Role of tartrate-resistant acid phosphatase in bone remodeling

Tartrate-resistant acid phosphatase is a metalloenzyme that exists as two isoforms: the monomeric TRAP 5a and the proteolytically cleaved TRAP 5b, responsible for phosphatase activity, which is highly expressed in osteoclasts (OCs). TRAP 5b has been used as a serum marker of bone resorption, as it correlates with the absolute number of OCs and with resorption markers such as CTX-I. Despite being used as biomarker for bone metabolic diseases, little is known about the role of TRAP isoforms in OCs and thus bone remodeling (the process of bone degradation by osteoclasts, and bone formation by osteoblasts). Therefore, this thesis aimed to investigate the role of TRAP isoforms in bone remodeling. To enable the investigation of TRAP 5a and 5b we (1) developed a sandwich TRAP 5a/5b ELISA for the quantification of human TRAP isoforms. This ELISA was then used for (2) evaluating the expression and secretion pattern of TRAP 5a and 5b in healthy individuals and during OC differentiation. Additionally, we used the ELISA to (3) investigated if TRAP protein levels correlate to osteoarthritis (OA) or rheu- matoid arthritis (RA). Here we correlated the phosphorylation status of the known TRAP in vivo substrate, osteopontin, to the TRAP isoforms. (4) Using a competitive inhibitor for TRAP 5b, we studied the role of TRAP in OCs differentiation. Lastly, we (5) developed a high throughput system to identify a subclone in a murine cell line that is a more homogeneous and stable OC precursors that could be used as a screening tool for OC biology studies. A double TRAP 5a/5b sandwich ELISA was developed and designed as a two-step process. Using the ELISA, we showed that in vitro cultures of OCs secrete not only TRAP 5b but also TRAP 5a and that both isoforms were present intracellular estab- lishing that 5b can also be formed intracellular in OCs. Correlation between TRAP 5a and 5b indicated a dependence between TRAP 5a and formation of 5b. There was a positive correlation in both serum from healthy men, and media from in vitro OC cultures of not only 5b but also TRAP 5a with CTX-I further suggesting that TRAP 5a also originates partly from OCs. Measurement of TRAP 5a and 5b in synovial fluid from OA and RA patients revealed a correlation between low TRAP 5b/ TRAP 5a ratio and phosphorylated osteopontin. This suggested that synovial fluid from RA patients contained an insufficient amount of TRAP 5b increasing levels of phos- phorylated OPN leading to a higher OC activation and bone destruction. Inhibition of TRAP 5b using the competitive inhibitor, 5-phenylnicotinic acid, decreased the number of OCs formed and the expression of several OC markers. However, some OCs were able to fuse and resorb bone. In this thesis we show that measurement of TRAP isoforms protein is an important tool in research and possibly also in diagnostic to understand the biological implications of TRAP 5a and 5b in OCs, which may lead to therapeutic targeting of certain isoforms for inflammatory and metabolic bone diseases. We further show that TRAP is involved in the bone remodeling process in OCs and defects in TRAP may cause alterations in OCs function and differentiation

Volumetric variation of peri-implant soft tissues in convergent collar implants and crowns using the biologically oriented preparation technique (BOPT)

To evaluate the changes in the peri-implant soft tissues of convergent collar implants with biologically oriented preparation technique (BOPT) crowns, 10 months after loading. A pilot study was carried out from January 2016 to October 2017 involving 14 patients with one or two implants in the posterior mandibular sector. A total of 32 convergent collar implants were placed using a non-submerged protocol. Three months later the provisional cemented crowns were fitted using the BOPT approach with the finish line 1-1.5 mm below the gingival margin, simulating coronal emergence of a natural tooth. The soft tissue changes were measured with an intraoral scanner at two different timepoints: a) on the day of provisionalization, before prosthetic loading; and b) 10 months later without the provisional prosthesis. The STL files were superimposed and the soft tissue changes were recorded using a color scale with measurement of the volumetric changes in mm3. A mean increase in peri-implant mucosal volume of 64.7 mm3 was observed in 29 implants. The zones with the greatest increase in soft tissue volume were the papillae of implants with adjacent teeth and the peri-implant buccal margin. Three implants showed a mean decrease in soft tissue volume of -25.1 mm3. The fitting and design of crowns using the biologically oriented preparation technique (BOPT) over convergent collar implants affords a significant increase in peri-implant soft tissue volume both at the level of the papillae and in the buccal margin

Longitudinal study of cytokine expression, lipid profile and neuronal growth factors in human breast milk from term and preterm deliveries

Breast milk (BM) is considered as a reference for infant nutrition. The role of bioactive components, such as cytokines, hormones, growth factors (GFs) and fatty acids (FAs) is poorly known, but they might be implicated in immune response development. The aim of this study was to identify the lipid profile and the spectrum of cytokines and neuronal GF in BM samples and analyse the influence of gestational age and lactation time on these components. This study used a longitudinal prospective method for the characterization of cytokines, FAs and GFs global profiles in 120 BM samples from 40 healthy mothers (20 preterm and 20 term) collected as colostrum, transitional and mature milk. The cytokines were analysed by protein array (Ray Bio® Human Cytokine Array G6. Ray Biotech, Inc. Norcross, GA, USA) and the FAs were analysed by gas chromatography. The FA profile was similar between the term and the preterm BM samples. Omega-3-α-linoleic and docosahexaenoic acid (DHA) and omega-6-linoleic acid were the most abundant in the term and preterm samples during lactation. Omega-3 ETA and omega-3 EPA we observed exclusively in the preterm samples. The cytokine profile showed a different trend based on gestational age. A significantly higher expression of neurotrophic factors was found in the mature preterm milk samples as compared to the mature term samples. Our study is the first to identify the influence and interactions of perinatal factors on cytokine, GFs and FAs in human milk. © 2015 by the authors; licensee MDPI, Basel, Switzerland.We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).Peer reviewe

The creation of the Web site of The Arqueological Museum of Alcoi

Aquest article dóna notícia de la creació de la pàgina web del Museu Arqueològic d’Alcoi, les seues característiques, continguts i especificacions tècniques. Paraules clau: Pàgina web. HTTP. HTML. Museu Arqueològic d’Alcoi (Alacant)The present article gives news of the creation of the Web site of El Museu Arqueològic d’Alcoi; its characteristics, contents and technical specifications. Key Words: Web site. HTTP. HTML. Arqueological Museum of Alcoi (province of Alicante).El presente artículo da noticia de la creación de la página web del Museu Arqueològic d’Alcoi; sus características, contenidos y especificaciones técnicas. Palabras Clave: página web. HTTP. HTML. Museo Arqueológico de Alcoi (Alicante)

Proposal of a clinical care pathway for quality and safe management of headache patients: a consensus study report

Background Headache is one of the most prevalent and disabling conditions. Its optimal management requires a coordinated and comprehensive response by health systems, but there is still a wide variability that compromises the quality and safety of the care process. Purpose To establish the basis for designing a care pathway for headache patients through identifying key subpathways in the care process and setting out quality and clinical safety standards that contribute to providing comprehensive, adequate and safe healthcare. Method A qualitative research study based on the consensus conference technique. Eleven professionals from the Spanish National Health System participated, seven of them with clinical experience in headache and four specialists in healthcare management and quality. First, identification of the key subpathways in the care process for headache, barriers/limitations for optimal quality of care, and quality and safety standards applied in each subpathway. Second, two consecutive consensus rounds were carried out to assess the content of the subpathway level descriptors, until the expert agreement was reached. Third, findings were assessed by 17 external healthcare professionals to determine their understanding, adequacy and usefulness. Results Seven key subpathways were identified: (1) primary care, (2) emergency department, (3) neurology department, (4) specialised headache unit, (5) hospitalisation, (6) outpatients and (7) governance and management. Sixty-seventh barriers were identified, the most frequent being related to diagnostic errors (36,1%), resource deficiency (25%), treatment errors (19,4%), lack of health literacy (13,9%) and inadequate communications with care transitions (5,6%). Fifty-nine quality and 31 safety standards were defined. They were related to evaluation (23.3%), patient safety (21.1%), comprehensive care (12.2%), treatment (12.2%), clinical practice guidelines (7.8%), counselling (6.7%), training (4.4%) and patient satisfaction (3.3%). Conclusions This proposal incorporates a set of indicators and standards, which can be used to define a pathway for headache patients and determine the levels of quality

Factores psicológicos y dolor en pacientes reumáticos

Este trabajo estudia 40 pacientes reumáticos del Hospital del S.V.S. de Alicante distribuidos en 4 grupos (Lupus, Artritis Reumatoide, Espondilitis Anquilosante y Síndrome Fibromiálgico Primario). Hemos analizado las posibles relaciones entre la ansiedad como rasgo de personalidad, el neuroticismo, el estrés atribuido a la enfermedad, características sociodemográficas y variables relativas al dolor (intensidad, frecuencia, limitación y actividad diaria). Los resultados muestran una relación positiva, pero débil, entre la ansiedad y el neuroticismo con algunas variables de dolor. Las características sociodemográficas son las que presentan las relaciones más fuertes y frecuentes con las variables de dolor.This work studies 40 rheumatic out-patients (Lupus, Rheumatoid Arthritis, Ankylosing Spondylitis and Primary Fibromyalgia Syndrome) from the Alicante General Hospital. We analyzed the relationships between trait-anxiety, neuroticism, stress appraisal, sociodemographic characteristics and pain variables (intensity, frequency, limitation and daily activity). Results show a positive, but weak, relationships of the trait-anxiety and neuroticism to pain variables. The strongest and the most frequent relationships with pain variables were showed for the sociodemographic characteristics.Este trabajo ha sido realizado con la ayuda de investigación PA85-0336 de la Comisión Asesora de investigación Científica y Técnica (CAICYT), Ministerio de Educación

Endosymbiotic bacteria nodulating a new endemic lupine Lupinus mariae-josephi from alkaline soils in Eastern Spain represent a new lineage within the Bradyrhizobium genus

Lupinus mariae-josephi is a recently described endemic Lupinus species from a small area in Eastern Spain where it thrives in soils with active lime and high pH. The L. mariae-josephi root symbionts were shown to be very slow-growing bacteria with different phenotypic and symbiotic characteristics from those of Bradyrhizobium strains nodulating other Lupinus. Their phylogenetic status was examined by multilocus sequence analyses of four housekeeping genes (16S rRNA, glnII, recA, and atpD) and showed the existence of a distinct evolutionary lineage for L. mariae-josephi that also included Bradyrhizobium jicamae. Within this lineage, the tested isolates clustered in three different sub-groups that might correspond to novel sister Bradyrhizobium species. These core gene analyses consistently showed that all the endosymbiotic bacteria isolated from other Lupinus species of the Iberian Peninsula were related to strains of the B. canariense or B. japonicum lineages and were separate from the L. mariae-josephi isolates. Phylogenetic analysis based on nodC symbiotic gene sequences showed that L. mariae-josephi bacteria also constituted a new symbiotic lineage distant from those previously defined in the genus Bradyrhizobium. In contrast, the nodC genes of isolates from other Lupinus spp. from the Iberian Peninsula were again clearly related to the B. canariense and B. japonicum bv. genistearum lineages. Speciation of L. mariae-josephi bradyrhizobia may result from the colonization of a singular habitat by their unique legume host

Interleukin-6, C-Reactive Protein, and Recurrence After Stroke:A Time-Course Analysis of Individual-Participant Data

BACKGROUND: Inflammation promotes atherogenesis. Randomized controlled trials of anti-inflammatory therapies for prevention after stroke have not yet demonstrated clear benefit. IL-6 (interleukin-6) and hsCRP (high-sensitivity C-reactive protein) are independently associated with major adverse cardiovascular events poststroke and may guide patient selection in future randomized controlled trials. Optimal timing of hsCRP/IL-6 measurement poststroke is unknown, as early blood levels may be confounded by the inflammatory response to brain infarction.METHODS: Using individual-participant data from a systematic review, we performed a time-course analysis to investigate the association between hsCRP/IL-6 and recurrent events stratified by timing of sampling. The prespecified coprimary end points after sample measurement were: (1) recurrent major adverse cardiovascular events (first major coronary event, recurrent stroke, or vascular death) and (2) recurrent stroke (ischemic, hemorrhagic, or unspecified). The poststroke dynamics of IL-6/hsCRP were analyzed by plotting their median (interquartile interval) concentrations within each tenth of the sampling timeframe. Acute/postacute phases were defined for each biomarker according to the shape of this relationship.RESULTS: There were data for 9798 patients from 11 studies (19 891 person-years follow-up, 10 observational cohorts, and 1 randomized trial). Each marker was measured once. IL-6 was markedly elevated &lt;24 hours poststroke compared with postacute levels (≥24 hours; 11.6 versus 3.02 pg/mL; P&lt;0.001). HsCRP was elevated for 10 days. IL-6 was associated with recurrent major adverse cardiovascular events in the postacute phase (≥24 hours; risk ratio, 1.30 [CI, 1.19-1.41], per unit log eIL-6), but not in the acute phase (&lt;24 hours; risk ratio, 1.10 [CI, 0.98-1.25]; P interaction=0.03). After adjustment for risk factors/medication, the association remained for postacute IL-6 when analyzed per log eunit (risk ratio, 1.16 [CI, 1.05-1.66]) and per quarter increase (risk ratio, 1.55 [CI, 1.19-2.02]; Q4 versus Q1), but not if measured acutely. Similar findings were observed for recurrent stroke. There was no evidence of time-dependent interaction with hsCRP. CONCLUSIONS: Timing of sample measurement after stroke modifies the association with recurrent major adverse cardiovascular events for IL-6 but not hsCRP. These data inform future randomized controlled trial designs incorporating biomarker-based selection of patients for anti-inflammatory therapies.</p

Xarxa de literatura catalana infantil (Grau d’Educació Infantil)

En aquesta memòria descrivim el treball en xarxa elaborat pels membres del projecte d’innovació docent “Xarxa de literatura catalana infantil (Grau d’Educació Infantil)” que, durant el curs 2014-2015, ha dut a terme diverses reunions presencials i virtuals per a modernitzar i millorar el procés d’ensenyament-aprenentatge relacionat amb la matèria objecte d’estudi. L’eix vertebral del projecte es basa l’ús de les TIC com a recurs motivador i dinàmic que cal implementar en la metodologia docent de les assignatures relacionades amb la literatura infantil del grau en Educació Infantil. En aquest sentit, s’hi descriuen els avantatges dels recursos relacionats amb l’univers Google (sobretot, Calendar, Sites, Drive i Youtube) i Prezi, la pàgina web que proporciona un entorn de presentacions en línia dinàmiques i interactives, molt en consonància amb les interessos de l’alumnat i els nous processos de comunicació i interacció docent. Per a il·lustrar el projecte, s’hi mostren imatges representatives dels materials que han sigut elaborats amb aquestos recursos