Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Rheumatoid Arthritis

Objective. Tumor necrosis factor (TNF) increases circulating osteoclast (OC) precursors numbers by promoting their proliferation and differentiation. The aim of this study was to assess the effect of TNF inhibitors (TNFi) on the differentiation and activity of OC in rheumatoid arthritis (RA) patients. Methods. Seventeen RA patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers, in vitro OC differentiation assays, and qRT-PCR for OC specific genes was performed. Results. After TNFi therapy, patients had reduced RANKL surface expression in B-lymphocytes and the frequency of circulating classical CD14(bright) CD16-monocytes was decreased. Serum levels of sRANKL, sRANKL/OPG ratio, and CTX-I were reduced in RA patients after TNFi treatment. Moreover, after exposure to TNFi, osteoclast differentiation and activity were decreased, as well as the expression of TRAF6 and cathepsin K. Conclusion. We propose that TNFi arrests bone loss and erosion, through two pathways: direct reduction of osteoclast precursor numbers and inhibition of intracellular signaling pathways acting through TRAF6.Peer reviewe

Levantamentos geofísicos no setor português da Faixa Piritosa Ibérica: perspetiva global da sua importância em prospeção de sulfuretos maciços e interpretação geológica

ABSTRACT: The application of geophysical techniques to massive sulphide deposits exploration has proven to be a success in the Iberian Pyrite Belt (IPB) metallogenetic province, both in Portugal and in Spain. Several hidden deposits were discovered through the interpretation of geological models, supported by geophysical data collected in land and airborne surveys, as well as applied using down hole techniques in selected drill holes. This paper presents an overview of the methodologies applied in Portugal in the South Portuguese Zone (SPZ) geological domain, where the IPB is included, mostly by the LNEG and mining companies, with emphasis on the interpretation of the regional gravity, magnetometry and radiometry surveys, published in 1/400 000 scale by the EXPLORA/Alentejo2020 Project. In this regional mapping program, the large volume of data collected by LNEG and mining companies since the 1960’s was compiled and processed. The integrated interpretation and correlation between these methods will enable a better planning of new IPB exploration investments. IPB Volcano-Sedimentary Complex (VSC, Famennian to Late Visean age) lineaments are well defined in the gravity and magnetic fields along the IPB western region (e.g. Alcoutim/Neves Corvo/Montinho/Sesmarias/Lousal/Caveira). Aeromagnetic data also reflect deep and large anomalies related with the SPZ basement. A rock density database is presented and used to interpret the gravity data. Radiometric map (Natural Radioactivity), based mostly in airborne radiometric surveys, show contrasts between rocks in Paleozoic, Mesozoic and Cenozoic formations and correlations with geological and hydrothermal mapping are highlighted. The use of geophysical techniques is particularly critical in areas where VSC is concealed by younger sediments (e.g. Baixo Alentejo Flysch Group and/or Cenozoic formations), allowing the selection of target areas. Case studies are discussed based on electromagnetic, seismic and magnetotelluric methods and on the high mineral potential of defined targets. Multilayered data correlation (geophysics including petrophysical data, geochemistry and stratigraphic high-resolution models) is a key prospecting methodology and is essential for the accurate modelling of ore horizons and geological structures. Considering the IPB potential for VMS deposits, including the possible discovery of new giant (> 200 Mt) deposits, an increase of investment in new geophysical methods can be predicted. LNEG development of R&D projects such as EXPLORA/Alentejo2020 and SmartExplorationTM/H2020 also contribute to a favourable setting in the province, both in near mining and green fields scenarios. Thus, new discoveries are expected, like others made in the recent times in the IPB Portuguese sector, such as Lagoa Salgada (SFM, 1992, SFM; Redcorp/EDM, 2011; Redcorp/Ascendant/EDM, 2017), Semblana (Somincor-AGC-Lundin Mining, 2010), Monte Branco (Somincor Lundin Mining, 2012) and Sesmarias (Maepa/Avrupa, 2014). The importance of these data goes beyond the mineral exploration purpose. Since some of them use rock and mineral physical properties that can be related with environmental contamination (e.g. radiometry and magnetics) they can also be used in geochemical background studies, acid mine drainage and metal dispersion. Therefore, they can also promote a deeper knowledge in other areas of research related with environment preservation.RESUMO: A aplicação de técnicas de prospeção geofísica na pesquisa de jazigos de sulfuretos maciços na Faixa Piritosa Ibérica (FPI) tem-se revelado um sucesso em Portugal e em Espanha. Vários jazigos ocultos foram descobertos a partir da interpretação de modelos geológicos, com o apoio de dados geofísicos recolhidos em levantamentos terrestres, aerotransportados ou em profundidade, em sondagens (diagrafias). Neste artigo, apresenta-se uma análise das metodologias aplicadas principalmente pelo LNEG e empresas mineiras em Portugal, na Zona Sul Portuguesa (ZSP), onde se insere a FPI. Destaca-se a interpretação dos levantamentos regionais, esc. 1/400 000, de gravimetria, magnetometria e radiometria (EXPLORA/Alentejo2020). Nestes programas, foi feito o processamento de um volume de informação significativo, a partir de dados obtidos desde a década de 1960. Neste contexto indicam-se diversos alinhamentos de gravimetria e de aeromagnetometria relativos a unidades geológicas com elevado potencial mineiro, como o Complexo Vulcano-Sedimentar (CVS, idade Famenniano a Viseano sup.), sobressaindo o eixo Alcoutim/Neves Corvo/Montinho/Sesmarias/Lousal/Caveira. Os dados de aeromagnetismo refletem também anomalias com origens mais profundas e relacionadas com a estrutura basal da ZSP. A base de dados de densidades de rocha é utilizada na interpretação gravimétrica da FPI. O mapa radiométrico (Radioatividade Natural), baseado fundamentalmente em radiometria aeroportada (contagens totais) mostra o contraste à superfície de litologias das formações paleozoicas, mesozoicas e cenozoicas, sendo salientado, no primeiro caso, a sua correlação com a cartografia de alterações hidrotermais. Em áreas onde o CVS se encontra subjacente sob sedimentos mais recentes (ex. Grupo Flysch Baixo Alentejo e formações cenozoicas), o uso de técnicas geofísicas é fundamental para a seleção de alvos. São também descritos exemplos sobre a aplicação de métodos eletromagnéticos, sísmicos e magnetotelúricos na identificação e caracterização de estruturas geológicas. A análise integrada de diferentes métodos geofísicos, complementados com informação geológica e geoquímica, constitui a melhor metodologia de prospeção, sendo essencial para a pesquisa de horizontes de mineralização. Considerando a FPI como uma das principais províncias metalogenéticas do mundo, é expectável que venham a ocorrer mais investimentos e assim serem identificados novos jazigos, inclusive com dimensão superior a 200 Mt. Através de projetos ID como o EXPLORA/Alentejo2020 e SmartExplorationTM/H2020 o LNEG contribui para um melhor conhecimento na FPI em cenários de prospeção near mining e green fields. Nesta perspetiva, são esperadas novas descobertas de jazigos à semelhança do que tem acontecido em Portugal, como por exemplo Lagoa Salgada (SFM-1992, Redcorp/EDM 2011, Redcorp/Ascendant/EDM-2017), Semblana (Somincor-AGC Lundin Mining, 2010), Monte Branco (Somincor-Lundin Mining, 2012) e Sesmarias (Maepa/Avrupa, 2014). A importância destes dados vai muito para além da prospeção mineira. Uma vez que alguns métodos utilizam propriedades físicas que podem ser relacionadas com contaminações ambientais. Certos métodos geofísicos como radiometria e magnetometria, resistividade e métodos elétricos em geral, podem ser utilizados também em trabalhos de investigação sobre background geoquímico, drenagem ácida de mina e dispersão de metais. Desta forma, a aplicação destes métodos promove também um conhecimento mais aprofundado noutras áreas de investigação relacionadas com a preservação do ambiente.info:eu-repo/semantics/publishedVersio

Evidence of Genetic Segregation among Meagre (Argyrosomus regius) Atlantic Spawning Areas

The meagre Argyrosomus regius, one of the largest sciaenidae in the world, is a valuable resource for fisheries and aquaculture. Despite its socioeconomic relevance, knowledge about population dynamics and wild stocks is still scarce, and conservation risks are associated with overexploitation. Two genetic distinct groups, one in the North Atlantic Ocean and one in the eastern Mediterranean Sea, were identified by previous studies. However, little is known about the genetic structure of the Atlantic group, where four important spawning areas have been identified. To assess if each spawning area is an independent breeding unit, the genetic diversity, populational structure, and demographic history of A. regius along the North-East and Eastern Central Atlantic coast were analyzed, using 15 microsatellite loci. Results corroborate the hypothesis tested, suggesting four genetic groups: a first group encompassing individuals from the Gironde spawning area, a second group encompassing individuals from the Tagus spawning area, a third group corresponding to individuals captured in the Algarve region, and a forth group gathering individuals from Morocco and Mauritania. This study reveals the need for specific fisheries management plans considering genetic structure information, and highlights the need for international cooperation

Comparison of PBO solvers in a dependency solving domain

Linux package managers have to deal with dependencies and conflicts of packages required to be installed by the user. As an NP-complete problem, this is a hard task to solve. In this context, several approaches have been pursued. Apt-pbo is a package manager based on the apt project that encodes the dependency solving problem as a pseudo-Boolean optimization (PBO) problem. This paper compares different PBO solvers and their effectiveness on solving the dependency solving problem.Comment: In Proceedings LoCoCo 2010, arXiv:1007.083

Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Ankylosing Spondylitis

Introduction Ankylosing Spondylitis (AS) is characterized by excessive local bone formation and concomitant systemic bone loss. Tumor necrosis factor (TNF) plays a central role in the inflammation of axial skeleton and enthesis of AS patients. Despite reduction of inflammation and systemic bone loss, AS patients treated with TNF inhibitors (TNFi) have ongoing local bone formation. The aim of this study was to assess the effect of TNFi in the differentiation and activity of osteoclasts (OC) in AS patients. Methods 13 AS patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. 25 healthy donors were recruited as controls. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers and cytokines, in vitro OC differentiation assay and qRT-PCR for OC specific genes were performed. Results RANKL(+) circulating lymphocytes (B and T cells) and IL-17A, IL-23 and TGF-beta levels were decreased after TNFi treatment. We found no differences in the frequency of the different monocyte subpopulations, however, we found decreased expression of CCR2 and increased expression of CD62L after TNFi treatment. OC number was reduced in patients at baseline when compared to controls. OC specific gene expression was reduced in circulating OC precursors after TNFi treatment. However, when cultured in OC differentiating conditions, OC precursors from AS TNFi-treated patients showed increased activity as compared to baseline. Conclusion In AS patients, TNFi treatment reduces systemic pro osteoclastogenic stimuli. However, OC precursors from AS patients exposed to TNFi therapy have increased in vitro activity in response to osteoclastogenic stimuli.Peer reviewe

Pertinence of salt-related knowledge and reported behaviour on salt intake in adults : a cross-sectional study

The association between salt-related knowledge, attitude, behaviour (KAB) and actual salt consumption in Greek adults is uncertain. This study investigates the correlation between salt intake, gauged by 24-h urinary sodium excretion, with salt-related KAB. It further explores how socio-demographic factors influence these behaviors. Salt consumption was evaluated using a 24-h urinary sodium test, and compared to self-reported KAB data. Knowledge and behavior scores related to salt were computed. An overall cohort-adjusted model examined the relationship between daily salt consumption, knowledge and behavior scores, and certain covariates. Through the stratification by the cohort random effect, two models were established (Cohort I Adults; Cohort II Students) examining the same relationships of the overall cohort model. 463 Greek adults participated. The average salt intake was 9.54 g/day, nearly double the WHO recommendation. Significant differences in knowledge scores were noted based on sex, age, education, and BMI. A trend suggesting lower discretionary salt use with increased salt intake was observed (p = 0.06). However, comprehensive analysis revealed no direct correlation between salt intake and either knowledge (p = 0.562) or behavior scores (p = 0.210). The results emphasize the need for food product reforms by industry stakeholders and accelerated efforts towards reducing salt intake

Brain structural covariance networks in obsessive-compulsive disorder: a graph analysis from the ENIGMA Consortium.

Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P < 0.0001), lower modularity (P < 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions

Brain structural covariance networks in obsessive-compulsive disorder : a graph analysis from the ENIGMA Consortium

In the largest brain structural covariance study of OCD to date, Yun et al. show a less segregated organization of structural covariance networks and a reorganization of brain hubs, including cingulate and orbitofrontal regions, in OCD. The findings point to altered trajectories of brain development and maturation. Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z -score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P < 0.0001), lower modularity (P < 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions