Effects of in vitro altered microflora on immunolocalization of ladderlectin and intelectin in trout intestine

Lectins are carbohydrate-binding proteins or glycoproteins present in all types of organisms. They serve different biological functions including the roles in the innate immune system by recognizing carbohydrates that are found on the surface of potential pathogens. Soluble lectins have been identified from the plasma and mucus of various fish species. Rainbow trout ladderlectin (RTLL) and intelectin (RTInt) are two plasma proteins implicated in innate immune surveillance and pathogen elimination based upon their ability to bind Gram-negative bacteria and chitin. The present work, by using an in vitro model, was aimed to evaluate the expression of RTLL and RTInt, as visualized by specific antibodies, in the trout intestine exposed to distinct experimental conditions. The removed intestines were separately exposed to a mixture of the probiotic bacteria Lactobacillus rhamnosus, e Lactobacillus paracasei (group 1), a suspension of the pathogen bacteria Vibrio anguillarum (group 2), a mixture of the probiotics above, followed by the pathogens V. anguillarum (group 3). In the control group (group 4), the intestines were exposed to sterile saline solution and TSBgs in the same conditions, as above. Following exposure to V. anguillarum, a higher lectin reactivity was found, as compared with the controls, at the apical cell membrane of the epithelium, probably as a consequence of a stronger secretion induced by the pathogen. Consistently, the intestinal goblet cells, which in the controls proved to be the main site of the lectin expression, in the group 2 appeared unstained and nearly devoid of their contents. An increased immunostaining was observed also within inflammatory leucocytes, club cells and SP-positive cells. Notably, in the group 3, both the immunohistochemical pattern and the Western blotting analysis indicated that exposure of intestine to probiotics prior to V.anguillarum affects positively the RTInt expression, by reducing the pathogen-induced effect. These preliminary findings support a role for both RTLL and RTInt as putative innate defence molecules on intestinal mucosal surfaces. Further studies are required to confirm a possible involvement of probiotics in the RTInt-mediated immunomodulation

Dog filariosis in the Lazio region (Central Italy): first report on the presence of Dirofilaria repens

BACKGROUND: Epidemiological investigations were carried out in the Lazio Region to assess the status of canine filariosis and to evaluate the actual risk for veterinary and medical public health. METHODS: Since August 2001 to June 2003, a total of 972 canine blood samples, collected in public kennels and from private owners animals of the 5 Provinces of the Region, were tested. The presence of filarial parasites was evaluated by microscopy and bio-molecular techniques; the species identification was performed by means of the same diagnostic tools. RESULTS: A total of 17/972 (1.75%; 95%CI 1.06%–2.85%) blood samples were parasitized by D. repens,13 out them drawn by dogs resident in the Province of Roma, and 4 in the other provinces. Multivariate analysis was performed in order to evaluate the association between filariosis and risk factors. The origin from coastal territories seems to be a significant risk factor to acquire the infection. CONCLUSION: This is the first report of canine filariosis in the Lazio Region, where D. repens was before reported only in foxes. The risk of human zoonotic infection is stressed, and the absence of other filarial species is discusse

Psychological treatments and psychotherapies in the neurorehabilitation of pain. Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation

BACKGROUND: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. OBJECTIVES: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. METHODS: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. RESULTS: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. CONCLUSIONS: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the pape

Cross-disease Meta-analysis of Genome-wide Association Studies for Systemic Sclerosis and Rheumatoid Arthritis Reveals IRF4 as a New Common Susceptibility Locus

Objectives: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that share clinical and immunological characteristics. To date, several shared SSc- RA loci have been identified independently. In this study, we aimed to systematically search for new common SSc-RA loci through an inter-disease meta-GWAS strategy. Methods: We performed a meta-analysis combining GWAS datasets of SSc and RA using a strategy that allowed identification of loci with both same-direction and opposingdirection allelic effects. The top single-nucleotide polymorphisms (SNPs) were followed-up in independent SSc and RA case-control cohorts. This allowed us to increase the sample size to a total of 8,830 SSc patients, 16,870 RA patients and 43,393 controls. Results: The cross-disease meta-analysis of the GWAS datasets identified several loci with nominal association signals (P-value < 5 x 10-6), which also showed evidence of association in the disease-specific GWAS scan. These loci included several genomic regions not previously reported as shared loci, besides risk factors associated with both diseases in previous studies. The follow-up of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these two diseases (Pcombined = 3.29 x 10-12). In addition, the analysis of the biological relevance of the known SSc-RA shared loci pointed to the type I interferon and the interleukin 12 signaling pathways as the main common etiopathogenic factors. Conclusions: Our study has identified a novel shared locus, IRF4, for SSc and RA and highlighted the usefulness of cross-disease GWAS meta-analysis in the identification of common risk loci

Psychological Treatments and Psychotherapies in the Neurorehabilitation of Pain: Evidences and Recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation

Background: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams.Objectives: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases.Methods: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions.Results: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive\u2014Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post\u2014Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache.Conclusions: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the paper

Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), "A way of making Europe".Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals

IRF4 Newly Identified as a Common Susceptibility Locus for Systemic Sclerosis and Rheumatoid Arthritis in a Cross-Disease Meta-Analysis of Genome-Wide Association Studies

Autoría conjunta: Spanish Scleroderma GrpObjective. Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that have similar clinical and immunologic characteristics. To date, several shared SSc-RA genetic loci have been identified independently. The aim of the current study was to systematically search for new common SSc-RA loci through an interdisease meta-genome-wide association (meta-GWAS) strategy. Methods. The study was designed as a meta-analysis combining GWAS data sets of patients with SSc and patients with RA, using a strategy that allowed identification of loci with both same-direction and opposite-direction allelic effects. The top single-nucleotide polymorphisms were followed up in independent SSc and RA case-control cohorts. This allowed an increase in the sample size to a total of 8,830 patients with SSc, 16,870 patients with RA, and 43,393 healthy controls. Results. This cross-disease meta-analysis of the GWAS data sets identified several loci with nominal association signals (P<5 x 10(-6)) that also showed evidence of association in the disease-specific GWAS scans. These loci included several genomic regions not previously reported as shared loci, as well as several risk factors that were previously found to be associated with both diseases. Follow-up analyses of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these 2 diseases (P-combined=3.29 x 10(-12)). Analysis of the biologic relevance of the known SSc-RA shared loci identified the type I interferon and interleukin-12 signaling pathways as the main common etiologic factors. Conclusion. This study identified a novel shared locus, IRF4, for the risk of SSc and RA, and highlighted the usefulness of a cross-disease GWAS meta-analysis strategy in the identification of common risk loci.Supported by a grant from the Ministerio de Educacion, Cultura y Deporte through the program FPU (to Dr. Lopez-Isac), grant 115565 from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking PRECISESADS (ref. no. 115565) and BIO-1395 from the Junta de Andalucia, grant PI-0590-2010 from the Consejeria de Salud y Bienestar Social, Junta de Andalucia, Spain (to Dr. Ortego-Centeno), a VIDI laureate from the Dutch Association of Research and Dutch Arthritis Foundation (to Dr. Radstake), and grant SAF2012-34435 from the Spanish Ministry of Economy and Competitiveness (to Dr. J. Martin). Dr. Assassi's work was supported by grants KL2-RR-024149-04 and K23-AR-061436 from the NIH, grant 3-UL1-RR-024148 from the NIH National Center for Research Resources, and grant U01-1U01AI09090 from the NIH National Institute of Allergy and Infectious Diseases. Dr. Mayes' work was supported by grant P50-AR-054144 from the NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Centers of Research Translation, grant N01-AR-0-2251 from the NIAMS SSc Family Registry and DNA Repository, grant PR-1206877 from the Department of Defense, and grant R01-AR-055258 from the NIAMS.Peer reviewe

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly