Locus coeruleus pathology in progressive supranuclear palsy, and its relation to disease severity
Sanne Simone Kaalund, Luca Passamonti, Kieren S. J. Allinson, Alexander G. Murley, Trevor W. Robbins, Maria Grazia Spillantini and James B. Rowe
4 February 2020
Summary:
The locus coeruleus is the major source of noradrenaline to the brain and contributes to a wide range of physiological and cognitive functions. Neurodegeneration and pathological aggregation of tau protein in the locus coeruleus are early features of progressive supranuclear palsy (PSP). It is proposed to contribute to the clinical expression of the disease, including the PSP Richardson’s syndrome. Researchers investigated whether the tau and neuronal loss are associated with clinical heterogeneity and severity in PSP.
Publication: Sleepmedicine
Aviva Stafford, Sheri Oduola, Sarah Reeve
Published online 10 September 2024
Highlights
- Sleep is minimally documented in severe mental illness (SMI) patient records.
- Recommended sleep interventions (e.g., CBT-I) are rarely delivered in SMI settings.
- Further work is needed to improve sleep assessment and intervention in SMI settings.
- Targeting sleep in SMI patients could significantly improve symptoms and wellbeing.
Publication: Social Psychiatry and Psychiatric Epidemiology
Kaminska J, Hodgekins J, Lewis JR, Cardinal RN, Oduola S
09 September 2024
Summary
This study examined de-identified NHS data about people having a first episode of psychosis, and looked at how the psychosis began (abruptly or slowly), how long it went untreated, and factors including rural or urban residence. Among such people, some factors differed between rural and urban settings, e.g. employment and living with family. A slow onset of psychosis was associated with a longer time untreated, but rural/urban differences in “time untreated” were not found.
View publicationPublication: Nature Communications
Samantha Ip, Teri-Louise North, Fatemeh Torabi, Yangfan Li, Hoda Abbasizanjani, Ashley Akbari, Elsie Horne, Rachel Denholm, Spencer Keene, Spiros Denaxas, Amitava Banerjee, Kamlesh Khunti, Cathie Sudlow, William N. Whiteley, Jonathan A. C. Sterne, Angela M. Wood, Venexia Walker, the CVD-COVID-UK/COVID-IMPACT Consortium & the Longitudinal Health and Wellbeing COVID-19 National Core Study
31 July 2024
Summary
A new study has found heart attacks and strokes were lower after COVID-19 vaccination than before or without vaccination.
View publicationPublication: American Journal of Human Genetics
Thomas Vanderstichele, Katie L. Burnham, Niek de Klein, Michael Inouye, Dirk S. Paul, Emma E. Davenport et al
24 July 2024
Gene misexpression is the aberrant transcription of a gene in a context where it is usually inactive. Despite its known pathological consequences in specific rare diseases, we have a limited understanding of its wider prevalence and mechanisms in humans. To address this, we analyzed gene misexpression in 4,568 whole-blood bulk RNA sequencing samples from INTERVAL study blood donors.
We found that while individual misexpression events occur rarely, in aggregate they were found in almost all samples and a third of inactive protein-coding genes. Using 2,821 paired whole-genome and RNA sequencing samples, we identified that misexpression events are enriched in cis for rare structural variants. We established putative mechanisms through which a subset of SVs lead to gene misexpression, including transcriptional readthrough, transcript fusions, and gene inversion. Overall, we develop misexpression as a type of transcriptomic outlier analysis and extend our understanding of the variety of mechanisms by which genetic variants can influence gene expression.
View publicationPublication: eClinicaMedicine
Liz Yuanxi Lee j, Delshad Vaghari j, Michael C. Burkhart, Peter Tino, Marcella Montagnese, Zhuoyu Li,
Katharina Zühlsdorff, Joseph Giorgio, Guy Williams, Eddie Chong, Christopher Chen, Benjamin R. Underwood, Timothy Rittman, Zoe Kourtzi
12 July 2024
Summary
Cambridge researchers have developed an artificially-intelligent tool capable of predicting in four cases out of five whether people with early signs of dementia will remain stable or develop Alzheimer’s disease. Read the full press release.
View publicationPublication: BMC Medicine
Chen S, Underwood BR, Cardinal RN, Chen X, Chen S, Amin J, Jin H, Mueller C, Yan LL, Brayne C, Kuper H
26 June 2024
Summary
This was an analysis of pre-existing data from the English Longitudinal Study of Ageing, examining changes over time in risk factors for dementia that have the potential to be altered (such as hypertension, obesity, hearing loss, and social isolation).
View publicationPublication: Magnetic Resonance Materials in Physics, Biology and Medicine
Jonathan Birchall, Ines Horvat-Menih, Joshua Kaggie, Arnold Benjamin, Martin Graves, Ian Wilkinson, Ferdia Gallagher, Mary McLean
1 June 2024
Summary
We estimated the sodium content and relaxation of organs within the abdomen of healthy human volunteers using magnetic resonance imaging (MRI). Existing techniques for measuring sodium content are non-specific or require an invasive biopsy. Clinical translation of sodium content monitoring may aid in diagnosis of disease such as cancer, chronic kidney disease and hypertension at earlier stages, and more regular monitoring may help to evaluate efficacy of treatment.
View publicationPublication: BJPsych
London SR, Chen S, Sidhom E, Lewis JR, Wolverson E, Cardinal RN, Roalf D, Mueller C, Underwood BR
13 May 2024
Summary
People diagnosed with dementia are often diagnosed in memory clinics and then discharged back to their GP. Some later need intensive mental health support (e.g. crisis teams, or inpatient admission) but others do not. This study shows that it’s possible to predict who will and who won’t, with useful accuracy, based on information collected routinely at the time of initial diagnosis.
View publicationPublication: The Lancet regional health - Europe
Isaac Allen, Hend Hassan, Walburga Yvonne Joko-Fru, Catherine Huntley, Lucy Loong, Tameera Rahman, Bethany Torr, Andrew Bacon, Craig Knott, Sophie Jose, Sally Vernon, Margreet Lüchtenborg, Joanna Pethick, Katrina Lavelle, Fiona McRonald, Diana Eccles, Eva J.A Morris, Steven Hardy, Clare Turnbull,
Marc Tischkowitz, Paul Pharoah, Antonis C. Antoniou,
25 April 2024
Summary
Survivors of breast cancer are at significantly higher risk of developing second cancers, including endometrial and ovarian cancer for women and prostate cancer for men, according to new research studying data from almost 600,000 NHS England patients. Read the full news item.
View publicationPublication: BJPsych
Emilio Fernandez-Egea, Shanquan Chen, Estela Sangüesa, Patricia Gassó, Marjan Biria, James Plaistow, Isaac Jarratt-Barnham, Nuria Segarra, Sergi Mas, Maria-Pilar Ribate, Cristina B García, Naomi A Fineberg, Yulia Worbe, Rudolf N Cardinal, Trevor W Robbins
Summary
This study looked at a group of people treated with clozapine for schizophrenia, examining obsessive-compulsive symptoms (OCS). For some, genetic variants were examined. OCS were common in this group (37.9%). Analysis suggested that both psychosis and clozapine may drive aspects of OCS.
View publicationPublication: Nature Neuroscience
Richard Dear, Konrad Wagstyl, Jakob Seidlitz, Ross D. Markello, Aurina Arnatkevičiūtė, Kevin M. Anderson, Richard A. I. Bethlehem, Lifespan Brain Chart Consortium, Armin Raznahan, Edward T. Bullmore & Petra E. Vértes
22 April 2024
Summary
Human brain organization involves the coordinated expression of thousands of genes. For example, the first principal component (C1) of cortical transcription identifies a hierarchy from sensorimotor to association regions. In this study, optimized processing of the Allen Human Brain Atlas revealed two new components of cortical gene expression architecture, C2 and C3, which are distinctively enriched for neuronal, metabolic and immune processes, specific cell types and cytoarchitectonics, and genetic variants associated with intelligence. Using additional datasets (PsychENCODE, Allen Cell Atlas and BrainSpan), we found that C1–C3 represent generalizable transcriptional programs that are coordinated within cells and differentially phased during fetal and postnatal development.
View publicationPublication: PNAS
Sofia C. Orellana Richard A. I. Bethlehem, Ivan L. Simpson-Kent and Edward T. Bullmore
9 April 2024
Summary
A new study has found that childhood maltreatment can have an impact into adulthood because of how it effects an individual’s risk of poor physical health and traumatic experiences many years later
View publicationPublication: Nature Genetics
Yajie Zhao, Maria Chukanova, Katherine A. Kentistou, Zammy Fairhurst-Hunter, Anna Maria Siegert, Raina Y. Jia, Georgina K. C. Dowsett, Eugene J. Gardner, Katherine Lawler, Felix R. Day, Lena R. Kaisinger, Yi-Chun Loraine Tung, Brian Yee Hong Lam, Hsiao-Jou Cortina Chen, Quanli Wang, Jaime Berumen-Campos, Pablo Kuri-Morales, Roberto Tapia-Conyer, Jesus Alegre-Diaz, Inês Barroso, Jonathan Emberson, Jason M. Torres, Rory Collins, Danish Saleheen, Katherine R. Smith, Dirk S. Paul, Florian Merkle, I. Sadaf Farooqi, Nick J. Wareham, Slavé Petrovski, Stephen O’Rahilly, Ken K. Ong, Giles S. H. Yeo & John R. B. Perry
4 April 2024
Summary
A study has identified genetic variants in two genes that have some of the largest impacts on obesity risk discovered to date.
The discovery of rare variants in the genes BSN and APBA1 are some of the first obesity-related genes identified for which the increased risk of obesity is not observed until adulthood.
View publicationPublication: Nature aging
Yang Liu, Scott C. Ritchie, Shu Mei Teo, Matti O. Ruuskanen, Oleg Kambur, Qiyun Zhu, Jon Sanders, Yoshiki Vázquez-Baeza, Karin Verspoor, Pekka Jousilahti, Leo Lahti, Teemu Niiranen, Veikko Salomaa, Aki S. Havulinna, Rob Knight, Guillaume Méric & Michael Inouye
25 March 2024
Summary
Researchers have shown that risk scores based on our genes and gut bacteria can improve the prediction of diseases such as type 2 diabetes and prostate cancer over traditional risk factors alone.
View publicationPublication: Nature Communications
Genevieve I. Cezard, Rachel E. Denholm, Rochelle Knight, Yinghui Wei, Lucy Teece, Renin Toms, Harriet J. Forbes, Alex J. Walker, Louis Fisher, Jon Massey, Lisa E. M. Hopcroft, Elsie M. F. Horne, Kurt Taylor, Tom Palmer, Marwa Al Arab, Jose Ignacio Cuitun Coronado, Samantha H. Y. Ip, Simon Davy, Iain Dillingham, Sebastian Bacon, Amir Mehrkar, Caroline E. Morton, Felix Greaves, Catherine Hyams, George Davey Smith, John Macleod, Nishi Chaturvedi, Ben Goldacre, William N. Whiteley, Angela M. Wood, Jonathan A. C. Sterne & Venexia Walker On behalf of the Longitudinal Health and Wellbeing and Data and Connectivity UK COVID-19 National Core Studies, CONVALESCENCE study and the OpenSAFELY collaborative
11 March 2024
Summary
Researchers looked at cardiovascular diseases in different vaccination and variant eras using linked electronic health records for ~40% of the English population. They studied distinct groups: a ‘pre-vaccination’ cohort in the wild-type/Alpha variant eras and ‘vaccinated’ and ‘unvaccinated’ cohorts in the Delta variant era.
They showed that people with COVID-19 are more likely to develop cardiovascular diseases in the first 4 weeks after diagnosis compared to people without COVID-19. The effects can be long lasting. The excess risk of cardiovascular disease remains elevated up to 6 months after COVID-19 diagnosis but it reduces over time. People who had COVID-19 in the wild-type/Alpha variant eras (before vaccination became available to them) are at higher risk of cardiovascular events up to two years after COVID-19.
View publicationPublication: Pediatrics
Grace H. Kromm; Hilary Patankar; Shubang Nagalotimath; Hilary Wong, Topun Austin,
5 March 2024
Summary
Babies who suffer brain injury before, during or shortly after birth because of lack of oxygen to the brain may face longer-term socioemotional and psychological complications, research supported by the NIHR Cambridge BRC has shown. Read the news article.
View publicationPublication: Nature
L. Peruzzotti-Jametti, C. M. Willis, G. Krzak, R. Hamel, L. Pirvan, R.-B. Ionescu, J. A. Reisz, H. A. Prag, M. E. Garcia-Segura, V. Wu, Y. Xiang, B. Barlas, A. M. Casey, A. M. R. van den Bosch, A. M. Nicaise, L. Roth, G. R. Bates, H. Huang, P. Prasad, A. E. Vincent, C. Frezza, C. Viscomi, G. Balmus, Z. Takats, J. C. Marioni, A. D’Alessandro, M. P. Murphy, I. Mohorianu & S. Pluchino
13 March 2024
Summary
Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species.
View publicationPublication: Nature
Minna K. Karjalainen, Savita Karthikeyan, Clare Oliver-Williams, Eeva Sliz, Elias Allara, Wing Tung Fung, Praveen Surendran, Weihua Zhang, Pekka Jousilahti, Kati Kristiansson, Veikko Salomaa, Matt Goodwin, David A. Hughes, Michael Boehnke, Lilian Fernandes Silva, Xianyong Yin, Anubha Mahajan, Matt J. Neville, Natalie R. van Zuydam, Renée de Mutsert, Ruifang Li-Gao, Dennis O. Mook-Kanamori, Ayse Demirkan, Jun Liu, China Kadoorie Biobank Collaborative Group, Estonian Biobank Research Team, FinnGen, …Johannes Kettunen
6 March 2024
Summary
Genome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism. This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases. Researchers present a genome-wide association study for 233 circulating metabolic traits quantified by nuclear magnetic resonance spectroscopy in up to 136,016 participants from 33 cohorts.
View publicationPublication: JAC-Antimicrobial Resistance
Nick K Jones, Brian Tom, Constantinos Simillis, John Bennet, Stavros Gourgiotis, Jo Griffin, Helen Blaza, Shuaib Nasser, Stephen Baker, Theodore Gouliouris
16 February 2024
Summary
Being labelled as allergic to penicillin has been associated with an increase in the risk of infection after surgery in a number of studies in USA, Canada and France. This is thought to be due to the use of inferior antibiotic regimens for preventing infection at the time of surgery. We studied a large cohort of patients that had undergone gastrointestinal surgery at Addenbrooke’s Hospital to see if this observation could be generalised to a UK population, where the range of preventative antibiotic regimens in routine use differs significantly. We found no evidence of association between penicillin allergy labels and likelihood of surgical site infection in this cohort, suggesting significant international variation in the impact of penicillin allergy labels on patients.
View publicationPublication: The Lancet
Nurulamin M Noor, James C Lee, Simon Bond, Francis Dowling, Biljana Brezina, Kamal V Patel, Tariq Ahmad, Paul J Banim, James W Berrill, Rachel Cooney, Juan De La Revilla Negro, Shanika de Silva, Shahida Din, Dharmaraj Durai, John N Gordon, Prof Peter M Irving, Matthew Johnson, Alexandra J Kent, Klaartje B Kok, Prof Gordon W Moran, Craig Mowat, Pritash Patel, Prof Chris S Probert, Tim Raine, Rebecca Saich, Abigail Seward, Dan Sharpstone, Melissa A Smith, Sreedhar Subramanian, Sara S Upponi, Alan Wiles, Horace R T Williams, Prof Gijs R van den Brink, Prof Séverine Vermeire, Prof Vipul Jairath, Prof Geert R D’Haens, Prof Eoin F McKinney, Paul A Lyons, Prof James O Lindsay, Nicholas A Kennedy, Prof Kenneth G C Smith, Prof Miles Parkes,
22 February 24
Summary
A large-scale clinical trial of treatment strategies for Crohn’s disease has shown that offering early advanced therapy to all patients straight after diagnosis can drastically improve outcomes, including by reducing the number of people requiring urgent abdominal surgery for treatment of their disease by ten-fold. Read the full news story.
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