Experiencia y resultados preliminares en el uso de cilindros intersomáticos para la artrodesis lumbar

El dolor lumbar crónico es una patología que puede llegar a ser incapacitante y en la que a menudo fracasan los tratamientos conservadores. Como alternativa entre las cirugías que pretenden atajar este problema mediante una artrodesis está la fusión intersomática con cilindros, que presenta algunas ventajas respecto a otras técnicas de fijación. Esta técnica ha sido introducida recientemente en nuestro país. Se presentan los primeros resultados obtenidos tras esta cirugía en los primeros 16 pacientes operados. Desde 1997 a diciembre de 2000 se han implantado 11 cilindros BAK y 5 LIFEC. Diez pacientes tenían un seguimiento mínimo de 1 año y éstos constituyen la serie evaluada. Siete pacientes (70%) no presentaban dolor. Cuatro pacientes (40%) se habían incorporado a sus trabajos respectivos. Seis pacientes (60%) no precisaban tratamiento médico. Los buenos resultados obtenidos hasta el momento nos invitan a pensar que esta técnica, de menor agresividad y que no cierra la puerta a otros tipos de instrumentación, es una opción válida para el tratamiento del dolor lumbar crónico.Chronic low back pain is a medical cause of disability in which conservative management is often not effective. As an alternative, interbody fusion with cylinders offers several advantages as compared to other surgical methods of fusion. This technique has been recently introduced in our Country. The preliminary results of 16 patients managed in our Department are shown. From 1997 to December 2000, eleven BAK devices and 5 LIFEC have been implanted. Ten patients had a minimum follow-up of 1 year and these constitute the series evaluated. Seven patients (70%) were free of pain. Four patients (40%) returned to their previous job. Six patients (60%) did not need medical treatment. The good results with this technique encourage us and suggest that these devices are a valid option for the management of chronic low back pain

Prótesis unicondílea de rodilla: Valoración clínica preliminar

Los pacientes afectados de artrosis unicompartimetal de rodilla pueden ser tratados con diferentes métodos quirúrgicos. Los más habituales son la osteonomía tibial en jóvenes y la prótesis total de rodilla en ancianos. Una alternativa que va adquiriendo adeptos es la prótesis unicondílea. Tras un período inicial de gran euforia se pasó a otro de escepticismo, dando los resultados. El propósito del presente estudio es evaluar un nuevo diseño de prótesis de rodilla unicondílea (Alpina, IQL) a corto plazo siguiendo criterios clínicos y de calidad de vida. Se revisan 13 pacientes intervenidos entre Junio de 2000 a Marzo del 2002. Siete eran varones y seis mujeres. La edad media fue de 65 años (r=55-72ª). En doce casos la etiología fue artrosis y en uno necrosis del cóndilo interno. La evaluación clínica se realizó mediante el cuestionario sobre la calidad de vida SF-12. Todos los pacientes consiguieron una flexión de 110º y extensión completa. Sólo un paciente presentó molestias leves.Patients who have unicompartimental knee osteoarthritis can be manager by different surgical techniques. Young people are usually treated by tibial osteotomy and elderly people by total knee replacement. Unicondylar knee prosthesis is becoming an attractive recognized alternative. After a period of enthusiastic regarding this technique, scepticism took place based on the clinical results. The aim of this study is to evaluate, in firs instance, a new knee unicondylar knee prosthesis design (Alpine, IQL) following clinical criteria and quality of life. Thirteen patients, managed in between June 2000 and March 2002, are reviewed. Seven were males and six females. The mean age was 65 years (range 55-77 years). Osteoarthritis was the aetiology in twelve cases and necrosis of the medial condyle in one patient. The clinical evaluation was based on quality of life through a questionnaire SF-12. All patients improved a knee flexion of 110º and a complete extension. Only one patient had slight pain and had some limitation

Cumulative acquisition of pathogenicity islands has shaped virulence potential and contributed to the emergence of LEE-negative Shiga toxinproducing Escherichia coli strains

Shiga toxin-producing Escherichia coli (STEC) are foodborne pathogens causing severe gastroenteritis, which may lead to hemolytic uremic syndrome. The Locus of Enterocyte Effacement (LEE), a Pathogenicity Island (PAI), is a major determinant of intestinal epithelium attachment of a group of STEC strains; however, the virulence repertoire of STEC strains lacking LEE, has not been fully characterized. The incidence of LEE-negative STEC strains has increased in several countries, highlighting the relevance of their study. In order to gain insights into the basis for the emergence of LEE-negative STEC strains, we performed a large-scale genomic analysis of 367 strains isolated worldwide from humans, animals, food and the environment. We identified uncharacterized genomic islands, including two PAIs and one Integrative Conjugative Element. Additionally, the Locus of Adhesion and Autoaggregation (LAA) was the most prevalent PAI among LEE-negative strains and we found that it contributes to colonization of the mice intestine. Our comprehensive and rigorous comparative genomic and phylogenetic analyses suggest that the accumulative acquisition of PAIs has played an important, but currently unappreciated role, in the evolution of virulence in these strains. This study provides new knowledge on the pathogenicity of LEE-negative STEC strains and identifies molecular markers for their epidemiological surveillance.This study was supported by FONDECYT grant 1161161 to R. Vidal and CONICYT-PCHA/2014-63140238 fellowship to D. Montero. Work at USC-LREC was supported by Project PI16/01477 from Plan Estatal de I+D+I 2013-2016, Instituto de Salud Carlos III, Subdirección General de Evaluación y Fomento de la Investigación and FEDER, Ministerio de Economia, Industria y Competitividad, Gobierno de España and Project ED431C 2017/57 from the Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia and FEDER. Fondecyt 11150966 to Felipe Del Canto. Consejo Nacional de Ciencia y Tecnología; [Fondo Nacional de Desarrollo Científico y Tecnológico].S

Understanding the key features of the spontaneous formation of bona fde prions through a novel methodology that enables their swift and consistent generation

Among transmissible spongiform encephalopathies or prion diseases afecting humans, sporadic forms such as spo‑ radic Creutzfeldt–Jakob disease are the vast majority. Unlike genetic or acquired forms of the disease, these idiopathic forms occur seemingly due to a random event of spontaneous misfolding of the cellular PrP (PrPC) into the patho‑ genic isoform (PrPSc). Currently, the molecular mechanisms that trigger and drive this event, which occurs in approximately one individual per million each year, remain completely unknown. Modelling this phenomenon in experimental settings is highly challenging due to its sporadic and rare occurrence. Previous attempts to model spontaneous prion misfolding in vitro have not been fully successful, as the spontaneous formation of prions is infre‑ quent and stochastic, hindering the systematic study of the phenomenon. In this study, we present the frst method that consistently induces spontaneous misfolding of recombinant PrP into bona fde prions within hours, providing unprecedented possibilities to investigate the mechanisms underlying sporadic prionopathies. By fne‑tuning the Pro‑ tein Misfolding Shaking Amplifcation method, which was initially developed to propagate recombinant prions, we have created a methodology that consistently produces spontaneously misfolded recombinant prions in 100% of the cases. Furthermore, this method gives rise to distinct strains and reveals the critical infuence of charged sur‑ faces in this process.The present work was partially funded by three different grants awarded by “Ministerio de Economía y Competitividad” (Spanish Government), grant numbers PID2021-122201OB-C21, PID2021-1222010B-C22 and PID2020-117465GB-I00, funded by MCIN/AEI/10.13039/501100011033 and co-financed by the European Regional Development Fund (ERDF), and by the Instituto de Salud Carlos III (ISCIII), grant number AC21_2/00024. Additionally, CIC bioGUNE currently holds a Severo Ochoa Excellence accreditation, CEX2021-001136-S, also funded by MCIN/AEI/10.13039/501100011033. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate´s phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.J.T.S. holds a research contract from the Fundación para la Formación e Investigación de los Profesionales de la Salud de Extremadura (FundeSalud), Instituto de Salud Carlos III. M.F.R. holds a clinical research contract “Juan Rodés” (JR14/00036) from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele