APARICIÓN TEMPRANA DEL PATRÓN DE DOLOR CRÓNICO EN PACIENTES MUSCULOESQUELÉTICOS SUBAGUDOS

The chronic pain pattern implies high levels of negative emotions, pain and perceived disability disability perceived. Up to date few studies have assessed when this chronic pain pattern appears. This study is aimed at exploring this issue. Methods: were evaluated  146 subjects with 4 weeks sick leave due to musculoskeletal diseases (MSDs) and 95 with Rheumatoid Arthritis (RA). All patients completed the following assessment instruments: the Sadness and Depression Questionnaire (CTD), Anxiety situations and responses. Inventory –Brief form- (ISRA-B), Health Assessment Questionnaire (HAQ), a visual analogy scale for intensity of pain and a likert type scale for the frequency of pain. The analyses included a comparison on the scores of the tests between patients on sick leave due to MD compared to RA patients. Descriptive and bivariate analyses were performed. Results: Patients on sick leave due to MD and RA patients reported similar perception of their disability, showing a high HAQ score mean. Patients on sick leave due to MD reported more perceived frequency and intensity of pain than RA patients. In relation to negative emotions, both groups reported similar high levels with some poorer levels for RA patients compared to patients on sick leave due to MD for cognitive, evaluation and life situations anxiety. Depression scores presented the same levels for both patients groups. Conclusions: Our study shows that patients with subacute pain/disability and chronic pain/disability report very similar pattern for negative emotions and perception of pain and disability, suggesting that these factors appear in an early stage and contributing to the transition from acute to chronic pain/disability.El patrón de dolor crónico implica altos niveles de emociones negativas, dolor y discapacidad percibida. Pocos estudios han evaluado el patrón de aparición del dolor crónico  y éste era nuestro objetivo. Método: fueron evaluados 146 participantes con 4 semanas la Baja Laboral por enfermedades musculoesqueléticas (DsMS) y 95 con artritis reumatoide (AR) mediante los siguientes instrumentos: el Cuestionario de Tristeza y Depresión (CTD), el  Inventario de Situaciones y Respuestas de Ansiedad–forma breve-. (ISRA-B), Cuestionario de Evaluación de Salud (HAQ), una escala analógica visual para la intensidad del dolor y una escala tipo Likert para la frecuencia del dolor. Los análisis (descriptivos y bivariados) incluyeron una comparación de las puntuaciones de las pruebas entre los pacientes con baja laboral por EM en comparación con los pacientes con AR.  Resultados: Los pacientes con Baja Laboral por enfermedades musculoesqueléticas y los pacientes con AR informaron de una percepción similarde su discapacidad, según el HAQ. Pacientes con Baja Laboral por enfermedades musculoesqueléticas informaron mayor frecuencia percibida y más intensidad de dolor que los pacientes con AR. En relación a las emociones negativas, ambos grupos presentaron niveles altos y similares, con algunos niveles más pobres de los pacientes con AR en comparación con Pacientes con Baja Laboral por enfermedades musculoesqueléticas para la ansiedad cognitiva, la ansiedad de evaluación y la de la vida cotidiana (en  ISRA-B). Las puntuaciones en depresión presentan los mismos niveles en ambos grupos de pacientes.Conclusión. Nuestro estudio muestra que los pacientes con dolor subagudo/discapacidad y dolor crónico/discapacidad reportan un patrón muy similar para las emociones negativas y la percepción del dolor y la discapacidad, lo que sugiere que estos factores aparecen en una etapa temprana y favorecen, por tanto, la transición de dolor agudo a crónico/discapacidad

El Argar y el Bronce Valenciano. Reflexiones en torno al mundo funerario

This paper is a review of a considerable amount of new data published about settlements in Alicante in which the presence of Bronze Age burials has been registered. At the same time we will state, based on the mortuary evidence, some reflections about the coexistence in Alicante of two different social formations: Argaric Culture and Bronce Valenciano.Con este texto pretendemos revisar un buen número de noticias publicadas sobre yacimientos de la Provincia de Alicante en los que se ha registrado la presencia de enterramientos adscribibles a la Edad del Bronce, y al mismo tiempo exponer, a partir de las evidencias funerarias, algunas reflexiones sobre la coexistencia en suelo alicantino de dos formaciones sociales diferentes: la Cultura Argárica y el denominado Bronce Valenciano

Diagnostic yield of early repeat colonoscopy after suboptimal bowel preparation in a fecal immunochemical test-based screening program

Background Current guidelines regarding surveillance after screening colonoscopy assume adequate bowel preparation. However, follow-up intervals after suboptimal cleansing are highly heterogeneous. We aimed to determine the diagnostic yield of early repeat colonoscopy in patients with suboptimal bowel preparation in fecal immunochemical test (FIT)-based screening colonoscopy. Methods An observational study including patients who underwent colonoscopy with suboptimal bowel preparation after positive FIT screening and then repeat colonoscopy within 1 year. Suboptimal preparation was defined as a Boston Bowel Preparation Scale (BBPS) score of 1 in any segment. Patients with a BBPS score of 0 in any segment or incomplete examination were excluded. The adenoma detection rate (ADR), advanced ADR (AADR), and colorectal cancer rate were calculated for the index and repeat colonoscopies. Results Of the 2474 patients with FIT-positive colonoscopy at our center during this period, 314 (12.7%) had suboptimal preparation. Of the 259 (82.5%) patients who underwent repeat colonoscopy, suboptimal cleansing persisted in 22 (9 %). On repeat colonoscopy, the ADR was 38.7% (95% CI 32.6% to 44.8%) and the AADR was 14.9% (95%CI 10.5% to 19.4%). The per-adenoma miss rate was 27.7% (95 %CI 24.0% to 31.6%), and the per-advanced adenoma miss rate was 17.6% (95%CI 13.3% to 22.7%). After repeat colonoscopy, the post-polypectomy surveillance recommendation changed from 10 to 3 years in 14.7% of the patients with previous 10-year surveillance recommendation. Conclusions Patients with suboptimal bowel preparation on FIT-positive colonoscopy present a high rate of advanced adenomas in repeat colonoscopy, with major changes in post-polypectomy surveillance recommendations

Aplicació d’un test d’esforç intervàlic (Test de Probst) per valorar la qualitat aeròbica en futbolistes de la lliga espanyola

Els tests continus realitzats en ergòmetres estandarditzats són poc específics per al futbol. El test intervàlic de Probst permet de valorar la velocitat màxima aeròbica (VMA) i el LAn (llindar anaeròbic) en el camp de futbol, car no existeixen dades de referència. Es pretenen de valorar aquests paràmetres en futbolistes espanyols per comprovar la sensibilitat a nivell de pràctica i la utilitat per determinar el LAn. Van participar-hi 231 futbolistes de categories juvenil (n = 26), amateur (n= 74), semiprofessional (n = 36) i professional (n = 95); es va registrar la VMA i la freqüència cardíaca (Fc), i es van calcular les velocitats i Fc en el LAn, determinat manualment (LAnI) i matemàticament (LAnM). Va existir inflexió de la Fc en més del 89 % dels tests. Les Fc en el LAn van ser similars a les descrites a la literatura (90-95% respecte a la màxima) i la velocitat en el LAn va obtenir rangs amplis de VMA (72-96%). El test va ser sensible al nivell de pràctica en les variables LAnI i VMA. El protocol intervàlic de Probst va permetre de realitzar un test de camp específic sensible al grau de professionalització dels futbolistes, i es van establir dades de referència per a les categories estudiades. L’anàlisi de la Fc va permetre d’identificar un punt d’inflexió que pogués correspondre’s amb el LAn

Aplicación de un test de esfuerzo interválico (Test de Probst) para valorar la cualidad aeróbica en futbolistas de la liga española

Los tests continuos realizados en ergómetros estandarizados son poco específicos para el fútbol. El test interválico de Probst permite valorar la velocidad máxima aeróbica (VMA) y el UAn en el campo de fútbol, no existiendo datos de referencia. Se pretenden valorar estos parámetros en futbolistas españoles para comprobar la sensibilidad al nivel de práctica y la utilidad para determinar el UAn. Participaron 231 futbolistas de categorías juvenil (n = 26), amateur (n = 74), semiprofesional (n = 36) y profesional (n = 95), registrando la VMA y la frecuencia cardíaca (Fc), y calculando las velocidades y Fc en el UAn determinado manualmente (UAnI) y matemáticamente (UAnM). Existió inflexión de la Fc en más del 89 % de los tests. Las Fc en el UAn fueron similares a las descritas en la literatura (90-95 % respecto a la máxima) y la velocidad en el UAn obtuvo rangos amplios de VMA (72-96 %). El test fue sensible al nivel de práctica en las variables UAnI y VMA. El protocolo interválico de Probst permitió realizar un test de campo específico sensible al grado de profesionalización de los futbolistas, estableciéndose datos de referencia para las categorías estudiadas. El análisis de la Fc permitió identificar un punto de inflexión que pudiera corresponderse con el UAn

An approach to the Spanish consumer's perception of the sensory quality of environmentally friendly seabass

[EN] Seabass is one of the leading aquaculture species in Europe. Sensory analysis is essential for new product development. This research focused on establishing and differentiating the opinion of consumers about seabass quality obtained with organic feeding. Fish were fed for 196 days with four treatments (a control diet with 30% fishmeal and three diets with different levels of fishmeal supplemented with organic vegetable ingredients: 25%, 30% and 35%). Experimental diets were compared with commercial samples from the retail industry that were considered as "adequate quality for fish ". Two sensory analyses were carried out, check-all-that-apply (CATA) to obtain feedback on consumers' characterization towards a different type of fish evaluated and projective mapping (PM) to measure the similarity among a set of products and establish a comparison between results provided by both methods. According to the CATA results, white color, softness, meaty taste and juicy texture were considered relevant attributes, also showing a good relationship with an adequate cooked fish description. A penalty analysis confirmed that the previous characteristics were considered essential while fibrous was an undesirable attribute. The projective mapping showed a similar sensory configuration to the CATA, corroborating these findings that showed that commercial fish were placed in a position away from the rest of the treatments, and the organic diet with a higher level of fishmeal (35%) was the most distant from the control diet.This Project was subsidized by the Biodiversity Foundation 1-2020, within the framework of the Pleamar Program, co-financed by the FEMP.Calanche Morales, JB.; Tomas-Vidal, A.; Cusiyunca Phoco, ER.; Martínez-Llorens, S.; Marquina, PL.; Jover Cerda, M.; Roncales, P.... (2021). An approach to the Spanish consumer's perception of the sensory quality of environmentally friendly seabass. Foods. 10(11):1-16. https://doi.org/10.3390/foods10112694S116101

Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage

Acetaminophen overdose is one of the leading causes of acute liver failure and liver transplantation in the Western world. Magnesium is essential in several cellular processess. The Cyclin M family is involved in magnesium transport across cell membranes. Herein, we identify that among all magnesium transporters, only Cyclin M4 expression is upregulated in the liver of patients with acetaminophen overdose, with disturbances in magnesium serum levels. In the liver, acetaminophen interferes with the mitochondrial magnesium reservoir via Cyclin M4, affecting ATP production and reactive oxygen species generation, further boosting endoplasmic reticulum stress. Importantly, Cyclin M4 mutant T495I, which impairs magnesium flux, shows no effect. Finally, an accumulation of Cyclin M4 in endoplasmic reticulum is shown under hepatoxicity. Based on our studies in mice, silencing hepatic Cyclin M4 within the window of 6 to 24 h following acetaminophen overdose ingestion may represent a therapeutic target for acetaminophen overdose induced liver injury.Acknowledgements: This work was supported by Ministerio de Ciencia, Innovación y Universidades MICINN: PID2020-117116RB-I00 integrado en el Plan Estatal de Investigación Cientifica y Técnica y Innovación, cofinanciado con Fondos FEDER (to MLM-C), Ministerio de Ciencia e Innovación CONSOLIDER-INGENIO 2010 Program Grant CSD2008-00005 (to LAMC); Spanish Ministry of Economy and Competitiveness Grant BFU2013-47531-R, BFU2016-77408-R, PID2019-109055RB-100 (to L.A.M.-C.) (MINECO/FEDER, UE); Asociación Española contra el Cáncer (MLM-C, TC-D), Fundación Científica de la Asociación Española Contra el Cáncer (AECC Scientific Foundation) Rare Tumor Calls 2017 (to M.L.M.-C.), La Caixa Foundation Program (to M.L.M.-C.), Fundacion BBVA UMBRELLA project (to M.L.M.-C.), Ayuda RYC2020-029316-I financiada por MICIN/AEI/10.13039/501100011033 (to TC-D), Plataforma de Investigación Clínica-SCReN (PT17 0017 0020) (to M.I.-L.), programa retos RTC2019-007125-1 (to M.L.M.-C, J.S.), Proyectos Investigacion en Salud DTS20/00138 (to M.L.M.-C., J.S), ERA-Net E-Rare EJP RD Joint Translational Call for Rare Diseases FIGHT-CNNM2 (EJPRD19-040) and from Instituto Carlos III, Spain (REF G95229142) (to L.A.M.-C.), US National Institutes of Health under grant CA217817 (to D.B.), Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos III. We thankMINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644) and PhD fellowship fromMINECO (REF BES-2017-080435) awarded to I.G.-R. The collection and storage of patients tissues was supported by the Newcastle Biomedicine Biobank and the European Community’s Seventh Framework Programme (FP7/2001–2013) and Cancer Research UK awards Cancer Research UK grants C18342/A23390; C9380/A18084 and C9380/A26813. Finally, we would like to acknowledge Begoña Rodríguez Iruretagoyena for the technical support provided

A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12

Background: Colorectal cancer (CRC) is a disease of complex aetiology, with much of the expected inherited risk being due to several common low risk variants. Genome-Wide Association Studies (GWAS) have identified 20 CRC risk variants. Nevertheless, these have only been able to explain part of the missing heritability. Moreover, these signals have only been inspected in populations of Northern European origin. Results: Thus, we followed the same approach in a Spanish cohort of 881 cases and 667 controls. Sixty-four variants at 24 loci were found to be associated with CRC at p-values <10-5. We therefore evaluated the 24 loci in another Spanish replication cohort (1481 cases and 1850 controls). Two of these SNPs, rs12080929 at 1p33 (Preplication=0.042; Ppooled=5.523x10-03; OR (CI95%)=0.866(0.782-0.959)) and rs11987193 at 8p12 (Preplication=0.039; Ppooled=6.985x10-5; OR (CI95%)=0.786(0.705-0.878)) were replicated in the second Phase, although they did not reach genome-wide statistical significance. Conclusions: We have performed the first CRC GWAS in a Southern European population and by these means we were able to identify two new susceptibility variants at 1p33 and 8p12 loci. These two SNPs are located near the SLC5A9 and DUSP4 loci, respectively, which could be good functional candidates for the association signals. We therefore believe that these two markers constitute good candidates for CRC susceptibility loci and should be further evaluated in other larger datasets. Moreover, we highlight that were these two SNPs true susceptibility variants, they would constitute a decrease in the CRC missing heritability fraction

BMP2/BMP4 colorectal cancer susceptibility loci in northern and southern european populations

Genome-wide association studies have successfully identified 20 colorectal cancer susceptibility loci. Amongst these, four of the signals are defined by tagging single nucleotide polymorphisms (SNPs) on regions 14q22.2 (rs4444235 and rs1957636) and 20p12.3 (rs961253 and rs4813802). These markers are located close to two of the genes involved in bone morphogenetic protein (BMP) signaling (BMP4 and BMP2, respectively). By investigating these four SNPs in an initial cohort of Spanish origin, we found substantial evidence that minor allele frequencies (MAFs) may be different in northern and southern European populations. Therefore, we genotyped three additional southern European cohorts comprising a total of 2028 cases and 4273 controls. The meta-analysis results show that only one of the association signals (rs961253) is effectively replicated in the southern European populations, despite adequate power to detect all four. The other three SNPs (rs4444235, rs1957636 and rs4813802) presented discordant results in MAFs and linkage disequilibrium patterns between northern and southern European cohorts. We hypothesize that this lack of replication could be the result of differential tagging of the functional variant in both sets of populations. Were this true, it would have complex consequences in both our ability to understand the nature of the real causative variants, as well as for further study designs

Correlation between in vitro cytotoxicity and in vivo lethal activity in mice of epsilon toxin mutants from Clostridium perfringens

Epsilon toxin (Etx) from Clostridium perfringens is a pore-forming protein with a lethal effect on livestock, producing severe enterotoxemia characterized by general edema and neurological alterations. Site-specific mutations of the toxin are valuable tools to study the cellular and molecular mechanism of the toxin activity. In particular, mutants with paired cysteine substitutions that affect the membrane insertion domain behaved as dominant-negative inhibitors of toxin activity in MDCK cells. We produced similar mutants, together with a well-known non-toxic mutant (Etx-H106P), as green fluorescent protein (GFP) fusion proteins to perform in vivo studies in an acutely intoxicated mouse model. The mutant (GFP-Etx-I51C/A114C) had a lethal effect with generalized edema, and accumulated in the brain parenchyma due to its ability to cross the blood-brain barrier (BBB). In the renal system, this mutant had a cytotoxic effect on distal tubule epithelial cells. The other mutants studied (GFP-Etx-V56C/F118C and GFP-Etx-H106P) did not have a lethal effect or cross the BBB, and failed to induce a cytotoxic effect on renal epithelial cells. These data suggest a direct correlation between the lethal effect of the toxin, with its cytotoxic effect on the kidney distal tubule cells, and the ability to cross the BBB