Review
Medicine, General & Internal
Rosario Vasta, Ruth Chia, Bryan J. Traynor, Adriano Chio
Summary: This review discusses the role of genetic and environmental factors in motor neuron degeneration and suggests that gene-environment interactions may contribute to the unknown etiology of ALS. Climate is the underlying basis for multiple environmental factors, and the impact of global temperature increase on gene-environment interactions should be monitored.
Article
Clinical Neurology
Zahra Nasr, Vinicius Andreoli Schoeps, Amin Ziaei, Akash Virupakshaiah, Cameron Adams, T. Charles Casper, Michael Waltz, John Rose, Moses Rodriguez, Jan-Mendelt Tillema, Tanuja Chitnis, Jennifer S. Graves, Leslie Benson, Mary Rensel, Lauren Krupp, Amy T. Waldman, Bianca Weinstock-Guttman, Tim Lotze, Benjamin Greenberg, Gregory Aaen, Soe Mar, Teri Schreiner, Janace Hart, Steve Simpson-Yap, Clementina Mesaros, Lisa F. Barcellos, Emmanuelle Waubant
Summary: Using a case-control study, the researchers estimated the gene-environment interaction between exposure to household chemicals and genotypes for risk of paediatric-onset multiple sclerosis. The study found associations between exposure to insect repellents, weed control products, and plant/tree insect or disease control products and an increased risk of paediatric-onset multiple sclerosis. Additionally, significant interactions were found between weed control products and the NFKB1 SNP GG genotype, as well as between plant or disease control products and absence of the HLA-A*02 genotype.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Clinical Neurology
Ruth Leadbetter, Michael MacAskill, Daniell J. Myall, Bruce Taylor, Purwa Joshi, Deborah F. Mason
Summary: A long-term study on multiple sclerosis patients in New Zealand found that their median survival age is 7.2 years lower than the general population and they have twice the mortality risk. The survival gap is greater for those with an early age of onset and progressive-onset disease.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Clinical Neurology
Katharine Elizabeth Harding, Gillian Ingram, Emma Clare Tallantyre, Fady Joseph, Mark Wardle, Trevor P. Pickersgill, Mark D. Willis, Valentina Tomassini, Owen Rhys Pearson, Neil P. Robertson
Summary: This study provides a detailed contemporary model of disability outcomes in a representative population-based MS cohort. The results support a trend of increasing time to disability milestones compared with historical reference populations, and document disability variation with the use of transitional matrices. This study has important implications for patient counseling, clinical trial design, and assessment of therapeutic interventions.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Clinical Neurology
Xin Lin, Yuanhao Yang, Valery Fuh-Ngwa, Xianyong Yin, Steve Simpson-Yap, Ingrid van der Mei, Simon A. Broadley, Anne-Louise Ponsonby, Kathryn P. Burdon, Bruce Taylor, Yuan Zhou
Summary: This study identifies serine as a potential biomarker for the onset and disability progression of multiple sclerosis (MS) through Mendelian randomisation methods.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Medicine, General & Internal
Yuting Jiang, Hongqi Feng, Zhe Jiao, Yang Du, Yuanyuan Li, Xiaona Liu, Simeng Tong, Xinhua Shao, BingYun Li, Hongna Sun, Fangang Meng, Yuncheng Shen, Mang Li, Qiaoshi Zhao, Dandan Li, Lin Gao, Xiaoyan Fu, Fuyuan Li, Silu Cui, Liwei Zhang, Xiaoye Zhang, Lixiang Liu, Yanhong Cao, Yafei Sun, Chenpeng Zhu, Dianjun Sun, Wei Zhang, Yanhui Gao
Summary: Long-term exposure to cold can increase the risk of chronic diseases, but there is limited research on the impact of environmental factors and lifestyle changes. To explore the association between environmental factors and prevalent risk of chronic diseases, a large cohort study was conducted, collecting questionnaire data, physical measurements, and samples. The first phase of the study has been completed with 10,694 participants.
Article
Clinical Neurology
Malthe Faurschou Wandall-Holm, Mathias Due Buron, Tine Iskov Kopp, Karsten Thielen, Finn Sellebjerg, Melinda Magyari
Summary: Initiating treatment early reduces the risk of disability pension in patients with RRMS. This finding highlights the importance of early diagnosis and treatment on a patient-centered, socioeconomic disability milestone.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Article
Clinical Neurology
Jeff Rodgers, Tim Friede, Frederick W. Vonberg, Cris S. Constantinescu, Alasdair Coles, Jeremy Chataway, Martin Duddy, Hedley Emsley, Helen Ford, Lennora Fisniku, Ian Galea, Timothy Harrower, Jeremy Hobart, Huseyin Huseyin, Christopher M. Kipps, Monica Marta, Gavin McDonnell, Brendan McLean, Owen R. Pearson, David Rog, Klaus Schmierer, Basil Sharrack, Agne Straukiene, Heather C. Wilson, David Ford, Rod M. Middleton, Richard Nicholas
Summary: The negative impact of smoking in multiple sclerosis is well documented, but there is limited evidence on the benefits of smoking cessation for disease progression. This study found that current smokers had higher disability scores compared to those who had never smoked, and there was no improvement in scores with increasing time since quitting. However, when smokers quit, the rate of motor disability deterioration slowed down to match that of non-smokers. This suggests that smoking cessation is beneficial for people with multiple sclerosis.
Review
Ophthalmology
Xi He, Shi-Ming Li
Summary: Myopia, a common health issue worldwide, is influenced by both genetic and environmental factors. More than 450 genetic loci have been associated with myopia, while near work and outdoor time are the main environmental risk factors. Gene-environment interactions have been found between certain genetic loci and near work or educational level. The study of gene-environment interactions in myopia can provide more accurate risk predictions and improve targeted treatments and preventive strategies.
OPHTHALMIC AND PHYSIOLOGICAL OPTICS
(2023)
Article
Biochemistry & Molecular Biology
Adela Gonzalez-Jimenez, Pilar Lopez-Cotarelo, Teresa Agudo-Jimenez, Marisa Martinez-Gines, Jose Manuel Garcia-Dominguez, Elena Urcelay, Laura Espino-Paisan
Summary: The study found that the polymorphism rs7923837 near the HHEX gene is significantly lower in lymphocytes of multiple sclerosis (MS) patients and shows divergent subcellular distributions compared to controls. It also suggests a perturbed reciprocal regulation between HHEX and BCL6 in MS patients. Furthermore, MS carriers of the homozygous mutant genotype exhibited distinct metabolic profiles and increased glycolytic rates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Clinical Neurology
M. Puthenparampil, P. Perini, R. Bergamaschi, M. Capobianco, M. Filippi, P. Gallo
Summary: Italy is considered a high-risk country for multiple sclerosis (MS), with the incidence and prevalence gradually increasing over the past years. Research suggests that environmental factors may better explain this trend than genetic heterogeneity.
JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Torbjorn Akerstedt, Tomas Olsson, Lars Alfredsson, Anna Karin Hedstroem
Summary: Insufficient sleep and low sleep quality may increase the risk of developing multiple sclerosis.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Julia Horjus, Tineke van Mourik-Banda, Marco A. P. Heerings, Marina Hakobjan, Ward De Witte, Dorothea J. Heersema, Anne J. Jansen, Eva M. M. Strijbis, Brigit A. de Jong, Astrid E. J. Slettenaar, Esther M. P. E. Zeinstra, Erwin L. J. Hoogervorst, Barbara Franke, Wiebe Kruijer, Peter J. Jongen, Leo J. Visser, Geert Poelmans
Summary: This study identified 12 rare genetic variants associated with multiple sclerosis through whole exome sequencing and co-segregation analysis, highlighting the involvement of various biological processes related to (de-/re-)myelination and auto-immunity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Friederike Neuss, Felix von Podewils, Zhong Irene Wang, Marie Suesse, Uwe Klaus Zettl, Matthias Grothe
Summary: This study described a cohort of patients with both MS and epileptic seizures, finding that a significant percentage of MS patients with seizures had competing causes at the time of the first seizure. A detailed diagnostic setup including patient history, EEG, and MRI is recommended for evaluation and treatment decisions.
JOURNAL OF NEUROLOGY
(2021)
Article
Clinical Neurology
Elisa Longinetti, Simon Englund, Joachim Burman, Katharina Fink, Anna Fogdell-Hahn, Martin Gunnarsson, Jan Hillert, Annette Magdalene Langer-Gould, Jan Lycke, Petra Nilsson, Jonatan Salzer, Anders Svenningsson, Johan Mellergard, Tomas Olsson, Fredrik Piehl, Thomas Frisell
Summary: This study analyzed a Swedish nationwide observational study on RRMS to identify trajectories of processing speed and physical disability after DMT start. The results showed that patients' processing speed remained stable over time, while those with moderate physical disability experienced deterioration in physical function. However, there was a strong association between processing speed and disability.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Editorial Material
Clinical Neurology
R. J. E. Armstrong, J. Downer, N. Evans, P. Anslow, G. C. Ebers
Letter
Clinical Neurology
Samuel Pace, Michael Orrell, Mark Woodhall, Jacqueline Palace, Maria Isabel Leite, Sarosh R. Irani, Patrick Waters, Adam E. Handel
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Article
Biology
Bergithe E. Oftedal, Stefano Maio, Adam E. Handel, Madeleine P. J. White, Duncan Howie, Simon Davis, Nicolas Prevot, Ioanna A. Rota, Mary E. Deadman, Benedikt M. Kessler, Roman Fischer, Nikolaus S. Trede, Erdinc Sezgin, Rick M. Maizels, Georg A. Hollander
Summary: This study shows that the absence of the chaperonin subunit CCT8 in T cells severely impairs T cell activation, differentiation, and immune function. The deficiency in CCT-controlled protein folding leads to abnormal cellular stress response and inefficient immune protection against pathogens such as helminths.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Martina Patone, Xue W. Mei, Lahiru Handunnetthi, Sharon Dixon, Francesco Zaccardi, Manu Shankar-Hari, Peter Watkinson, Kamlesh Khunti, Anthony Harnden, Carol A. C. Coupland, Keith M. Channon, Nicholas L. Mills, Aziz Sheikh, Julia Hippisley-Cox
Summary: The study found that there is an increased risk of myocarditis associated with the first dose of ChAdOx1 and BNT162b2 vaccines, as well as the first and second doses of the mRNA-1273 vaccine in the 1-28 days post-vaccination period. Additionally, individuals with SARS-CoV-2 infection also face a greater risk of myocarditis, pericarditis, and cardiac arrhythmia.
Article
Multidisciplinary Sciences
Ioanna A. Rota, Adam E. Handel, Stefano Maio, Fabian Klein, Fatima Dhalla, Mary E. Deadman, Stanley Cheuk, Joseph A. Newman, Yale S. Michaels, Saulius Zuklys, Nicolas Prevot, Philip Hublitz, Philip D. Charles, Athina Soragia Gkazi, Eleni Adamopoulou, Waseem Qasim, Edward Graham Davies, Imelda Hanson, Alistair T. Pagnamenta, Carme Camps, Helene M. Dreau, Andrea White, Kieran James, Roman Fischer, Opher Gileadi, Jenny C. Taylor, Tudor Fulga, B. Christoffer Lagerholm, Graham Anderson, Erdinc Sezgin, Georg A. Hollaender
Summary: The transcription factor FOXN1 plays a crucial role in thymic epithelial cell development and function, with its expression being differentially regulated during organogenesis. It forms multimolecular nuclear condensates important for transcriptional activity, where the C-terminal sequence regulates diffusion velocity and binding to gene regulatory regions. Mutant FOXN1 with modified C-terminal sequence is transcriptionally inactive and acts as a dominant negative factor, causing athymia and severe lymphopenia. This gain-of-function mutant disrupts TEC differentiation in mice, showing gene dose dependency for specific TEC subtypes.
Article
Multidisciplinary Sciences
Adam E. Handel, Stanley Cheuk, Fatima Dhalla, Stefano Maio, Tania Huebscher, Ioanna Rota, Mary E. Deadman, Olov Ekwall, Matthias Lutolf, Kenneth Weinberg, Georg Hollaender
Summary: This study explores the complex composition and dynamic changes of the non-epithelial stromal compartment in the thymus, and reveals the heterogeneity of different stromal subtypes and their roles in thymus organogenesis and tissue maintenance.
Article
Multidisciplinary Sciences
Valentina Damato, Jakob Theorell, Adam Al-Diwani, Anne-Kathrin Kienzler, Mateusz Makuch, Bo Sun, Adam Handel, Deniz Akdeniz, Antonio Berretta, Sudarshini Ramanathan, Andrew Fower, Daniel Whittam, Emily Gibbons, Nicholas McGlashan, Edward Green, Saif Huda, Mark Woodhall, Jacqueline Palace, Fintan Sheerin, Patrick Waters, Maria Leite, Anu Jacob, Sarosh R. Irani
Summary: This study reveals the relationship between clinical relapses and germinal center activity in patients with neuromyelitis optica spectrum disorders (NMOSDs), and shows that rituximab can suppress germinal center activity and reduce the production of AQP4 antibodies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cardiac & Cardiovascular Systems
Martina Patone, Xue W. Mei, Lahiru Handunnetthi, Sharon Dixon, Francesco Zaccardi, Manu Shankar-Hari, Peter Watkinson, Kamlesh Khunti, Anthony Harnden, Carol A. C. Coupland, Keith M. Channon, Nicholas L. Mills, Aziz Sheikh, Julia Hippisley-Cox
Summary: Myocarditis is more common after SARS-CoV-2 infection than after COVID-19 vaccination. The risk of myocarditis is higher in younger men, especially after the second dose of mRNA-1273 vaccine.
Article
Cell Biology
Jimena Monzon-Sandoval, Elena Burlacu, Devika Agarwal, Adam E. Handel, Liting Wei, John Davis, Sally A. Cowley, M. Zameel Cader, Caleb Webber
Summary: This study investigated the relevance of different immune stimuli on the transcriptional response of iPSC-microglia, a model of Alzheimer's disease (AD). The results showed a shared core transcriptional response to ATP gamma S and LPS+IFN-gamma, indicating a convergent mechanism of action. However, there was directional inconsistency in the expression levels of genes related to these stimuli in human microglia from AD patients.
DISEASE MODELS & MECHANISMS
(2022)
Book Review
Neurosciences
Adam Handel
Article
Immunology
Edward Drydale, Phalguni Rath, Katie Holden, Gregory Holt, Laurissa Havins, Thomas Johnson, James Bancroft, Lahiru Handunnetthi
Summary: This study created a novel three-dimensional neurosphere assay using induced pluripotent stem cell differentiation and live cell imaging techniques to investigate the effect of a simulated viral infection on cortical development. The findings demonstrated that the infection led to reduced radial glial growth and neural migration.
BRAIN BEHAVIOR AND IMMUNITY
(2024)
Article
Immunology
Defne Saatci, Thomas Johnson, Madeleine Smee, Adrienne van Nieuwenhuizen, Lahiru Handunnetthi
Summary: This study found a higher number of schizophrenia births in December, January, and February. There was no association between latitude and daylight, but a significant negative correlation between monthly severe enterovirus cases and schizophrenia births.
BRAIN, BEHAVIOR, & IMMUNITY - HEALTH
(2022)
Article
Clinical Neurology
Adam Al-Diwani, Jakob Theorell, Valentina Damato, Joshua Bull, Nicholas McGlashan, Edward Green, Anne-Kathrin Kienzler, Ruby Harrison, Tasneem Hassanali, Leticia Campo, Molly Browne, Alistair Easton, Hooman Soleymani Majd, Keiko Tenaka, Raffaele Iorio, Russell C. Dale, Paul Harrison, John Geddes, Digby Quested, David Sharp, Soon-Tae Lee, David W. Nauen, Mateusz Makuch, Belinda Lennox, Darren Fowler, Fintan Sheerin, Patrick Waters, M. Isabel Leite, Adam E. Handel, Sarosh R. Irani
Summary: This study provides evidence that NR1-autoantibody production originates from active germinal centres in ovarian teratomas and cervical lymph nodes. These findings suggest the importance of studying immune activity in these anatomical locations.
Article
Clinical Neurology
Lahiru Handunnetthi, Defne Saatci, Joseph C. Hamley, Julian C. Knight
Summary: The study found that maternal immune activation mimicking viral infections can downregulate genes associated with schizophrenia, particularly those involved in neurodevelopment such as neuronal cell adhesion. These results provide insight into the interaction between genetic and environmental factors in schizophrenia pathogenesis.
BRAIN COMMUNICATIONS
(2021)
Review
Immunology
Piero Alberti, Adam E. Handel
Summary: This article investigates the relationship between thymic selection and the pathogenesis of central nervous system autoimmune diseases. Both animal models and clinical data suggest that thymic function plays a role in susceptibility to these diseases. However, a better understanding of this relationship is still needed.
SEMINARS IN IMMUNOPATHOLOGY
(2021)