Search

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, with higher prevalence in women, that leads to neurological disability. The disease course and clinical phenotype are highly variable, and therefore, biomarkers for the diagnosis, classification, monitoring of the disease and treatment assessment are needed. Studies have shown a dysregulation in the coding and non-coding RNAs and proposed some as biomarkers. However, still none of them have reached the clinical practice. Recently, circular RNAs (circRNAs) have emerged as new players in the transcriptome that hold a great potential as biomarkers in several diseases. Leukocytes from 30 MS patients and 20 healthy controls (HCs) were RNA-sequenced to study the linear and circular transcriptome. Differential expression analysis was performed by DESeq, and circRNA candidates were studied in a second cohort (70 MS and 46 HC) by RT-qPCR and in paired samples drawn during the relapse and remission phases (20 patients). Among the differentially expressed circRNAs, 96.1% are upregulated in patients compared with controls, but similar circRNA profiles are found between MS types. The same upregulation trend was observed in females but not in males or in the linear transcriptome. The upregulation of 6 circRNAs was validated, and a change in their expression was found between relapse and remission. The 6 circRNAs showed a good performance to discriminate patients from HC with a combined area under the curve of 0.852. There is global, specific and sex-dependent increase of circRNA expression in MS, and 6 circRNAs are proposed as potential biomarkers.

Introduction: Mooren’s ulcer is a painful, inflammatory chronic keratitis that affects corneal periphery, progressing centripetally, ultimately ending in perforation. The first line of treatment includes systemic immunomodulators, with surgery being the last option. We present a case of bilateral Boston keratoprosthesis implantation for severe Mooren’s ulcer that responded differently in each eye. Clinical case: A 32-year-old male with corneal opacification, anterior staphylomas, vision of hand movement, was started on systemic immunosuppression with cyclosporine. After two failed penetrating keratoplasties in each eye, high intraocular pressure despite diode cyclophotocoagulation, and cystic macular edema, we performed Boston keratoprosthesis type 1 in both eyes. The right eye responded initially well, with a best-corrected visual acuity of 20/80 and normal intraocular pressure. The left eye presented high intraocular pressure, which required cyclophotocoagulation, ultimately resulting in hypotony. Boston keratoprosthesis was performed but had peripheral corneal necrosis that progressed despite amniotic membrane transplantation and aggressive intensive treatment with medroxyprogesterone, autologous platelet-rich-in-growth-factors eye drops, and oral doxycycline. Thus, replacement of the semi-exposed Boston keratoprosthesis with tectonic penetrating keratoplasty was necessary. However, both eyes developed phthisis bulbi with final visual acuity of perception of light with poor localization. Conclusion: Mainstay treatment of Mooren’s ulcer is systemic immunomodulation. Surgical treatment must be considered only when risk of perforation, preferably with inflammation under control. Penetrating keratoplasty frequently fails, and Boston keratoprosthesis may be a viable option. However, postoperative complications, especially uncontrolled high intraocular pressure, corneal necrosis, and recurrence of Mooren’s ulcer may jeopardize the outcomes and need to be addressed promptly with intensive topical and systemic treatment.

Este trabajo estudia los sistemas offshore y los distintos apoyos que requiere para su correcto funcionamiento. Detallando la finalidad de cada tipo de transporte y analizando sus riesgos para los trabajadores y para el medio ambiente mediante factores de riesgo e historial de accidentes. También se enfoca resumidamente hacia dónde va el futuro del offshore. El objetivo que tiene es que personas ajenas al sector náutico tengan al alcance información de cómo actúan las distintas partes en un sistema offshore y el peligro que conlleva trabajar en ellos.

Introduction: Lung cancer is the second most frequent malignancy worldwide, but its aetiology is still unclear. Inflammatory cytokines and Th cells, including Th17, are now emerging as being involved in NSCLC pathways, thus postulating a role of IL-17 in tumour angiogenesis by stimulating the vascular endothelial growth factor and the release of nitric oxide. Despite the fact that many biomarkers are used for chest malignancy diagnosis, data on FeNO levels and inflammatory cytokines in NSCLC are still few. Our study aimed to evaluate the relationship between pulmonary nitric oxide production and VEGF and Th17-related cytokines in the EBC of patients affected by early-stage NSCLC. Methods: FeNO measurement and lung function tests were performed in both patients affected by NCSLC and controls, EBC samples were also taken, and Th1 (IL-1, IL-6, IL-12, IFN-g, TNF-a), Th17 (IL-17, IL-23) and Th2 (IL-4, IL-5, IL-13) related cytokines were measured. Results: Th1 and Th17-related cytokines in EBC, except for IFN-gamma and TNF-alpha, were significantly higher in patients than in healthy controls, whereas no differences were seen for Th2-related cytokines. FeNO at the flow rate of 50 mL/s, JawNO and CalvNO levels were significantly higher in patients affected by NSCLC compared to controls. Significant correlations were found between FeNO 50 mL/s and IL-17, IL-1 and VEGF. JawNO levels positively correlated with IL-6, IL-17 and VEGF. No correlations were found between FeNO and Th2-related cytokines. Conclusion: This is the first report assessing a relationship between FeNO levels and Th17-related cytokines in the EBC of patients affected by early-stage NSCLC. IL-17, which could promote angiogenesis through the VEGF pathway, might be indirectly responsible for the increased lung production of NO in patients with NSCLC.

Canvi climàtic; Seguretat alimentària; Perill alimentari; Risc emergent Cambio climático; Seguridad alimentaria; Peligro alimentario; Riesgo emergente Climate change; Food safety; Foodborne hazard; Emerging risk El canvi climàtic és un dels reptes que la societat haurà d’afrontar durant les properes dècades ja que els seus efectes incideixen, directament i indirectament i cada cop amb més intensitat, a tot el planeta. Actualment, es tenen moltes evidències i previsions dels efectes que està causant i que causarà el canvi climàtic en la producció i el proveïment d’aliments per a la població, especialment pel que fa a l’obtenció d’aliments suficients i segurs. Aquest document se centra en els efectes sobre un aspecte particular d’aquesta obtenció segura dels aliments, la seguretat alimentària -és a dir, els perills físics, químics i biològics que hi podem trobar potencialment. Així, s’hi revisen quins efectes sobre els perills alimentaris causats pel canvi climàtic ja s’han identificat avui dia, ja siguin reals, emergents o previsibles en el futur. A més, també identifica les eines i els posicionaments estratègics que s’han de desenvolupar i promoure per preveure, prevenir i gestionar els problemes emergents derivats dels efectes del canvi climàtic sobre els perills alimentaris. El cambio climático es uno de los retos que la sociedad deberá afrontar durante las próximas décadas debido a que sus efectos inciden, directamente e indirectamente y cada vez con más intensidad, en todo el planeta. Actualmente, se tienen muchas evidencias y previsiones de los efectos que está causando y que causará el cambio climático en la producción y el abastecimiento de alimentos para la población, especialmente en lo que se refiere a la obtención de alimentos suficientes y seguros. Este documento se centra en los efectos sobre un aspecto particular de esta obtención segura de los alimentos, la seguridad alimentaria –es decir, los peligros físicos, químicos y biológicos que potencialmente podemos encontrar. Así, se revisan qué efectos sobre los peligros alimentarios causados por el cambio climático ya se han identificado a día de hoy, ya sean estos reales, emergentes o previsibles en un futuro. Además, también identifica las herramientas y los posicionamientos estratégicos que se deben desarrollar y promover para prever, prevenir y gestionar los problemas emergentes derivados de los efectos del cambio climático sobre los peligros alimentarios. Climate change is one of the challenges that society will have to face over the next few decades, as its effects are, directly and indirectly, and increasingly, on the whole planet. There is currently much evidence and forecasts of the effects that climate change is causing and will cause on for food production and supply for a population, especially in terms of obtaining sufficient and safe food. This document focuses on the effects on a particular aspect of this safe food procurement – food safety, i. e. physical, chemical and biological hazards that we can potentially encounter –. Thus, it is reviewed what effects on food hazards caused by climate change are already identified today, whether real, emerging or foreseeable in the future. It also identifies tools and strategic positions to be developed and promoted to anticipate, prevent and manage emerging problems arising from the effects of climate change on food hazards.

Aging is a universal and complex process that affects all tissues and cells types, including immune cells, in a process known as immunosenescence. However, many aspects of immunosenescence are not completely understood, as the characteristics of the immune cells of nonagenarians and centenarians or the features and implications of extracellular vesicles (EVs). In this study, we analyzed blood samples from 51 individuals aged 20-49 and 70-104 years. We found that senescent CD8 cells accumulate with age, while there is a partial reduction of senescent CD4 cells in nonagenarians and centenarians. Moreover, plasma EVs carry T cell specific markers, but no accumulation of "senescent-like EVs" was found within any of analyzed age groups. Our functional studies of cocultures of peripheral blood mononuclear cells and EVs showed that EVs enhance T cell viability and, under phytohemagglutinin stimulation, they influence cytokine secretion and cell activation in an age-dependent manner. These results underline the importance of EVs on the immune system functioning, and open new perspectives to further study their implication in human aging.

Purpose To compare anatomical and functional results between three types of keratoprosthesis (KPro) in chemical injury and autoimmune disease. Methods 70 clinically comparable cases were included as follows: Boston KPro Type 1 25 eyes, osteo-odonto-keratoprosthesis (OOKP) 23 eyes, Tibial bone KPro 22 eyes. Survival times for anatomical and functional success were evaluated with Kaplan-Meier estimations and Log-rank tests. KPro exchange was considered a complication, not as failure. Results Prosthesis retention in chemical injury group at 5 years was 86% for OOKP, 100% for Tibial bone KPro, and 65% for Boston KPro (p = 0.09), while in the autoimmune disease group it was 66% for Tibial bone KPro and 50% for Boston KPro (p = 0.19; OOKP only one case). Functional success in the chemical injury group at 5 years was 86% for OOKP, 84% for Tibial bone KPro and 71% for Boston KPro (p = 0.38), while in the autoimmune group, it was 44% for Tibial bone KPro and 15% for Boston KPro (p = 0.15; OOKP only one case). The post-operative complications in all groups were: retinal detachment, vitreous hemorrhage, endophthalmitis, retro-prosthetic membrane, uncontrolled glaucoma, the last two being more common in Boston KPro. Conclusions For both diagnoses, chemical injury and autoimmune diseases, there was a tendency for better long-term anatomical and functional results with Tibial bone KPro followed by OOKP and Boston KPro Type 1. However, these results were not statistically significant.

Adult stem cells are a promising tool to positively influence bone regeneration. Concentrated bone marrow therapy entails isolating osteoprogenitor cells during surgery with, however, only low cells yield. Two step stem cell therapy requires an additional harvesting procedure but generates high numbers of progenitor cells that facilitate osteogenic pre-differentiation. To further improve bone regeneration, stem cell therapy can be combined with growth factors from platelet rich plasma (PRP) or its lysate (PL) to potentially fostering vascularization. The aim of this study was to investigate the effects of bone marrow concentrate (BMC), osteogenic pre-differentiation of mesenchymal stromal cells (MSCs), and PL on bone regeneration and vascularization. Bone marrow from four different healthy human donors was used for either generation of BMC or for isolation of MSCs. Seventy-two mice were randomized to six groups (Control, PL, BMC, BMC + PL, pre-differentiated MSCs, pre-differentiated MSCs + PL). The influence of PL, BMC, and pre-differentiated MSCs was investigated systematically in a 2 mm femoral bone defect model. After a 6-week follow-up, the pre-differentiated MSCs + PL group showed the highest bone volume, highest grade of histological defect healing and highest number of bridged defects with measurable biomechanical stiffness. Using expanded and osteogenically pre-differentiated MSCs for treatment of a critical-size bone defect was favorable with regards to bone regeneration compared to treatment with cells from BMC. The addition of PL alone had no significant influence; therefore the role of PL for bone regeneration remains unclear. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1318-1328, 2019.

Experimental autoimmune encephalomyelitis (EAE) is the most widely used animal model for multiple sclerosis (MS). It is a rapid model, commonly induced in rodents. Even if EAE does not replicate all MS characteristics, it is appropriate to investigate the development of the disease, including the immune and neuroinflammatory aspects. Besides, EAE has also been shown to be a relevant model for pre-clinical studies, as several drugs effective in the model are beneficial for MS patients. However, despite its widespread use, there is no consensus on the clinical assessment of animals. Most researchers perform a daily evaluation and classify them on a 5-point scale, but many authors also use in-between scores or apply other systems. Besides, among the 5-point scale, different score definitions are used, and most of them do not recapitulate the signs or symptoms each animal can show. Thus, based on our experience with EAE, the aim of the present work was to develop a new scoring system.We designed the "I AM D EAE" tool that independently evaluates 9 different items - an innovative and detailed scoring system, yet simple for non-experts to use. The new scale was tested in EAE-induced mice at three experiments, and different evaluators assessed the animals blindly.The "I AM D EAE" scoring system highly correlates to the commonly used 5-point scale and, importantly, it enables a more detailed evaluation.Considering its high reproducibility and inter-rater reliability, "I AM D EAE" is a useful tool for EAE monitoring.

Multiple sclerosis (MS) is a chronic and neurodegenerative disease of the central nervous system (CNS) characterized by the immune mediated attack on axons and the subsequent demyelination. There is growing evidence that the gut microbiota of MS patients is altered; however, the connection between demyelination events and changes in the gut microbiota has not been determined. The objective of the current work was to characterize the microbial dysbiosis in two murine demyelinating models and to study the correlation between them. Concurrently, their suitability as predictors of microbial changes in MS patients was assessed. To this purpose, experimental autoimmune encephalomyelitis (EAE) and cuprizone (CPZ) models were induced in C57BL/6 mice that were monitored for 4 and 9 weeks, respectively. Fecal samples were collected during disease progression. Motor skill performance was evaluated by EAE scale measurement in EAE mice and demyelination by magnetic resonance imaging (MRI) in CPZ ones. EAE and CPZ mice revealed drastic microbial changes according to disease progression, adding a new layer of complexity to the understanding of demyelination and remyelination processes. Besides, the reported microbial changes replicate most of the characteristics that define the potential dysbiosis in MS patients. The controlled environment and stable diet that animals have in research centers offer an exceptional scenario to modify animal's microbiota and provide opportunities to study host microbiota interplay with restrained conditions not achievable in human studies. Nevertheless the slight differences from murine model's and patient's microbiota should be considered in the design of studies aiming to modulate the microbiota.

Multiple Sclerosis (MS) is a heterogeneous disease on its clinic and evolution, on which the myelin sheath of the axons is attacked by the own immune system. The origin of MS is still unknown; however, genetic, epigenetic and environmental factors seem to be implicated in its development. In the last years, much effort has been made to describe the gut microbiota dysbiosis of MS patients. Nevertheless, differences in geographical location, diets and lifestyles have made this goal difficult to achieve; therefore, the role of the bacterial dysbiosis in the MS is unclear. The microbiota produces thousands of biologically active substances among which are notable the Short Chain Fatty Acids (SCFAs) excretion. These metabolites are the main mediators of the interaction with the immune and neuroendocrine systems; in consequence, their analysis in the MS could be of great interest. The aim of this study is to determine the microbial dysbiosis and its SCFAs production in a Spanish cohort of MS patients. The gut microbiota of the Spanish cohort of MS patients is characterized by an increment in members of the phylum Proteobacteria, especially marked on those patients that are not receiving any disease modifying treatment. Regarding SCFAs production, a lack in total SCFAs excretion and an altered profile of SCFAs in MS patients, (characterized by a decrease of butyric acid production) could be observed. This alteration is more evident when patients with an Expanded Disability Status Scale (EDSS) score higher than 1 were considered, also presenting a significative reduction of caproic acid and an increase of acetic acid excretion. The abundance of Proteobacteria and acetate and the low excretion of total SCFAs, especially butyrate, are common characteristics of MS patients and, besides, both are associated with a worse prognosis of the disease. Funding Statement: This work was supported by the Spanish Network of Multiple Sclerosis (REEM) under the grant (BIOD19- 021). Declaration of Interests: The authors report no conflict of interest. Ethics Approval Statement: The local ethical committee approved this trial with the reference 09/157.