Inter-observer reliability of ultrasound detection of tendon abnormalities at the wrist and ankle in patients with rheumatoid arthritis

OBJECTIVE: To assess inter-observer reliability in US detection of tendon inflammatory and structural changes at wrists and ankles in RA patients. METHODS: Fourteen consecutive RA patients underwent bilateral US assessment of the extensor carpi ulnaris (ECUT) and tibialis posterior tendons (TPTs) by two blinded rheumatologists, with different level of experience in musculoskeletal (MS) US. Grey scale and power Doppler (PD) US assessment was focused on detection of tenosynovitis, tenosynovial and intra-tendon PD signal and structural lesions (i.e. tendinosis, tendon erosion, partial or total rupture). RESULTS: The frequency of US findings detected by Investigator 1 was 28.6% for inflammatory changes and 51.8% for structural damage changes while Investigator 2 detected 34 and 53.6% for the corresponding abnormalities. A high overall agreement (82.7%) was found for inflammatory pathology and 89.7% for structural lesions in all tendons. Mean kappa (κ) values for all tendons and pathology was moderate (κ = 0.42), with fair level of agreement for the wrist region (0.27-0.34) and moderate to good values for the ankle region (κ = 0.47-0.62). Subclinical abnormalities were detected in 37.5% of the tendons by Investigator 1 and 28.6% of the tendons by Investigator 2. CONCLUSIONS: MSUS showed high overall agreement and fair to moderate inter-observer κ-values between investigators with different levels of experience in detection of tendon pathology at the wrist and ankle in RA patients. Further standardization of scanning method and pathology definitions may improve MSUS reproducibility

Helianthemum bilyanense (Cistaceae) catalogued according to IUCN categories (2001)

Helianthemum bilyanense (Cistaceae) es un endemismo local del noroeste de la provincia de Alicante que habita exclusivamente sobre substratos yesíferos, bajo un bioclima mesomediterráneo-inferior seco-inferior. Actualmente se conoce una única población en los alrededores de Villena, con un área de ocupación de 1037 m2 donde se han censado tan sólo 432 individuos, la cual está sometida a una fuerte presión por parte no sólo de la ganadería, sino por el hecho de que existe un proyecto de instalación de una planta fotovoltaica en ese terreno. Estos datos la convierten en una población extremadamente frágil, con un riesgo de extinción muy alto, por lo que se propone que se catalogue a H. bilyanense en la categoría de amenaza “en peligro crítico” (categoría CR), siguiendo los criterios objetivos para la clasificación de especies según su riesgo de extinción propuestos por la UICN. En consecuencia, se sugiere la urgente inclusión de esta especie en los catálogos de flora protegida de la Comunidad Valenciana y de España.Helianthemum bilyanense is a local endemism from the northwestern part of Alicante province (E of Spain), which occurs exclusively on gypsum substrates, under lower-mesomediterranean lower-dry bioclimate. A sole population is currently known in the surroundings of Villena, with an Area of Occupancy of 1037 m2 and only 432 individuals recorded, this site suffering a severe anthropic pressure not only from livestock overgrazing, but also from a project to develop a photovoltaic plant on that area. In consequence, this population has become extremely fragile and shows a very high risk of extinction, which suggests H. bilyanense to be labelled as “critically endangered" (CR), according to the IUCN categories and criteria. Consequently, the species should be urgently included in the lists of protected flora of the Valencian Community, and also Spain

Advancing manufacture of hiPSC-derived hepatocytes with improved functionality: A nature-inspired protocol

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Prevalence estimation of significant fibrosis because of NASH in Spain combining transient elastography and histology

Acord transformatiu CRUE-CSICBackground & Aims: Non-alcoholic fatty liver disease (NAFLD) has become a major public health problem, but the prevalence of fibrosis associated with non-alcoholic steatohepatitis (NASH) is largely unknown in the general population. This study aimed to provide an updated estimation of the prevalence of NASH fibrosis in Spain. Methods: This was an observational, retrospective, cross-sectional, population-based study with merged data from two Spanish datasets: a large (N = 12 246) population-based cohort (ETHON), including transient elastography (TE) data, and a contemporary multi-centric biopsy-proven NASH cohort with paired TE data from tertiary centres (N = 501). Prevalence for each NASH fibrosis stage was estimated by crossing TE data from ETHON dataset with histology data from the biopsy-proven cohort. Results: From the patients with valid TE in ETHON dataset (N = 11 440), 5.61% (95% confidence interval [95% CI]: 2.53-11.97) had a liver stiffness measurement (LSM) ≥ 8 kPa. The proportion attributable to NAFLD (using clinical variables and Controlled Attenuation Parameter) was 57.3% and thus, the estimated prevalence of population with LSM ≥ 8 kPa because of NAFLD was 3.21% (95% CI 1.13-8.75). In the biopsy-proven NASH cohort, 389 patients had LSM ≥ 8 kPa. Among these, 37% did not have significant fibrosis (F2-4). The estimated prevalence of NASH F2-3 and cirrhosis in Spain's adult population were 1.33% (95% CI 0.29-5.98) and 0.70% (95% CI 0.10-4.95) respectively. Conclusions: These estimations provide an accurate picture of the current prevalence of NASH-related fibrosis in Spain and can serve as reference point for dimensioning the therapeutic efforts that will be required as NASH therapies become available

Partial loss of Tip60 slows mid-stage neurodegeneration in a spinocerebellar ataxia type 1 (SCA1) mouse model

Spinocerebellar ataxia type 1 (SCA1) is one of nine dominantly inherited neurodegenerative diseases caused by polyglutamine tract expansion. In SCA1, the expanded polyglutamine tract is in the ataxin-1 (ATXN1) protein. ATXN1 is part of an in vivo complex with retinoid acid receptor-related orphan receptor alpha (Rora) and the acetyltransferase tat-interactive protein 60 kDa (Tip60). ATXN1 and Tip60 interact directly via the ATXN1 and HMG-box protein 1 (AXH) domain of ATXN1. Moreover, the phospho-mimicking Asp amino acid at position 776, previously shown to enhance pathogenesis, increases the ability of ATXN1 to interact with Tip60. Using a genetic approach, the biological relevance of the ATXN1/Tip60 interaction was assessed by crossing ATXN1[82Q] mice with Tip60+/−animals. Partial Tip60 loss increased Rora and Rora-mediated gene expression and delayed ATXN1[82]-mediated cerebellar degeneration during mid-stage disease progression. These results suggested a specific, temporal role for Tip60 during disease progression. We also showed that genetic background modulated ATXN1[82Q]-induced phenotypes. Of interest, these latter studies showed that some phenotypes are enhanced on a mixed background while others are suppressed

Prospective associations between a priori dietary patterns adherence and kidney function in an elderly Mediterranean population at high cardiovascular risk.

PURPOSE: To assess the association between three different a priori dietary patterns adherence (17-item energy reduced-Mediterranean Diet (MedDiet), Trichopoulou-MedDiet and Dietary Approach to Stop Hypertension (DASH)), as well as the Protein Diet Score and kidney function decline after one year of follow-up in elderly individuals with overweight/obesity and metabolic syndrome (MetS). METHODS: We prospectively analyzed 5675 participants (55-75 years) from the PREDIMED-Plus study. At baseline and at one year, we evaluated the creatinine-based estimated glomerular filtration rate (eGFR) and food-frequency questionnaires-derived dietary scores. Associations between four categories (decrease/maintenance and tertiles of increase) of each dietary pattern and changes in eGFR (ml/min/1.73m2) or ≥ 10% eGFR decline were assessed by fitting multivariable linear or logistic regression models, as appropriate. RESULTS: Participants in the highest tertile of increase in 17-item erMedDiet Score showed higher upward changes in eGFR (β: 1.87 ml/min/1.73m2; 95% CI: 1.00-2.73) and had lower odds of ≥ 10% eGFR decline (OR: 0.62; 95% CI: 0.47-0.82) compared to individuals in the decrease/maintenance category, while Trichopoulou-MedDiet and DASH Scores were not associated with any renal outcomes. Those in the highest tertile of increase in Protein Diet Score had greater downward changes in eGFR (β: - 0.87 ml/min/1.73m2; 95% CI: - 1.73 to - 0.01) and 32% higher odds of eGFR decline (OR: 1.32; 95% CI: 1.00-1.75). CONCLUSIONS: Among elderly individuals with overweight/obesity and MetS, only higher upward change in the 17-item erMedDiet score adherence was associated with better kidney function after one year. However, increasing Protein Diet Score appeared to have an adverse impact on kidney health. TRIAL REGISTRATION NUMBER: ISRCTN89898870 (Data of registration: 2014)

Partial Loss of Ataxin-1 Function Contributes to Transcriptional Dysregulation in Spinocerebellar Ataxia Type 1 Pathogenesis

Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused by expansion of a CAG repeat that encodes a polyglutamine tract in ATAXIN1 (ATXN1). Molecular and genetic data indicate that SCA1 is mainly caused by a gain-of-function mechanism. However, deletion of wild-type ATXN1 enhances SCA1 pathogenesis, whereas increased levels of an evolutionarily conserved paralog of ATXN1, Ataxin 1-Like, ameliorate it. These data suggest that a partial loss of ATXN1 function contributes to SCA1. To address this possibility, we set out to determine if the SCA1 disease model (Atxn1154Q/+ mice) and the loss of Atxn1 function model (Atxn1−/− mice) share molecular changes that could potentially contribute to SCA1 pathogenesis. To identify transcriptional changes that might result from loss of function of ATXN1 in SCA1, we performed gene expression microarray studies on cerebellar RNA from Atxn1−/− and Atxn1154Q/+ cerebella and uncovered shared gene expression changes. We further show that mild overexpression of Ataxin-1-Like rescues several of the molecular and behavioral defects in Atxn1−/− mice. These results support a model in which Ataxin 1-Like overexpression represses SCA1 pathogenesis by compensating for a partial loss of function of Atxn1. Altogether, these data provide evidence that partial loss of Atxn1 function contributes to SCA1 pathogenesis and raise the possibility that loss-of-function mechanisms contribute to other dominantly inherited neurodegenerative diseases

An Extended Gene Protein/Products Boolean Network Model Including Post-Transcriptional Regulation

Background: Networks Biology allows the study of complex interactions between biological systems using formal, well structured, and computationally friendly models. Several different network models can be created, depending on the type of interactions that need to be investigated. Gene Regulatory Networks (GRN) are an effective model commonly used to study the complex regulatory mechanisms of a cell. Unfortunately, given their intrinsic complexity and non discrete nature, the computational study of realistic-sized complex GRNs requires some abstractions. Boolean Networks (BNs), for example, are a reliable model that can be used to represent networks where the possible state of a node is a boolean value (0 or 1). Despite this strong simplification, BNs have been used to study both structural and dynamic properties of real as well as randomly generated GRNs. Results: In this paper we show how it is possible to include the post-transcriptional regulation mechanism (a key process mediated by small non-coding RNA molecules like the miRNAs) into the BN model of a GRN. The enhanced BN model is implemented in a software toolkit (EBNT) that allows to analyze boolean GRNs from both a structural and a dynamic point of view. The open-source toolkit is compatible with available visualization tools like Cytoscape and allows to run detailed analysis of the network topology as well as of its attractors, trajectories, and state-space. In the paper, a small GRN built around the mTOR gene is used to demonstrate the main capabilities of the toolkit. Conclusions: The extended model proposed in this paper opens new opportunities in the study of gene regulation. Several of the successful researches done with the support of BN to understand high-level characteristics of regulatory networks, can now be improved to better understand the role of post-transcriptional regulation for example as a network-wide noise-reduction or stabilization mechanism

Interplay of Linker Functionalization and Hydrogen Adsorption in the Metal–Organic Framework MIL-101

Functionalization of metal–organic frameworks results in higher hydrogen uptakes owing to stronger hydrogen–host interactions. However, it has not been studied whether a given functional group acts on existing adsorption sites (linker or metal) or introduces new ones. In this work, the effect of two types of functional groups on MIL-101 (Cr) is analyzed. Thermal-desorption spectroscopy reveals that the −Br ligand increases the secondary building unit’s hydrogen affinity, while the −NH2 functional group introduces new hydrogen adsorption sites. In addition, a subsequent introduction of −Br and −NH2 ligands on the linker results in the highest hydrogen-store interaction energy on the cationic nodes. The latter is attributed to a push-and-pull effect of the linkers