Non-invasive biomarkers for the prediction of disease progression in metabolic associated fatty liver disease

BACKGROUND e OBIETTIVI: La NAFLD/MAFLD comprende un ampio spettro di patologie a carico del parenchima epatico (steatosi -NAFL-, steatoepatite -NASH-, cirrosi). La patogenesi \ue8 relata ad una complessa interazione multiorgano in cui fattori genetici, ormonali e ambientali giocano un ruolo centrale e sono coinvolti nello sviluppo del carcinoma epatocellulare (HCC). La biopsia epatica \ue8 il \u201cgold standard\u201d per la diagnosi. Tuttavia ad oggi mancano dei marcatori non invasivi per la predizione del rischio di progressione della NAFLD. Alcune varianti genetiche (PNPLA3, TM6SF2, MBOAT7 e GCKR) sono coinvolte nella determinazione del contenuto di grasso epatico (HFC) e nella progressione della epatopatia. Recentemente in pazienti con HCC o cirrosi secondaria ad abuso alcolico od a infezione virale, \ue8 stata descritta la presenza di elevati livelli sierici di SCCA-IgM. Il principale scopo dello studio \ue8 quello di indagare l'associazione tra concentrazione di SCCA-IgM e gravit\ue0 della epatopatia in una coorte di pazienti con NAFLD caratterizzata dal punto di vista istologico. In secondo luogo, nel contesto di uno studio di coorte trasversale multicentrico, abbiamo esaminato, in soggetti con NAFLD, l'impatto di un punteggio di rischio poligenico del contenuto di grasso epatico (PRS-HFC) sullo sviluppo del HCC, ottimizzato lo score introducendo HSD17B13 (PRS-5), ed infine, identificato la migliore soglia diagnostica. MATERIALI E METODI: La prima coorte comprende 84 pazienti con diagnosi istologica di NAFLD (39 con NAFL e 45 con NASH). Le concentrazioni di SCCA-IgM sono state misurate tramite test ELISA con kit HepaIC\uae. Nella coorte multicentrica sono stati arruolati 1.699 pazienti (82 dei quali provenienti dal nostro centro) con diagnosi di NAFLD in diversi stadi di malattia (steatosi, cirrosi, HCC) e 865 controlli sani. I partecipanti sono stati genotipizzati (TaqMan 5'-nucleasi) per rs738409 (PNPLA3 I148M), rs58542926 (TM6SF2 E167K), rs641738 C>T MBOAT7, rs1260326 (GCKR P446L), e rs72613567 (HSD17B13:TA). E' stato creato uno score di rischio (PRS-HFC), ulteriormente sviluppato nel PRS-5. Per valutare il ruolo causale della predisposizione genetica sullo sviluppo di HCC si \ue8 ricorsi all\u2019analisi di randomizzazione mendeliana. L'accuratezza diagnostica \ue8 stata valutata tramite le curve ROC. RISULTATI: I livelli di SCCA-IgM sono risultati significativamente pi\uf9 elevati nei pazienti con NASH rispetto a quelli con NAFL (p = 0,007). Gradi maggiori di fibrosi all'esame istologico si associano a maggiori concertazioni di SACCA-IgM (p <0,05). I livelli di SCCA-IgM correlano con et\ue0 (p <0,05), BMI (p = 0,01), omocisteina (p = 0,02) e grado di fibrosi (p <0,05). Il punteggio di PRS \ue8 influenzato dalla gravit\ue0 dell\u2019epatopatia. PRSs conferiscono un aumento del rischio di HCC, proporzionale all'aumento del rischio di NAFLD (p = 0,02). Il miglior valore soglia per PRS-HFC \ue8 0,532 (AUROC 0.64). La precisione del PRS-5 \ue8 simile, con cut-off pari a 0,495. PRS-HFC positivi hanno migliorato la rilevazione di HCC in individui di et\ue0 superiore a 40 anni ed in pazienti diabetici, indipendentemente dalla fibrosi grave. PRS-5 permette di predire il rischio di HCC anche in soggetti non obesi. CONCLUSIONI: Nei pazienti con NAFLD, i livelli di SCCA-IgM risultano associati alla diagnosi di NASH ed alla gravit\ue0 istologica della fibrosi epatica. I nostri dati sono coerenti con l\u2019esistenza di un'associazione causale tra HFC geneticamente determinato e sviluppo di HCC, che \ue8 principalmente mediato dalla predisposizione alla fibrosi grave. Un PRS alto risulta possedere una specificit\ue0 del circa 80% per rilievo di HCC e pu\uf2 essere utile per stratificarne il rischio e guidare la sorveglianza nei pazienti con fattori di rischio metabolico per HCC, indipendentemente dalla gravit\ue0 della fibrosi. Studi prospettici sono necessari per valutare il ruolo di SCCA-IgM e dei PRS nella stratificazione del rischio dei pazienti con NAFLD.BACKGROUND and AIMS: NAFLD/MAFLD includes a broad spectrum of pathologies affecting the liver parenchyma (steatosis -NAFL-, steatohepatitis -NASH-, cirrhosis). Its pathogenesis is related to a complex multi-organ interaction in which genetic, hormonal and environmental factors play a central role and are involved in the development of hepatocellular carcinoma (HCC). Liver biopsy is the "gold standard" for diagnosis. The major unmet need of this condition is the lack of non-invasive biomarkers useful in the prediction of disease progression risk. Some genetic variants (PNPLA3, TM6SF2, MBOAT7 and GCKR) are strongly involved in the determination of the liver fat content (HFC) and in the progression of liver disease. Recently high levels of SCCA-IgM were described in patients with HCC or cirrhosis due to viruses or alcohol abuse. The principal aim of the study was to investigate the association between serum concentration of SCCA-IgM and severity of liver disease in a cohort of patients with histological well characterize NAFLD. Secondly, we examined the impact of a polygenic risk score of hepatic fat content (PRS-HFC) on NAFLD-HCC in a cross-sectional cohort of at-risk individuals (NAFLD cross-sectional cohort), we tried to optimize it by adjustment for a protective variant in HSD17B13 (PRS-5); finally, we identified the best diagnostic threshold. MATERIAL AND METHODS: The first cohort includes 84 patients with a histological diagnosis of NAFLD (39 with NAFL and 45 with NASH). Concentrations of SCCA-IgM were measured by ELISA test with HepaIC\uae kit. In the NAFLD cross-sectional cohort, were enrolled 1,699 patients (82 of which from our center) with NAFLD in different stages of disease (steatosis, cirrhosis, HCC) and 865 healthy controls. Participants were genotyped (TaqMan 5'-nuclease) for rs738409 (PNPLA3 I148M variant), rs58542926 (TM6SF2 E167K), rs641738 C>T variant at MBOAT7, rs1260326 (GCKR P446L), and rs72613567 (HSD17B13:TA). A risk score (PRS-HFC) was created, further developed in the PRS-5. Mendelian randomization analyses were used to assess the causal role of genetic predisposition to NAFLD on HCC development. Diagnostic accuracy was evaluated by ROC curves. RESULTS: SCCA-IgM levels were better in patients with NASH than in those with NAFL (p = 0.007). Higher degrees of fibrosis on histological examination are associated with higher concentrations of SACCA-IgM (p <0.05). SCCA-IgM levels correlate with age (p <0.05), BMI (p = 0.01), homocysteine (p = 0.02) and degree of fibrosis (p <0.05). The PRS score is influenced by the severity of the liver disease. PRS confer an increased risk of HCC proportional to the increased risk of NAFLD (p = 0.02). The best cutoff for scoring was 0.532 (AUROC 0.64). The accuracy of the PRS-5 is similar, with a cut-off of 0.495. Positive PRS-HFC improved the detection of HCC in people over 40 years of age and in diabetic patients regardless of severe fibrosis. PRS-5 allows to predict the risk of HCC even in non-obese subjects. CONCLUSION: In patients with NAFLD, SCCA-IgM levels were associated with the diagnosis of NASH and histological severity of liver fibrosis. In NAFLD cross-sectional cohort, our data are consistent with a causal association between genetically determined hepatic fat and HCC development, which was mainly mediated by predisposition to severe fibrosis. High PRS had a quite good specificity (80%) for detection HCC, and may be useful to stratify NAFLD-HCC risk and guide surveillance in patients with metabolic risk factors for HCC, independently of fibrosis severity. The role of SCCA-IgM and PRS in NAFLD risk stratification should be evaluated in further prospective studies

Chemical analysis of cultural heritage: applications and perspectives

Los estudios químicos de los materiales y sus procesos de degradación en bienes culturales han tenido un notable desarrollo en la última década, no sólo en museos e institutos de conservación sino particularmente en ámbitos académicos. En este trabajo se resume brevemente el estado del arte de estas investigaciones, las cuales se ilustran con algunos ejemplos del arte colonial sudamericano.Chemical studies on materials and their degradation reactions in cultural heritage objects have notably developed in the last decade in museums and conservation institutes, but particularly in the academic field. In this work, a brief state of the art of these investigations is presented with focus on South American colonial art studies.Fil: Maier, Marta Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentin

Estudio sobre rutas biosintéticas alternativas del anillo butenólido de cardenólidos en Digitalis purpurea

La digitoxina es el principal glicósido cardenólido en plantas del género Digitalis, encontrándose en menor proporción los glicósidos gitoxina y digoxina. El presente trabajo tuvo por objeto el estudio de los últimos pasos de la biosíntesis de estos glicósidos en la planta Digitalis purpurea, en particular la formación y cierre del anillo lactónico que poseen. En el mismo se describen los siguientes temas: 1. Los antecedentes que dieron origen a este trabajo de investigación; entre ellos los glicósidos cardenólidos presentes en la planta Digitalis purpurea, su concentración, su acción farmacológica y los estudios sobre su biosíntesis. 2. Las síntesis de los distintos precursores, radiactivos o no, empleados en el estudio de los últimos pasos del camino biosintético, es decir: a) la serie de compuestos con cadena lateral tipo β-hidroxiácido: ácido 2O(R,S)-hidroxi-23-norcolanoicos-24-14C. b) la serie de compuestos con cadena lateral de ácido α,β no saturado: ácidos 23-norcol-20(22)(E)-énicos-24-14C. 3. La búsqueda de un buen método de inoculación de los compuestos radiactivos sintetizados, así como, las mejores condiciones para el aislamiento de los glicósidos cardenólidos y su posterior purificación. 4. Los estudios realizados por espectroscopía de RMN-13C de los efectos derivados por la quiralidad de C-20 en los ácidos 20(R,S)-hidroxi-23-norcolanoicos y en sus ésteres etílicos. Para poder efectuar una correlación efectiva con compuestos análogos a los mismos, se sintetizaron como compuestos modelos 3β, 20-hidroxi-20-metil-pregn-5-eno y su 3β-acetoxi derivado, los cuales fueron analizados por espectroscopía de RMN-13C. 5. Las inoculaciones de los ácidos 20 (R,S)-hidroxi-23-norcolanoicos-24-14C y 23-norcol-20(22)(E)-énicos-24-14C, en plantas enteras de Digitalis purpurea, del mismo grado de desarrollo y en condiciones controladas y reproducibles y el análisis de las incorporaciones absolutas logradas. 6. La degradacidn de la digitoxina radiactiva proveniente de uno de los ensayos de inoculación de un precursor radiactivo, con el objeto de comprobar que la radiactividad se hallaba localizada en el anillo lactónico de los glicósidos cardenólidos. Con los resultados de las distintas experiencias se propuso y discutió la existencia de una ruta alternativa para la formación del anillo, butenólido en la biosíntesis de los cardenólidos.Fil:Maier, Marta Silvia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

A Sharp-Interface Model of the Diffusive Phase Transformation in a Nickel-Based Superalloy

A sharp-interface model employing the extended finite element method is presented. It is designed to capture the prominent γ-γ′ phase transformation in nickel-based superalloys. The novel combination of crystal plasticity and sharp-interface theory outlines a good modeling alternative to approaches based on the Cahn–Hilliard equation. The transformation is driven by diffusion of solute γ′-forming elements in the γ-phase. Boundary conditions for the diffusion problem are computed by the stress-modified Gibbs–Thomson equation. The normal mass balance of solute atoms at the interface yields the normal interface velocity, which is integrated in time by a level set procedure. In order to capture the influence of dislocation glide and climb on interface motion, a crystal plasticity model is assumed to describe the constitutive behaviour of the γ-phase. Cuboidal equilibrium shapes and Ostwald ripening can be reproduced. According to the model, in low γ′ volume-fraction alloys with separated γ′-precipitates, interface movement does not have a significant effect on tensile creep behaviour at various lattice orientations

The role of ultrasound in the diagnosis of temporal arteritis

Temporal arteritis (TA), also known as giant cell arteritis, is a chronic vasculitis of medium and large-sized blood vessels, in particular the main cervical branches of the aorta, with particular affinity to the temporal arteries and eye-supplying arteries. Temporal artery biopsy is still a gold standard for diagnosis, however in recent years colour duplex ultrasound examination has been proposed as a useful diagnostic screening tool in cases of TA suspicion. We report three cases of TA in which the ultrasonographical examination of the temporal arteries had a decisive role in the diagnosis

High performance liquid chromatography as a micro-destructive technique for the identification of anthraquinone red dyestuffs in cultural heritage objects

This article describes two of the most common natural sources of red anthraquinones that have been used since antiquity for textile dyeing and as lake pigments, namely cochineal insect and the roots of Rubia and Relbunium plants. Carminic acid is the main component of carmine, the red colorant obtained from cochineal. Alizarin and purpurin are found in the extracts of Rubia roots, but Relbunium roots contain only purpurin. These red anthraquinones have been identified in a variety of cultural heritage objects. High performance liquid chromatography with diode array detection (HPLC-DAD) is described as the most suitable analytical technique for the identification of these dyestuffs, particularly in micro-samples from textiles or pigment layers in paintings and polychrome sculptures. Finally, application of HPLC-DAD analysis to the identification of lake pigments in micro-samples of mural paintings of two eighteenth century Andean churches in Peru is described.Fil: Careaga Quiroga, Valeria Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; ArgentinaFil: Blanco Guerrero, Astrid Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; ArgentinaFil: Siracusano, Gabriela Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Tres de Febrero. Instituto de Investigaciones en Arte y Cultura "Dr. Norberto Griffa"; ArgentinaFil: Maier, Marta Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad Nacional de Tres de Febrero. Instituto de Investigaciones en Arte y Cultura "Dr. Norberto Griffa"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentin

Análise de materiais artísticos utilizando espectroscopia de absorção no infravermelho por reflectância total atenuada

Eeste trabajo describe el análisis por espectroscopia infrarroja utilizando la técnica de reflectancia total atenuada de pinturas al óleo y acrílicas comerciales conteniendo blanco de titanio, azul de Prusia y verde de ftalocianina como pigmentos. Las pinturas al óleo con azul de Prusia mostraron la presencia de cargas como carbonato de calcio y sulfato de bario. El análisis de una réplica de una pintura acrílica con blanco de titanio sobre la que se aplicó una capa de barniz Paraloid B-67 dio un espectro infrarrojo correspondiente al barniz, no registrándose bandas de la capa de la formulación con blanco de titanio. Por otra parte, en las pinturas al óleo y acrílicas con verde de ftalocianina se diferenciaron claramente ambos aglutinantes y se identificó el pigmento en base a algunas señales características en la zona de la huella digital. Los resultados muestran la versatilidad de la técnica vibracional en el estudio de materiales artísticos.Este trabalho descreve a análise por espectroscopia de infravermelho usando a técnica de reflectância total atenuada de tintas a óleo e acrílicos comerciais contendo branco de titânio, azul da Prússia e verde de ftalocianina como pigmentos. As pinturas a óleo com azul da Prússia mostraram a presença de cargas como carbonato de cálcio e sulfato de bário. A análise de uma réplica de uma tinta acrílica com branco de titânio sobre a qual foi aplicada uma camada de verniz Paraloid B-67 produziu um espectro infravermelho correspondente ao verniz, não registrando bandas da camada de formulação com branco de titânio. Por outro lado, no óleo e acrílicos com verde de ftalocianina, ambos os aglutinantes foram claramente diferenciados e o pigmento foi identificado com base em alguns sinais característicos em áreas de fingerprint. Os resultados mostram a versatilidade da técnica vibracional no estudo de materiais artísticos.This work describes the analysis by attenuated total reflectance infrared spectroscopy of oil and acrylic commercial paintings with titanium white, Prussian blue and green phthalocyanine as pigments. Oil paintings with Prussian blue showed the presence of calcium carbonate and barium sulfate as extenders. Analysis of a mock-up of an acrylic painting with titanium white with the application of Paraloid B-67 as varnish showed the infrared spectrum of the varnish and no bands of the titanium white painting. On the other hand, in the oil and acrylic paintings with green phthalocyanine both binders were clearly differentiated and the pigment was identified by some characteristic bands in the fingerprint region. Our results show the versatility of the vibrational technique in the study of pictorial materials.Fil: Blanco Guerrero, Astrid Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Maier, Marta Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentin

Hematite vs. Clays: their potential as red pigments and their use in three sites at the Puna of Jujuy (Argentina)

El análisis de pinturas rojas en pictografías de tres sitios de la Puna jujeña puso de manifiesto el uso exclusivo de hematita en su realización. Este pigmento rojo fue utilizado en la región desde inicios de la ocupación humana y su reiterada presencia en representaciones pictóricas diacrónicas revela la especificidad de esa materia prima en Hornillos 2, Cueva Quispe y Tres Pozos. Los pigmentos rojizos recuperados de los niveles estratigráficos en dos de los sitios están constituidos por hematita y por arcillas rojas. El uso de uno u otro tipo de pigmento estaría relacionado con las propiedades intrínsecas de ambas especies minerales, por tal motivo, planteamos que fueron utilizadas con fines diferentes.Physical-chemical characterization of red paints from pictographs found at three sites in the Puna of Jujuy shows that hematite was the only pigment used in their execution. Hematite pigment was used in the region from the earliest human occupations and its recurring presence in diachronic rock paintings reveals the specificity of this material in Hornillos 2, Cueva Quispe and Tres Pozos. In addition to hematite, reddish pigments recovered from stratigraphic levels include clay pigments. As the use of one kind of pigment over another would be linked to its intrinsic properties, we propose that these different pigments were used for different purposes.Fil: Sola, Patricia. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Arqueología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Yacobaccio, Hugo Daniel. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Arqueología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rosenbusch, Mariana Lidia. Comision Nacional de Energia Atomica. Centro Atomico Constituyentes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alonso, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Basicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Basicas, Aplicadas y Ambientales de Buenos Aires; ArgentinaFil: Maier, Marta Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Vázquez, Cristina. Comision Nacional de Energia Atomica. Centro Atomico Constituyentes; ArgentinaFil: Cata, Maria Paz. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Arqueología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Exercises for adolescent idiopathic scoliosis

Background: Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of the spine . While AIS can progress during growth and cause a surface deformity, it is usually not symptomatic. However, in adulthood, if the final spinal curvature surpasses a certain critical threshold, the risk of health problems and curve progression is increased. The use of scoliosis-specific exercises (SSE) to reduce progression of AIS and postpone or avoid other more invasive treatments is controversial.Objectives: To evaluate the efficacy of SSE in adolescent patients with AIS.Search methods: The following databases (up to 30 March 2011) were searched with no language limitations: CENTRAL (The Cochrane Library 2011, issue 2), MEDLINE (from January 1966), EMBASE (from January 1980), CINHAL (from January 1982), SportDiscus (from January 1975), PsycInfo (from January 1887), PEDro (from January 1929). We screened reference lists of articles and also conducted an extensive handsearch of grey literature.Selection criteria: Randomised controlled trials and prospective cohort studies with a control group comparing exercises with no treatment, other treatment, surgery, and different types of exercises.Data collection and analysis: Two review authors independently selected studies, assessed risk of bias and extracted data.Main results: Two studies (154 participants) were included. There is low quality evidence from one randomised controlled study that exercises as an adjunctive to other conservative treatments increase the efficacy of these treatments (thoracic curve reduced: mean difference (MD) 9.00, (95% confidence interval (CI) 5.47 to 12.53); lumbar curve reduced:MD 8.00, (95% CI 5.08 to 10.92)). There is very low quality evidence from a prospective controlled cohort study that scoliosis-specific exercises structured within an exercise programme can reduce brace prescription (risk ratio (RR) 0.24, (95% CI 0.06 to1.04) as compared to usual physiotherapy (many different kinds of general exercises according to the preferences of the single therapists within different facilities).Authors' conclusions: There is a lack of high quality evidence to recommend the use of SSE for AIS. One very low quality study suggested that these exercises may be more effective than electrostimulation, traction and postural training to avoid scoliosis progression, but better quality research needs to be conducted before the use of SSE can be recommended in clinical practice