La política de desarrollo rural integrado en la unión europea: viejos enfoques y nuevas tendencias

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Disorganization of chondrocyte columns in the growth plate does not aggravate experimental osteoarthritis in mice

Osteoarthritis (OA) is a multifactorial joint disease mainly affecting articular cartilage (AC) with a relevant biomechanical component. During endochondral ossification growth plate (GP) chondrocytes arrange in columns. GPs do not ossify in skeletally mature rodents. In neonatal mice, an altered joint loading induces GP chondrocyte disorganization. We aimed to study whether experimental OA involves GP disorganization in adult mice and to assess if it may have additional detrimental effects on AC damage. Knee OA was induced by destabilization of the medial meniscus (DMM) in wild-type (WT) adult mice, and in Tamoxifen-inducible Ellis-van-Creveld syndrome protein (Evc) knockouts (Evc ), used as a model of GP disorganization due to Hedgehog signalling disruption. Chondrocyte column arrangement was assessed in the tibial GP and expressed as Column Index (CI). Both DMM-operated WT mice and non-operated-Evc showed a decreased CI, indicating GP chondrocyte column disarrangement, although in the latter, it was not associated to AC damage. The most severe GP chondrocyte disorganization occurred in DMM-Evc mice, in comparison to the other groups. However, this altered GP structure in DMM-Evc mice did not exacerbate AC damage. Further studies are needed to confirm the lack of interference of GP alterations on the analysis of AC employing OA mice. cKO cKO cKO cKOThis work was financially supported by grants from the Instituto de Salud Carlos III [PI15/00340, PI16/00065, PI18/00261] to RL and GH-B, and Fondo Europeo de Desarrollo Regional (FEDER) by grants SAF-2013–43365-R and SAF2016-75434-R to VL R-P. AL and PG were funded by Fundación Conchita Rábago

Molecular characterization and clinical impact of TMPRSS2-ERG rearrangement on prostate cancer: comparison between FISH and RT-PCR

Prostate cancer (PCa) is a very heterogeneous disease, and there are constraints in its current diagnosis. Serum PSA levels, digital rectal examination (DRE), and histopathologic analysis often drive to overdiagnosis and overtreatment. Since 2005, the presence of the genetic rearrangement between transmembrane-serine protease gene (TMPRSS2) and the erythroblast transformation-specific (ETS)member ERG (v-ets erythroblastosis virus E26 oncogene homolog avian) has been demonstrated in almost half of PCa cases. Both FISH and RT-PCR are useful tools for detecting these rearrangements, but very few comparatives between both techniques have been published. In this study, we included FFPE tumors from 294 PCa patients treated with radical prostatectomy with more than 5 years of followup.We constructed a total of 20 tissue microarrays in order to perform break-apart and tricolor probe FISH approaches that were compared with RT-PCR, showing a concordance of 80.6% ( P < 0.001). The presence of TMPRSS2-ERG rearrangement was observed in 56.6% of cases. No association between TMPRSS2-ERG status and clinicopathological parameters nor biochemical progression and clinical progression free survival was found. In conclusion, this study demonstrates that both FISH and RT-PCR are useful tools in the assessment of the TMPRSS2-ERG fusion gene status in PCa patients and that this genetic feature per se lacks prognostic value.This study has been funded by the Grants FIS PI06/01619 and PI10/01206 from the Instituto de Salud Carlos III, Madrid, ACOMP 12/029 from the Generalitat Valenciana, Valencia, and Astra Zeneca, Spain

External validation of a prognostic model based on total tumor load of sentinel lymph node for early breast cancer patients

Background: A prognostic model based on the results of molecular analysis of sentinel lymph nodes (SLN) is needed to replace the information that staging the entire axilla provided. The aim of the study is to conduct an external validation of a previously developed model for the prediction of 5-year DFS in a group of breast cancer patients that had undergone SLN biopsy assessed by the One Step Nucleic Acid Amplification (OSNA) method. Methods: We collected retrospective data of 889 patients with breast cancer, who had not received systemic treatment before surgery, and who underwent SLN biopsy and evaluation of all SLN by OSNA. The discrimination ability of the model was assessed by the area under the ROC curve (AUC ROC), and its calibration by comparing 5-years DFS Kaplan–Meier estimates in quartile groups of model predicted probabilities (MPP). Results: The AUC ROC ranged from 0.78 (at 2 years) to 0.73 (at 5 years) in the training set, and from 0.78 to 0.71, respectively, in the validation set. The MPP allowed to distinguish four groups of patients with heterogeneous DFS (log-rank test p &lt; 0.0001). In the highest risk group, the HR were 6.04 [95% CI 2.70, 13.48] in the training set and 4.79 [2.310, 9.93] in the validation set. Conclusions: The model for the prediction of 5-year DFS was successfully validated using the most stringent form of validation, in centers different from those involved in the development of the model. The external validation of the model confirms its utility for the prediction of 5-year DFS and the usefulness of the TTL value as a prognostic variable.This study was supported by Sysmex España S.L

Eduarda Mansilla: la Biografía, Redes familiares y amicales. Los Epistolarios. Los escritos dispersos. Hacia un estudio crítico integral

El estudio de la vida y obra de Eduarda Mansilla se enmarca en la crítica sobre literatura argentina decimonónica escrita por mujeres, así como en la historia de la vida privada y su interconexión con el mapa político-social de la época, especialmente visible en las grandes familias de la clase dirigente. El corpus específicamente literario de Mansilla aún no había sido efectivamente cerrado y determinado. Se sabía, sobre todo por las memorias de su hijo Daniel García-Mansilla (1950), de la existencia de obras varias, y de escritos de crítica de arte que no han podido ubicarse. Nos constaba además, por compulsas ya realizadas, que diversos textos de la autora subsisten dispersos en publicaciones periódicas de la época, nacionales y en el extranjero. Tanto ese material, como cuanto se pudiera conseguir en lo que hace a epistolarios, crónicas, memorias, diarios y escritos testimoniales de todo tipo guardados en archivos públicos y privados, era precario y se hallaba expuesto a la desaparición y al deterioro. Hasta el presente los asedios a la vida/obra de nuestra autora se han mantenido dentro de marcos más o menos acotados, subordinados a un objetivo mayor: una edición textual, la presentación de un panorama femenino (“argentinas”, “mujer romántica”), la historia de la composición musical en la Argentina, en el que esta figura singular se engarza, pero no constituyeron investigaciones de envergadura autónoma. Lo antedicho confirmó la necesidad de localizar y rescatar la producción total de la autora a través de la compulsa de archivos públicos y privados, lo que nos permitió establecer una biografía confiable de Eduarda Mansilla que, aspiramos, se constituya en obra de consulta. Los resultados de esta investigación se publicaron en la Colección EALA de la editorial Corregidor.Our study of Eduarda Mansilla´s life and works is carried on within the field of criticism about Argentine Nineteenth-Century literature written by women, as well as in the history of private lifeand its interconnection with the political and social map of that period, which was especially visiblein certain traditional families. The specifically literary corpus of Mansilla has not yet been closednor clearly determined. Thanks to the memories written by one of her sons, Daniel García-Mansilla(1950), it is known that Mansilla has produced several literary pieces that disappeared and are notavailable to us nowadays. In addition, there are many other diverse literary works that have beenoriginally published nationally and abroad in a series of periodicals, newspapers and literary journalsthat are still inaccessible to the researchers. These materials, along with memoires, travel journals,personal notes, and any other disperse writing production by Eduarda are scattered, hidden inlibraries, unpublished and in danger of material destruction. Until today, research about Mansillahas been framed within certain fields such as the study of romanticism, Women writings, musicalcomposition, always with the goal of pursuing a critical edition. But none of them constitutes initself an independent research project. The above-mentioned confirmed the necessity of localizingand rescuing the total production of this writer nowadays scattered in public as well as in privatearchives, with the goal of achieving a serious and reliable biography of Eduarda Mansilla which,we expect, will become a referent in our discipline. The results of this research were published inthe EALA Collection Corregidor publisher

A polymorphism at the 3'-UTR region of the aromatase gene defines a subgroup of postmenopausal breast cancer patients with poor response to neoadjuvant letrozole

<p>Abstract</p> <p>Background</p> <p>Aromatase (<it>CYP19A1</it>) regulates estrogen biosynthesis. Polymorphisms in <it>CYP19A1 </it>have been related to the pathogenesis of breast cancer (BC). Inhibition of aromatase with letrozole constitutes the best option for treating estrogen-dependent BC in postmenopausal women. We evaluate a series of polymorphisms of <it>CYP19A1 </it>and their effect on response to neoadjuvant letrozole in early BC.</p> <p>Methods</p> <p>We analyzed 95 consecutive postmenopausal women with stage II-III ER/PgR [+] BC treated with neoadjuvant letrozole. Response to treatment was measured by radiology at 4^thmonth by World Health Organization (WHO) criteria. Three polymorphisms of <it>CYP19A1</it>, one in exon 7 (rs700519) and two in the 3'-UTR region (rs10046 and rs4646) were evaluated on DNA obtained from peripheral blood.</p> <p>Results</p> <p>Thirty-five women (36.8%) achieved a radiological response to letrozole. The histopathological and immunohistochemical parameters, including hormonal receptor status, were not associated with the response to letrozole. Only the genetic variants (AC/AA) of the rs4646 polymorphism were associated with poor response to letrozole (p = 0.03). Eighteen patients (18.9%) reported a progression of the disease. Those patients carrying the genetic variants (AC/AA) of rs4646 presented a lower progression-free survival than the patients homozygous for the reference variant (p = 0.0686). This effect was especially significant in the group of elderly patients not operated after letrozole induction (p = 0.009).</p> <p>Conclusions</p> <p>Our study reveals that the rs4646 polymorphism identifies a subgroup of stage II-III ER/PgR [+] BC patients with poor response to neoadjuvant letrozole and poor prognosis. Testing for the rs4646 polymorphism could be a useful tool in order to orientate the treatment in elderly BC patients.</p

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

La industria electrónica en la Unión Europea

Este artículo analiza, en primer lugar, la situación de la producción mundial de la industria electrónica, y pone de manifiesto la importancia de la producción en la Unión Europea, que sitúa al conjunto europeo en el tercer puesto del ranking mundial, detrás de Estados Unidos y Japón. El artículo señala la creciente integración de países terceros en la producción de la industria electrónica. Dentro del comercio internacional se determina, para los países con peso significativo en panorama mundial, y a través de indicadores, la incidencia de los intercambios de estos productos en su comercio total; y en la vertiente exportadora, se profundiza en la situación la Unión Europea comparada con la de los otros países líderes. También se analiza, con cierto detalle la posición de los 15 países de la Unión Europea, identificándose en cada uno ellos y para los distintos subsectores, las especializaciones exportadoras y los saldos comerciales y tasas de cobertura de los intercambios de productos electrónicos. Por último, se reflexiona sobre los diversos aspectos en los que deberían incidir los países de la Unión Europea a fin de reducir el déficit crónico del sector y mejorar su competitividad estructuraPeer reviewe