Differential expression in humans of the viral entry receptor ACE2 compared with the short deltaACE2 isoform lacking SARS-CoV-2 binding sites.

ACE2 is a membrane protein that regulates the cardiovascular system. Additionally, ACE2 acts as a receptor for host cell infection by human coronaviruses, including SARS-CoV-2 that emerged as the cause of the on-going COVID-19 pandemic and has brought unprecedented burden to economy and health. ACE2 binds the spike protein of SARS-CoV-2 with high affinity and shows little variation in amino acid sequence meaning natural resistance is rare. The discovery of a novel short ACE2 isoform (deltaACE2) provides evidence for inter-individual differences in SARS-CoV-2 susceptibility and severity, and likelihood of developing subsequent 'Long COVID'. Critically, deltaACE2 loses SARS-CoV-2 spike protein binding sites in the extracellular domain, and is predicted to confer reduced susceptibility to viral infection. We aimed to assess the differential expression of full-length ACE2 versus deltaACE2 in a panel of human tissues (kidney, heart, lung, and liver) that are implicated in COVID-19, and confirm ACE2 protein in these tissues. Using dual antibody staining, we show that deltaACE2 localises, and is enriched, in lung airway epithelia and bile duct epithelia in the liver. Finally, we also confirm that a fluorescently tagged SARS-CoV-2 spike protein monomer shows low binding at lung and bile duct epithelia where dACE2 is enriched.This research was funded in whole, or in part by: Wellcome Trust (WT107715/Z/15/Z, A.P.D., and J.J.M.); Wellcome Trust Programme in Metabolic and Cardiovascular Disease (203814/Z/16/A, T.L.W., D.N.), Wellcome Trust Major Award (208363/Z/17/Z) for Imaging Core (G.S.); British Heart Foundation (FS/17/61/33473 A.P.D., R.G.C.M; TG/18/4/33770, A.P.D., J.J.M.; FS/18/46/33663, S.S.). Cambridge Biomedical Research Centre Biomedical Resources Grant (University of Cambridge, Cardiovascular Theme, RG64226). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care

Increased incidence of glucose disorders during pregnancy is not explained by pre-pregnancy obesity in London, Canada

<p>Abstract</p> <p>Background</p> <p>The increasing incidence of impaired glucose tolerance (IGT), gestational diabetes (GDM) and type 2 diabetes (T2D) during pregnancy was hypothesized to be associated with increases in pre-pregnancy body mass index (BMI). The aims were to 1) determine the prevalence of IGT/GDM/T2 D over a 10 year period; 2) examine the relationship between maternal overweight/obesity and IGT/GDM/T2D; and 3) examine the extent to which maternal metabolic complications impact maternal and fetal pregnancy outcomes.</p> <p>Methods</p> <p>Data arose from a perinatal database which contains maternal characteristics and perinatal outcome for all singleton infants born in London, Canada between January 1, 2000 and December 31, 2009. Univariable and multivariable odds ratios (OR) were estimated using logistic regression with IGT/GDM/T2 D being the outcome of interest.</p> <p>Results</p> <p>A total of 36,597 women were included in the analyses. Population incidence of IGT, GDM and T2 D rose from 0.7%, 2.9% and 0.5% in 2000 to 1.2%, 4.2% and 0.9% in 2009. The univariable OR for IGT, GDM and T2 D were 1.65, 1.52 and 2.06, respectively, over the ten year period. After controlling for maternal age, parity and pre-pregnancy BMI the OR did not decrease. Although there was a positive relationship between pre-pregnancy BMI and prevalence of IGT/GDM/T2 D, this did not explain the time trends in the latter. Diagnosis of IGT/GDM/T2 D increased the risk of having an Apgar score <7 at 5 minutes, which was partially explained by gestational hypertension, high placental ratio, gestational age and large for gestational age babies.</p> <p>Conclusions</p> <p>We found a significant increase in the incidence of IGT/GDM/T2 D for the decade between 2000-2009 which was not explained by rising prevalence of maternal overweight/obesity.</p

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

Progressing from multidisciplinary to interdisciplinary restoration science: monitoring and applied studies on the Nisqually River Delta

Restoration science is often described as an ultimate test of ecological theory; assessing the value of restoration actions is challenged by difficulties in measuring complex interactions between restored physical processes and the response of biological resources. Yet, demonstrating the value of restoration is a key to sustaining future public investment, especially in light of uncertainty of future climate change effects. At the Nisqually River Delta, a restoration partnership between the U. S. Fish and Wildlife Service Nisqually National Wildlife Refuge (Refuge), the Nisqually Indian Tribe (Tribe), and Ducks Unlimited culminated in re-established tidal flow to 360 ha of historic floodplain and delta representing the largest estuarine restoration in the Pacific Northwest. Restoration of this large delta was expected to result in a substantial improvement in ecological functions and services in southern Puget Sound. The goal of our scientific team, led by the U. S. Geological Survey (USGS) for the project partners, was to assess the biophysical response to restoration. Science objectives were built into a monitoring framework to include hydrodynamics, geomorphology, sedimentation and nearshore processes with vegetation, invertebrate food resources, waterbird, and fisheries. Our science partners included the U. S. Geological Survey, Refuge, Tribe, non-governmental organizations, and universities representing several disciplines. Funding the science was challenging, since as with most wetland restoration projects, adequate funds are rarely included in costs. Instead, the managers and scientists worked together to raise funds through special funds and competitive grants including addressing climate change. With this funding model, a major challenge for the team was communicating and sustaining a vision to make separate multidisciplinary efforts into unified interdisciplinary science. Here, we use lessons learned from early results of the Nisqually River Delta restoration to discuss restoration science in planning processes, funding costs and approaches, monitoring versus applied studies, and advancing interdisciplinary findings from multidisciplinary efforts

The Comprehensive Post-Acute Stroke Services (COMPASS) study: design and methods for a cluster-randomized pragmatic trial

Background: Patients discharged home after stroke face significant challenges managing residual neurological deficits, secondary prevention, and pre-existing chronic conditions. Post-discharge care is often fragmented leading to increased healthcare costs, readmissions, and sub-optimal utilization of rehabilitation and community services. The COMprehensive Post-Acute Stroke Services (COMPASS) Study is an ongoing cluster-randomized pragmatic trial to assess the effectiveness of a comprehensive, evidence-based, post-acute care model on patient-centered outcomes. Methods: Forty-one hospitals in North Carolina were randomized (as 40 units) to either implement the COMPASS care model or continue their usual care. The recruitment goal is 6000 patients (3000 per arm). Hospital staff ascertain and enroll patients discharged home with a clinical diagnosis of stroke or transient ischemic attack. Patients discharged from intervention hospitals receive 2-day telephone follow-up; a comprehensive clinic visit within 2 weeks that includes a neurological evaluation, assessments of social and functional determinants of health, and an individualized COMPASS Care PlanTM integrated with a community-specific resource database; and additional follow-up calls at 30 and 60 days post-stroke discharge. This model is consistent with the Centers for Medicare and Medicaid Services transitional care management services provided by physicians or advanced practice providers with support from a nurse to conduct patient assessments and coordinate follow-up services. Patients discharged from usual care hospitals represent the control group and receive the standard of care in place at that hospital. Patient-centered outcomes are collected from telephone surveys administered at 90 days. The primary endpoint is patient-reported functional status as measured by the Stroke Impact Scale 16. Secondary outcomes are: caregiver strain, all-cause readmissions, mortality, healthcare utilization, and medication adherence. The study engages patients, caregivers, and other stakeholders (including policymakers, advocacy groups, payers, and local community coalitions) to advise and support the design, implementation, and sustainability of the COMPASS care model. Discussion: Given the high societal and economic burden of stroke, identifying a care model to improve recovery, independence, and quality of life is critical for stroke survivors and their caregivers. The pragmatic trial design provides a real-world assessment of the COMPASS care model effectiveness and will facilitate rapid implementation into clinical practice if successful

Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial.

BACKGROUND: Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. METHODS: In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. FINDINGS: Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). INTERPRETATION: Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use. FUNDING: Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research

Expert range maps of global mammal distributions harmonised to three taxonomic authorities

Aim: Comprehensive, global information on species' occurrences is an essential biodiversity variable and central to a range of applications in ecology, evolution, biogeography and conservation. Expert range maps often represent a species' only available distributional information and play an increasing role in conservation assessments and macroecology. We provide global range maps for the native ranges of all extant mammal species harmonised to the taxonomy of the Mammal Diversity Database (MDD) mobilised from two sources, the Handbook of the Mammals of the World (HMW) and the Illustrated Checklist of the Mammals of the World (CMW). Location: Global. Taxon: All extant mammal species. Methods: Range maps were digitally interpreted, georeferenced, error-checked and subsequently taxonomically aligned between the HMW (6253 species), the CMW (6431 species) and the MDD taxonomies (6362 species). Results: Range maps can be evaluated and visualised in an online map browser at Map of Life (mol.org) and accessed for individual or batch download for non-commercial use. Main conclusion: Expert maps of species' global distributions are limited in their spatial detail and temporal specificity, but form a useful basis for broad-scale characterizations and model-based integration with other data. We provide georeferenced range maps for the native ranges of all extant mammal species as shapefiles, with species-level metadata and source information packaged together in geodatabase format. Across the three taxonomic sources our maps entail, there are 1784 taxonomic name differences compared to the maps currently available on the IUCN Red List website. The expert maps provided here are harmonised to the MDD taxonomic authority and linked to a community of online tools that will enable transparent future updates and version control.Fil: Marsh, Charles J.. Yale University; Estados UnidosFil: Sica, Yanina. Yale University; Estados UnidosFil: Burguin, Connor. University of New Mexico; Estados UnidosFil: Dorman, Wendy A.. University of Yale; Estados UnidosFil: Anderson, Robert C.. University of Yale; Estados UnidosFil: del Toro Mijares, Isabel. University of Yale; Estados UnidosFil: Vigneron, Jessica G.. University of Yale; Estados UnidosFil: Barve, Vijay. University Of Florida. Florida Museum Of History; Estados UnidosFil: Dombrowik, Victoria L.. University of Yale; Estados UnidosFil: Duong, Michelle. University of Yale; Estados UnidosFil: Guralnick, Robert. University Of Florida. Florida Museum Of History; Estados UnidosFil: Hart, Julie A.. University of Yale; Estados UnidosFil: Maypole, J. Krish. University of Yale; Estados UnidosFil: McCall, Kira. University of Yale; Estados UnidosFil: Ranipeta, Ajay. University of Yale; Estados UnidosFil: Schuerkmann, Anna. University of Yale; Estados UnidosFil: Torselli, Michael A.. University of Yale; Estados UnidosFil: Lacher, Thomas. Texas A&M University; Estados UnidosFil: Wilson, Don E.. National Museum of Natural History; Estados UnidosFil: Abba, Agustin Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Estudios Parasitológicos y de Vectores. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Estudios Parasitológicos y de Vectores; ArgentinaFil: Aguirre, Luis F.. Universidad Mayor de San Simón; BoliviaFil: Arroyo Cabrales, Joaquín. Instituto Nacional de Antropología E Historia, Mexico; MéxicoFil: Astúa, Diego. Universidade Federal de Pernambuco; BrasilFil: Baker, Andrew M.. Queensland University of Technology; Australia. Queensland Museum; AustraliaFil: Braulik, Gill. University of St. Andrews; Reino UnidoFil: Braun, Janet K.. Oklahoma State University; Estados UnidosFil: Brito, Jorge. Instituto Nacional de Biodiversidad; EcuadorFil: Busher, Peter E.. Boston University; Estados UnidosFil: Burneo, Santiago F.. Pontificia Universidad Católica del Ecuador; EcuadorFil: Camacho, M. Alejandra. Pontificia Universidad Católica del Ecuador; EcuadorFil: de Almeida Chiquito, Elisandra. Universidade Federal do Espírito Santo; BrasilFil: Cook, Joseph A.. University of New Mexico; Estados UnidosFil: Cuéllar Soto, Erika. Sultan Qaboos University; OmánFil: Davenport, Tim R. B.. Wildlife Conservation Society; TanzaniaFil: Denys, Christiane. Muséum National d'Histoire Naturelle; FranciaFil: Dickman, Christopher R.. The University Of Sydney; AustraliaFil: Eldridge, Mark D. B.. Australian Museum; AustraliaFil: Fernandez Duque, Eduardo. University of Yale; Estados UnidosFil: Francis, Charles M.. Environment And Climate Change Canada; CanadáFil: Frankham, Greta. Australian Museum; AustraliaFil: Freitas, Thales. Universidade Federal do Rio Grande do Sul; BrasilFil: Friend, J. Anthony. Conservation And Attractions; AustraliaFil: Giannini, Norberto Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Gursky-Doyen, Sharon. Texas A&M University; Estados UnidosFil: Hackländer, Klaus. Universitat Fur Bodenkultur Wien; AustriaFil: Hawkins, Melissa. National Museum of Natural History; Estados UnidosFil: Helgen, Kristofer M.. Australian Museum; AustraliaFil: Heritage, Steven. University of Duke; Estados UnidosFil: Hinckley, Arlo. Consejo Superior de Investigaciones Científicas. Estación Biológica de Doñana; EspañaFil: Holden, Mary. American Museum of Natural History; Estados UnidosFil: Holekamp, Kay E.. Michigan State University; Estados UnidosFil: Humle, Tatyana. University Of Kent; Reino UnidoFil: Ibáñez Ulargui, Carlos. Consejo Superior de Investigaciones Científicas. Estación Biológica de Doñana; EspañaFil: Jackson, Stephen M.. Australian Museum; AustraliaFil: Janecka, Mary. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Jenkins, Paula. Natural History Museum; Reino UnidoFil: Juste, Javier. Consejo Superior de Investigaciones Científicas. Estación Biológica de Doñana; EspañaFil: Leite, Yuri L. R.. Universidade Federal do Espírito Santo; BrasilFil: Novaes, Roberto Leonan M.. Universidade Federal do Rio de Janeiro; BrasilFil: Lim, Burton K.. Royal Ontario Museum; CanadáFil: Maisels, Fiona G.. Wildlife Conservation Society; Estados UnidosFil: Mares, Michael A.. Oklahoma State University; Estados UnidosFil: Marsh, Helene. James Cook University; AustraliaFil: Mattioli, Stefano. Università degli Studi di Siena; ItaliaFil: Morton, F. Blake. University of Hull; Reino UnidoFil: Ojeda, Agustina Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; ArgentinaFil: Ordóñez Garza, Nicté. Instituto Nacional de Biodiversidad; EcuadorFil: Pardiñas, Ulises Francisco J.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Diversidad y Evolución Austral; ArgentinaFil: Pavan, Mariana. Universidade de Sao Paulo; BrasilFil: Riley, Erin P.. San Diego State University; Estados UnidosFil: Rubenstein, Daniel I.. University of Princeton; Estados UnidosFil: Ruelas, Dennisse. Museo de Historia Natural, Lima; PerúFil: Schai-Braun, Stéphanie. Universitat Fur Bodenkultur Wien; AustriaFil: Schank, Cody J.. University of Texas at Austin; Estados UnidosFil: Shenbrot, Georgy. Ben Gurion University of the Negev; IsraelFil: Solari, Sergio. Universidad de Antioquia; ColombiaFil: Superina, Mariella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Tsang, Susan. American Museum of Natural History; Estados UnidosFil: Van Cakenberghe, Victor. Universiteit Antwerp; BélgicaFil: Veron, Geraldine. Université Pierre et Marie Curie; FranciaFil: Wallis, Janette. Kasokwa-kityedo Forest Project; UgandaFil: Whittaker, Danielle. Michigan State University; Estados UnidosFil: Wells, Rod. Flinders University.; AustraliaFil: Wittemyer, George. State University of Colorado - Fort Collins; Estados UnidosFil: Woinarski, John. Charles Darwin University; AustraliaFil: Upham, Nathan S.. University of Yale; Estados UnidosFil: Jetz, Walter. University of Yale; Estados Unido

The dynamic cilium in human diseases

Cilia are specialized organelles protruding from the cell surface of almost all mammalian cells. They consist of a basal body, composed of two centrioles, and a protruding body, named the axoneme. Although the basic structure of all cilia is the same, numerous differences emerge in different cell types, suggesting diverse functions. In recent years many studies have elucidated the function of 9+0 primary cilia. The primary cilium acts as an antenna for the cell, and several important pathways such as Hedgehog, Wnt and planar cell polarity (PCP) are transduced through it. Many studies on animal models have revealed that during embryogenesis the primary cilium has an essential role in defining the correct patterning of the body. Cilia are composed of hundreds of proteins and the impairment or dysfunction of one protein alone can cause complete loss of cilia or the formation of abnormal cilia. Mutations in ciliary proteins cause ciliopathies which can affect many organs at different levels of severity and are characterized by a wide spectrum of phenotypes. Ciliary proteins can be mutated in more than one ciliopathy, suggesting an interaction between proteins. To date, little is known about the role of primary cilia in adult life and it is tempting to speculate about their role in the maintenance of adult organs. The state of the art in primary cilia studies reveals a very intricate role. Analysis of cilia-related pathways and of the different clinical phenotypes of ciliopathies helps to shed light on the function of these sophisticated organelles. The aim of this review is to evaluate the recent advances in cilia function and the molecular mechanisms at the basis of their activity

Smaller total and subregional cerebellar volumes in posttraumatic stress disorder:a mega-analysis by the ENIGMA-PGC PTSD workgroup

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p -FDR &lt; 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.</p

Smaller total and subregional cerebellar volumes in posttraumatic stress disorder:a mega-analysis by the ENIGMA-PGC PTSD workgroup

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p -FDR &lt; 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.</p