigrantes que contactan con AP lo hacen con mayor frecuencia en las consultas de medicina de familia y de ginecología, y además se realizan más pruebas complementarias. Sin embargo, la frecuentación del colectivo inmigrante a las consultas de enfermería parece ser inferior.ObjectiveTo evaluate and compare the use of the different primary care (PC) services between immigrants and the indigenous population.DesignCross-sectional observation study of a population seen in (PC).SettingPatients seen by 15 PC doctors, in 5 basic health areas (BHA) in the city of Lleida, Spain, from March to August 2005.ParticipantsAll immigrants (1599 patients of immigrant origin) who seen during the study period were included. A random sample of 300 patients was taken from each of the 15 participating clinics (4156 autochthonous patients). The autochthonous was considered as those whose country of origin is Spain and the immigrant population those who come from low and medium income countries, regardless of the time of residence in the BHA.Primary measurementsAge, sex, type of visit made, and referrals made. Multinomial regression models were used to calculate the relative risk (RR) of having made visits.ResultsImmigrants have a higher probability to make 3 visits than the indigenous population, who would make 1 or 2 visits (RR, 1.23; 95% confidence interval, 1.04-1.91). The estimation of the RR of having made visits is higher in the immigrants for all categories, except nursing.ConclusionsImmigrants who come into contact with PC, make more frequent visits to the family doctor and gynaecology, and also have more complementary tests done. However, the frequency of use of the immigrant group for nursing visits seems to be less
PiwiRNA-651 as marker of treatment response and survival in classical Hodgkin lymphoma.
PiwiRNAs, small non-coding RNAs processed by Piwi proteins, are involved in maintaining genome stability in germline cells. Recently, piwiRNA expression has been identified in some tumors. We have examined the potential reactivation of the Piwi/piwiRNA pathway in classical Hodgkin lymphoma (cHL). We found that Piwi proteins and three selected piwiRNAs, including piR-651, were expressed in cHL patients and cell lines, indicating that the Piwi/piwiRNA pathway is active in cHL. Interestingly, low levels of piR-651 were associated with lack of complete response to first-line treatment, as well as shorter disease-free and overall survival in a cohort of 94 cHL patients. At diagnosis, piR-651 was underexpressed in cHL serum samples compared to healthy controls, while after complete remission, piR-651 levels increased to levels similar to healthy controls. This is the first evidence that piwiRNAs are active in tumor and serum samples and impact prognosis in cHL
Lestaurtinib Inhibition of the JAK/STAT Signaling Pathway in Hodgkin Lymphoma Inhibits Proliferation and Induces Apoptosis
Standard cytotoxic chemotherapy for Hodgkin Lymphoma (HL) has changed little in 30 years; the treatment for patients with relapsed or refractory disease remains challenging and novel agents are under development. JAK/STAT constitutive activation plays an important role in the pathogenesis of HL. Lestaurtinib is an orally bioavailable multikinase inhibitor that has recently been shown to inhibit JAK2 in myeloproliferative disorders. The potential role of Lestaurtinib in HL therapy is unknown. We have analyzed the effect of Lestaurtinib treatment in five HL cell lines from refractory patients, L-428, L-1236, L-540, HDML-2 and HD-MY-Z. At 48 h, a dose-dependent cell growth inhibition (23%–66% at 300 nM) and apoptotic increment (10%–64% at 300 nM) were observed. Moreover, Lestaurtinib inhibited JAK2, STAT5 and STAT3 phosphorylation and reduced the mRNA expression of its downstream antiapoptotic target Bcl-xL. In addition, we have analyzed the effect of Lestaurtinib treatment in lymph nodes from four classic HL patients. We observed a decrease in cell viability at 24 hours of treatment in three patients (mean decrease of 27% at 300 nM). Our findings provide, for the first time, a molecular rationale for testing JAK2 inhibitors, specifically Lestaurtinib, in HL patients
Development and Validation of a New Prognostic System for Patients with Hepatocellular Carcinoma
BACKGROUND:
Prognostic assessment in patients with hepatocellular carcinoma (HCC) remains controversial. Using the Italian Liver Cancer (ITA.LI.CA) database as a training set, we sought to develop and validate a new prognostic system for patients with HCC.
METHODS AND FINDINGS:
Prospective collected databases from Italy (training cohort, n = 3,628; internal validation cohort, n = 1,555) and Taiwan (external validation cohort, n = 2,651) were used to develop the ITA.LI.CA prognostic system. We first defined ITA.LI.CA stages (0, A, B1, B2, B3, C) using only tumor characteristics (largest tumor diameter, number of nodules, intra- and extrahepatic macroscopic vascular invasion, extrahepatic metastases). A parametric multivariable survival model was then used to calculate the relative prognostic value of ITA.LI.CA tumor stage, Eastern Cooperative Oncology Group (ECOG) performance status, Child-Pugh score (CPS), and alpha-fetoprotein (AFP) in predicting individual survival. Based on the model results, an ITA.LI.CA integrated prognostic score (from 0 to 13 points) was constructed, and its prognostic power compared with that of other integrated systems (BCLC, HKLC, MESIAH, CLIP, JIS). Median follow-up was 58 mo for Italian patients (interquartile range, 26-106 mo) and 39 mo for Taiwanese patients (interquartile range, 12-61 mo). The ITA.LI.CA integrated prognostic score showed optimal discrimination and calibration abilities in Italian patients. Observed median survival in the training and internal validation sets was 57 and 61 mo, respectively, in quartile 1 (ITA.LI.CA score 64 1), 43 and 38 mo in quartile 2 (ITA.LI.CA score 2-3), 23 and 23 mo in quartile 3 (ITA.LI.CA score 4-5), and 9 and 8 mo in quartile 4 (ITA.LI.CA score > 5). Observed and predicted median survival in the training and internal validation sets largely coincided. Although observed and predicted survival estimations were significantly lower (log-rank test, p < 0.001) in Italian than in Taiwanese patients, the ITA.LI.CA score maintained very high discrimination and calibration features also in the external validation cohort. The concordance index (C index) of the ITA.LI.CA score in the internal and external validation cohorts was 0.71 and 0.78, respectively. The ITA.LI.CA score's prognostic ability was significantly better (p < 0.001) than that of BCLC stage (respective C indexes of 0.64 and 0.73), CLIP score (0.68 and 0.75), JIS stage (0.67 and 0.70), MESIAH score (0.69 and 0.77), and HKLC stage (0.68 and 0.75). The main limitations of this study are its retrospective nature and the intrinsically significant differences between the Taiwanese and Italian groups.
CONCLUSIONS:
The ITA.LI.CA prognostic system includes both a tumor staging-stratifying patients with HCC into six main stages (0, A, B1, B2, B3, and C)-and a prognostic score-integrating ITA.LI.CA tumor staging, CPS, ECOG performance status, and AFP. The ITA.LI.CA prognostic system shows a strong ability to predict individual survival in European and Asian populations
Chemokine C-C motif ligand 2 overexpression drives tissue-specific metabolic responses in the liver and muscle of mice
Chemokine (C-C motif) ligand 2 (CCL2) has been associated with chronic metabolic diseases. We aimed to investigate whether Ccl2 gene overexpression is involved in the regulation of signaling pathways in metabolic organs. Biochemical and histological analyses were used to explore tissue damage in cisgenic mice that overexpressed the Ccl2 gene. Metabolites from energy and one-carbon metabolism in liver and muscle extracts were measured by targeted metabolomics. Western blot analysis was used to explore the AMP-activated protein kinase (AMPK) and mammalian target of rapamycin pathways. Ccl2 overexpression resulted in steatosis, decreased AMPK activity and altered mitochondrial dynamics in the liver. These changes were associated with decreased oxidative phosphorylation and alterations in the citric acid cycle and transmethylation. In contrast, AMPK activity and its downstream mediators were increased in muscle, where we observed an increase in oxidative phosphorylation and increased concentrations of different metabolites associated with ATP synthesis. In conclusion, Ccl2 overexpression induces distinct metabolic alterations in the liver and muscle that affect mitochondrial dynamics and the regulation of energy sensors involved in cell homeostasis. These data suggest that CCL2 may be a therapeutic target in metabolic diseases
Rol de la resonancia magnética renal en la monitorización del aclaramiento de los depósitos de hemosiderina en la hemoglobinuria paroxística nocturna
La hemoglobinuria paroxística nocturna (HPN) es un trastorno secundario a la deficiencia de CD55 y CD59, proteínas de superficie reguladoras del complemento, resultando en hemólisis crónica mediada por el complemento1. La afectación renal oscila entre la lesión renal aguda durante las crisis hemolíticas, la disfunción tubular proximal (DTP) y la enfermedad renal crónica (ERC)2. La hemoglobinuria solo ocurre en el 25% de los pacientes3, en series recientes se ha reportado una incidencia del 64% de ERC, con hasta un 20% de ERC estadio 3-54. Se presentan 2 casos de HPN en el que los depósitos de hemosiderina visualizadas por resonancia magnética (IRM) parecen ser los primeros signos de afectación renal
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