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{ "count": 24565, "next": "http://api.gregory-ms.com/articles/?format=api&page=2441", "previous": "http://api.gregory-ms.com/articles/?format=api&page=2439", "results": [ { "article_id": 174, "title": "Untreated patients with multiple sclerosis: a study of French expert centers", "summary": "<div><p>Eur J Neurol. 2021 Mar 1. doi: 10.1111/ene.14790. 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\">BACKGROUND: Disease modifying therapies (DMTs), have an impact on relapses and disease progression. Nonetheless, many patients with multiple sclerosis (pwMS) remain untreated. The objective of the present study was to determine the proportion of untreated patients with multiple sclerosis (pwMS) followed in expert centers in France and determine the predictive factors of non-treatment.</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\">METHODS: Retrospective cohort study. Data were extracted from the 38 centers participating in the European Database for Multiple Sclerosis (EDMUS) on 12/15/2018 and pwMS seen at least once during the study period (from June 15, 2016 to June 14, 2017) were included. Results Among the 21,189 pwMS (age 47.1±13.1; EDSS 3.4±2.4), 6,631 (31.3%; 95%CI=30.7-31.9) of the patients were not receiving any DMT. Although patients with a relapsing-remitting course (n = 11,693) were the most likely to receive DMT, 14.8% (95%CI = 14.2-15.4) were still untreated (6.8% never treated). After multivariate analysis among relapsing-remitting pwMS, the main factors explaining never having been treated were not having ≥9 lesions on brain MRI (OR = 0.52 [0.44-0.61]) and lower EDSS (OR = 0.78 [0.74-0.82]). Most patients with progressive MS (50.4% for secondary and 64.2% for primary progressive MS) did not receive any DMT during the study period, 11.6% for secondary and 34.0% for primary progressive MS had never received any DMT.</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: A significant proportion of pwMS did not receive any DMT, even though such treatments are reimbursed by the healthcare system for French patients. This result highlights the unmet need for current DMTs for a large subgroup of pwMS.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33650261/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210302181644&v=2.14.2\">33650261</a> | DOI:<a href=\"https://doi.org/10.1111/ene.14790\">10.1111/ene.14790</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33650261/#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": "Wiley", "container_title": "European Journal of Neurology", "authors": [ { "author_id": 149927, "given_name": "Xavier", "family_name": "Moisset", "ORCID": "http://orcid.org/0000-0002-8799-0750", "country": null }, { "author_id": 240663, "given_name": "Audrey‐Anne", "family_name": "Fouchard", "ORCID": null, "country": null }, { "author_id": 240664, "given_name": "Bruno", "family_name": "Pereira", "ORCID": null, "country": null }, { "author_id": 240665, "given_name": "Frédéric", "family_name": "Taithe", "ORCID": null, "country": null }, { "author_id": 149930, "given_name": "Guillaume", "family_name": "Mathey", "ORCID": "http://orcid.org/0000-0002-5747-9169", "country": null }, { "author_id": 168069, "given_name": "Gilles", "family_name": "Edan", "ORCID": "http://orcid.org/0000-0002-9641-6734", "country": null }, { "author_id": 149104, "given_name": "Jonathan", "family_name": "Ciron", "ORCID": "http://orcid.org/0000-0002-3386-6308", "country": "FR" }, { "author_id": 164938, "given_name": "Bruno", "family_name": "Brochet", "ORCID": "http://orcid.org/0000-0003-3824-2796", "country": "FR" }, { "author_id": 240666, "given_name": "Jérôme", "family_name": "De Sèze", "ORCID": null, "country": null }, { "author_id": 143476, "given_name": "Caroline", "family_name": "Papeix", "ORCID": "http://orcid.org/0000-0003-4074-6125", "country": null }, { "author_id": 166338, "given_name": "Patrick", "family_name": "Vermersch", "ORCID": "http://orcid.org/0000-0003-0997-8817", "country": null }, { "author_id": 169730, "given_name": "Pierre", "family_name": "Labauge", "ORCID": "http://orcid.org/0000-0001-7759-8555", "country": null }, { "author_id": 240668, "given_name": "Christine", "family_name": "Lebrun‐Frenay", "ORCID": null, "country": null }, { "author_id": 240669, "given_name": "Thibault", "family_name": "Moreau", "ORCID": null, "country": null }, { "author_id": 240670, "given_name": "David", "family_name": "Laplaud", "ORCID": null, "country": null }, { "author_id": 182588, "given_name": "Eric", "family_name": "Berger", "ORCID": "http://orcid.org/0000-0002-5003-9793", "country": null }, { "author_id": 324605, "given_name": "Jean", "family_name": "Pelletier", "ORCID": "http://orcid.org/0000-0001-9730-7567", "country": null }, { "author_id": 149339, "given_name": "Bruno", "family_name": "Stankoff", "ORCID": "http://orcid.org/0000-0002-9631-4674", "country": null }, { "author_id": 182589, "given_name": "Olivier", "family_name": "Gout", "ORCID": "http://orcid.org/0000-0001-6435-0761", "country": null }, { "author_id": 176046, "given_name": "Eric", "family_name": "Thouvenot", "ORCID": "http://orcid.org/0000-0001-8671-7747", "country": "FR" }, { "author_id": 318069, "given_name": "Olivier", "family_name": "Heinzlef", "ORCID": "http://orcid.org/0000-0002-4634-8542", "country": null }, { "author_id": 240672, "given_name": "Abdullatif", "family_name": "Al‐Khedr", "ORCID": null, "country": null }, { "author_id": 176047, "given_name": "Bertrand", "family_name": "Bourre", "ORCID": "http://orcid.org/0000-0002-2459-2480", "country": null }, { "author_id": 240673, "given_name": "Olivier", "family_name": "Casez", "ORCID": null, "country": null }, { "author_id": 240674, "given_name": "Philippe", "family_name": "Cabre", "ORCID": null, "country": null }, { "author_id": 149933, "given_name": "Alexis", "family_name": "Montcuquet", "ORCID": "http://orcid.org/0000-0002-7202-0399", "country": null }, { "author_id": 149934, "given_name": "Alain", "family_name": "Créange", "ORCID": "http://orcid.org/0000-0003-3838-1622", "country": "FR" }, { "author_id": 149935, "given_name": "Jean‐Philippe", "family_name": "Camdessanché", "ORCID": "http://orcid.org/0000-0002-5282-6707", "country": "FR" }, { "author_id": 240675, "given_name": "Serge", "family_name": "Bakchine", "ORCID": null, "country": null }, { "author_id": 240676, "given_name": "Aude", "family_name": "Maurousset", "ORCID": null, "country": null }, { "author_id": 240677, "given_name": "Karolina", "family_name": "Hankiewicz", "ORCID": null, "country": null }, { "author_id": 182593, "given_name": "Corinne", "family_name": "Pottier", "ORCID": "http://orcid.org/0000-0001-5422-7364", "country": null }, { "author_id": 149120, "given_name": "Nicolas", "family_name": "Maubeuge", "ORCID": "http://orcid.org/0000-0002-1618-6079", "country": null }, { "author_id": 240678, "given_name": "Dalia", "family_name": "Dimitri Boulos", "ORCID": null, "country": null }, { "author_id": 240679, "given_name": "Chantal", "family_name": "Nifle", "ORCID": null, "country": null }, { "author_id": 147248, "given_name": "Sandra", "family_name": "Vukusic", "ORCID": "http://orcid.org/0000-0001-7337-7122", "country": null }, { "author_id": 324604, "given_name": "Pierre", "family_name": "Clavelou", "ORCID": "http://orcid.org/0000-0003-2363-9352", "country": null }, { "author_id": 330404, "given_name": "Gilles", "family_name": "Defer", "ORCID": "http://orcid.org/0000-0003-1343-5858", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-02T23:16:45Z", "noun_phrases": [ "Untreated patients", "multiple sclerosis", "a study", "French expert centers" ], "doi": "10.1111/ene.14790", "access": "open", "takeaways": " Many patients with multiple sclerosis (pwMS) remain untreated . Disease modifying therapies (DMTs) have an impact on relapses and disease progression . Most patients with progressive MS did not receive any DMT during the study period .", "categories": [] }, { "article_id": 175, "title": "Benign monomelic amyotrophy of lower limb in a cohort of chinese patients", "summary": "<div><p>Brain Behav. 2021 Mar 2:e02073. doi: 10.1002/brb3.2073. 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\">BACKGROUND: Benign monomelic amyotrophy of lower limb (BMALL) is a neurogenic syndrome representing an unclear field. Further studies might be helpful to elucidate uncertainties regarding causation, outcome, and the risk of progression to amyotrophic lateral sclerosis (ALS).</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\">METHODS: According to the inclusion and exclusion criteria, 37 patients with BMALL were retrospectively collected in three neuromuscular centers from January 2012 to October 2018. The detailed medical data were summarized. Multiple laboratory tests were examined. Routine electrophysiological examinations, muscle MRI of lower limbs, and muscle biopsy were conducted.</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 cohort included 24 male and 13 female cases with median age of onset 47 years. Muscle MRI revealed that the distribution of involved muscles matched with the extent of fat infiltration, so the pattern muscle atrophy can be divided into the following four types: six patients with thigh atrophy (type I), 14 patients with leg atrophy (type II); 10 patients with disproportionate atrophy in both thigh and leg (type III); and seven patients with well-proportionate atrophy in both thigh and leg (type IV). Electrophysiological findings showed neurogenic pattern, spontaneous activity, and abnormal H reflex, which suggested a disorder of spinal anterior horn cell in the patients with types I-III. However, no electrophysiological abnormalities were found in the patients with type IV. Muscle pathology varied from almost normal pattern to advanced neurogenic pattern in nine biopsied patients. Follow-up showed that two patients with type II developed to ALS four years later, and all patients with type IV were in stable condition without any complaints.</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: Muscle MRI was useful to exactly localize the distribution of involved muscles in BMALL patients. The distribution of atrophic muscles can be roughly divided into four types based on the MRI features. The classification of distributing types might be as an indicator for the prognosis of BMALL.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33650811/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210302181644&v=2.14.2\">33650811</a> | DOI:<a href=\"https://doi.org/10.1002/brb3.2073\">10.1002/brb3.2073</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33650811/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-01-04T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Wiley", "container_title": "Brain and Behavior", "authors": [ { "author_id": 240637, "given_name": "Lulu", "family_name": "Wang", "ORCID": null, "country": null }, { "author_id": 240638, "given_name": "Han", "family_name": "Wen", "ORCID": null, "country": null }, { "author_id": 240639, "given_name": "Shuyun", "family_name": "Chen", "ORCID": null, "country": null }, { "author_id": 191457, "given_name": "Huan", "family_name": "Wang", "ORCID": "http://orcid.org/0000-0002-3816-9552", "country": "CN" }, { "author_id": 240640, "given_name": "Yilei", "family_name": "Zheng", "ORCID": null, "country": null }, { "author_id": 240641, "given_name": "Ran", "family_name": "Chen", "ORCID": null, "country": null }, { "author_id": 240642, "given_name": "Jingjing", "family_name": "Li", "ORCID": null, "country": null }, { "author_id": 240643, "given_name": "Kaiyan", "family_name": "Jiang", "ORCID": null, "country": null }, { "author_id": 240644, "given_name": "Haijie", "family_name": "Xiang", "ORCID": null, "country": null }, { "author_id": 240645, "given_name": "Min", "family_name": "Zhu", "ORCID": null, "country": null }, { "author_id": 240646, "given_name": "Meihong", "family_name": "Zhou", "ORCID": null, "country": null }, { "author_id": 240647, "given_name": "Sheng", "family_name": "Yao", "ORCID": null, "country": null }, { "author_id": 209914, "given_name": "Daojun", "family_name": "Hong", "ORCID": "http://orcid.org/0000-0003-1380-3534", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-02T23:16:45Z", "noun_phrases": [ "Benign monomelic amyotrophy", "lower limb", "a cohort", "chinese patients" ], "doi": "10.1002/brb3.2073", "access": "open", "takeaways": " Benign monomelic amyotrophy of lower limb (BMALL) is a neurogenic syndrome representing an unclear field . Muscle MRI revealed that the distribution of involved muscles matched with the extent of fat infiltration .", "categories": [] }, { "article_id": 171, "title": "Neuroimmunology of COVID-19", "summary": "<div><p>Nervenarzt. 2021 Mar 2. doi: 10.1007/s00115-021-01077-1. 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\">Many neuroimmunological diseases, such as encephalopathy, encephalitis, myelitis and acute disseminated encephalomyelitis (ADEM) have occurred more frequently after infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which indicates a parainfectious or postinfectious association. The most likely underlying mechanisms include virus-triggered overactivation of the immune system with hyperinflammation and cytokine storm but potentially also the development of specific autoantibodies against central nervous system (CNS) tissue. These were predominantly detected in the cerebrospinal fluid of severely ill coronavirus disease 2019 (COVID-19) patients. In contrast, direct damage after invasion of SARS-CoV‑2 into the brain and spinal cord does not seem to play a relevant role. Susceptibility to infection with SARS-CoV‑2 in patients with multiple sclerosis, myasthenia or other neuroimmunological diseases including the risk for severe disease courses, is not determined by the administered immunotherapy but by known risk factors, such as age, comorbidities and the disease-related degree of disability. Therefore, immunotherapy in these patients should not be delayed or discontinued. The contribution of neuroimmunological mechanisms to long-term sequelae after survival of a COVID-19 illness, such as fatigue, impairment of memory, sleep dysfunction or anxiety, will require long-term clinical follow-up, preferentially in COVID-19 register studies.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33651117/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210302181644&v=2.14.2\">33651117</a> | DOI:<a href=\"https://doi.org/10.1007/s00115-021-01077-1\">10.1007/s00115-021-01077-1</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33651117/#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": "Der Nervenarzt", "authors": [ { "author_id": 212886, "given_name": "Thomas", "family_name": "Skripuletz", "ORCID": "http://orcid.org/0000-0001-8550-335X", "country": null }, { "author_id": 240648, "given_name": "Nora", "family_name": "Möhn", "ORCID": null, "country": null }, { "author_id": 240649, "given_name": "Christiana", "family_name": "Franke", "ORCID": null, "country": null }, { "author_id": 240650, "given_name": "Harald", "family_name": "Prüß", "ORCID": null, "country": null } ], "relevant": false, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-02T23:16:45Z", "noun_phrases": [ "Neuroimmunology", "COVID-19" ], "doi": "10.1007/s00115-021-01077-1", "access": "open", "takeaways": " Many neuroimmunological diseases, such as encephalopathy, encephalitis, myelitis and acute disseminated encephalomyelitis (ADEM) have occurred more frequently after infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) The most likely underlying mechanisms include virus-triggered overactivation of the immune system .", "categories": [] }, { "article_id": 172, "title": "Metformin Protects Myelin from Degeneration in A Mouse Model of Iysophosphatidylcholine-Induced Demyelination in The Optic Chiasm", "summary": "<div><p>Cell J. 2021 Apr;23(1):119-128. doi: 10.22074/cellj.2021.7174. Epub 2021 Mar 1.</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\">OBJECTIVE: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. The autoimmune pathology and long-term inflammation lead to substantial demyelination. These events lead to a substantial loss of oligodendrocytes (OLs), which in a longer period, results in axonal loss and long-term disabilities. Neural cells protection approaches decelerate or inhibit the disease progress to avoid further disability. Previous studies showed that metformin has beneficial effects against neurodegenerative conditions. In this study, we examined possible protective effects of metformin on toxin-induced myelin destruction in adult mice brains.</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 experimental study, lysophosphatidylcholine (LPC) was used to induce demyelination in mice optic chiasm. We examined the extent of demyelination at different time points post LPC injection using myelin staining and evaluated the severity of inflammation. Functional state of optic pathway was evaluated by visual evoked potential (VEP) recording.</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: Metformin attenuated LPC-induced demyelination (P<0.05) and inflammation (P<0.05) and protected against significant decrease (P<0.05) in functional conductivity of optic tract. These data indicated that metformin administration attenuates the myelin degeneration following LPC injection which led to functional enhancement.</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: Our findings suggest metformin for combination therapy for patients suffering from the myelin degenerative diseases, especially multiple sclerosis; however, additional mechanistic studies are required.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33650828/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210302181644&v=2.14.2\">33650828</a> | DOI:<a href=\"https://doi.org/10.22074/cellj.2021.7174\">10.22074/cellj.2021.7174</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33650828/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-01-04T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": null, "container_title": null, "authors": [], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-02T23:16:45Z", "noun_phrases": [ "Metformin", "Myelin", "Degeneration", "A Mouse Model", "Iysophosphatidylcholine-Induced Demyelination", "The Optic Chiasm" ], "doi": "10.22074/cellj.2021.7174", "access": "restricted", "takeaways": " Multiple sclerosis (MS) is a demyelinating disease of the central nervous system . Previous studies showed that metformin has beneficial effects against neurodegenerative conditions .", "categories": [ { "category_id": 6, "category_description": "", "category_name": "Metformin", "category_slug": "metformin", "category_terms": [ "metformin" ], "article_count": 22 } ] }, { "article_id": 173, "title": "Development of a Web-Based Mindfulness Program for People With Multiple Sclerosis: Qualitative Co-Design Study", "summary": "<div><p>J Med Internet Res. 2021 Mar 2;23(3):e19309. doi: 10.2196/19309.</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\">BACKGROUND: Mindfulness-based stress reduction is an efficacious treatment for people with chronic health problems; however, it is highly intensive and time-consuming, which is a barrier for service provision.</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\">OBJECTIVE: This study aims to develop an internet-delivered adapted version of mindfulness-based stress reduction for people with multiple sclerosis to make the intervention more accessible.</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\">METHODS: We co-designed a web-based mindfulness program with end users, that is, people with multiple sclerosis (N=19). Iterative feedback was also collected from a subsample of the initial group of end users (n=11), and the program was reviewed by experts (n=8).</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: We identified three main themes common to people with multiple sclerosis: dealing with uncertainty and fears for the future, grief and loss, and social isolation. These themes were incorporated into narratives throughout the program. People with multiple sclerosis who reviewed the program gave feedback that the program was relatable, feasible, and acceptable. Experts agreed that the program appropriately represented the main tenets of mindfulness. Iterative feedback was used to further refine the program.</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\">CONCLUSIONS: The web-based mindfulness program that we developed was viewed positively by both experts and end users. The program reflects common concerns for people with multiple sclerosis and has the potential to meet important unmet psychological needs. A randomized controlled trial was planned to determine the efficacy of the program.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33650980/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210302181644&v=2.14.2\">33650980</a> | DOI:<a href=\"https://doi.org/10.2196/19309\">10.2196/19309</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33650980/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-03-02T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "JMIR Publications Inc.", "container_title": "Journal of Medical Internet Research", "authors": [ { "author_id": 225055, "given_name": "Amy-Lee", "family_name": "Sesel", "ORCID": "http://orcid.org/0000-0002-9698-2699", "country": null }, { "author_id": 227779, "given_name": "Louise", "family_name": "Sharpe", "ORCID": "http://orcid.org/0000-0002-8790-6272", "country": null }, { "author_id": 227780, "given_name": "Heidi N", "family_name": "Beadnall", "ORCID": "http://orcid.org/0000-0003-3734-4133", "country": null }, { "author_id": 148639, "given_name": "Michael H", "family_name": "Barnett", "ORCID": "http://orcid.org/0000-0002-2156-8864", "country": null }, { "author_id": 225057, "given_name": "Marianna", "family_name": "Szabo", "ORCID": "http://orcid.org/0000-0002-8825-7921", "country": null }, { "author_id": 227781, "given_name": "Sharon L", "family_name": "Naismith", "ORCID": "http://orcid.org/0000-0001-9076-2778", "country": "AU" } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-02T23:16:45Z", "noun_phrases": [ "Development", "a Web-Based Mindfulness Program", "People", "Multiple Sclerosis", "Qualitative Co-Design Study" ], "doi": "10.2196/19309", "access": "open", "takeaways": " Mindfulness-based stress reduction is an efficacious treatment for people with chronic health problems . However, it is highly intensive and time-consuming, which is a barrier for service provision . We developed a web-based mindfulness program with end users, that is, people with multiple sclerosis . We identified three themes common to people with MS: dealing with uncertainty and fears for the future, grief and loss .", "categories": [] }, { "article_id": 169, "title": "Congruent microbiome signatures in fibrosis-prone autoimmune diseases: IgG4-related disease and systemic sclerosis", "summary": "<div><p>Genome Med. 2021 Feb 28;13(1):35. doi: 10.1186/s13073-021-00853-7.</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\">BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) and systemic sclerosis (SSc) are rare autoimmune diseases characterized by the presence of CD4+ cytotoxic T cells in the blood as well as inflammation and fibrosis in various organs, but they have no established etiologies. Similar to other autoimmune diseases, the gut microbiome might encode disease-triggering or disease-sustaining factors.</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\">METHODS: The gut microbiomes from IgG4-RD and SSc patients as well as healthy individuals with no recent antibiotic treatment were studied by metagenomic sequencing of stool DNA. De novo assembly-based taxonomic and functional characterization, followed by association and accessory gene set enrichment analysis, were applied to describe microbiome changes associated with both diseases.</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: Microbiomes of IgG4-RD and SSc patients distinctly separated from those of healthy controls: numerous opportunistic pathogenic Clostridium and typically oral Streptococcus species were significantly overabundant, while Alistipes, Bacteroides, and butyrate-producing species were depleted in the two diseases compared to healthy controls. Accessory gene content analysis in these species revealed an enrichment of Th17-activating Eggerthella lenta strains in IgG4-RD and SSc and a preferential colonization of a homocysteine-producing strain of Clostridium bolteae in SSc. Overabundance of the classical mevalonate pathway, hydroxyproline dehydratase, and fibronectin-binding protein in disease microbiomes reflects potential functional differences in host immune recognition and extracellular matrix utilization associated with fibrosis. Strikingly, the majority of species that were differentially abundant in IgG4-RD and SSc compared to controls showed the same directionality in both diseases. Compared with multiple sclerosis and rheumatoid arthritis, the gut microbiomes of IgG4-RD and SSc showed similar signatures; in contrast, the most differentially abundant taxa were not the facultative anaerobes consistently identified in inflammatory bowel diseases, suggesting the microbial signatures of IgG4-RD and SSc do not result from mucosal inflammation and decreased anaerobism.</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\">CONCLUSIONS: These results provide an initial characterization of gut microbiome ecology in fibrosis-prone IgG4-RD and SSc and reveal microbial functions that offer insights into the pathophysiology of these rare diseases.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33648559/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210302080909&v=2.14.2\">33648559</a> | DOI:<a href=\"https://doi.org/10.1186/s13073-021-00853-7\">10.1186/s13073-021-00853-7</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33648559/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-02-28T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Springer Science and Business Media LLC", "container_title": "Genome Medicine", "authors": [ { "author_id": 298659, "given_name": "Damian R.", "family_name": "Plichta", "ORCID": null, "country": null }, { "author_id": 298660, "given_name": "Juhi", "family_name": "Somani", "ORCID": null, "country": null }, { "author_id": 298661, "given_name": "Matthieu", "family_name": "Pichaud", "ORCID": null, "country": null }, { "author_id": 298662, "given_name": "Zachary S.", "family_name": "Wallace", "ORCID": null, "country": null }, { "author_id": 298663, "given_name": "Ana D.", "family_name": "Fernandes", "ORCID": null, "country": null }, { "author_id": 298664, "given_name": "Cory A.", "family_name": "Perugino", "ORCID": null, "country": null }, { "author_id": 298665, "given_name": "Harri", "family_name": "Lähdesmäki", "ORCID": null, "country": null }, { "author_id": 298666, "given_name": "John H.", "family_name": "Stone", "ORCID": null, "country": null }, { "author_id": 272648, "given_name": "Hera", "family_name": "Vlamakis", "ORCID": null, "country": null }, { "author_id": 298667, "given_name": "Daniel C.", "family_name": "Chung", "ORCID": null, "country": null }, { "author_id": 150600, "given_name": "Dinesh", "family_name": "Khanna", "ORCID": "http://orcid.org/0000-0003-1412-4453", "country": null }, { "author_id": 242878, "given_name": "Shiv", "family_name": "Pillai", "ORCID": null, "country": null }, { "author_id": 182956, "given_name": "Ramnik J.", "family_name": "Xavier", "ORCID": "http://orcid.org/0000-0002-5630-5167", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-02T13:09:11Z", "noun_phrases": [ "Congruent microbiome signatures", "fibrosis-prone autoimmune diseases", "IgG4-related disease", "systemic sclerosis" ], "doi": "10.1186/s13073-021-00853-7", "access": "open", "takeaways": " Immunoglobulin G4-related disease (IgG4-RD) and systemic sclerosis (SSc) are rare autoimmune diseases characterized by the presence of CD4+ cytotoxic T cells in the blood as well as inflammation and fibrosis in various organs . Similar to other autoimmune diseases, the gut microbiome might encode disease-triggering or disease-sustaining factors .", "categories": [] }, { "article_id": 167, "title": "Autoimmune encephalitis: proposed recommendations for symptomatic and long-term management", "summary": "<div><p>J Neurol Neurosurg Psychiatry. 2021 Mar 1:jnnp-2020-325302. doi: 10.1136/jnnp-2020-325302. 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\">The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft. Where evidence was lacking or controversial, an electronic survey was distributed to all members to solicit individual responses. Sixty-eight members from 17 countries answered the survey. The most popular bridging therapy was oral prednisone taper chosen by 38% of responders while rituximab was the most popular maintenance therapy chosen by 46%. Most responders considered maintenance immunosuppression after a second relapse in patients with neuronal surface antibodies (70%) or seronegative autoimmune encephalitis (61%) as opposed to those with onconeuronal antibodies (29%). Most responders opted to cancer screening for 4 years in patients with neuronal surface antibodies (49%) or limbic encephalitis (46%) as opposed to non-limbic seronegative autoimmune encephalitis (36%). Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33649021/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210302080909&v=2.14.2\">33649021</a> | DOI:<a href=\"https://doi.org/10.1136/jnnp-2020-325302\">10.1136/jnnp-2020-325302</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33649021/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-12-19T00:11:58.555000Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "BMJ", "container_title": "Journal of Neurology, Neurosurgery & Psychiatry", "authors": [ { "author_id": 146943, "given_name": "Hesham", "family_name": "Abboud", "ORCID": "http://orcid.org/0000-0001-5346-8254", "country": null }, { "author_id": 240619, "given_name": "John", "family_name": "Probasco", "ORCID": null, "country": null }, { "author_id": 146945, "given_name": "Sarosh", "family_name": "Irani", "ORCID": "http://orcid.org/0000-0002-7667-9748", "country": null }, { "author_id": 240582, "given_name": "Beau", "family_name": "Ances", "ORCID": null, "country": null }, { "author_id": 240583, "given_name": "David R", "family_name": "Benavides", "ORCID": null, "country": null }, { "author_id": 240584, "given_name": "Michael", "family_name": "Bradshaw", "ORCID": null, "country": null }, { "author_id": 229289, "given_name": "Paulo Pereira", "family_name": "Christo", "ORCID": "http://orcid.org/0000-0003-1224-5243", "country": null }, { "author_id": 240585, "given_name": "Russell C", "family_name": "Dale", "ORCID": null, "country": null }, { "author_id": 240586, "given_name": "Mireya", "family_name": "Fernandez-Fournier", "ORCID": null, "country": null }, { "author_id": 146952, "given_name": "Eoin P.", "family_name": "Flanagan", "ORCID": "http://orcid.org/0000-0002-6661-2910", "country": null }, { "author_id": 240587, "given_name": "Avi", "family_name": "Gadoth", "ORCID": null, "country": null }, { "author_id": 240588, "given_name": "Pravin", "family_name": "George", "ORCID": null, "country": null }, { "author_id": 195444, "given_name": "Elena", "family_name": "Grebenciucova", "ORCID": "http://orcid.org/0000-0002-4255-9617", "country": "US" }, { "author_id": 240589, "given_name": "Adham", "family_name": "Jammoul", "ORCID": null, "country": null }, { "author_id": 240590, "given_name": "Soon-Tae", "family_name": "Lee", "ORCID": null, "country": null }, { "author_id": 240591, "given_name": "Yuebing", "family_name": "Li", "ORCID": null, "country": null }, { "author_id": 240592, "given_name": "Marcelo", "family_name": "Matiello", "ORCID": null, "country": null }, { "author_id": 240593, "given_name": "Anne Marie", "family_name": "Morse", "ORCID": null, "country": null }, { "author_id": 240594, "given_name": "Alexander", "family_name": "Rae-Grant", "ORCID": null, "country": null }, { "author_id": 240595, "given_name": "Galeno", "family_name": "Rojas", "ORCID": null, "country": null }, { "author_id": 240596, "given_name": "Ian", "family_name": "Rossman", "ORCID": null, "country": null }, { "author_id": 240597, "given_name": "Sarah", "family_name": "Schmitt", "ORCID": null, "country": null }, { "author_id": 240598, "given_name": "Arun", "family_name": "Venkatesan", "ORCID": null, "country": null }, { "author_id": 240599, "given_name": "Steven", "family_name": "Vernino", "ORCID": null, "country": null }, { "author_id": 146967, "given_name": "Sean J.", "family_name": "Pittock", "ORCID": "http://orcid.org/0000-0002-6140-5584", "country": null }, { "author_id": 146968, "given_name": "Maarten J", "family_name": "Titulaer", "ORCID": "http://orcid.org/0000-0002-1033-3840", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-02T13:09:11Z", "noun_phrases": [ "Autoimmune encephalitis", "proposed recommendations", "symptomatic and long-term management" ], "doi": "10.1136/jnnp-2020-325302", "access": "open", "takeaways": " The most popular bridging therapy was oral prednisone taper chosen by 38% of responders . Most responders opted to cancer screening for 4 years in patients with neuronal surface antibodies . Rituximab was the most popular maintenance therapy chosen by 46% .", "categories": [] }, { "article_id": 166, "title": "Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management", "summary": "<div><p>J Neurol Neurosurg Psychiatry. 2021 Mar 1:jnnp-2020-325300. doi: 10.1136/jnnp-2020-325300. 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\">The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft. Where evidence was lacking or controversial, an electronic survey was distributed to all members to solicit individual responses. Sixty-eight members from 17 countries answered the survey. Corticosteroids alone or combined with other agents (intravenous IG or plasmapheresis) were selected as a first-line therapy by 84% of responders for patients with a general presentation, 74% for patients presenting with faciobrachial dystonic seizures, 63% for NMDAR-IgG encephalitis and 48.5% for classical paraneoplastic encephalitis. Half the responders indicated they would add a second-line agent only if there was no response to more than one first-line agent, 32% indicated adding a second-line agent if there was no response to one first-line agent, while only 15% indicated using a second-line agent in all patients. As for the preferred second-line agent, 80% of responders chose rituximab while only 10% chose cyclophosphamide in a clinical scenario with unknown antibodies. Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33649022/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210302080909&v=2.14.2\">33649022</a> | DOI:<a href=\"https://doi.org/10.1136/jnnp-2020-325300\">10.1136/jnnp-2020-325300</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33649022/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-01-07T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "BMJ", "container_title": "Journal of Neurology, Neurosurgery & Psychiatry", "authors": [ { "author_id": 146943, "given_name": "Hesham", "family_name": "Abboud", "ORCID": "http://orcid.org/0000-0001-5346-8254", "country": null }, { "author_id": 240581, "given_name": "John C", "family_name": "Probasco", "ORCID": null, "country": null }, { "author_id": 146945, "given_name": "Sarosh", "family_name": "Irani", "ORCID": "http://orcid.org/0000-0002-7667-9748", "country": null }, { "author_id": 240582, "given_name": "Beau", "family_name": "Ances", "ORCID": null, "country": null }, { "author_id": 240583, "given_name": "David R", "family_name": "Benavides", "ORCID": null, "country": null }, { "author_id": 240584, "given_name": "Michael", "family_name": "Bradshaw", "ORCID": null, "country": null }, { "author_id": 229289, "given_name": "Paulo Pereira", "family_name": "Christo", "ORCID": "http://orcid.org/0000-0003-1224-5243", "country": null }, { "author_id": 240585, "given_name": "Russell C", "family_name": "Dale", "ORCID": null, "country": null }, { "author_id": 240586, "given_name": "Mireya", "family_name": "Fernandez-Fournier", "ORCID": null, "country": null }, { "author_id": 146952, "given_name": "Eoin P.", "family_name": "Flanagan", "ORCID": "http://orcid.org/0000-0002-6661-2910", "country": null }, { "author_id": 240587, "given_name": "Avi", "family_name": "Gadoth", "ORCID": null, "country": null }, { "author_id": 240588, "given_name": "Pravin", "family_name": "George", "ORCID": null, "country": null }, { "author_id": 195444, "given_name": "Elena", "family_name": "Grebenciucova", "ORCID": "http://orcid.org/0000-0002-4255-9617", "country": "US" }, { "author_id": 240589, "given_name": "Adham", "family_name": "Jammoul", "ORCID": null, "country": null }, { "author_id": 240590, "given_name": "Soon-Tae", "family_name": "Lee", "ORCID": null, "country": null }, { "author_id": 240591, "given_name": "Yuebing", "family_name": "Li", "ORCID": null, "country": null }, { "author_id": 240592, "given_name": "Marcelo", "family_name": "Matiello", "ORCID": null, "country": null }, { "author_id": 240593, "given_name": "Anne Marie", "family_name": "Morse", "ORCID": null, "country": null }, { "author_id": 240594, "given_name": "Alexander", "family_name": "Rae-Grant", "ORCID": null, "country": null }, { "author_id": 240595, "given_name": "Galeno", "family_name": "Rojas", "ORCID": null, "country": null }, { "author_id": 240596, "given_name": "Ian", "family_name": "Rossman", "ORCID": null, "country": null }, { "author_id": 240597, "given_name": "Sarah", "family_name": "Schmitt", "ORCID": null, "country": null }, { "author_id": 240598, "given_name": "Arun", "family_name": "Venkatesan", "ORCID": null, "country": null }, { "author_id": 240599, "given_name": "Steven", "family_name": "Vernino", "ORCID": null, "country": null }, { "author_id": 146967, "given_name": "Sean J.", "family_name": "Pittock", "ORCID": "http://orcid.org/0000-0002-6140-5584", "country": null }, { "author_id": 146968, "given_name": "Maarten J", "family_name": "Titulaer", "ORCID": "http://orcid.org/0000-0002-1033-3840", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-02T13:09:11Z", "noun_phrases": [ "Autoimmune encephalitis", "best practice recommendations", "diagnosis", "acute management" ], "doi": "10.1136/jnnp-2020-325300", "access": "open", "takeaways": " Corticosteroids were selected as a first-line therapy by 84% of responders for patients with a general presentation, 74% for patients presenting with faciobrachial dystonic seizures, 63% for NMDAR-IgG encephalitis .", "categories": [] }, { "article_id": 168, "title": "Nrf2 through Aryl Hydrocarbon Receptor Regulates IL-22 Response in CD4+ T Cells", "summary": "<div><p>J Immunol. 2021 Mar 1:ji1900656. doi: 10.4049/jimmunol.1900656. 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\">IL-17A and IL-22 derived from Th17 cells play a significant role in mucosal immunity and inflammation. TGF-β and IL-6 promote Th17 differentiation; however, these cytokines have multiple targets. The identification and screening of additional molecules that regulate IL-17A and IL-22 responses in certain inflammatory conditions is of great clinical significance. In this study, we show that CDDO-Im, a specific Nrf2 activator, promotes IL-17A and IL-22 responses in murine Th17 cells. In contrast, CDDO-Im inhibits IL-17A response in multiple sclerosis patient-derived PBMCs. However, Nrf2 specifically regulates IL-22 response in vivo. Nrf2 acts through the regulation of antioxidant response element (ARE) binding motifs in target genes to induce or repress transcription. Promoter analysis revealed that <i>Il17a</i>, <i>Rorc</i>, and <i>Ahr</i> genes have several ARE motifs. We showed that Nrf2 bound to ARE repressor (ARE-R2) of <i>Rorc</i> and inhibited <i>Rorc</i>-dependent IL-17A transactivation. The luciferase reporter assay data showed that CDDO-Im regulated <i>Ahr</i> promoter activity. Chromatin immunoprecipitation quantitative PCR data showed that Nrf2 bound to ARE of AhR. Finally, we confirmed that the CDDO-Im-mediated induction of IL-22 production in CD4<sup>+</sup> T cells was abrogated in CD4-specific <i>Ahr</i> knockout mice (<i>Ahr<sup>CD4</sup></i> ). CH-223191, a specific AhR antagonist, inhibits CDDO-Im-induced IL-22 production in CD4<sup>+</sup> T cells, which further confirmed the AhR-dependent regulation. Collectively, our data showed that Nrf2 via AhR pathways regulated IL-22 response in CD4<sup>+</sup> T cells.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33648937/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210302080909&v=2.14.2\">33648937</a> | DOI:<a href=\"https://doi.org/10.4049/jimmunol.1900656\">10.4049/jimmunol.1900656</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33648937/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-03-31T23:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "The American Association of Immunologists", "container_title": "The Journal of Immunology", "authors": [ { "author_id": 159147, "given_name": "Xun", "family_name": "Lin", "ORCID": "http://orcid.org/0000-0003-1860-3996", "country": null }, { "author_id": 240681, "given_name": "Suzanne", "family_name": "Tawch", "ORCID": null, "country": null }, { "author_id": 240682, "given_name": "Hoi Tong", "family_name": "Wong", "ORCID": null, "country": null }, { "author_id": 175667, "given_name": "Suyasha", "family_name": "Roy", "ORCID": "http://orcid.org/0000-0002-0332-4962", "country": null }, { "author_id": 240683, "given_name": "Stephen", "family_name": "Gaudino", "ORCID": null, "country": null }, { "author_id": 159152, "given_name": "Patricia", "family_name": "Castillo", "ORCID": "http://orcid.org/0000-0001-6290-4361", "country": null }, { "author_id": 159153, "given_name": "Waleed", "family_name": "Elsegeiny", "ORCID": "http://orcid.org/0000-0003-1170-4890", "country": "US" }, { "author_id": 159154, "given_name": "Nobunao", "family_name": "Wakabayashi", "ORCID": "http://orcid.org/0000-0003-4643-7841", "country": "US" }, { "author_id": 159155, "given_name": "Tim D.", "family_name": "Oury", "ORCID": "http://orcid.org/0000-0002-4253-3214", "country": null }, { "author_id": 159156, "given_name": "Derek", "family_name": "Pociask", "ORCID": "http://orcid.org/0000-0002-1256-6410", "country": null }, { "author_id": 159157, "given_name": "Kong", "family_name": "Chen", "ORCID": "http://orcid.org/0000-0001-6980-5454", "country": null }, { "author_id": 240684, "given_name": "Nancy", "family_name": "McLinskey", "ORCID": null, "country": null }, { "author_id": 159159, "given_name": "Patricia", "family_name": "Melville", "ORCID": "http://orcid.org/0000-0002-5754-6560", "country": null }, { "author_id": 240685, "given_name": "Olga", "family_name": "Syritsyna", "ORCID": null, "country": null }, { "author_id": 240686, "given_name": "Patricia", "family_name": "Coyle", "ORCID": null, "country": null }, { "author_id": 159162, "given_name": "Misty", "family_name": "Good", "ORCID": "http://orcid.org/0000-0002-0264-5721", "country": null }, { "author_id": 159163, "given_name": "Amit", "family_name": "Awasthi", "ORCID": "http://orcid.org/0000-0002-2563-1971", "country": null }, { "author_id": 159164, "given_name": "Jay K.", "family_name": "Kolls", "ORCID": "http://orcid.org/0000-0001-5151-6304", "country": null }, { "author_id": 240687, "given_name": "Pawan", "family_name": "Kumar", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-02T13:09:11Z", "noun_phrases": [ "Nrf2", "Aryl Hydrocarbon Receptor", "IL-22 Response", "CD4+ T Cells" ], "doi": "10.4049/jimmunol.1900656", "access": "open", "takeaways": " CDDO-Im, a specific Nrf2 activator, promotes IL-17A and IL-22 responses in murine Th17 cells . In contrast, CDDO inhibits IL-16 response in multiple sclerosis patient-derived PBMCs . Nrf 2 acts through the regulation of antioxidant response element binding motifs .", "categories": [] }, { "article_id": 170, "title": "Neuronal hibernation following hippocampal demyelination", "summary": "<div><p>Acta Neuropathol Commun. 2021 Mar 1;9(1):34. doi: 10.1186/s40478-021-01130-9.</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\">Cognitive dysfunction occurs in greater than 50% of individuals with multiple sclerosis (MS). Hippocampal demyelination is a prominent feature of postmortem MS brains and hippocampal atrophy correlates with cognitive decline in MS patients. Cellular and molecular mechanisms responsible for neuronal dysfunction in demyelinated hippocampi are not fully understood. Here we investigate a mouse model of hippocampal demyelination where twelve weeks of treatment with the oligodendrocyte toxin, cuprizone, demyelinates over 90% of the hippocampus and causes decreased memory/learning. Long-term potentiation (LTP) of hippocampal CA1 pyramidal neurons is considered to be a major cellular readout of learning and memory in the mammalian brain. In acute slices, we establish that hippocampal demyelination abolishes LTP and excitatory post-synaptic potentials of CA1 neurons, while pre-synaptic function of Schaeffer collateral fibers is preserved. Demyelination also reduced Ca<sup>2+</sup>-mediated firing of hippocampal neurons in vivo. Using three-dimensional electron microscopy, we investigated the number, shape (mushroom, stubby, thin), and post-synaptic densities (PSDs) of dendritic spines that facilitate LTP. Hippocampal demyelination did not alter the number of dendritic spines. Surprisingly, dendritic spines appeared to be more mature in demyelinated hippocampi, with a significant increase in mushroom-shaped spines, more perforated PSDs, and more astrocyte participation in the tripartite synapse. RNA sequencing experiments identified 400 altered transcripts in demyelinated hippocampi. Gene transcripts that regulate myelination, synaptic signaling, astrocyte function, and innate immunity were altered in demyelinated hippocampi. Hippocampal remyelination rescued synaptic transmission, LTP, and the majority of gene transcript changes. We establish that CA1 neurons projecting demyelinated axons silence their dendritic spines and hibernate in a state that may protect the demyelinated axon and facilitates functional recovery following remyelination.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33648591/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210302080909&v=2.14.2\">33648591</a> | DOI:<a href=\"https://doi.org/10.1186/s40478-021-01130-9\">10.1186/s40478-021-01130-9</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33648591/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-03-01T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Springer Science and Business Media LLC", "container_title": "Acta Neuropathologica Communications", "authors": [ { "author_id": 244155, "given_name": "Selva", "family_name": "Baltan", "ORCID": null, "country": null }, { "author_id": 244156, "given_name": "Safdar S.", "family_name": "Jawaid", "ORCID": null, "country": null }, { "author_id": 244157, "given_name": "Anthony M.", "family_name": "Chomyk", "ORCID": null, "country": null }, { "author_id": 244158, "given_name": "Grahame J.", "family_name": "Kidd", "ORCID": null, "country": null }, { "author_id": 244159, "given_name": "Jacqueline", "family_name": "Chen", "ORCID": null, "country": null }, { "author_id": 244161, "given_name": "Harsha D.", "family_name": "Battapady", "ORCID": null, "country": null }, { "author_id": 244163, "given_name": "Ricky", "family_name": "Chan", "ORCID": null, "country": null }, { "author_id": 173429, "given_name": "Ranjan", "family_name": "Dutta", "ORCID": "http://orcid.org/0000-0001-8502-4455", "country": null }, { "author_id": 191471, "given_name": "Bruce D.", "family_name": "Trapp", "ORCID": "http://orcid.org/0000-0001-6682-3737", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-02T13:09:11Z", "noun_phrases": [ "Neuronal hibernation", "hippocampal demyelination" ], "doi": "10.1186/s40478-021-01130-9", "access": "open", "takeaways": " Hippocampal demyelination is a prominent feature of postmortem MS brains and correlates with cognitive decline in MS patients . Long-term potentiation (LTP) of CA1 pyramidal neurons is considered to be a major cellular readout of learning and memory in the mammalian brain .", "categories": [] } ] }