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{ "count": 24730, "next": "http://api.gregory-ms.com/articles/?format=api&page=2392", "previous": "http://api.gregory-ms.com/articles/?format=api&page=2390", "results": [ { "article_id": 840, "title": "Meningeal inflammation in multiple sclerosis induces phenotypic changes in cortical microglia that differentially associate with neurodegeneration", "summary": "<div><p>Acta Neuropathol. 2021 Mar 29. doi: 10.1007/s00401-021-02293-4. Online ahead of print.</p><p><b>ABSTRACT</b></p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">Meningeal inflammation strongly associates with demyelination and neuronal loss in the underlying cortex of progressive MS patients, thereby contributing significantly to clinical disability. However, the pathological mechanisms of meningeal inflammation-induced cortical pathology are still largely elusive. By extensive analysis of cortical microglia in post-mortem progressive MS tissue, we identified cortical areas with two MS-specific microglial populations, termed MS1 and MS2 cortex. The microglial population in MS1 cortex was characterized by a higher density and increased expression of the activation markers HLA class II and CD68, whereas microglia in MS2 cortex showed increased morphological complexity and loss of P2Y12 and TMEM119 expression. Interestingly, both populations associated with inflammation of the overlying meninges and were time-dependently replicated in an in vivo rat model for progressive MS-like chronic meningeal inflammation. In this recently developed animal model, cortical microglia at 1-month post-induction of experimental meningeal inflammation resembled microglia in MS1 cortex, and microglia at 2 months post-induction acquired a MS2-like phenotype. Furthermore, we observed that MS1 microglia in both MS cortex and the animal model were found closely apposing neuronal cell bodies and to mediate pre-synaptic displacement and phagocytosis, which coincided with a relative sparing of neurons. In contrast, microglia in MS2 cortex were not involved in these synaptic alterations, but instead associated with substantial neuronal loss. Taken together, our results show that in response to meningeal inflammation, microglia acquire two distinct phenotypes that differentially associate with neurodegeneration in the progressive MS cortex. Furthermore, our in vivo data suggests that microglia initially protect neurons from meningeal inflammation-induced cell death by removing pre-synapses from the neuronal soma, but eventually lose these protective properties contributing to neuronal loss.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33779783/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210330000823&v=2.14.3\">33779783</a> | DOI:<a href=\"https://doi.org/10.1007/s00401-021-02293-4\">10.1007/s00401-021-02293-4</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33779783/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-01-06T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Springer Science and Business Media LLC", "container_title": "Acta Neuropathologica", "authors": [ { "author_id": 175989, "given_name": "Lynn", "family_name": "van Olst", "ORCID": "http://orcid.org/0000-0001-7569-0470", "country": null }, { "author_id": 175990, "given_name": "Carla", "family_name": "Rodriguez-Mogeda", "ORCID": "http://orcid.org/0000-0002-7849-9302", "country": null }, { "author_id": 295780, "given_name": "Carmen", "family_name": "Picon", "ORCID": null, "country": null }, { "author_id": 263914, "given_name": "Svenja", "family_name": "Kiljan", "ORCID": null, "country": null }, { "author_id": 295781, "given_name": "Rachel E.", "family_name": "James", "ORCID": null, "country": null }, { "author_id": 175991, "given_name": "Alwin", "family_name": "Kamermans", "ORCID": "http://orcid.org/0000-0002-3601-395X", "country": null }, { "author_id": 295782, "given_name": "Susanne M. A.", "family_name": "van der Pol", "ORCID": null, "country": null }, { "author_id": 295783, "given_name": "Lydian", "family_name": "Knoop", "ORCID": null, "country": null }, { "author_id": 273416, "given_name": "Iliana", "family_name": "Michailidou", "ORCID": null, "country": null }, { "author_id": 295784, "given_name": "Evelien", "family_name": "Drost", "ORCID": null, "country": null }, { "author_id": 295785, "given_name": "Marc", "family_name": "Franssen", "ORCID": null, "country": null }, { "author_id": 191536, "given_name": "Geert J.", "family_name": "Schenk", "ORCID": "http://orcid.org/0000-0002-9984-120X", "country": null }, { "author_id": 199658, "given_name": "Jeroen J. G.", "family_name": "Geurts", "ORCID": "http://orcid.org/0000-0002-4367-4641", "country": "CH" }, { "author_id": 197689, "given_name": "Sandra", "family_name": "Amor", "ORCID": "http://orcid.org/0000-0001-6169-9845", "country": null }, { "author_id": 295786, "given_name": "Nicholas D.", "family_name": "Mazarakis", "ORCID": null, "country": null }, { "author_id": 164525, "given_name": "Jack", "family_name": "van Horssen", "ORCID": "http://orcid.org/0000-0003-4078-7402", "country": null }, { "author_id": 254964, "given_name": "Helga E.", "family_name": "de Vries", "ORCID": null, "country": null }, { "author_id": 172132, "given_name": "Richard", "family_name": "Reynolds", "ORCID": "http://orcid.org/0000-0003-4622-4694", "country": "GB" }, { "author_id": 200460, "given_name": "Maarten E.", "family_name": "Witte", "ORCID": "http://orcid.org/0000-0002-1407-6220", "country": "NL" } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-30T04:08:25Z", "noun_phrases": [ "Meningeal inflammation", "multiple sclerosis", "phenotypic changes", "cortical microglia", "that", "neurodegeneration" ], "doi": "10.1007/s00401-021-02293-4", "access": "open", "takeaways": " Meningeal inflammation strongly associates with demyelination and neuronal loss in the underlying cortex of progressive MS patients . MS1 cortex was characterized by a higher density and increased expression of the activation markers HLA class II and CD68 . MS2 cortex showed increased morphological complexity and loss of P2Y12 and TMEM119 expression .", "categories": [] }, { "article_id": 834, "title": "Prevalence and factors related to urinary incontinence in older adults women worldwide: a comprehensive systematic review and meta-analysis of observational studies", "summary": "Background: Urinary incontinence is a common condition in the general population and, in particular, the older adults population, which reduces the quality of life of these people, so this study aims to systematically examine and meta-analyse the overall prevalence of urinary incontinence in older women around the world and the related and influential factors.MethodsThis report is a comprehensive systematic review and meta-analysis of the findings of research on urinary incontinence in older adults people across the world through looking for MEDLINE, Cochrane Library Sciencedirect, Embase, Scopus, ProQuest and Persian databases, namely iranmedex, magiran, and SID from January 2000 to April 2020, the heterogeneity of the experiments was measured using the I2 index and the data processing was done in the Systematic Meta-Analysis programme.ResultsIn 29 studies and the sample size of 518,465 people in the age range of 55–106 years, urinary incontinence in older adults’ women in the world based on a meta-analysis of 37.1% (95% CI: 29.6–45.4%) was obtained. The highest prevalence of urinary incontinence was reported in older adults’ women in Asia with 45.1% (95% CI: 36.9–53.5%). Meta-regression also showed that with increasing the sample size and year of the study, the overall prevalence of urinary incontinence in the older adults women of the world decreased and increased, respectively, which were statistically significant differences (P < 0.05). According to studies, the most important factors influencing the incidence of urinary incontinence in older women are women’s age (p < 0.001), obesity (p < 0.001), diabetes (p < 0.001), women’s education (p < 0.001), delivery rank (p < 0.001), hypertension (p < 0.001), smoking (p < 0.001). They also have urinary tract infections (p < 0.001).ConclusionGiven the high prevalence of urinary incontinence in older women around the world, health policy makers must consider control and diagnostic measures in older women and prioritize treatment and rehabilitation activities.", "link": "https://bmcgeriatr.biomedcentral.com/articles/10.1186/s12877-021-02135-8", "published_date": "2021-03-28T23:00:00Z", "sources": [ "BioMedCentral" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Springer Science and Business Media LLC", "container_title": "BMC Geriatrics", "authors": [ { "author_id": 246995, "given_name": "Sedighe", "family_name": "Batmani", "ORCID": null, "country": null }, { "author_id": 246996, "given_name": "Rostam", "family_name": "Jalali", "ORCID": null, "country": null }, { "author_id": 148106, "given_name": "Masoud", "family_name": "Mohammadi", "ORCID": "http://orcid.org/0000-0002-5722-8300", "country": "IR" }, { "author_id": 246997, "given_name": "Shadi", "family_name": "Bokaee", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-29T18:18:54Z", "noun_phrases": [ "Prevalence", "factors", "urinary incontinence", "older adults", "women", "a comprehensive systematic review", "meta-analysis", "observational studies" ], "doi": "10.1186/s12877-021-02135-8", "access": "open", "takeaways": " Urinary incontinence is a common condition in the general population and, in particular, the older adults population, which reduces the quality of life of these people . This study aims to systematically examine and meta-analyse the overall prevalence of urinary incontinent in older women around the world and the related and influential factors . The highest prevalence was reported in older adults’ women in Asia with 45.1% .", "categories": [] }, { "article_id": 835, "title": "Viscoelastic properties of white and gray matter-derived microglia differentiate upon treatment with lipopolysaccharide but not upon treatment with myelin", "summary": "Background: The biomechanical properties of the brain have increasingly been shown to relate to brain pathology in neurological diseases, including multiple sclerosis (MS). Inflammation and demyelination in MS induce significant changes in brain stiffness which can be linked to the relative abundance of glial cells in lesions. We hypothesize that the biomechanical, in addition to biochemical, properties of white (WM) and gray matter (GM)-derived microglia may contribute to the differential microglial phenotypes as seen in MS WM and GM lesions.MethodsPrimary glial cultures from WM or GM of rat adult brains were treated with either lipopolysaccharide (LPS), myelin, or myelin+LPS for 24 h or left untreated as a control. After treatment, microglial cells were indented using dynamic indentation to determine the storage and loss moduli reflecting cell elasticity and cell viscosity, respectively, and subsequently fixed for immunocytochemical analysis. In parallel, gene expression of inflammatory-related genes were measured using semi-quantitative RT-PCR. Finally, phagocytosis of myelin was determined as well as F-actin visualized to study the cytoskeletal changes.ResultsWM-derived microglia were significantly more elastic and more viscous than microglia derived from GM. This heterogeneity in microglia biomechanical properties was also apparent when treated with LPS when WM-derived microglia decreased cell elasticity and viscosity, and GM-derived microglia increased elasticity and viscosity. The increase in elasticity and viscosity observed in GM-derived microglia was accompanied by an increase in Tnfα mRNA and reorganization of F-actin which was absent in WM-derived microglia. In contrast, when treated with myelin, both WM- and GM-derived microglia phagocytose myelin decrease their elasticity and viscosity.ConclusionsIn demyelinating conditions, when myelin debris is phagocytized, as in MS lesions, it is likely that the observed differences in WM- versus GM-derived microglia biomechanics are mainly due to a difference in response to inflammation, rather than to the event of demyelination itself. Thus, the differential biomechanical properties of WM and GM microglia may add to their differential biochemical properties which depend on inflammation present in WM and GM lesions of MS patients.", "link": "https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-021-02134-x", "published_date": "2021-03-28T23:00:00Z", "sources": [ "BioMedCentral" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Springer Science and Business Media LLC", "container_title": "Journal of Neuroinflammation", "authors": [ { "author_id": 201308, "given_name": "Thecla A.", "family_name": "Wageningen", "ORCID": "http://orcid.org/0000-0002-5304-9487", "country": null }, { "author_id": 305963, "given_name": "Nelda", "family_name": "Antonovaite", "ORCID": null, "country": null }, { "author_id": 305964, "given_name": "Erik", "family_name": "Paardekam", "ORCID": null, "country": null }, { "author_id": 290127, "given_name": "John J. P.", "family_name": "Brevé", "ORCID": null, "country": null }, { "author_id": 305965, "given_name": "Davide", "family_name": "Iannuzzi", "ORCID": null, "country": null }, { "author_id": 290129, "given_name": "Anne-Marie", "family_name": "van Dam", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-29T18:18:54Z", "noun_phrases": [ "Viscoelastic properties", "white and gray matter-derived microglia", "treatment", "lipopolysaccharide", "treatment", "myelin" ], "doi": "10.1186/s12974-021-02134-x", "access": "open", "takeaways": " Inflammation and demyelination in MS induce significant changes in brain stiffness which can be linked to the relative abundance of glial cells in lesions . We hypothesize that the biomechanical properties of white (WM) and gray matter (GM)-derived microglia may contribute to the differential microglial phenotypes as seen in MS WM and GM lesions .", "categories": [] }, { "article_id": 836, "title": "A systematic review exploring the bidirectional relationship between puberty and autoimmune rheumatic diseases", "summary": "Background: Autoimmune rheumatic diseases (ARDs) are associated with a significant sex-bias, which becomes more evident post-puberty. This systematic review aims to elucidate the bidirectional relationship between puberty and ARD-related outcomes.MethodsStudies published in English until October 2019 were identified using a systematic search of endocrinology and rheumatology literature. Information was extracted on study design, sample size, demographics, puberty outcome measures, disease outcome measures, and main findings. The methodological quality of the studies included was analysed using the Newcastle-Ottawa Scale (NOS).ResultsSixteen non-randomised studies reporting on the impact of puberty on ARD outcomes (n = 7), ARD impact on puberty-related outcomes (n = 8), or both (n = 1) have been identified. The impact of puberty on ARD outcomes were investigated in patients with juvenile idiopathic arthritis (JIA)-associated uveitis (n = 1), juvenile systemic lupus erythematosus (JSLE) (n = 5) or in healthy controls who developed adult-onset SLE (n = 1) or had non-specific symptoms (n = 1). The impact of ARD on puberty outcomes was explored in JIA (n = 4) and JSLE (n = 3). Quality assessment of studies showed a small to moderate risk of bias overall (NOS 4–9/9). Due to large heterogeneity of the studies it was not possible to perform a meta-analysis. Multiple studies reported on delayed puberty in patients with JIA/JSLE, menstrual and hormonal abnormalities, and lower height and weight than controls. Earlier (pre-pubertal) onset of JSLE was correlated with more severe disease and more need for systemic treatment.ConclusionA bidirectional relationship exists between puberty and ARDs; however, more and better research is required to elucidate the complexity of this relationship. We propose puberty-related clinical assessments in patients with ARDs, which can improve patient outcomes and facilitate future research.", "link": "https://ped-rheum.biomedcentral.com/articles/10.1186/s12969-021-00528-y", "published_date": "2021-03-28T23:00:00Z", "sources": [ "BioMedCentral" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Springer Science and Business Media LLC", "container_title": "Pediatric Rheumatology", "authors": [ { "author_id": 282939, "given_name": "Nina M.", "family_name": "de Gruijter", "ORCID": null, "country": null }, { "author_id": 282942, "given_name": "Meena", "family_name": "Naja", "ORCID": null, "country": null }, { "author_id": 282943, "given_name": "Hannah", "family_name": "Peckham", "ORCID": null, "country": null }, { "author_id": 282945, "given_name": "Anna", "family_name": "Radziszewska", "ORCID": null, "country": null }, { "author_id": 282947, "given_name": "Matthew", "family_name": "Kinsella", "ORCID": null, "country": null }, { "author_id": 282948, "given_name": "James", "family_name": "Glenister", "ORCID": null, "country": null }, { "author_id": 282950, "given_name": "Elizabeth C.", "family_name": "Rosser", "ORCID": null, "country": null }, { "author_id": 282951, "given_name": "Gary E.", "family_name": "Butler", "ORCID": null, "country": null }, { "author_id": 252771, "given_name": "Elizabeth C.", "family_name": "Jury", "ORCID": null, "country": null }, { "author_id": 195905, "given_name": "Coziana", "family_name": "Ciurtin", "ORCID": "http://orcid.org/0000-0002-8911-4113", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-29T18:18:54Z", "noun_phrases": [ "A systematic review", "the bidirectional relationship", "puberty", "autoimmune rheumatic diseases" ], "doi": "10.1186/s12969-021-00528-y", "access": "open", "takeaways": " Autoimmune rheumatic diseases (ARDs) are associated with a significant sex-bias, which becomes more evident post-puberty . This systematic review aims to elucidate the bidirectional relationship between puberty and ARD-related outcomes .", "categories": [] }, { "article_id": 830, "title": "Multiple sclerosis patients and COVID-19", "summary": "<div><p>Egypt J Neurol Psychiatr Neurosurg. 2021;57(1):43. doi: 10.1186/s41983-021-00287-3. Epub 2021 Mar 23.</p><p><b>ABSTRACT</b></p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">Coronavirus disease 2019 (COVID-19) is now a major issue for all fields of medicine. Due to the higher mortality rate among patients with chronic diseases, it has also caused concern in patients with multiple sclerosis (MS), who in addition are often receiving immunosuppressive drugs. The aim of this article is to discuss what is currently known about the severity of COVID-19 in MS patients.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33776407/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210329132823&v=2.14.3\">33776407</a> | PMC:<a href=\"https://www.ncbi.nlm.nih.gov/pmc/PMC7985914/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210329132823&v=2.14.3\">PMC7985914</a> | DOI:<a href=\"https://doi.org/10.1186/s41983-021-00287-3\">10.1186/s41983-021-00287-3</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33776407/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-01-01T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Springer Science and Business Media LLC", "container_title": "The Egyptian Journal of Neurology, Psychiatry and Neurosurgery", "authors": [ { "author_id": 164716, "given_name": "Hubert", "family_name": "Mado", "ORCID": "http://orcid.org/0000-0002-1610-036X", "country": "PL" }, { "author_id": 164717, "given_name": "Monika", "family_name": "Adamczyk-Sowa", "ORCID": "http://orcid.org/0000-0002-6894-9891", "country": null } ], "relevant": false, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-29T17:28:24Z", "noun_phrases": [ "Multiple sclerosis patients" ], "doi": "10.1186/s41983-021-00287-3", "access": "open", "takeaways": " The aim of this article is to discuss what is currently known about the severity of COVID-19 in MS patients . Egypt J Neurol Psychiatr Neurosurg. 2021;", "categories": [] }, { "article_id": 826, "title": "Comparative Analysis of BTK Inhibitors and Mechanisms Underlying Adverse Effects", "summary": "<div><p>Front Cell Dev Biol. 2021 Mar 11;9:630942. doi: 10.3389/fcell.2021.630942. eCollection 2021.</p><p><b>ABSTRACT</b></p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">The cytoplasmic protein-tyrosine kinase BTK plays an essential role for differentiation and survival of B-lineage cells and, hence, represents a suitable drug target. The number of BTK inhibitors (BTKis) in the clinic has increased considerably and currently amounts to at least 22. First-in-class was ibrutinib, an irreversible binder forming a covalent bond to a cysteine in the catalytic region of the kinase, for which we have identified 228 active trials listed at ClinicalTrials.gov. Next-generation inhibitors, acalabrutinib and zanubrutinib, are approved both in the United States and in Europe, and zanubrutinib also in China, while tirabrutinib is currently only registered in Japan. In most cases, these compounds have been used for the treatment of B-lymphocyte tumors. However, an increasing number of trials instead addresses autoimmunity and inflammation in multiple sclerosis, rheumatoid arthritis, pemphigus and systemic lupus erythematosus with the use of either irreversibly binding inhibitors, e.g., evobrutinib and tolebrutinib, or reversibly binding inhibitors, like fenebrutinib. Adverse effects (AEs) have predominantly implicated inhibition of other kinases with a BTKi-binding cysteine in their catalytic domain. Analysis of the reported AEs suggests that ibrutinib-associated atrial fibrillation is caused by binding to ERBB2/HER2 and ERBB4/HER4. However, the binding pattern of BTKis to various additional kinases does not correlate with the common assumption that skin manifestations and diarrhoeas are off-target effects related to EGF receptor inhibition. Moreover, dermatological toxicities, diarrhoea, bleedings and invasive fungal infections often develop early after BTKi treatment initiation and subsequently subside. Conversely, cardiovascular AEs, like hypertension and various forms of heart disease, often persist.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33777941/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210329132823&v=2.14.3\">33777941</a> | PMC:<a href=\"https://www.ncbi.nlm.nih.gov/pmc/PMC7991787/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210329132823&v=2.14.3\">PMC7991787</a> | DOI:<a href=\"https://doi.org/10.3389/fcell.2021.630942\">10.3389/fcell.2021.630942</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33777941/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-03-11T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Frontiers Media SA", "container_title": "Frontiers in Cell and Developmental Biology", "authors": [ { "author_id": 246944, "given_name": "H. Yesid", "family_name": "Estupiñán", "ORCID": null, "country": null }, { "author_id": 246945, "given_name": "Anna", "family_name": "Berglöf", "ORCID": null, "country": null }, { "author_id": 246946, "given_name": "Rula", "family_name": "Zain", "ORCID": null, "country": null }, { "author_id": 246947, "given_name": "C. I. Edvard", "family_name": "Smith", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-29T17:28:24Z", "noun_phrases": [ "BTK Inhibitors", "Mechanisms" ], "doi": "10.3389/fcell.2021.630942", "access": "open", "takeaways": " The number of BTK inhibitors (BTKis) in the clinic has increased considerably and currently amounts to at least 22 . First-in-class was ibrutinib, an irreversible binder forming a covalent bond to a cysteine in the catalytic region of the kinase, for which we have identified 228 active trials listed at ClinicalTrials.gov .", "categories": [] }, { "article_id": 827, "title": "Immune Soluble Factors in the Cerebrospinal Fluid of Progressive Multiple Sclerosis Patients Segregate Into Two Groups", "summary": "<div><p>Front Immunol. 2021 Mar 10;12:633167. doi: 10.3389/fimmu.2021.633167. eCollection 2021.</p><p><b>ABSTRACT</b></p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">Primary-progressive (PP) and secondary-progressive (SP) multiple sclerosis (MS) are characterized by neurological deficits caused by a permanent neuronal damage, clinically quantified by the expanded disability status scale (EDSS). Neuronal tissue damage is also mediated by immune infiltrates producing soluble factors, such as cytokines and chemokines, which are released in the cerebrospinal fluid (CSF). The mechanisms regulating the production of a soluble factor are not completely defined. Using multiplex bead-based assays, we simultaneously measured 27 immune soluble factors in the CSF collected from 38 patients, 26 with PP-MS and 12 with SP-MS. Then, we performed a correlation matrix of all soluble factors expressed in the CSF. The CSF from patients with PP-MS and SP-MS had similar levels of cytokines and chemokines; however, the stratification of patients according to active or inactive magnetic resonance imaging (MRI) unveils some differences. Correlative studies between soluble factors in the CSF of patients with PP-MS and SP-MS revealed two clusters of immune mediators with pro-inflammatory functions, namely IFN-γ, MCP-1, MIP-1α, MIP-1β, IL-8, IP-10, and TNF-α (group 1), and anti-inflammatory functions, namely IL-9, IL-15, VEGF, and IL-1ra (group 2). However, most of the significant correlations between cytokines of group 1 and of group 2 were lost in patients with more severe disability (EDSS ≥ 4) compared to patients with mild to moderate disability (EDSS < 4). These results suggest a common regulation of cytokines and chemokines belonging to the same group and indicate that, in patients with more severe disability, the production of those factors is less coordinated, possibly due to advanced neurodegenerative mechanisms that interfere with the immune response.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33777018/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210329132823&v=2.14.3\">33777018</a> | PMC:<a href=\"https://www.ncbi.nlm.nih.gov/pmc/PMC7988186/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210329132823&v=2.14.3\">PMC7988186</a> | DOI:<a href=\"https://doi.org/10.3389/fimmu.2021.633167\">10.3389/fimmu.2021.633167</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33777018/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-03-10T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Frontiers Media SA", "container_title": "Frontiers in Immunology", "authors": [ { "author_id": 246924, "given_name": "Gloria", "family_name": "Donninelli", "ORCID": null, "country": null }, { "author_id": 240828, "given_name": "Valeria", "family_name": "Studer", "ORCID": null, "country": null }, { "author_id": 243429, "given_name": "Laura", "family_name": "Brambilla", "ORCID": null, "country": null }, { "author_id": 151309, "given_name": "Chiara", "family_name": "Zecca", "ORCID": "http://orcid.org/0000-0002-9990-3431", "country": "CH" }, { "author_id": 246925, "given_name": "Daniele", "family_name": "Peluso", "ORCID": null, "country": null }, { "author_id": 217612, "given_name": "Alice", "family_name": "Laroni", "ORCID": "http://orcid.org/0000-0001-5599-9788", "country": null }, { "author_id": 246926, "given_name": "Daniele", "family_name": "Michelis", "ORCID": null, "country": null }, { "author_id": 244136, "given_name": "Renato", "family_name": "Mantegazza", "ORCID": null, "country": null }, { "author_id": 244505, "given_name": "Paolo", "family_name": "Confalonieri", "ORCID": null, "country": null }, { "author_id": 246928, "given_name": "Elisabetta", "family_name": "Volpe", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-29T17:28:24Z", "noun_phrases": [ "Immune Soluble Factors", "the Cerebrospinal Fluid", "Progressive Multiple Sclerosis Patients", "Two Groups" ], "doi": "10.3389/fimmu.2021.633167", "access": "open", "takeaways": " Neuronal tissue damage is also mediated by immune infiltrates producing soluble factors, such as cytokines and chemokines, which are released in the cerebrospinal fluid . The mechanisms regulating the production of a soluble factor are not completely defined .", "categories": [] }, { "article_id": 832, "title": "mTOR Inhibitor Therapy for Tuberous Sclerosis Complex: Longitudinal Study of Muscle Mass Determined by Abdominal Cross-sectional Imaging with CT and MRI", "summary": "<div><p>Radiol Imaging Cancer. 2020 Sep 18;2(5):e190091. doi: 10.1148/rycan.2020190091. eCollection 2020 Sep.</p><p><b>ABSTRACT</b></p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">PURPOSE: To determine the effect of chronic mammalian target of rapamycin (mTOR) inhibition on skeletal muscle mass in patients with tuberous sclerosis complex (TSC).</p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">MATERIALS AND METHODS: In this retrospective study, patients with TSC who were taking mTOR inhibitors and who underwent at least two abdominal CT or MRI examinations between 2005 and 2017 were included (<i>n</i> = 24; 14 males; mean age, 14.5 years ± 7.8 [standard deviation] at first examination). One reviewer drew regions of interest around psoas muscles at L3 to measure cross-sectional area. Multiple linear mixed-effect modeling was performed to evaluate the association between muscle mass and the covariates over time.</p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">RESULTS: The 24 patients underwent a total of 129 abdominal CT or MRI examinations. Median duration of mTOR inhibition at last examination was 106 months (range, 1310-3717 days). There was no significant association between the duration of mTOR inhibitor therapy and psoas muscle area on multiple linear mixed-effect modeling (<i>P</i> = .055); however, patient height and height squared were significant predictors of psoas area (<i>P</i> = .014 and <i>P</i> < .0001, respectively).</p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">CONCLUSION: Duration of mTOR inhibition in TSC was not significantly associated with a decrease in psoas muscle area, suggesting that chronic mTOR inhibition is not associated with sarcopenia.<b>Keywords:</b> CT, MR-Imaging, Pediatrics© RSNA, 2020.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33778734/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210329132823&v=2.14.3\">33778734</a> | PMC:<a href=\"https://www.ncbi.nlm.nih.gov/pmc/PMC7983794/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210329132823&v=2.14.3\">PMC7983794</a> | DOI:<a href=\"https://doi.org/10.1148/rycan.2020190091\">10.1148/rycan.2020190091</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33778734/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2020-09-17T23:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Radiological Society of North America (RSNA)", "container_title": "Radiology: Imaging Cancer", "authors": [ { "author_id": 246988, "given_name": "Caroline", "family_name": "Raab", "ORCID": null, "country": null }, { "author_id": 213724, "given_name": "Leah A.", "family_name": "Gilligan", "ORCID": "http://orcid.org/0000-0002-4632-7004", "country": null }, { "author_id": 213725, "given_name": "Andrew T.", "family_name": "Trout", "ORCID": "http://orcid.org/0000-0003-1431-4054", "country": "US" }, { "author_id": 244886, "given_name": "Darcy A.", "family_name": "Krueger", "ORCID": null, "country": null }, { "author_id": 244885, "given_name": "David N.", "family_name": "Franz", "ORCID": null, "country": null }, { "author_id": 213726, "given_name": "Bin", "family_name": "Zhang", "ORCID": "http://orcid.org/0000-0003-0607-1806", "country": null }, { "author_id": 212615, "given_name": "Alexander J.", "family_name": "Towbin", "ORCID": "http://orcid.org/0000-0003-1729-5071", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-29T17:28:24Z", "noun_phrases": [ "mTOR Inhibitor Therapy", "Tuberous Sclerosis Complex", "Longitudinal Study", "Muscle", "Abdominal Cross-sectional Imaging", "CT", "MRI" ], "doi": "10.1148/rycan.2020190091", "access": "open", "takeaways": " Radiol Imaging Cancer. 2020 Sep 18;2(5):e190091 . Median duration of mTOR inhibition at last examination was 106 months (range, 1310-3717 days)", "categories": [] }, { "article_id": 831, "title": "Interleukin-19 Abrogates Experimental Autoimmune Encephalomyelitis by Attenuating Antigen-Presenting Cell Activation", "summary": "<div><p>Front Immunol. 2021 Mar 11;12:615898. doi: 10.3389/fimmu.2021.615898. eCollection 2021.</p><p><b>ABSTRACT</b></p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">Interleukin-19 (IL-19) acts as a negative-feedback regulator to limit proinflammatory response of macrophages and microglia in autocrine/paracrine manners in various inflammatory diseases. Multiple sclerosis (MS) is a major neuroinflammatory disease in the central nervous system (CNS), but it remains uncertain how IL-19 contributes to MS pathogenesis. Here, we demonstrate that IL-19 deficiency aggravates experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by promoting IL-17-producing helper T cell (Th17 cell) infiltration into the CNS. In addition, IL-19-deficient splenic macrophages expressed elevated levels of major histocompatibility complex (MHC) class II, co-stimulatory molecules, and Th17 cell differentiation-associated cytokines such as IL-1β, IL-6, IL-23, TGF-β1, and TNF-α. These observations indicated that IL-19 plays a critical role in suppression of MS pathogenesis by inhibiting macrophage antigen presentation, Th17 cell expansion, and subsequent inflammatory responses. Furthermore, treatment with IL-19 significantly abrogated EAE. Our data suggest that IL-19 could provide significant therapeutic benefits in patients with MS.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33776998/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210329132823&v=2.14.3\">33776998</a> | PMC:<a href=\"https://www.ncbi.nlm.nih.gov/pmc/PMC7990911/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210329132823&v=2.14.3\">PMC7990911</a> | DOI:<a href=\"https://doi.org/10.3389/fimmu.2021.615898\">10.3389/fimmu.2021.615898</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33776998/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-03-11T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Frontiers Media SA", "container_title": "Frontiers in Immunology", "authors": [ { "author_id": 307235, "given_name": "Hiroshi", "family_name": "Horiuchi", "ORCID": null, "country": null }, { "author_id": 300328, "given_name": "Bijay", "family_name": "Parajuli", "ORCID": null, "country": null }, { "author_id": 253851, "given_name": "Hiroyasu", "family_name": "Komiya", "ORCID": null, "country": null }, { "author_id": 261630, "given_name": "Yuki", "family_name": "Ogawa", "ORCID": null, "country": null }, { "author_id": 268128, "given_name": "Shijie", "family_name": "Jin", "ORCID": null, "country": null }, { "author_id": 253862, "given_name": "Keita", "family_name": "Takahashi", "ORCID": null, "country": null }, { "author_id": 307236, "given_name": "Yasu-Taka", "family_name": "Azuma", "ORCID": null, "country": null }, { "author_id": 165173, "given_name": "Fumiaki", "family_name": "Tanaka", "ORCID": "http://orcid.org/0000-0002-9961-2693", "country": null }, { "author_id": 268134, "given_name": "Akio", "family_name": "Suzumura", "ORCID": null, "country": null }, { "author_id": 253865, "given_name": "Hideyuki", "family_name": "Takeuchi", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-29T17:28:24Z", "noun_phrases": [ "Interleukin-19 Abrogates Experimental Autoimmune Encephalomyelitis", "Antigen-Presenting Cell Activation" ], "doi": "10.3389/fimmu.2021.615898", "access": "open", "takeaways": " Interleukin-19 (IL-19) acts as a negative-feedback regulator to limit proinflammatory response of macrophages and microglia in various inflammatory diseases . Multiple sclerosis (MS) is a major neuroinflammatory disease in the central nervous system . IL-19 deficiency aggravates experimental autoimmune encephalomyelitis (EAE), a mouse model of MS .", "categories": [] }, { "article_id": 829, "title": "Prospects for the Use of Cannabinoids in Psychiatric Disorders", "summary": "<div><p>Front Psychiatry. 2021 Mar 12;12:620073. doi: 10.3389/fpsyt.2021.620073. eCollection 2021.</p><p><b>ABSTRACT</b></p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">Increasing evidence suggests an essential role of the endocannabinoid system in modulating cognitive abilities, mood, stress, and sleep. The psychoactive effects of cannabis are described as euphoric, calming, anxiolytic, and sleep-inducing and positively affect the mood, but can also adversely affect therapy. The responses to cannabinoid medications depend on the patient's endocannabinoid system activity, the proportion of phytocannabinoids, the terpenoid composition, and the dose used. There is some evidence for a therapeutic use of phytocannabinoids in psychiatric conditions. THC and CBD may have opposing effects on anxiety. Current guidelines recommend caution in using THC in patients with anxiety or mood disorders. In a small number of clinical trials, cannabinoids used to treat cancer, HIV, multiple sclerosis, hepatitis C, Crohn's disease, and chronic neuropathic pain report decreases in anxiety or depression symptoms and presented sedative and anxiolytic effects. Several studies have investigated the influence of potential genetic factors on psychosis and schizophrenia development after cannabis use. THC may increase the risk of psychosis, especially in young patients with an immature central nervous system. There is limited evidence from clinical trials that cannabinoids are effective therapy for sleep disorders associated with concomitant conditions. There is evidence for a possible role of cannabis as a substitute for alcohol and drugs, also in the context of the risks of opioid use (e.g., opioid-related mortality). In this narrative review of the recent evidence, we discuss the prospects of using the psychoactive effects of cannabinoids in treating mental and psychiatric disorders. However, this evidence is weak for some clinical conditions and well-designed randomized controlled trials are currently lacking. Furthermore, some disorders may be worsened by cannabis use.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33776815/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210329132823&v=2.14.3\">33776815</a> | PMC:<a href=\"https://www.ncbi.nlm.nih.gov/pmc/PMC7994770/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210329132823&v=2.14.3\">PMC7994770</a> | DOI:<a href=\"https://doi.org/10.3389/fpsyt.2021.620073\">10.3389/fpsyt.2021.620073</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33776815/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-03-12T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Frontiers Media SA", "container_title": "Frontiers in Psychiatry", "authors": [ { "author_id": 246937, "given_name": "Michał", "family_name": "Graczyk", "ORCID": null, "country": null }, { "author_id": 246938, "given_name": "Małgorzata", "family_name": "Łukowicz", "ORCID": null, "country": null }, { "author_id": 246939, "given_name": "Tomasz", "family_name": "Dzierzanowski", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-29T17:28:24Z", "noun_phrases": [ "Prospects", "the Use", "Cannabinoids", "Psychiatric Disorders" ], "doi": "10.3389/fpsyt.2021.620073", "access": "open", "takeaways": " There is some evidence for a therapeutic use of phytocannabinoids in psychiatric conditions . THC and CBD may have opposing effects on anxiety . THC may increase the risk of psychosis, especially in young patients with an immature central nervous system . Some disorders may be worsened by cannabis use .", "categories": [] } ] }