Suchergebnisse

This project was funded by DPUK through MRC (grant no. MR/L023784/2) and the UK Medical Research Council Award to the University of Oxford (grant no. MC_PC_17215). L.S is funded by the Virtual Brain Cloud from European comission (grant no. H2020-SC1-DTH-2018-1). C.R.B is funded by National Institutes of Health (NIH) research grant R01AG054628. S.R.C is funded by National Institutes of Health (NIH) research grant (R01AG054628), Medical Research Council (MR/R024065/1), Age UK and Economic and Social Research Council. R.E.M. was supported by Alzheimer's Research UK major project grant ARUKPG2017B-10. C.H was supported by an MRC Human Genetics Unit programme grant "Quantitative traits in health and disease" (U.MC_UU_00007/10). H.C.W received funding from Wellcome Trust. J.W is funded by TauRx pharmaceuticals Ltd and received Educational grant from Biogen paid to Alzheimer Scotland/Brain Health Scotland. G.W received GRAMPIAN UNIVERSITY HOSPITALS NHS TRUST, Scottish Government—Chief Scientist Office, ROLAND SUTTON ACADEMIC TRUST, Medical Research Scotland, Sutton Academic Trust and ROLAND SUTTON ACADEMIC TRUST. J.M.W received Wellcome Trust Strategic Award, MRC UK Dementia Research Institute and MRC project grants, Fondation Leducq, Stroke Association, British Heart Foundation, Alzheimer Society, and the European Union H2020 PHC-03-15 SVDs@Target grant (666881). D.S received MRC (MR/S010351/1), MRC (MR/W002388/1) and MRC (MR/W002566/1). A.M is supported by the Wellcome Trust (104036/Z/14/Z, 216767/Z/19/Z, 220857/Z/20/Z) and UKRI MRC (MC_PC_17209, MR/S035818/1). This work is part of a project that has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 847776. In addition, A.M has received grant support from The Sackler Trust, outside of the work presented. N.B received grant to institution from GSK as part of GSK/Oxford FxG initiative. A.N.H received John Black Charitable Fund-Rosetrees, H2020 funding from European Comission-Project Virtual Brain Cloud, AI for the Discovery of new therapies in Parkinson's (A2926), Rising Start Initiative—stage 2, Brain-Gut Microbiome (Call: PAR-18-296; Award ID: 1U19AG063744-01), Gut-liver-brain biochemical axis in Alzheimer's disease (5RF1AG057452-01), Virtual Brain Cloud (Call: H2020-SC1-DTH- 2018-1; Grant agreement ID: 826421). Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006) and is currently supported by the Wellcome Trust (216767/Z/19/Z). Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Edinburgh Clinical Research Facility, University of Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award "STratifying Resilience and Depression Longitudinally" [STRADL] Reference 104036/Z/14/Z). We are grateful to all the families who took part; the general practitioners and the Scottish School of Primary Care for their help in recruiting them; and the whole Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, health-care assistants, and nurses. ; Peer reviewed ; Publisher PDF

Around the world we are coming to realise what Indigenous and First Nations peoples have long known: the creative arts are crucially important for our health and wellbeing. Today we have extensive evidence for how, in hospitals, the arts can help patients cope with serious illness, use less pain medication, stay fewer days in hospital, and rehabilitate much faster; how creative activity is often key to healing from trauma and mental illness; how the arts offer us pathways to death and through grief; how they bring communities together, preventing illness and keeping those with dementia and chronic ill health active, involved and flourishing for as long as possible. The Institute for Creative Health (ICH) is a national peak advocacy organisation that works to give all Australians more access to the creative arts, to support their health. In 2013 the ICH assisted both the Federal and State Health and Arts Ministers to endorse The National Arts and Health Framework, which stated that the Arts contribute to the health and wellbeing of Australian individuals and communities. This provides an ongoing policy commitment to including the Arts as a core component in supporting and improving the health of all Australians. BACKGROUND The Waiting Room Words Project is the Arts and Health Leadership Group NSW/ACT's 2018 commitment to HAALP. It is our offering to the network of NSW Health and the Arts key contacts established by the NSW Health and the Arts Framework, to the Local Government Cultural Officers whose projects keep communities cohesive, to the doctors, nurses and allied health practitioners who include arts in wards and offices and clinics, to the patients and families and friends and carers and community who we serve. To further this momentum, the ICH designed the Health Arts Action Leadership Project (HAALP) 2017, which established Leadership Groups in Arts and Health in each state, who could undertake advocacy and lead efforts to consolidate principles and best practices in the sector. The University of Technology Sydney: Shopfront Community Program Graphic Design Students including Claudia Carroll, Daniel Giannone, Jessica Burdfield, Sylvia Zheng and Xinyue Wang Local Government Local Health Districts (LHD's) health and arts contact personnel, NSW Health Australia Council, Catalyst Grant The Institute for Creative Health Sydney Health Ethics, Sydney School of Public Health, University of Sydney The Making Space Conference, Belfast, Northern Ireland 2002 'Yes they said we would happy to be involved' And we are a little amazed, and touched, - if not a little grateful and inspired! We wish to acknowledge everyone who has been involved in this project. We have contributors from rural, remote, regional and inner city areas of NSW - from an inner city Men's Shed, Aboriginal and Torres Strait Islander art groups, an older women's drumming group, community individuals, a year 5 class from a Sydney Public School and the staff, university students and lecturers, readers groups, artists, arts facilitators and the people from all walks of life who put their hand up to be involved.

Neurofilament light chain (NfL) is an axonal protein that when measured in cerebrospinal fluid (CSF) serves as a biomarker of neurodegeneration. We aimed at investigating the association among CSF NfL, presence of Subjective Cognitive Decline (SCD) and hippocampal volume, and how CSF amyloid-β (Aβ) modifies these associations. We included 278 cognitively unimpaired participants from the Alfa+ cohort (78 SCD and 200 Controls). Linear models accounting for covariates (age, gender, and mood) were used to test the association between CSF NfL and SCD status, and between CSF NfL and bilateral hippocampal volumes. Interactions with Aβ were also explored. Individuals with SCD had higher CSF NfL and lower CSF Aβ42/40 than Controls. There was a significant interaction between SCD and CSF-Aβ42/40 levels. Stratified analyses showed a significant association between SCD and NfL only in Aβ+ individuals. Higher CSF NfL was significantly associated with lower hippocampal volume specifically in Aβ+ individuals with SCD. The presence of SCD in Aβ+ individuals may represent an early symptom in the Alzheimer's continuum related to incipient neurodegeneration. ; The research leading to these results has received funding from "la Caixa" Foundation (LCF/PR/GN17/1030 0 0 04) and the Alzheimer's Association and an international anonymous char ity foundation through the TriBEKa Imaging Platform project (TriBEKa-17-519007). Additional support has been received from the Universities and Research Secretariat, Ministry of Business and Knowledge of the Catalan Government under the grant no. 2017-SGR-892. MS-C received funding from the European Union's Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie action grant agreement No 752310, and currently receives funding from the Spanish Ministry of Science, Innovation and Universities (Juan de la Cierva Programme grant IJC2018-037478-I ). EMA-U is supported by the Spanish Ministry of Science, Innovation and Universities - Spanish State Research Agency ( RYC2018-026053-I ) and is recipient of the Alzheimer's Association Research Grant ( AARC 2019-AARG 6 446 41). OG-R is supported by the Spanish Ministry of Science, Innovation and Universities ( FJCI-2017-33437 ). JDG holds a 'Ramón y Cajal' fellowship ( RYC-2013-13054 ). NV-T is funded by a post-doctoral grant, Juan de la Cierva Programme ( FJC2018-038085-I ), Ministry of Science and Innovation–Spanish State Research Agency. ASV is the recipient of an Instituto de Salud Carlos III Miguel Servet II fellowship ( CP II 17/0 0 029 ). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (# 2018-02532 ), the European Research Council (# 681712 ), Swedish State Support for Clinical Research (# ALFGBG-720931 ), the Alzheimer Drug Discovery Foundation (ADDF), USA (# 201809-2016862 ), and the UK Dementia Research Institute at UCL. KB is supported by the Alzheimer Drug Discovery Foundation (ADDF), USA (# RDAPB-201809-2016615 ), the Swedish Alzheimer Foundation (# AF-742881 ), Hjärnfonden, Sweden (# FO2017-0243 ), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (# ALFGBG-715986 ), and European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236 )

Inklusion hat immer auch eine räumliche Komponente - doch wie vollzieht sie sich und in welcher Abhängigkeit stehen dabei Raum und (Nicht-)Teilhabe? Diese Fragen sind der Ausgangspunkt (des Buches), die qualitative und quantitative Szenarien beschreiben, anhand derer Praxen von Ausschluss und vor allem Inklusionspotenziale offengelegt werden. Diese Betrachtungen nehmen sie im Anschluss an raumtheoretische Überlegungen vor, die Raum als relationalen Vollzugsort von Teilhabe entfalten. Im Ergebnis zeigt sich, dass Teilhabe je situativ in der Auseinandersetzung mit vielfältig bestehenden Barrieren ausgehandelt wird - und es vielfältiges Potenzial gibt, bislang ausgeschlossenen Personen Teilhabemöglichkeiten zu eröffnen.

Keynote address: Revaluing the orbital prefrontal cortex / R.J. Dolan -- Specialized elements of orbitofrontal cortex in primates / H. Barbas -- The orbitofrontal cortex: Novelty, deviation from expectation, and memory / M. Petrides -- Definition of the orbital cortex in relation to specific connections with limbic and visceral structures and other cortical regions / J.L. Price -- Role of orbitofrontal cortex connections in emotion / N.L. Rempel-Clower -- Perspectives on olfactory processing, conscious perception, and orbitofrontal cortex / G.M. Shepherd -- What can an orbitofrontal cortex-endowed animal do with smells? / J.A. Gottfried -- Taste in the medial orbitofrontal cortex of the macaque / T.C. Pritchard, G.J. Schwartz, T.R. Scott. -- The role of the human orbitofrontal cortex in taste and flavor processing / D.M. Small ... [et al.] -- The role of the orbitofrontal cortex in sensory-specific encoding of associations in Pavlovian and instrumental conditioning / A.R. Delamater -- The contribution of orbitofrontal cortex to action selection / S.B. Ostlund, B.W. Balleine -- Neural encoding in the orbitofrontal cortex related to goal-directed behavior / T. Furuyashiki, M. Gallagher -- Interactions between the orbitofrontal cortex and the hippocampal memory system during the storage of long-term memory / S.J. Ramus ... [et al.] -- Orbitofrontal cortex and the computation of economic value / C. Padoa-Schioppa -- Lights, camembert, action! The role of human orbitofrontal cortex in encoding stimuli, rewards, and choices / J.P. O'Doherty -- Orbitofrontal cortex and amygdala contributions to affect and action in primates / E.A. Murray, A. Izquierdo -- Synergistic and regulatory effects of orbitofrontal cortex on amygdala-dependent appetitive behavior / A.C. Roberts, K. Reekie, K. Braesicle -- Reconciling the roles of orbitofrontal cortex in reversal learning and the encoding of outcome expectancies / G. Schoenbaum ... [et al.] -- Flexible neural representations of value in the primate brain / C.D. Salzman ... [et al.] -- The contribution of the medial prefrontal cortex, orbitofrontal cortex, and dorsomedial striatum to behavioral flexibility / M.E. Ragozzino -- A comparison of reward-contingent neuronal activity in monkey orbitofrontal cortex and ventral striatum. Guiding actions toward rewards / J.M. Simmons ... [et al.] -- Orbital versus dorsolateral prefrontal cortex. Anatomical insights into content versus process differentiation models of the prefrontal cortex / D.H. Zald -- Difficulty overcoming learned non-reward during reversal learning in rats with ibotenic acid lesions of orbital prefrontal cortex / D.S. Tait, V.J. Brown -- The role of orbitofrontal cortex in decision making. A component process account / L.K. Fellows -- Neuronal activity related to anticipated reward in frontal cortex. Does it represent value or reflect motivation? / M.R. Roesch, C.R. Olson -- Neuronal mechanisms in prefrontal cortex underlying adaptive choice behavior / J.D. Wallis -- Dysfunctions of medial and lateral orbitofrontal cortex in psychopathy / R.J.R. Blair -- The orbitofrontal cortex, real-world decision making, and normal aging / N.L. Denburg ... [et al.] -- Orbitofrontal cortex function and structure in depression / W.C. Drevets -- Symptoms of frontotemporal dementia provide insights into orbitofrontal cortex function and social behavior / I.V. Viskontas, K.L. Possin, B.L. Miller -- The role of the orbitofrontal cortex in anxiety disorders / M.R. Milad, S.L. Rauch -- Vulnerability of the orbitofrontal cortex to age-associated structural and functional brain changes / S.M. Resnick ... [et al.] -- The orbital prefrontal cortex and drug addiction in laboratory animals and humans / B.J. Everitt ... [et al.] -- Neural correlates of inflexible behavior in the orbitofrontal-amygdalar circuit after cocaine exposure / T.A. Stalnaker ... [et al.] -- Orbitofrontal cortex and cognitive-motivational impairments in psychostimulant addiction. Evidence from experiments in the non-human primate / P. Olausson ... [et al.] -- The orbitofrontal cortex, impulsivity, and addiction. Probing orbitofrontal dysfunction at the neural, neurochemical, and molecular level / C.A. Winstanley

AR is supported by the Swedish Research Council (#2019-01035); the Swedish state under the agreement between the Swedish government and the country councils, the ALF-agreement (#ALFGBG-717541); and King Gustaf V's 80-year foundation (#FAI-2019-0603). MS is supported by the Gothenburg Society of Medicine (#GLS-935039). DN is supported by The Academy of Finland, Finska Läkaresällskapet, and Institutional grant of Helsinki University Hospital. KB is supported by the Swedish Research Council (#2017-00915); the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB-201809-2016615); the Swedish Alzheimer Foundation (#AF-742881); Hjärnfonden, Sweden (#FO2017-0243); the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986); the European Union Joint Program for Neurodegenerative Disorders (#JPND2019-466-236); and the National Institute of Health (NIH), USA (grant #1R01AG068398-01). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532); the European Research Council (#681712); Swedish State Support for Clinical Research (#ALFGBG-720931); the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862); the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C, and #ADSF-21-831377-C); the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019-0228); and the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE) and the UK Dementia Research Institute at UCL. Open access funding is provided by the Gothenburg University library. Publisher Copyright: © 2021, The Author(s). ; Background: The type I interferon (IFN) gene signature is present in a subgroup of patients with early rheumatoid arthritis (RA). Protein levels of IFNα have not been measured in RA and it is unknown whether they associate with clinical characteristics or treatment effect. Methods: Patients with early untreated RA (n = 347) were randomized to methotrexate combined with prednisone, certolizumab-pegol, abatacept, or tocilizumab. Plasma IFNα protein levels were determined by single molecular array (Simoa) before and 24 weeks after treatment initiation and were related to demographic and clinical factors including clinical disease activity index, disease activity score in 28 joints, swollen and tender joint counts, and patient global assessment. Results: IFNα protein positivity was found in 26% of the patients, and of these, 92% were double-positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). IFNα protein levels were reduced 24 weeks after treatment initiation, and the absolute change was similar irrespective of treatment. IFNα protein positivity was associated neither with disease activity nor with achievement of CDAI remission 24 weeks after randomization. Conclusion: IFNα protein positivity is present in a subgroup of patients with early RA and associates with double-positivity for autoantibodies but not with disease activity. Pre-treatment IFNα positivity did not predict remission in any of the treatment arms, suggesting that the IFNα system is distinct from the pathways of TNF, IL-6, and T-cell activation in early RA. A spin-off study of the NORD-STAR randomized clinical trial, NCT01491815 (ClinicalTrials), registered 12/08/2011, https://clinicaltrials.gov/ct2/show/NCT01491815. ; Peer reviewed

In recent years, it has become accepted that α-synuclein (αSyn) has a key role in the microglia-mediated neuroinflammation, which accompanies the development of Parkinson's disease and other related disorders, such as Dementia with Lewy Bodies and Alzheimer's disease. Nevertheless, the cellular and molecular mechanisms underlying its pathological actions, especially in the sporadic forms of the diseases, are not completely understood. Intriguingly, several epidemiological and animal model studies have revealed a link between certain microbial infections and the onset or progression of sporadic forms of these neurodegenerative disorders. In this work, we have characterized the effect of toll-like receptor (TLR) stimulation on primary murine microglial cultures and analysed the impact of priming cells with extracellular wild-type (Wt) αSyn on the subsequent TLR stimulation of cells with a set of TLR ligands. By assaying key interleukins and chemokines we report that specific stimuli, in particular Pam3Csk4 (Pam3) and single-stranded RNA40 (ssRNA), can differentially affect the TLR2/1- and TLR7-mediated responses of microglia when pre-conditioned with αSyn by augmenting IL-6, MCP-1/CCL2 or IP-10/CXCL10 secretion levels. Furthermore, we report a skewing of αSyn-primed microglia stimulated with ssRNA (TLR7) or Pam3 (TLR2/1) towards intermediate but at the same time differential, M1/M2 phenotypes. Finally, we show that the levels and intracellular location of activated caspase-3 protein change significantly in αSyn-primed microglia after stimulation with these particular TLR agonists. Overall, we report a remarkable impact of non-aggregated αSyn pre-sensitization of microglia on TLR-mediated immunity, a phenomenon that could contribute to triggering the onset of sporadic α-synuclein-related neuropathologies. Figures 123 Citation: Roodveldt C, Labrador-Garrido A, Gonzalez-Rey E, Lachaud CC, Guilliams T, et al. (2013) Preconditioning of Microglia by α-Synuclein Strongly Affects the Response Induced by Toll-like Receptor (TLR) Stimulation. PLoS ONE 8(11): e79160. doi:10.1371/journal.pone.0079160 Editor: Nick Gay, University of Cambridge, United Kingdom Received: June 18, 2013; Accepted: September 18, 2013; Published: November 13, 2013 Copyright: © 2013 Roodveldt et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Financial support was provided by the Spanish Ministry of Science and Innovation-Carlos III Institute of Health according to the 'Plan Nacional de I+D+i 2008-2011' (PS09-2252 to DP, and CP10/00527 to CR) with co-funding by FEDER funds, the Andalusian Ministry of Health (PI-2010-0824 to DP), Economy, Science and Innovation (P10-CTS-6928 and P11-CTS-8161 to DP) and the PAIDI Program from the Andalusian Government (CTS-677 to DP). ALG holds a FPU Predoctoral Fellowship from the Spanish Ministry of Education (AP-2009/3816). The work of CMD is supported by the Wellcome Trust and the UK Medical and Biotechnological and Biological Sciences Research Council. TG is supported by Parkinson's UK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. ; Peer reviewed

IMPORTANCE: Oxidative stress and vascular impairment are believed to partly mediate age-related cognitive decline, a strong risk factor for development of dementia. Epidemiologic studies suggest that a Mediterranean diet, an antioxidant-rich cardioprotective dietary pattern, delays cognitive decline, but clinical trial evidence is lacking. OBJECTIVE: To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet. DESIGN, SETTING, AND PARTICIPANTS: Parallel-group randomized clinical trial of 447 cognitively healthy volunteers from Barcelona, Spain (233 women [52.1%]; mean age, 66.9 years), at high cardiovascular risk were enrolled into the Prevención con Dieta Mediterránea nutrition intervention trial from October 1, 2003, through December 31, 2009. All patients underwent neuropsychological assessment at inclusion and were offered retesting at the end of the study. INTERVENTIONS: Participants were randomly assigned to a Mediterranean diet supplemented with extravirgin olive oil (1 L/wk), a Mediterranean diet supplemented with mixed nuts (30 g/d), or a control diet (advice to reduce dietary fat). MAIN OUTCOMES AND MEASURES: Rates of cognitive change over time based on a neuropsychological test battery: Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT), Animals Semantic Fluency, Digit Span subtest from the Wechsler Adult Intelligence Scale, Verbal Paired Associates from the Wechsler Memory Scale, and the Color Trail Test. We used mean z scores of change in each test to construct 3 cognitive composites: memory, frontal (attention and executive function), and global. RESULTS: Follow-up cognitive tests were available in 334 participants after intervention (median, 4.1 years). In multivariate analyses adjusted for confounders, participants allocated to a Mediterranean diet plus olive oil scored better on the RAVLT (P = .049) and Color Trail Test part 2 (P = .04) compared with controls; no between-group differences were observed for the other cognitive tests. Similarly adjusted cognitive composites (mean z scores with 95% CIs) for changes above baseline of the memory composite were 0.04 (-0.09 to 0.18) for the Mediterranean diet plus olive oil, 0.09 (-0.05 to 0.23; P = .04 vs controls) for the Mediterranean diet plus nuts, and -0.17 (-0.32 to -0.01) for the control diet. Respective changes from baseline of the frontal cognition composite were 0.23 (0.03 to 0.43; P = .003 vs controls), 0.03 (-0.25 to 0.31), and -0.33 (-0.57 to -0.09). Changes from baseline of the global cognition composite were 0.05 (-0.11 to 0.21; P = .005 vs controls) for the Mediterranean diet plus olive oil, -0.05 (-0.27 to 0.18) for the Mediterranean diet plus nuts, and -0.38 (-0.57 to -0.18) for the control diet. All cognitive composites significantly (P < .05) decreased from baseline in controls. CONCLUSIONS AND RELEVANCE: In an older population, a Mediterranean diet supplemented with olive oil or nuts is associated with improved cognitive function. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN35739639. ; The PREDIMED trial was supported by the official funding agency for biomedical research of the Spanish government, Instituto de Salud Carlos III, through grants provided to research networks specifically developed for the trial: RTICG03/140 (Dr Estruch, principal investigator), RTICRD06/0045 (Dr Martínez-González, principal investigator), and Ciber Fisiopatología de la Obesidad y Nutrición (a network of biomedical research groups; DrsCorella, Martínez-González, Fitó, Salas-Salvadó, Estruch, and Ros, principal investigators).

Background and scope of reviewVarying severities and frequencies of head trauma may result in dynamic acute and chronic pathophysiologic responses in the brain. Heightened attention to long-term effects of head trauma, particularly repetitive head trauma, has sparked recent efforts to identify neuroimaging biomarkers of underlying disease processes. Imaging modalities like structural magnetic resonance imaging (MRI) and positron emission tomography (PET) are the most clinically applicable given their use in neurodegenerative disease diagnosis and differentiation. In recent years, researchers have targeted repetitive head trauma cohorts in hopes of identifying in vivo biomarkers for underlying biologic changes that might ultimately improve diagnosis of chronic traumatic encephalopathy (CTE) in living persons. These populations most often include collision sport athletes (e.g., American football, boxing) and military veterans with repetitive low-level blast exposure. We provide a clinically-oriented review of neuroimaging data from repetitive head trauma cohorts based on structural MRI, FDG-PET, Aβ-PET, and tau-PET. We supplement the review with two patient reports of neuropathology-confirmed, clinically impaired adults with prior repetitive head trauma who underwent structural MRI, FDG-PET, Aβ-PET, and tau-PET in addition to comprehensive clinical examinations before death.Review conclusionsGroup-level comparisons to controls without known head trauma have revealed inconsistent regional volume differences, with possible propensity for medial temporal, limbic, and subcortical (thalamus, corpus callosum) structures. Greater frequency and severity (i.e., length) of cavum septum pellucidum (CSP) is observed in repetitive head trauma cohorts compared to unexposed controls. It remains unclear whether CSP predicts a particular neurodegenerative process, but CSP presence should increase suspicion that clinical impairment is at least partly attributable to the individual's head trauma exposure (regardless of underlying disease). PET imaging similarly has not revealed a prototypical metabolic or molecular pattern associated with repetitive head trauma or predictive of CTE based on the most widely studied radiotracers. Given the range of clinical syndromes and neurodegenerative pathologies observed in a subset of adults with prior repetitive head trauma, structural MRI and PET imaging may still be useful for differential diagnosis (e.g., assessing suspected Alzheimer's disease).

Black Mental Health and the New Millennium: Historical and Current Perspective on Cultural Trauma and 'Everyday' Racism in White Mental Health Spaces -- The Impact on the Psychological Well-being of Black Mental Health Professionals; Richard Majors Chapter 1. Systemic Racism: Big, Black, Mad and Dangerous in the Criminal Justice System; Sharon Walker Chapter 2. In the name of our humanity: challenging academic racism and its effects on the emotional wellbeing of women of colour professors; Philomena Essed and Karen Carberry Chapter 3. Racial Battle Fatigue: The Long-Term Effects of Racial Microaggressions on African American Boys and Men; William Smith, R. David and G. Stanton Chapter 4. Racism in Academia: (How to) Stay Black, Sane and Proud as the doctoral supervisory relationship implodes; Sharon Walker Chapter 5. Implicit Provider Bias and its Implications for Black/African American Mental Health; Andra D Rivers Johnson Chapter 6. Thirty years of Black History Month and thirty years of overrepresentation in the mental health system; Patrick Vernon Chapter 7. Race and Risk -- exploring UK social policy and the development of modern mental health; Patricia Clarke Chapter 8. Remaining Mindful about Young People; Mhemooda Malek and Simon Newitt Chapter 9. Cultural competencies in delivering counselling and psychotherapy services to a black multi-cultural population: time for change and action; Nicholas Banks Chapter 10. Social and Emotional Education and Emotional Wellness: A Cultural Competence Model for Black Boys and Teachers; Richard Majors, Llewellyn E Simmons and Corneilus Ani Chapter 11. ASD & Cultural Competence: An ASD Multi-Cultural Treatment Led Model; Mary Henderson and Richard Majors Chapter 12. Moving Young Black Men Beyond Survival Mode: Protective Factors for Their Mental Health; Ivan Juzang Chapter 13. African Americans and the Vocational Rehabilitation Service System in the United States: The Impact on Mental Health; Fabricio E Balcazar and Julie Vryhof Chapter 14: Targeted Intervention in Education and the Empowerment and Emotional Well-Being of Black Boys; Cheron Byfield and Tony Talburt Chapter 15. Towards a position of Spiritual Reflexivity as a resource: Emerging themes and issues for systemic practice, leadership and supervision within Black mental health; Maureen Greaves Chapter 16. 'Marginal Leaders': Making Visible the Leadership Experiences of Black Women in a Therapeutic Service for Disenfranchised Young People; Romana Farooq and Tania Rodrigues Chapter 17. 40 Years in The Wilderness: A Review of Systemic Barriers to Reducing The Over-representation of Black Men in the UK Psychiatric System; Gail Coleman-Oluwabusola Chapter 18. Oppositional and Defiant Behaviours Among Black Boys in Schools: Techniques to Facilitate Change; Steve Clarke Chapter 19. Black Therapists -- White Families, therapists' perceptions of cultural competence in clinical practice; Karen Carberry and Belinda Brooks-Gordon Chapter 20. Transracial Adoption and Mental Health; Nicholas Banks Chapter 21. Dementia and its impact on minority ethnic and migrant communities; David Trusswell Chapter 22. Mental Health/Illness Revisited in People of African Caribbean Heritage in Britain; Tony Leiba and Gwen Rose Chapter 23. Researching African-Caribbean Mental Health in the UK: An Assets-based Approach to developing psychosocial interventions for schizophrenia and related psychoses; Dawn Edge, Amy Degan and Sonya Rafiq Chapter 24. 'Lone wolf' case study considerations of terrorist radicalisation from the black experience -- impact on mental health; Nicholas Banks Chapter 25. Spotlight on Sensory Processing Difficulties; Lisa Prior and Tiffany Howl Chapter 26. Forced Marriage as a Representation of a Belief System in the UK and its Psychological Impact on Well-being; Doreen Robinson and Reenee Singh Chapter 27. Systemic Family therapy with transgenerational communities in Haiti and the Dominican Republic; Karen Carberry, Gerald Jean Lafleur and Genel Jean-Claude Chapter 28. Engaging with racialized process in clinical supervision. Political or personal; Isha McKenzie-Mavinga .

Foreword to the second edition: the dire warning of mental health experts / Jeffrey D. Sachs -- Prologue to the second edition: professions and activism / Stephen Soldz and Bandy X. Lee -- Foreword to the first edition: our witness to malignant normality / Robert Jay Lifton -- Prologue to the first edition: professions and politics / Judith Lewis Herman and Bandy X. Lee. Introduction: our duty to warn and to protect / Bandy X. Lee. Part 1 The Trump phenomenon : Unbridled and extreme present hedonism: how the leader of the free world has proven time and again he is unfit for duty / Philip Zimbardo and Rosemary Sword -- Pathological narcissism and politics; a lethal mix / Craig Malkin -- I wrote "The Art of the Deal" with Donald Trump: his self-sabotage is rooted in his past / Tony Schwartz -- Trump's trust deficit is the core problem / Gail Sheehy -- Sociopathy / Lance Dodes -- Donald Trump is (A) bad, (B) mad, (C) all of the above / John D. Gartner -- Why "crazy like a fox" versus "crazy like a crazy" really matters: delusional disorder, admiration of brutal dictators, the nuclear codes, and Trump / Michael J. Tansey -- Cognitive impairment, dementia, and POTUS / David M. Reiss -- Donald J. Trump, alleged incapacitated person: mental incapacity, the electoral college, and the twenty-fifth amendment / James A. Herb. Part 2 The Trump dilemma : Should psychiatrists refrain from commenting on Trump's psychology / Leonard L. Glass -- On seeing what you see and saying what you know: a psychiatrist's responsibility / Henry J. Friedman -- The issue is dangerousness, not mental illness / James Gilligan -- A clinical case for the dangerousness of Donald J. Trump / Diane Jhueck -- Health, risk, and the duty to protect the community / Howard H. Covitz -- New opportunities for therapy in the age of Trump / William J. Doherty. Part 3 The Trump effect : Trauma, time, truth, and Trump: how a president freezes healing and promotes crisis / Betty P. Teng -- Trump anxiety disorder: the Trump effect on the mental health of half the nation and special populations / Jennifer Contarino Panning -- In relationship with an abusive president / Harper West -- Birtherism and the deployment of the Trumpian mind-set / Luba Kessler -- Trump's daddy issues: a toxic mix for America / Steve Wruble -- Trump and the American collective psyche / Thomas Singer -- Who goes Trump? Tyranny as a triumph of narcissism / Elizabeth Mika -- The loneliness of fateful decisions: social contexts and psychological vulnerability / Edwin B. Fisher -- He's got the world in his hands and his finger on the trigger: the twenty-fifth amendment solution / Nanette Gartrell and Dee Mosbacher. Part 4 Sociocultural consequences : Persistent enslavement systemic trauma: the deleterious impact of Trump's rhetoric on black and brown people / Kevin Washington -- Traumatic consequences for immigrant populations in the United States / Rosa Maria Bramble -- To Trump, some lives matter / Ellyn Uram Kaschak -- The charismatic leader-follower relationship and Trump's base / Jerrold M. Post. Part 5 Humanity's perpetuation and survival : The myth of nuclear war / James R. Merikangas, with Tarannum M. Lateef -- The age of Thanatos: environmental consequences of the Trump presidency / Lise Van Sustern and H. Steven Moffic -- The Goldwater rule and the silence of American psychiatry: a 2017 symposium / Nassir Ghaemi -- Is the Commander in Chief fit to serve? A nonpartisan test that marries U.S. Army leadership standards with psychoanalytic theory / Prudence Gourguechon -- Disordered minds: democracy as a defense against dangerous personalities / Ian Hughes -- Congress should establish an alternative body to assess the President / Norman Eisen and Richard Painter. Epilogue: reaching beyond the professions / Noam Chomsky, with Bandy X. Lee. Appendix: transcript of the Yale Conference (online).

Mild traumatic brain injury (mTBI)/ concussion accounts for 70-90% of all reported TBI cases in the United States and can cause long-term neurological outcomes that negatively impact quality of life. Previous studies revealed that increased blood-brain barrier (BBB) leakage is correlated with poor neurological outcomes after mTBI, yet the biological mechanisms linking BBB damage to the onset of neurological deficits after mTBI are not well understood. Previously, we found that astrocytes lose expression of homeostatic proteins after mTBI, characterizing the changes in astrocytic protein expression as an "atypical astrocyte response." Yet, the upstream mechanisms that induce this atypical astrocyte response after mTBI have yet to be elucidated. In models of more severe TBI, exposure to blood-borne factors triggers astrogliosis via upregulation in markers, such as glial fibrillary acidic protein (GFAP), but how exposure to blood-borne factors affects astrocyte protein expression in the context of mTBI is not well understood. Therefore, we hypothesized that mTBI-induced BBB damage causes atypical astrocytes via exposure to blood-borne factors. To test this hypothesis, we use a mTBI mouse model, two-photon microscopy, an endothelial cell-specific genetic ablation model, and serum-free primary astrocyte cultures. Here, we found that mTBI causes BBB damage through the loss of proteins involved in maintaining the BBB's physical and metabolic barriers, and BBB damage is sustained long-term after injury. Also, we demonstrated that leakage of blood-borne factors is sufficient to trigger atypical astrocytes, and plasma exposure triggers a similar response in vitro. Overall, these findings suggest that mTBI induces long-term BBB damage, and exposure to blood-borne factors triggers the loss of key homeostatic astrocytic proteins involved in maintaining healthy neuronal function. ; Doctor of Philosophy ; Mild traumatic brain injury (mTBI)/ concussion makes up 70-90% of all TBI cases reported in the United States and is commonly observed after car crashes, sports-related tackles, and blast exposure during military combat. People who experience mTBI develop debilitating long-term neurological consequences, such as sleep disturbances, depression, and dementia. Clinical data suggests mTBI causes damage to the barrier between the brain and blood, known as the blood-brain barrier (BBB). This damage has been correlated to the onset of poor neurological deficits, yet how damage to this barrier is causally linked to long-term neurological consequences remains to be fully understood. In our lab, we found that mTBI causes loss of proteins important for maintaining a healthy environment in the brain in specialized cells called astrocytes. However, the biological events that trigger the loss of protein expression in astrocytes after mTBI have yet to be fully investigated. Thus, we hypothesized that mTBI causes loss of these proteins via leakage of blood-borne factors. To test this hypothesis, we used a mTBI mouse model, two-photon microscopy, genetic manipulation, and cell cultures. In our studies, we found that mTBI triggers BBB damage via loss of proteins that make up its protective properties. Also, we demonstrated that leakage of blood-borne factors is sufficient to cause loss of astrocyte-specific proteins both in brain and cell cultures. Altogether, we show that a single mTBI is sufficient to cause loss of astrocyte-specific protein expression via exposure to blood-borne factors. These findings may point to targeting either the blood-borne factor(s) or their corresponding receptor pathways in astrocytes to halt the progression of long-term neurological deficits after mTBI.

Several psychiatric, neurologic and neurodegenerative disorders present increased brain ventricles volume, being hydrocephalus the disease with the major manifestation of ventriculomegaly caused by the accumulation of high amounts of cerebrospinal fluid (CSF). The molecules and pathomechanisms underlying cerebral ventricular enlargement are widely unknown. Kinase D interacting substrate of 220 kDa (KIDINS220) gene has been recently associated with schizophrenia and with a novel syndrome characterized by spastic paraplegia, intellectual disability, nystagmus and obesity (SINO syndrome), diseases frequently occurring with ventriculomegaly. Here we show that Kidins220, a transmembrane protein effector of various key neuronal signalling pathways, is a critical regulator of CSF homeostasis. We observe that both KIDINS220 and the water channel aquaporin-4 (AQP4) are markedly downregulated at the ventricular ependymal lining of idiopathic normal pressure hydrocephalus (iNPH) patients. We also find that Kidins220 deficient mice develop ventriculomegaly accompanied by water dyshomeostasis and loss of AQP4 in the brain ventricular ependymal layer and astrocytes. Kidins220 is a known cargo of the SNX27-retromer, a complex that redirects endocytosed plasma membrane proteins (cargos) back to the cell surface, thus avoiding their targeting to lysosomes for degradation. Mechanistically, we show that AQP4 is a novel cargo of the SNX27-retromer and that Kidins220 deficiency promotes a striking and unexpected downregulation of the SNX27-retromer that results in AQP4 lysosomal degradation. Accordingly, SNX27 silencing decreases AQP4 levels in wild-type astrocytes whereas SNX27 overexpression restores AQP4 content in Kidins220 deficient astrocytes. Together our data suggest that the KIDINS220-SNX27-retromer-AQP4 pathway is involved in human ventriculomegaly and open novel therapeutic perspectives. ; This work was supported by Spanish grants SAF2017-88885-R to TI and SAF2017-88881-R to MRC from the Spanish Ministerio de Economía y Competitividad/Agencia Estatal de Investigación/European Union Funds for Regional Development (MINECO/AEI/ FEDER, EU); by Comunidad de Madrid through the European Social Fund (ESF)-financed programme NEUROMETAB-CM (B2017/BMD-3700) to TI and AORTASANA-CM (B2017/BMD-3676) to MRC; by 'La Caixa' Banking Foundation project HR18-00068 to MRC; by Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED, Instituto de Salud Carlos III, Spain) CB06/05/1122 to TI and collaborative grant CIBERNED PI2018/06 to TI and IFa; by grant PID2019-104763RB-100 and Ramón y Cajal programme contract (RYC-2014-15991), both from MINECO/AEI/FEDER (EU) to EP; by Wellcome Trust Senior Investigator Award (107116/Z/15/Z), the European Union's Horizon 2020 Research and Innovation programme under grant agreement 739572 and a UK Dementia Research Institute Foundation award, all to GS; by grant PI19/00778 to AJJ from the Spanish Instituto de Salud Carlos III, co-funded by FEDER (EU); by Spanish grants from FEDER/Ministerio de Ciencia e Innovación (MICI)–AEI (SAF2017-86690-R), Network of Excellence iDIFFER (RED2018-102723-T), Instituto de Salud Carlos III (CIBERNED CB06/05/0086 and RETIC Tercel RD16/0011/0017) and Generalitat Valenciana (Prometeo 2017/030) to IFa. ADP was funded by a Juan de la Cierva Formación programme contract (FJCI-2014-19673; MINECO) and CIBERNED; JP-U was contracted by SAF2017-88885-R grant; AS-S was contracted by grants CIBERNED-PI2015-2/06 and PI2018/06, and SAF2017-88885-R; AS-G was funded by a contract from B2017/BMD-3700 grant and LSMP by a PhD training contract (PRE2018-086989) associated to grant SAF2017-88885-R.

Background: Concerns regarding potential neurological complications of COVID-19 are being increasingly reported, primarily in small series. Larger studies have been limited by both geography and specialty. Comprehensive characterisation of clinical syndromes is crucial to allow rational selection and evaluation of potential therapies. The aim of this study was to investigate the breadth of complications of COVID-19 across the UK that affected the brain. Methods: During the exponential phase of the pandemic, we developed an online network of secure rapid-response case report notification portals across the spectrum of major UK neuroscience bodies, comprising the Association of British Neurologists (ABN), the British Association of Stroke Physicians (BASP), and the Royal College of Psychiatrists (RCPsych), and representing neurology, stroke, psychiatry, and intensive care. Broad clinical syndromes associated with COVID-19 were classified as a cerebrovascular event (defined as an acute ischaemic, haemorrhagic, or thrombotic vascular event involving the brain parenchyma or subarachnoid space), altered mental status (defined as an acute alteration in personality, behaviour, cognition, or consciousness), peripheral neurology (defined as involving nerve roots, peripheral nerves, neuromuscular junction, or muscle), or other (with free text boxes for those not meeting these syndromic presentations). Physicians were encouraged to report cases prospectively and we permitted recent cases to be notified retrospectively when assigned a confirmed date of admission or initial clinical assessment, allowing identification of cases that occurred before notification portals were available. Data collected were compared with the geographical, demographic, and temporal presentation of overall cases of COVID-19 as reported by UK Government public health bodies. Findings: The ABN portal was launched on April 2, 2020, the BASP portal on April 3, 2020, and the RCPsych portal on April 21, 2020. Data lock for this report was on April 26, 2020. During this period, the platforms received notification of 153 unique cases that met the clinical case definitions by clinicians in the UK, with an exponential growth in reported cases that was similar to overall COVID-19 data from UK Government public health bodies. Median patient age was 71 years (range 23–94; IQR 58–79). Complete clinical datasets were available for 125 (82%) of 153 patients. 77 (62%) of 125 patients presented with a cerebrovascular event, of whom 57 (74%) had an ischaemic stroke, nine (12%) an intracerebral haemorrhage, and one (1%) CNS vasculitis. 39 (31%) of 125 patients presented with altered mental status, comprising nine (23%) patients with unspecified encephalopathy and seven (18%) patients with encephalitis. The remaining 23 (59%) patients with altered mental status fulfilled the clinical case definitions for psychiatric diagnoses as classified by the notifying psychiatrist or neuropsychiatrist, and 21 (92%) of these were new diagnoses. Ten (43%) of 23 patients with neuropsychiatric disorders had new-onset psychosis, six (26%) had a neurocognitive (dementia-like) syndrome, and four (17%) had an affective disorder. 18 (49%) of 37 patients with altered mental status were younger than 60 years and 19 (51%) were older than 60 years, whereas 13 (18%) of 74 patients with cerebrovascular events were younger than 60 years versus 61 (82%) patients older than 60 years. Interpretation: To our knowledge, this is the first nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID-19. Altered mental status was the second most common presentation, comprising encephalopathy or encephalitis and primary psychiatric diagnoses, often occurring in younger patients. This study provides valuable and timely data that are urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy. Funding: None.

Background: To effectively prevent, detect, and treat health conditions that affect people during their lifecourse, health-care professionals and researchers need to know which sections of the population are susceptible to which health conditions and at which ages. Hence, we aimed to map the course of human health by identifying the 50 most common health conditions in each decade of life and estimating the median age at first diagnosis. Methods: We developed phenotyping algorithms and codelists for physical and mental health conditions that involve intensive use of health-care resources. Individuals older than 1 year were included in the study if their primary-care and hospital-admission records met research standards set by the Clinical Practice Research Datalink and they had been registered in a general practice in England contributing up-to-standard data for at least 1 year during the study period. We used linked records of individuals from the CALIBER platform to calculate the sex-standardised cumulative incidence for these conditions by 10-year age groups between April 1, 2010, and March 31, 2015. We also derived the median age at diagnosis and prevalence estimates stratified by age, sex, and ethnicity (black, white, south Asian) over the study period from the primary-care and secondary-care records of patients. Findings: We developed case definitions for 308 disease phenotypes. We used records of 2 784 138 patients for the calculation of cumulative incidence and of 3 872 451 patients for the calculation of period prevalence and median age at diagnosis of these conditions. Conditions that first gained prominence at key stages of life were: atopic conditions and infections that led to hospital admission in children (<10 years); acne and menstrual disorders in the teenage years (10-19 years); mental health conditions, obesity, and migraine in individuals aged 20-29 years; soft-tissue disorders and gastro-oesophageal reflux disease in individuals aged 30-39 years; dyslipidaemia, hypertension, and erectile dysfunction in individuals aged 40-59 years; cancer, osteoarthritis, benign prostatic hyperplasia, cataract, diverticular disease, type 2 diabetes, and deafness in individuals aged 60-79 years; and atrial fibrillation, dementia, acute and chronic kidney disease, heart failure, ischaemic heart disease, anaemia, and osteoporosis in individuals aged 80 years or older. Black or south-Asian individuals were diagnosed earlier than white individuals for 258 (84%) of the 308 conditions. Bone fractures and atopic conditions were recorded earlier in male individuals, whereas female individuals were diagnosed at younger ages with nutritional anaemias, tubulointerstitial nephritis, and urinary disorders. Interpretation: We have produced the first chronological map of human health with cumulative-incidence and period-prevalence estimates for multiple morbidities in parallel from birth to advanced age. This can guide clinicians, policy makers, and researchers on how to formulate differential diagnoses, allocate resources, and target research priorities on the basis of the knowledge of who gets which diseases when. We have published our phenotyping algorithms on the CALIBER open-access Portal which will facilitate future research by providing a curated list of reusable case definitions. Funding: Wellcome Trust, National Institute for Health Research, Medical Research Council, Arthritis Research UK, British Heart Foundation, Cancer Research UK, Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Department of Health and Social Care (England), Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), Economic and Social Research Council, Engineering and Physical Sciences Research Council, National Institute for Social Care and Health Research, and The Alan Turing Institute.