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Fu Y, Chen SJ, Wang ZB, Zhang DD, Gao PY, Ou YN, Feng JF, Cheng W, Tan L, Yu JT. Dietary inflammatory index and brain disorders: a Large Prospective Cohort study. Transl Psychiatry 2025; 15:99. [PMID: 40148290 PMCID: PMC11950238 DOI: 10.1038/s41398-025-03297-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Revised: 02/01/2025] [Accepted: 02/24/2025] [Indexed: 03/29/2025] Open
Abstract
There is emerging evidence that diet plays a key contributor to brain health, however, limited studies focused on the association of dietary inflammatory potential with brain disorders. This study aimed to examine the association of dietary inflammation with brain disorders in the UK biobank. The prospective cohort study used data from 2006 to 2010 from the UK Biobank, with the median follow-up duration for different outcomes ranging between 11.37 to 11.38. Dietary inflammatory index and Energy-adjusted dietary inflammatory index [DII and EDII] were assessed through plausible dietary recalls. Outcomes included brain disorders (all-cause dementia [ACD], Alzheimer's disease [AD], Parkinson's disease [PD], stroke, sleep disorder, anxiety and depression disorder) and brain magnetic resonance imaging measures. Cox proportional-hazard models, restricted cubic spline model [RCS], Ordinary least squares regressions, and structural equation models were used to estimate associations. Of 164,863 participants with available and plausible dietary recalls, 87,761 (53.2%) were female, the mean (SD) age was 58.97 (8.05) years, and the mean (SD) education years was 7.49 (2.97) years. Vegetables and fresh fruits show significant anti-inflammatory properties, while low-fiber bread and animal fats show pro-inflammatory properties. The nonlinear associations of DII and EDII scores with ACD, AD, sleep disorder, stroke, anxiety, and depression were observed. Multivariable-adjusted HRs for participants in highest DII score VS lowest DII score were 1.165 (95% CI 1.038-1.307) for ACD, 1.172 (95% CI 1.064-1.291) for sleep disorder, 1.110 (95% CI 1.029-1.197) for stroke, 1.184 (95% CI 1.111-1.261) for anxiety, and 1.136 (95% CI 1.057-1.221) for depression. Similar results were observed with regard to EDII score. Compared with the lowest EDII score group, the highest group showed a higher risk of anxiety, depression, sleep disorder, stroke and dementia. Results from sensitivity analyses and multivariable analyses were similar to the main results. Pro-inflammatory diets were associated with a higher risk of brain disorders. Our findings suggest a potential means of diet to lower risk of anxiety, depression, sleep disorder, stroke, and dementia.
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Affiliation(s)
- Yan Fu
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Si-Jia Chen
- Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhi-Bo Wang
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Dan-Dan Zhang
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Pei-Yang Gao
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Ya-Nan Ou
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Jian-Feng Feng
- Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China
- Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Ministry of Education, Shanghai, China
| | - Wei Cheng
- Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China
- Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Ministry of Education, Shanghai, China
| | - Lan Tan
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
| | - Jin-Tai Yu
- Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
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Bai L, Yu L, Ran M, Zhong X, Sun M, Xu M, Wang Y, Yan X, Lee RJ, Tang Y, Xie J. Harnessing the Potential of Exosomes in Therapeutic Interventions for Brain Disorders. Int J Mol Sci 2025; 26:2491. [PMID: 40141135 PMCID: PMC11942545 DOI: 10.3390/ijms26062491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Revised: 03/05/2025] [Accepted: 03/07/2025] [Indexed: 03/28/2025] Open
Abstract
Exosomes, which are nano-sized natural vesicles secreted by cells, are crucial for intercellular communication and interactions, playing a significant role in various physiological and pathological processes. Their characteristics, such as low toxicity and immunogenicity, high biocompatibility, and remarkable drug delivery capabilities-particularly their capacity to traverse the blood-brain barrier-make exosomes highly promising vehicles for drug administration in the treatment of brain disorders. This review provides a comprehensive overview of exosome biogenesis and isolation techniques, strategies for the drug loading and functionalization of exosomes, and exosome-mediated blood-brain barrier penetration mechanisms, with a particular emphasis on recent advances in exosome-based drug delivery for brain disorders. Finally, we address the opportunities and challenges associated with utilizing exosomes as a drug delivery system for the brain, summarizing the barriers to clinical translation and proposing future research directions.
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Affiliation(s)
- Lu Bai
- School of Pharmacy and Bioengineering, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
- Center for Nanomedicine and Gene Therapy, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
| | - Leijie Yu
- School of Pharmacy and Bioengineering, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
- Center for Nanomedicine and Gene Therapy, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
| | - Mengqiong Ran
- School of Pharmacy and Bioengineering, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
- Center for Nanomedicine and Gene Therapy, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
| | - Xing Zhong
- School of Pharmacy and Bioengineering, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
- Center for Nanomedicine and Gene Therapy, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
| | - Meng Sun
- School of Pharmacy and Bioengineering, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
- Center for Nanomedicine and Gene Therapy, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
| | - Minhao Xu
- School of Pharmacy and Bioengineering, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
- Center for Nanomedicine and Gene Therapy, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
| | - Yu Wang
- School of Pharmacy and Bioengineering, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
- Center for Nanomedicine and Gene Therapy, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
| | - Xinlei Yan
- School of Pharmacy and Bioengineering, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
- Center for Nanomedicine and Gene Therapy, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
| | - Robert J. Lee
- School of Pharmacy and Bioengineering, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
- Center for Nanomedicine and Gene Therapy, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
| | - Yaqin Tang
- School of Pharmacy and Bioengineering, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
- Center for Nanomedicine and Gene Therapy, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
| | - Jing Xie
- School of Pharmacy and Bioengineering, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
- Center for Nanomedicine and Gene Therapy, Chongqing University of Technology, 69 Hongguang Road, Chongqing 400054, China
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Fan W, Ma Q, Guan Q, Wang F, Li H. Forecasting the Worldwide Impact of Stroke for Individuals Aged 45 and Above. Neuroepidemiology 2024:1-13. [PMID: 39532081 DOI: 10.1159/000542366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 10/08/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND We aimed to assess the global impact of stroke in people aged 45 years and older between 1990 and 2030, focusing on morbidity, mortality, and disability-adjusted life years (DALYs). METHODS Generalized additive models were used to project disease burden from 2020 to 2030. Additionally, the association between sociodemographic index (SDI) and stroke burden was investigated, and regional differences were assessed by Mann-Whitney U test. RESULTS The overall age-standardized stroke incidence rate (ASIR) among adults aged 45 years and older is projected to increase from 2020 to 2030, with an estimated annual percentage change (EAPC) of 1.29. Conversely, the age-standardized death rate (ASDR) in EAPC is expected to decrease by -1.48, and the age-standardized DALY in EAPC is expected to decrease by -1.66. By 2030, men are expected to have higher ASIR (181.81) and ASDR (87.31) than women (ASIR: 151.85, ASDR: 65.20). Regional differences are large. East Asia is expected to have the highest ASIR in 2030 (265.55). Age estimates show that older age groups, particularly those aged 75-79, are at higher risk of stroke. In addition, there is a significant inverse relationship between SDI and stroke severity, with areas with higher SDI tending to have lower morbidity, mortality, and DALYs. CONCLUSION From 1990 to 2030, ASIR is expected to upgrade, especially in East Asia and regions with lower SDI. Men will bear a greater burden than women.
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Affiliation(s)
- Weinv Fan
- Department of Neurology, Ningbo No. 2 Hospital, Ningbo, China
| | - Qinghua Ma
- Department of Prevention and Health Care, The Third People's Hospital of Xiangcheng District in Suzhou, Suzhou, China
| | - Qiongfeng Guan
- Department of Neurology, Ningbo No. 2 Hospital, Ningbo, China
| | - Feng Wang
- Department of Health Promotion, Center for Disease Control and Prevention, Ningbo, China
| | - Hui Li
- Ningbo Municipal Center for Disease Control and Prevention, Ningbo, China
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Olesen J. From fragmentation to collaboration in European brain research: The early history of the European Brain Council (EBC), an organization that changed our perspective of advocacy. Eur J Neurol 2024; 31:e16130. [PMID: 37955553 PMCID: PMC11464389 DOI: 10.1111/ene.16130] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 10/02/2023] [Accepted: 10/19/2023] [Indexed: 11/14/2023]
Abstract
BACKGROUND The European Academy of Neurology (EAN) is a member of the European Brain Council (EBC), a coalition of neurologists, psychiatrists, neurosurgeons, neuroscientists, patient organizations and industry with an interest in the brain and its diseases. It was founded by the present author. Here, its formation, early history and the results of its advocacy are described. METHOD Eyewitness report and relevant literature were considered. RESULTS After a long and difficult inception, the European Brain Council (EBC) brought all major players with an interest in the brain and its diseases to work closely together. Important data on the cost of brain diseases, lack of funding and fantastic research possibilities were generated and effectively used in advocacy. During the early years of the collaborative effort, the funding of brain research increased from €85 million in framework program (FP) 5 to €260 million in FP6 and to more than €2000 million in FP7. CONCLUSION The EBC has been extremely successful. It is essential that advocacy in the European Union continues to be united so that those involved in brain research are able to speak with one voice to policy makers. An even bigger task, still insufficiently pursued, is for national brain councils to achieve prioritization of brain research in their national political agenda to bring about improved provision of care to those living with a brain disease.
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Affiliation(s)
- Jes Olesen
- Department of Neurology, Danish Headache CenterCopenhagen University HospitalGlostrupDenmark
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Goraya SA, Ding S, Arif MK, Kong H, Masud A. Effect of Circadian Rhythm Modulated Blood Flow on Nanoparticle based Targeted Drug Delivery in Virtual In Vivo Arterial Geometries. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.06.05.597680. [PMID: 38895445 PMCID: PMC11185639 DOI: 10.1101/2024.06.05.597680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/21/2024]
Abstract
Delivery of drug using nanocarriers tethered with vasculature-targeting epitopes aims to maximize the therapeutic efficacy of the drug while minimizing the drug side effects. Circadian rhythm which is governed by the central nervous system has implications for targeted drug delivery due to sleep-wake cycle changes in blood flow dynamics. This paper presents an advanced fluid dynamics modeling method that is based on viscous incompressible shear-rate fluid (blood) coupled with an advection-diffusion equation to simulate the formation of drug concentration gradients in the blood stream and buildup of concentration at the targeted site. The method is equipped with an experimentally calibrated nanoparticle-endothelial cell adhesion model that employs Robin boundary conditions to describe nanoparticle retention based on probability of adhesion, a friction model accounting for surface roughness of endothelial cell layer, and a dispersion model based on Taylor-Aris expression for effective diffusion in the boundary layer. The computational model is first experimentally validated and then tested on engineered bifurcating arterial systems where impedance boundary conditions are applied at the outflow to account for the downstream resistance at each outlet. It is then applied to a virtual geometric model of an in vivo arterial tree developed through MRI-based image processing techniques. These simulations highlight the potential of the computational model for drug transport, adhesion, and retention at multiple sites in virtual in vivo models. The model provides a virtual platform for exploring circadian rhythm modulated blood flow for targeted drug delivery while minimizing the in vivo experimentation. Statement of Significance A novel integration of nanoparticle-based drug delivery framework with shear-rate dependent blood flow model is presented. The framework is comprised of a unique combination of mechanics-based dispersion model, an asperity model for endothelium surface roughness, and a stochastic nanoparticle-endothelial cell adhesion model. Simulations of MRI based in vivo carotid artery system showcase the effects of vessel geometry on nanoparticle adhesion and retention at the targeted site. Vessel geometry and target site location impact nanoparticle adhesion; curved and bifurcating regions favor local accumulation of drug. It is also shown that aligning drug administration with circadian rhythm and sleep cycle can enhance the efficacy of drug delivery processes. These simulations highlight the potential of the computational modeling for exploring circadian rhythm modulated blood flow for targeted drug delivery while minimizing the in vivo experimentation.
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Affiliation(s)
- Shoaib A. Goraya
- Department of Civil and Environmental Engineering, University of Illinois Urbana–Champaign
| | - Shengzhe Ding
- Department of Chemical and Biomolecular Engineering, University of Illinois Urbana–Champaign
| | | | - Hyunjoon Kong
- Department of Chemical and Biomolecular Engineering, University of Illinois Urbana–Champaign
- Department of Biomedical and Translational Sciences, Carle Illinois College of Medicine, University of Illinois Urbana–Champaign
| | - Arif Masud
- Department of Civil and Environmental Engineering, University of Illinois Urbana–Champaign
- Department of Biomedical and Translational Sciences, Carle Illinois College of Medicine, University of Illinois Urbana–Champaign
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Zeighami Y, Bakken TE, Nickl-Jockschat T, Peterson Z, Jegga AG, Miller JA, Schulkin J, Evans AC, Lein ES, Hawrylycz M. A comparison of anatomic and cellular transcriptome structures across 40 human brain diseases. PLoS Biol 2023; 21:e3002058. [PMID: 37079537 PMCID: PMC10118126 DOI: 10.1371/journal.pbio.3002058] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 03/02/2023] [Indexed: 04/21/2023] Open
Abstract
Genes associated with risk for brain disease exhibit characteristic expression patterns that reflect both anatomical and cell type relationships. Brain-wide transcriptomic patterns of disease risk genes provide a molecular-based signature, based on differential co-expression, that is often unique to that disease. Brain diseases can be compared and aggregated based on the similarity of their signatures which often associates diseases from diverse phenotypic classes. Analysis of 40 common human brain diseases identifies 5 major transcriptional patterns, representing tumor-related, neurodegenerative, psychiatric and substance abuse, and 2 mixed groups of diseases affecting basal ganglia and hypothalamus. Further, for diseases with enriched expression in cortex, single-nucleus data in the middle temporal gyrus (MTG) exhibits a cell type expression gradient separating neurodegenerative, psychiatric, and substance abuse diseases, with unique excitatory cell type expression differentiating psychiatric diseases. Through mapping of homologous cell types between mouse and human, most disease risk genes are found to act in common cell types, while having species-specific expression in those types and preserving similar phenotypic classification within species. These results describe structural and cellular transcriptomic relationships of disease risk genes in the adult brain and provide a molecular-based strategy for classifying and comparing diseases, potentially identifying novel disease relationships.
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Affiliation(s)
- Yashar Zeighami
- Douglas Research Centre, Department of Psychiatry, McGill University, Montreal, Canada
- Montreal Neurological Institute, McGill University, Montreal, Canada
| | - Trygve E. Bakken
- Allen Institute for Brain Science, Seattle, Washington, United States of America
| | - Thomas Nickl-Jockschat
- Department of Psychiatry, Neuroscience and Pharmacology, Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, United States of America
| | - Zeru Peterson
- Department of Psychiatry, Neuroscience and Pharmacology, Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, United States of America
| | - Anil G. Jegga
- Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
- Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America
| | - Jeremy A. Miller
- Allen Institute for Brain Science, Seattle, Washington, United States of America
| | - Jay Schulkin
- Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington, United States of America
| | - Alan C. Evans
- Montreal Neurological Institute, McGill University, Montreal, Canada
| | - Ed S. Lein
- Allen Institute for Brain Science, Seattle, Washington, United States of America
| | - Michael Hawrylycz
- Allen Institute for Brain Science, Seattle, Washington, United States of America
- University of Washington, Department of Genome Sciences, Seattle, Washington, United States of America
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Huang C, Wang J, Wang SH, Zhang YD. Applicable artificial intelligence for brain disease: A survey. Neurocomputing 2022. [DOI: 10.1016/j.neucom.2022.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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Rodríguez-Sevilla P, Marin R, Ximendes E, del Rosal B, Benayas A, Jaque D. Luminescence Thermometry for Brain Activity Monitoring: A Perspective. Front Chem 2022; 10:941861. [PMID: 35903194 PMCID: PMC9315374 DOI: 10.3389/fchem.2022.941861] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 06/22/2022] [Indexed: 11/13/2022] Open
Abstract
Minimally invasive monitoring of brain activity is essential not only to gain understanding on the working principles of the brain, but also for the development of new diagnostic tools. In this perspective we describe how brain thermometry could be an alternative to conventional methods (e.g., magnetic resonance or nuclear medicine) for the acquisition of thermal images of the brain with enough spatial and temperature resolution to track brain activity in minimally perturbed animals. We focus on the latest advances in transcranial luminescence thermometry introducing a critical discussion on its advantages and shortcomings. We also anticipate the main challenges that the application of luminescent nanoparticles for brain thermometry will face in next years. With this work we aim to promote the development of near infrared luminescence for brain activity monitoring, which could also benefit other research areas dealing with the brain and its illnesses.
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Affiliation(s)
- Paloma Rodríguez-Sevilla
- Departamento de Física de Materiales, Nanomaterials for Bioimaging Group (NanoBIG), Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain
- Nanomaterials for Bioimaging Group (NanoBIG), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Ramón y Cajal, Madrid, Spain
| | - Riccardo Marin
- Departamento de Física de Materiales, Nanomaterials for Bioimaging Group (NanoBIG), Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain
| | - Erving Ximendes
- Departamento de Física de Materiales, Nanomaterials for Bioimaging Group (NanoBIG), Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain
- Nanomaterials for Bioimaging Group (NanoBIG), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Ramón y Cajal, Madrid, Spain
| | | | - Antonio Benayas
- Departamento de Física de Materiales, Nanomaterials for Bioimaging Group (NanoBIG), Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain
- Nanomaterials for Bioimaging Group (NanoBIG), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Ramón y Cajal, Madrid, Spain
| | - Daniel Jaque
- Departamento de Física de Materiales, Nanomaterials for Bioimaging Group (NanoBIG), Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain
- Nanomaterials for Bioimaging Group (NanoBIG), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Ramón y Cajal, Madrid, Spain
- *Correspondence: Daniel Jaque,
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Neurology Worldwide. Neurology 2022. [DOI: 10.1002/9781119235699.ch1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
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Cost of diagnosing and treating cognitive complaints: One-year cost-evaluation study in a patient cohort from a Slovenian memory clinic. Zdr Varst 2022; 61:76-84. [PMID: 35432609 PMCID: PMC8937588 DOI: 10.2478/sjph-2022-0011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 12/10/2021] [Indexed: 11/21/2022] Open
Abstract
Abstract
Introduction
Dementias present a global health challenge and give rise to significant economic costs. This study aims to evaluate the economic impact of one-year outpatient healthcare, nursing home, and formal and informal home help costs for all patients referred to the Centre for Cognitive Impairments at the Department of Neurology, Ljubljana University Medical Centre, Slovenia.
Methods
Data was acquired retrospectively from physicians’ records and the costs for 2015 were calculated. Total costs were estimated by means of a bottom-up calculation of outpatient visits, diagnostic examinations and anti-dementia medication. In a subgroup of 120 patients with dementia, the Resource Utilization in Dementia questionnaire was used to estimate formal and informal care costs.
Results
A total of 720 patients visited the memory clinic in 2015. Diagnosis at first visit was subjective cognitive or mild cognitive impairment (SCI/ MCI) for 322 patients, dementia for 258 patients, and psychiatric or other disorders for 140 patients. The average annual cost per patient was EUR 578. It was highest for patients with dementia (EUR 751), EUR 550 for patients with SCI/MCI, and lowest for patients with psychiatric and other disorders (EUR 324). Monthly informal and social care costs were between EUR 1,037 and EUR 3,369, depending on the methodology used.
Conclusion
The cost of diagnosing a cognitive disorder depends on how extensive the diagnosis is. With an estimated prevalence of 34,137 persons with dementia in Slovenia, basic diagnostic investigations incur costs of approximately EUR 7 million. Direct medical costs represent a smaller portion of total dementia costs; this is because annual costs for formal and informal home help are estimated at EUR 265 million and nursing home placements at EUR 105 million.
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Luo Y, Chen Hsu C, Jui Lin K, Kai Fu S, Ru Chen J, Lai CC. Effectiveness of a Water Intake Program at the Workplace in Physical and Mental Health Outcomes. INQUIRY: THE JOURNAL OF HEALTH CARE ORGANIZATION, PROVISION, AND FINANCING 2022; 59:469580221085778. [PMID: 35403464 PMCID: PMC8998380 DOI: 10.1177/00469580221085778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
Abstract
Introduction Adequate water intake is a low-cost and effectively non-invasive strategy for individual health outcomes. We aimed to demonstrate the efficacy of water intake intervention in intensive-labor and static-type workplaces. Method Smart drinking cups were provided to the participants, and a built-in application (App) associated with the cup was downloaded on their phones. The App collected and recorded the amount of drinking water consumed by the participants set reminders for drinking water and drinking water health education information. We assessed the data, including the amount of and time interval between water intake, sedentary time, the degree of physical and psychological importance of oneself, self-satisfaction, and physical fitness. Results After the intervention, water intake in the two companies significantly increased during the reminder period compared with the non-reminder period. A significant increase was noted in week 3 in the amount of water intake by the participants after using the App, and the total sedentary time considerably decreased. Furthermore, the interval between water consumption decreased compared with the preintervention interval. The systolic and diastolic blood pressure decreased in the participants working at the static-type and intensive-labor workplaces after the intervention, respectively. The participants ' lower limb muscle performance also improved significantly, and the emphasis on self-care was significantly improved. Conclusions The health-promoting effects of the water intake wellness intervention were akin to the butterfly effect. Besides significantly increasing water intake, the intervention improved other health behaviors, thereby benefiting physical and mental health. Hence, promoting water consumption in workplaces till it becomes a habit may benefit the employees.
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Affiliation(s)
- Yin Luo
- Graduate Institute of Sports Training, University of Taipei, Taipei City, Taiwan
| | - Chia Chen Hsu
- Graduate Institute of Gerontology and Health Care Management, Chang Gung University of Science and Technology, Taoyuan City, Taiwan
- Department of Otorhinolaryngology, Taipei City Hospital, Taipei City, Taiwan
- Department of Exercise and Health Sciences, University of Taipei, Taipei City, Taiwan
| | - Kuo Jui Lin
- Department of Physical Education, University of Taipei, Taipei City, Taiwan
| | - Szu Kai Fu
- Graduate Institute of Sports Training, University of Taipei, Taipei City, Taiwan
| | - Jyun Ru Chen
- Department of Exercise and Health Sciences, University of Taipei, Taipei City, Taiwan
| | - Chang-Chi Lai
- Department of Exercise and Health Sciences, University of Taipei, Taipei City, Taiwan
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Ko DWK. Transcutaneous vagus nerve stimulation (tVNS) as a potential therapeutic application for neurodegenerative disorders - A focus on dysautonomia in Parkinson's disease. Auton Neurosci 2021; 235:102858. [PMID: 34365230 DOI: 10.1016/j.autneu.2021.102858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 07/12/2021] [Accepted: 07/20/2021] [Indexed: 11/29/2022]
Abstract
The understandings of pathogenic processes in major neurodegenerative diseases has significantly advanced in recent years, with evidence showing pathological spread of intraneuronal proteinaceous inclusions as a fundamental factor. In Parkinson's disease (PD), the culprit protein has been identified as α-synuclein as the main component for mediating progressive neurodegeneration. With severe pathology evident in the autonomic nervous system prior to clinical manifestations of PD, pathogenic spread can occur from the peripheral nervous system through key nuclei, such as the anterior olfactory nucleus and dorsal motor nucleus of the glossopharyngeal and vagal nerves, gradually reaching the brainstem, midbrain and cerebral cortex. With this understanding and the proposed involvement of the vagus nerve in disease progression in PD, notably occurring prior to characterized clinical motor features, it raises intriguing questions as to whether vagal nerve pathology can be accurately detected, and importantly used as a reliable marker for determining early neurodegeneration. Along with this is the potential use of vagus nerve neuromodulation for treatment of early disease symptoms like dysautonomia, for modulating sympatho-vagal imbalances and easing severe comorbidities of the disease. In this article, we take a closer look at the pathogenic transmission processes in neurodegenerative disorders that impact the vagus nerve, and how vagus nerve neuromodulation can be potentially applied as a therapeutic approach for major neurodegenerative disorders.
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Affiliation(s)
- Daniel W K Ko
- Neuropix Company Ltd, Core F, Cyberport 3, 100 Cyberport Road, Hong Kong Special Administrative Region.
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13
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Lin CW, Hong Y, Liu J. Aggregation-and-Attention Network for brain tumor segmentation. BMC Med Imaging 2021; 21:109. [PMID: 34243703 PMCID: PMC8267236 DOI: 10.1186/s12880-021-00639-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Accepted: 06/30/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Glioma is a malignant brain tumor; its location is complex and is difficult to remove surgically. To diagnosis the brain tumor, doctors can precisely diagnose and localize the disease using medical images. However, the computer-assisted diagnosis for the brain tumor diagnosis is still the problem because the rough segmentation of the brain tumor makes the internal grade of the tumor incorrect. METHODS In this paper, we proposed an Aggregation-and-Attention Network for brain tumor segmentation. The proposed network takes the U-Net as the backbone, aggregates multi-scale semantic information, and focuses on crucial information to perform brain tumor segmentation. To this end, we proposed an enhanced down-sampling module and Up-Sampling Layer to compensate for the information loss. The multi-scale connection module is to construct the multi-receptive semantic fusion between encoder and decoder. Furthermore, we designed a dual-attention fusion module that can extract and enhance the spatial relationship of magnetic resonance imaging and applied the strategy of deep supervision in different parts of the proposed network. RESULTS Experimental results show that the performance of the proposed framework is the best on the BraTS2020 dataset, compared with the-state-of-art networks. The performance of the proposed framework surpasses all the comparison networks, and its average accuracies of the four indexes are 0.860, 0.885, 0.932, and 1.2325, respectively. CONCLUSIONS The framework and modules of the proposed framework are scientific and practical, which can extract and aggregate useful semantic information and enhance the ability of glioma segmentation.
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Affiliation(s)
- Chih-Wei Lin
- College of Computer and Information Science, Fujian Agriculture and Forestry University, Fuzhou, China.
- College of Forestry, Fujian Agriculture and Forestry University, Fuzhou, China.
- Forestry Post-Doctoral Station of Fujian Agriculture and Forestry University, Fuzhou, China.
- Key Laboratory for Ecology and Resource Statistics of Fujian Province, Fuzhou, China.
| | - Yu Hong
- College of Forestry, Fujian Agriculture and Forestry University, Fuzhou, China
- Key Laboratory for Ecology and Resource Statistics of Fujian Province, Fuzhou, China
| | - Jinfu Liu
- College of Computer and Information Science, Fujian Agriculture and Forestry University, Fuzhou, China
- College of Forestry, Fujian Agriculture and Forestry University, Fuzhou, China
- Key Laboratory for Ecology and Resource Statistics of Fujian Province, Fuzhou, China
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14
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European Clinical Neuropsychology: Role in Healthcare and Access to Neuropsychological Services. Healthcare (Basel) 2021; 9:healthcare9060734. [PMID: 34203802 PMCID: PMC8232602 DOI: 10.3390/healthcare9060734] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 06/06/2021] [Accepted: 06/10/2021] [Indexed: 12/30/2022] Open
Abstract
This study analyzed aspects of the work of clinical neuropsychologists across Europe. There are no published comparisons between European countries regarding the nature of clinical neuropsychologists' work. Forty-one national psychological and neuropsychological societies were approached, of which 31 (76%) responded. Data from seven countries with less than 10 neuropsychologists were excluded. A license is required to practice clinical neuropsychology in 50% of the countries. Clinical neuropsychologists work independently in 62.5%. Diagnostic/assessment work is the most frequently reported activity (54%). Most neuropsychologists work in public hospitals, followed by health centers. Adult neuropsychology was the most frequent area of activity. Services in public institutions are covered by public entities (45.8%), or by a combination of patient funds and public entities (29.2%) and only 4.2% by the patient; whereas services in private institutions are covered by the patient (26.1%) and the combination of patient, public entities (21.7%) or patient and private entities (17.4%). The data suggest that the number of neuropsychologists working across European countries is considerably low in comparison to other medical professionals. The results of the survey identified similar aspects of neuropsychologists' work, despite variations in terms of reimbursement and mechanisms, reflecting economic and healthcare differences. Estimates on the number of clinical neuropsychologists suggest insufficient access to neuropsychological services.
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15
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Barron HC, Mars RB, Dupret D, Lerch JP, Sampaio-Baptista C. Cross-species neuroscience: closing the explanatory gap. Philos Trans R Soc Lond B Biol Sci 2021; 376:20190633. [PMID: 33190601 PMCID: PMC7116399 DOI: 10.1098/rstb.2019.0633] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/20/2020] [Indexed: 12/17/2022] Open
Abstract
Neuroscience has seen substantial development in non-invasive methods available for investigating the living human brain. However, these tools are limited to coarse macroscopic measures of neural activity that aggregate the diverse responses of thousands of cells. To access neural activity at the cellular and circuit level, researchers instead rely on invasive recordings in animals. Recent advances in invasive methods now permit large-scale recording and circuit-level manipulations with exquisite spatio-temporal precision. Yet, there has been limited progress in relating these microcircuit measures to complex cognition and behaviour observed in humans. Contemporary neuroscience thus faces an explanatory gap between macroscopic descriptions of the human brain and microscopic descriptions in animal models. To close the explanatory gap, we propose adopting a cross-species approach. Despite dramatic differences in the size of mammalian brains, this approach is broadly justified by preserved homology. Here, we outline a three-armed approach for effective cross-species investigation that highlights the need to translate different measures of neural activity into a common space. We discuss how a cross-species approach has the potential to transform basic neuroscience while also benefiting neuropsychiatric drug development where clinical translation has, to date, seen minimal success. This article is part of the theme issue 'Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity'.
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Affiliation(s)
- Helen C. Barron
- Medical Research Council Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Mansfield Road, Oxford OX1 3TH, UK
- Wellcome Centre for Integrative Neuroimaging, University of Oxford, FMRIB, John Radcliffe Hospital, Oxford OX3 9DU, UK
| | - Rogier B. Mars
- Wellcome Centre for Integrative Neuroimaging, University of Oxford, FMRIB, John Radcliffe Hospital, Oxford OX3 9DU, UK
- Donders Institute for Brain, Cognition and Behavior, Radboud University, 6525 AJ Nijmegen, The Netherlands
| | - David Dupret
- Medical Research Council Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Mansfield Road, Oxford OX1 3TH, UK
| | - Jason P. Lerch
- Wellcome Centre for Integrative Neuroimaging, University of Oxford, FMRIB, John Radcliffe Hospital, Oxford OX3 9DU, UK
- Department of Medical Biophysics, University of Toronto, Toronto, Ontario, CanadaM5G 1L7
| | - Cassandra Sampaio-Baptista
- Wellcome Centre for Integrative Neuroimaging, University of Oxford, FMRIB, John Radcliffe Hospital, Oxford OX3 9DU, UK
- Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QB, UK
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16
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Hokkanen L, Barbosa F, Ponchel A, Constantinou M, Kosmidis MH, Varako N, Kasten E, Mondini S, Lettner S, Baker G, Persson BA, Hessen E. Clinical Neuropsychology as a Specialist Profession in European Health Care: Developing a Benchmark for Training Standards and Competencies Using the Europsy Model? Front Psychol 2020; 11:559134. [PMID: 33123042 PMCID: PMC7573555 DOI: 10.3389/fpsyg.2020.559134] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Accepted: 09/08/2020] [Indexed: 12/21/2022] Open
Abstract
The prevalence and negative impact of brain disorders are increasing. Clinical Neuropsychology is a specialty dedicated to understanding brain-behavior relationships, applying such knowledge to the assessment of cognitive, affective, and behavioral functioning associated with brain disorders, and designing and implementing effective treatments. The need for services goes beyond neurological diseases and has increased in areas of neurodevelopmental and psychiatric conditions, among others. In Europe, a great deal of variability exists in the education and training of Clinical Neuropsychologists. Training models include master’s programs, continuing education courses, doctoral programs, and/or post-doctoral specialization depending on the country, with no common framework of requirements, although patients’ needs demand equal competencies across Europe. In the past 5 years, the Standing Committee on Clinical Neuropsychology of the European Federation of Psychologists’ Association has conducted a series of surveys and interviews with experts in the field representing 30 European countries. The information, along with information from the existing literature, is used in presenting an overview of current and relevant topics related to policy and guidelines in the training and competencies in Clinical Neuropsychology. An option for the way forward is the EuroPsy Specialist Certificate, which is currently offered in Work and Organizational Psychology, and in psychotherapy. It builds upon the basic certificate and complements national standards without overriding them. General principles can be found that can set the basis for a common, solid, and comprehensive specialty education/training, sharpening the Neuropsychologists’ competencies across Europe. The requirements in Clinical Neuropsychology should be comparable to those for the existing specialty areas in the EuroPsy model. Despite the perceived challenges, developing a specialist certificate appears a step forward for the development of Clinical Neuropsychology. Recommendations are proposed toward a shared framework of competencies by the means of a common level of education/training for the professionals in Europe. Benchmarking training standards and competencies across Europe has the potential of providing protection against unqualified and ethically questionable practice, creating transparency, raising the general European standard, and promoting mobility of both Clinical Neuropsychologists and patients in Europe, for the benefit of the professional field and the population.
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Affiliation(s)
- Laura Hokkanen
- Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Fernando Barbosa
- Laboratory of Neuropsychophysiology, Faculty of Psychology and Education Sciences, University of Porto, Porto, Portugal
| | | | | | - Mary H Kosmidis
- Lab of Cognitive Neuroscience, School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Nataliya Varako
- Research Center of Neurology, Lomonosov Moscow State University, Moscow, Russia
| | - Erich Kasten
- Department of Psychology - Neurosciences, MSH University of Applied Sciences & Medical University, Hamburg, Germany
| | - Sara Mondini
- Department of Philosophy, Sociology, Education and Applied Psychology, University of Padova, Padova, Italy
| | - Sandra Lettner
- Clinical Neuropsychology Unit, Hospital of the Sisters of Charity, Ried, Austria
| | - Gus Baker
- Division of Neurosciences, University of Liverpool, Liverpool, United Kingdom
| | - Bengt A Persson
- Department of Psychology, Linnaeus University, Växjö, Sweden
| | - Erik Hessen
- Department of Psychology, University of Oslo, Oslo, Norway.,Department of Neurology, Akershus University Hospital, Lørenskog, Norway
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17
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Kim HJ, Ho SH, Lee S, Oh IH, Kim JH, Kim EJ, Lee SJ. The Economic Burden of Brain Disability in Korea, 2008-2011. INQUIRY: The Journal of Health Care Organization, Provision, and Financing 2020; 57:46958020936396. [PMID: 32613880 PMCID: PMC7333489 DOI: 10.1177/0046958020936396] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
This study estimated the economic burden of people with brain disability in Korea during 2008-2011 using nationally representative data and was conducted to use the results as an evidence for determining the resources allocation of people with brain disability. We used a prevalence-based approach to estimate the economic burden, classified by direct costs (medical costs and nonmedical costs) and indirect costs (productivity loss of morbidity and premature death). Data from the National Health Insurance Service, the National Disability Registry, the National survey on persons with disabilities, the Korea National Statistical Office's records of causes of death, and the Labor Statistics were used to calculate direct and indirect costs. The treated prevalence of brain disability increased from 0.26% (2008) to 0.35% (2011). Total economic burden of brain-related diseases was US$1.88 billion in 2008 and increased to US$2.90 billion in 2011, with a 54% rate of increase. The economic burden of all diseases, which was 1.2 to 1.4 times higher than that of brain-related diseases, accounted for US$2.61 billion in 2008 and US$3.62 billion in 2011, increasing by 39%. Owing to the growing occurrence of brain disability, the annual prevalence and related costs are increasing. Health management programs are necessary to reduce the economic burden of brain disability in Korea.
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Affiliation(s)
- Hyun-Jin Kim
- Department of Clinical Research for Rehabilitation, Korea National Rehabilitation Research Institute, Seoul, South Korea
| | - Seung Hee Ho
- Department of Healthcare and Public Health Research, Korea National Rehabilitation Research Institute, Seoul, South Korea
| | - Sol Lee
- Department of Healthcare and Public Health Research, Korea National Rehabilitation Research Institute, Seoul, South Korea
| | - In-Hwan Oh
- Department of Preventive Medicine, Kyung Hee University School of Medicine, Seoul, South Korea
| | - Ju Hee Kim
- Department of Healthcare and Public Health Research, Korea National Rehabilitation Research Institute, Seoul, South Korea
| | - Eun Joo Kim
- Department of Community Reintegration Service, Korea National Rehabilitation Hospital, Seoul, South Korea
| | - Seong Jae Lee
- Department of Rehabilitation Medicine, College of Medicine, Dankook University, Cheonan, South Korea
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18
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Nowak M, Brown TD, Graham A, Helgeson ME, Mitragotri S. Size, shape, and flexibility influence nanoparticle transport across brain endothelium under flow. Bioeng Transl Med 2020; 5:e10153. [PMID: 32440560 PMCID: PMC7237148 DOI: 10.1002/btm2.10153] [Citation(s) in RCA: 120] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Revised: 11/28/2019] [Accepted: 12/11/2019] [Indexed: 12/19/2022] Open
Abstract
Nanoparticle-based therapeutic formulations are being increasingly explored for the treatment of various ailments. Despite numerous advances, the success of nanoparticle-based technologies in treating brain diseases has been limited. Translational hurdles of nanoparticle therapies are attributed primarily to their limited ability to cross the blood-brain barrier (BBB), which is one of the body's most exclusive barriers. Several efforts have been focused on developing affinity-based agents and using them to increase nanoparticle accumulation at the brain endothelium. Very little is known about the role of fundamental physical parameters of nanoparticles such as size, shape, and flexibility in determining their interactions with and penetration across the BBB. Using a three-dimensional human BBB microfluidic model (μHuB), we investigate the impact of these physical parameters on nanoparticle penetration across the BBB. To gain insights into the dependence of transport on nanoparticle properties, two separate parameters were measured: the number of nanoparticles that fully cross the BBB and the number that remain associated with the endothelium. Association of nanoparticles with the brain endothelium was substantially impacted by their physical characteristics. Hard particles associate more with the endothelium compared to soft particles, as do small particles compared to large particles, and spherical particles compared to rod-shaped particles. Transport across the BBB also exhibited a dependence on nanoparticle properties. A nonmonotonic dependence on size was observed, where 200 nm particles exhibited higher BBB transport compared to 100 and 500 nm spheres. Rod-shaped particles exhibited higher BBB transport when normalized by endothelial association and soft particles exhibited comparable transport to hard particles when normalized by endothelial association. Tuning nanoparticles' physical parameters could potentially enhance their ability to cross the BBB for therapeutic applications.
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Affiliation(s)
- Maksymilian Nowak
- John A. Paulson School of Engineering and Applied SciencesHarvard University29 Oxford St. CambridgeMA02138
- Wyss Institute of Biologically Inspired EngineeringHarvard University3 Blackfan CircleBostonMA02115
| | - Tyler D. Brown
- John A. Paulson School of Engineering and Applied SciencesHarvard University29 Oxford St. CambridgeMA02138
- Wyss Institute of Biologically Inspired EngineeringHarvard University3 Blackfan CircleBostonMA02115
| | - Adam Graham
- Center for Nanoscale SystemsHarvard University11 Oxford St. CambridgeMA02138
| | - Matthew E. Helgeson
- Department of Chemical EngineeringUniversity of California, Santa BarbaraSanta BarbaraCA93106
| | - Samir Mitragotri
- John A. Paulson School of Engineering and Applied SciencesHarvard University29 Oxford St. CambridgeMA02138
- Wyss Institute of Biologically Inspired EngineeringHarvard University3 Blackfan CircleBostonMA02115
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19
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Cameron LP, Nazarian A, Olson DE. Psychedelic Microdosing: Prevalence and Subjective Effects. J Psychoactive Drugs 2020; 52:113-122. [PMID: 31973684 PMCID: PMC7282936 DOI: 10.1080/02791072.2020.1718250] [Citation(s) in RCA: 61] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 09/01/2019] [Accepted: 09/23/2019] [Indexed: 12/28/2022]
Abstract
Anecdotal reports suggest that the administration of sub-hallucinogenic doses of psychedelic compounds on a chronic, intermittent schedule - a practice known as psychedelic microdosing - is becoming increasingly popular among young adults due to its purported ability to reduce symptoms of depression and anxiety while improving cognitive function and promoting social interaction. Using an anonymous online survey, we collected data from 2347 people to 1) assess the prevalence of psychedelic microdosing and characterize the demographics of microdosers, 2) determine whether microdosers associate the practice with changes in mood, cognitive function, social interaction, or physiology, and 3) investigate frequent motives for discontinuing the practice. Fifty-nine percent of respondents (NT = 2183) reported familiarity with the concept of psychedelic microdosing, with 17% (383 respondents, NT = 2200) having engaged in this practice. Microdosers attributed psychedelic microdosing with improving their mood, decreasing their anxiety, and enhancing their memory, attention, and sociability. The most frequently cited reasons for quitting microdosing (NT = 243) were the risks associated with taking an illegal substance (24.28%) and the difficulty of obtaining psychedelic compounds (22.63%). Overall, our findings suggest that psychedelic microdosing is relatively common and is subjectively associated with a broad spectrum of socio-affective, cognitive, and physical outcomes.
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Affiliation(s)
- Lindsay P. Cameron
- Neuroscience Graduate Program, University of California, Davis, 1544 Newton Ct, Davis, CA, 95618, USA
| | - Angela Nazarian
- Center for Mind and Brain, University of California, Davis, 267 Cousteau Place, Davis, CA, 95618, USA
| | - David E. Olson
- Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, CA, 95616, USA
- Department of Biochemistry & Molecular Medicine, School of Medicine, University of California, Davis, 2700 Stockton Blvd, Suite 2102, Sacramento, CA 95817, USA
- Center for Neuroscience, University of California, Davis, 1544 Newton Ct, Davis, CA 95618, USA
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20
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Hoffmann L, Rust MB, Culmsee C. Actin(g) on mitochondria - a role for cofilin1 in neuronal cell death pathways. Biol Chem 2020; 400:1089-1097. [PMID: 31256058 DOI: 10.1515/hsz-2019-0120] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Accepted: 04/16/2019] [Indexed: 11/15/2022]
Abstract
Actin dynamics, the coordinated assembly and disassembly of actin filaments (F-actin), are essential for fundamental cellular processes, including cell shaping and motility, cell division or organelle transport. Recent studies highlighted a novel role for actin dynamics in the regulation of mitochondrial morphology and function, for example, through mitochondrial recruitment of dynamin-related protein 1 (Drp1), a key factor in the mitochondrial fission machinery. Mitochondria are dynamic organelles, and permanent fission and fusion is essential to maintain their function in energy metabolism, calcium homeostasis and regulation of reactive oxygen species (ROS). Here, we summarize recent insights into the emerging role of cofilin1, a key regulator of actin dynamics, for mitochondrial shape and function under physiological conditions and during cellular stress, respectively. This is of peculiar importance in neurons, which are particularly prone to changes in actin regulation and mitochondrial integrity and function. In neurons, cofilin1 may contribute to degenerative processes through formation of cofilin-actin rods, and through enhanced mitochondrial fission, mitochondrial membrane permeabilization, and the release of cytochrome c. Overall, mitochondrial impairment induced by dysfunction of actin-regulating proteins such as cofilin1 emerge as important mechanisms of neuronal death with relevance to acute brain injury and neurodegenerative diseases, such as Parkinson's or Alzheimer's disease.
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Affiliation(s)
- Lena Hoffmann
- Institute of Pharmacology and Clinical Pharmacy, Biochemical-Pharmacological Center Marburg, University of Marburg, Karl-von-Frisch Straße 2, D-35043 Marburg, Germany.,Center for Mind, Brain and Behavior (CMBB), University of Marburg and Justus-Liebig-University Gießen, Hans-Meerwein-Straße 6, D-35032 Marburg, Germany
| | - Marco B Rust
- Center for Mind, Brain and Behavior (CMBB), University of Marburg and Justus-Liebig-University Gießen, Hans-Meerwein-Straße 6, D-35032 Marburg, Germany.,Molecular Neurobiology Group, Institute of Physiological Chemistry, Biochemical-Pharmacological Center Marburg, University of Marburg, Karl-von-Frisch Straße 2, D-35043 Marburg, Germany
| | - Carsten Culmsee
- Institute of Pharmacology and Clinical Pharmacy, Biochemical-Pharmacological Center Marburg, University of Marburg, Karl-von-Frisch Straße 2, D-35043 Marburg, Germany.,Center for Mind, Brain and Behavior (CMBB), University of Marburg and Justus-Liebig-University Gießen, Hans-Meerwein-Straße 6, D-35032 Marburg, Germany.,Third Affiliated Hospital, Zhengzhou University, Zhengzhou, China
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21
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Raggi A, Leonardi M. Burden of brain disorders in Europe in 2017 and comparison with other non-communicable disease groups. J Neurol Neurosurg Psychiatry 2020; 91:104-105. [PMID: 31208991 DOI: 10.1136/jnnp-2019-320466] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Revised: 05/13/2019] [Accepted: 06/02/2019] [Indexed: 11/04/2022]
Affiliation(s)
- Alberto Raggi
- Neurology, Public Health and Disability Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
| | - Matilde Leonardi
- Neurology, Public Health and Disability Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
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22
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Nowak M, Helgeson ME, Mitragotri S. Delivery of Nanoparticles and Macromolecules across the Blood–Brain Barrier. ADVANCED THERAPEUTICS 2019. [DOI: 10.1002/adtp.201900073] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Affiliation(s)
- Maksymilian Nowak
- School of Engineering and Applied Sciences Harvard University 29 Oxford St. Cambridge MA 02318 USA
- Wyss Institute of Biologically Inspired Engineering Harvard University 3 Blackfan Circle Boston MA 02115 USA
| | - Matthew E. Helgeson
- Department of Chemical Engineering University of California Santa Barbara Santa Barbara CA 93106 USA
| | - Samir Mitragotri
- School of Engineering and Applied Sciences Harvard University 29 Oxford St. Cambridge MA 02318 USA
- Wyss Institute of Biologically Inspired Engineering Harvard University 3 Blackfan Circle Boston MA 02115 USA
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23
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Cameron L, Benson CJ, DeFelice BC, Fiehn O, Olson DE. Chronic, Intermittent Microdoses of the Psychedelic N, N-Dimethyltryptamine (DMT) Produce Positive Effects on Mood and Anxiety in Rodents. ACS Chem Neurosci 2019; 10:3261-3270. [PMID: 30829033 PMCID: PMC6639775 DOI: 10.1021/acschemneuro.8b00692] [Citation(s) in RCA: 108] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Accepted: 02/14/2019] [Indexed: 12/21/2022] Open
Abstract
Drugs capable of ameliorating symptoms of depression and anxiety while also improving cognitive function and sociability are highly desirable. Anecdotal reports have suggested that serotonergic psychedelics administered in low doses on a chronic, intermittent schedule, so-called "microdosing", might produce beneficial effects on mood, anxiety, cognition, and social interaction. Here, we test this hypothesis by subjecting male and female Sprague Dawley rats to behavioral testing following the chronic, intermittent administration of low doses of the psychedelic N,N-dimethyltryptamine (DMT). The behavioral and cellular effects of this dosing regimen were distinct from those induced following a single high dose of the drug. We found that chronic, intermittent, low doses of DMT produced an antidepressant-like phenotype and enhanced fear extinction learning without impacting working memory or social interaction. Additionally, male rats treated with DMT on this schedule gained a significant amount of body weight during the course of the study. Taken together, our results suggest that psychedelic microdosing may alleviate symptoms of mood and anxiety disorders, though the potential hazards of this practice warrant further investigation.
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Affiliation(s)
- Lindsay
P. Cameron
- Neuroscience
Graduate Program, University of California,
Davis, 1544 Newton Ct, Davis, California 95618, United States
| | - Charlie J. Benson
- Department
of Chemistry, University of California,
Davis, One Shields Avenue, Davis, California 95616, United States
| | - Brian C. DeFelice
- West
Coast Metabolomics Center, University of
California, Davis, One
Shields Avenue, Davis, California 95616, United States
| | - Oliver Fiehn
- West
Coast Metabolomics Center, University of
California, Davis, One
Shields Avenue, Davis, California 95616, United States
- Biochemistry
Department, King Abdulaziz University, Jeddah, Saudi-Arabia
| | - David E. Olson
- Department
of Chemistry, University of California,
Davis, One Shields Avenue, Davis, California 95616, United States
- Department
of Biochemistry & Molecular Medicine, School of Medicine, University of California, Davis, 2700 Stockton Blvd, Suite 2102, Sacramento, California 95817, United States
- Center for
Neuroscience, University of California,
Davis, 1544 Newton Ct, Davis, California 95618, United States
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24
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Fekadu S, Alemayehu E, Dewil R, Van der Bruggen B. Pharmaceuticals in freshwater aquatic environments: A comparison of the African and European challenge. THE SCIENCE OF THE TOTAL ENVIRONMENT 2019; 654:324-337. [PMID: 30448654 DOI: 10.1016/j.scitotenv.2018.11.072] [Citation(s) in RCA: 247] [Impact Index Per Article: 41.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Revised: 11/04/2018] [Accepted: 11/05/2018] [Indexed: 05/23/2023]
Abstract
Hundreds of tons of pharmaceutical compounds are annually dispensed and consumed worldwide. Pharmaceuticals are an important class of emerging environmental micropollutants: their presence in water bodies is an increasing environmental concern. The aim of this review paper is to provide a comprehensive review of the occurrence of pharmaceuticals in freshwater aquatic environments in the African and European context. A literature survey has been performed, resulting in 3024 data points related to environmental occurrence. The concentration levels of 71 pharmaceuticals were assessed. The top ten most frequently detected and quantified compounds in both continents were sulfamethoxazole, carbamazepine, diclofenac, trimethoprim, ibuprofen, naproxen, paracetamol (acetaminophen), ketoprofen, venlafaxine and clarithromycin. The maximum concentrations of 17β-estradiol, estriol, ciprofloxacin, sulfamethoxazole, paracetamol, naproxen reported in African aquatic environments were ~3140, ~20,000, ~125, ~100, ~215 and ~171 times higher, respectively, than the concentrations reported in European based studies. The variation in pharmaceutical consumption, partial removal of pharmaceuticals in wastewater treatment processes, and the direct discharge of livestock animal farm wastewater were identified among the major reasons for the observed differences. Several pharmaceuticals were found in aquatic environments of both continents in concentration levels higher than their ecotoxicity endpoints. In Europe, compounds such as diclofenac, ibuprofen, triclosan, sulfadimidine, carbamazepine and fluoxetine were reported in a concentration higher than the available ecotoxicity endpoints. In Africa, much more compounds reached concentrations more than the ecotoxicity endpoints, including diclofenac, ibuprofen, paracetamol, naproxen, ciprofloxacin, triclosan, trimethoprim, sulfamethoxazole, carbamazepine and fluoxetine, estriol and 17β-estradiol. Details for each therapeutic group are presented in this review.
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Affiliation(s)
- Samuel Fekadu
- KU Leuven, Department of Chemical Engineering, Process Engineering for Sustainable Systems Section, Celestijnenlaan 200F, 3001 Leuven, Belgium; Jimma University, Faculty of Civil and Environmental Engineering, Ethiopia; Jimma University, Department of Environmental Health Science and Technology, Ethiopia
| | - Esayas Alemayehu
- Jimma University, Faculty of Civil and Environmental Engineering, Ethiopia
| | - Raf Dewil
- KU Leuven, Department of Chemical Engineering, Process and Environmental Technology Lab, J. De Nayerlaan 5, 2860 Sint-Katelijne-Waver, Belgium
| | - Bart Van der Bruggen
- KU Leuven, Department of Chemical Engineering, Process Engineering for Sustainable Systems Section, Celestijnenlaan 200F, 3001 Leuven, Belgium; Faculty of Engineering and the Built Environment, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South Africa.
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Nitric oxide signalling and antidepressant action revisited. Cell Tissue Res 2019; 377:45-58. [PMID: 30649612 DOI: 10.1007/s00441-018-02987-4] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2018] [Accepted: 12/21/2018] [Indexed: 12/20/2022]
Abstract
Studies about the pathogenesis of mood disorders have consistently shown that multiple factors, including genetic and environmental, play a crucial role on their development and neurobiology. Multiple pathological theories have been proposed, of which several ultimately affects or is a consequence of dysfunction in brain neuroplasticity and homeostatic mechanisms. However, current clinical available pharmacological intervention, which is predominantly monoamine-based, suffers from a partial and lacking response even after weeks of continuous treatment. These issues raise the need for better understanding of aetiologies and brain abnormalities in depression, as well as developing novel treatment strategies. Nitric oxide (NO) is a gaseous unconventional neurotransmitter, which regulates and governs several important physiological functions in the central nervous system, including processes, which can be associated with the development of mood disorders. This review will present general aspects of the NO system in depression, highlighting potential targets that may be utilized and further explored as novel therapeutic targets in the future pharmacotherapy of depression. In particular, the review will link the importance of neuroplasticity mechanisms governed by NO to a possible molecular basis for the antidepressant effects.
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Haghighatdoost F, Feizi A, Esmaillzadeh A, Rashidi-Pourfard N, Keshteli AH, Roohafza H, Adibi P. Drinking plain water is associated with decreased risk of depression and anxiety in adults: Results from a large cross-sectional study. World J Psychiatry 2018; 8:88-96. [PMID: 30254979 PMCID: PMC6147771 DOI: 10.5498/wjp.v8.i3.88] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Revised: 04/23/2018] [Accepted: 06/09/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To investigate the relation between plain water drinking and risk of depression and anxiety among a large sample of Iranian adults. METHODS A total of 3327 Iranian general adults were included in this cross-sectional study. Validated Iranian version of the Hospital Anxiety and Depression Scale was used to assess anxiety and depression. Water consumption was assessed by asking about the number of glasses of water that consumed daily. Water consumption was categorized into < 2, 2-5, and ≥ 5 glasses of water/d. RESULTS In the crude model, the lowest level of water drinking (< 2 glasses/d) compared with reference group (≥ 5 glasses/d) doubled the risk of depression and anxiety (P < 0.0001). After adjusting potential confounders, this inverse link remained significant for depression (OR: 1.79; 95%CI: 1.32, 2.42; P < 0.0001), but not for anxiety (OR: 1.49; 95%CI: 0.98, 2.25; P = 0.109). In stratified analyses by sex, after controlling for potential confounders, water drinking < 2 glasses/d was associated with 73% and 54% increment in the risk of depression in men and women, respectively (P < 0.05), whilst no significant association was observed for anxiety either in men or in women. CONCLUSION We found inverse associations between plain water consumption and depression. Also, these findings showed a tended risky association, but not statistically significant, between lower levels of water consumption and anxiety. These findings warrant evaluation in prospective and clinical trials studies to establish the plausible role of water in mental health status.
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Affiliation(s)
- Fahimeh Haghighatdoost
- Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran
| | - Awat Feizi
- Psychosomatic Research Center, Integrative Functional Gastrointestinal Research Center and Biostatistics and Epidemiology Department, School of Health Isfahan University of Medical Sciences, Hezarjarib, Isfahan 81746-73461, Iran
| | - Ahmad Esmaillzadeh
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran 14176-53761, Iran
| | | | - Ammar Hassanzadeh Keshteli
- Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AL 54321, Canada
| | - Hamid Roohafza
- Cardiac Rehabilitation Research Center, Isfahan Cardiovascular Research Institute Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran
| | - Payman Adibi
- Integrative Functional Gastrointestinal Research Center and Gastroenterology Section, Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran
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Hokkanen L, Lettner S, Barbosa F, Constantinou M, Harper L, Kasten E, Mondini S, Persson B, Varako N, Hessen E. Training models and status of clinical neuropsychologists in Europe: Results of a survey on 30 countries. Clin Neuropsychol 2018; 33:32-56. [PMID: 29923448 DOI: 10.1080/13854046.2018.1484169] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
OBJECTIVE The aims of the study were to analyze the current European situation of specialist education and training within clinical neuropsychology, and the legal and professional status of clinical neuropsychologists in different European countries. METHOD An online survey was prepared in 2016 by a Task Force established by the European Federation of Psychological Associations, and representatives of 30 countries gave their responses. Response rate was 76%. RESULTS Only three countries were reported to regulate the title of clinical neuropsychologist as well as the education and practice of clinical neuropsychologists by law. The most common university degree required to practice clinical neuropsychology was the master's degree; a doctoral degree was required in two countries. The length of the specialist education after the master's degree varied between 12 and 60 months. In one third of the countries, no commonly agreed upon model for specialist education existed. A more systematic training model and a longer duration of training were associated with independence in the work of clinical neuropsychologists. CONCLUSIONS As legal regulation is mostly absent and training models differ, those actively practicing clinical neuropsychology in Europe have a very heterogeneous educational background and skill level. There is a need for a European standardization of specialist training in clinical neuropsychology. Guiding principles for establishing the common core requirements are presented.
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Affiliation(s)
- Laura Hokkanen
- a Department of Psychology and Logopedics, Faculty of Medicine , University of Helsinki , Helsinki , Finland
| | - Sandra Lettner
- b Clinical Neuropsychology Unit , Hospital of the Sisters of Charity , Ried , Austria
| | - Fernando Barbosa
- c Laboratory of Neuropsychophysiology, Faculty of Psychology and Education Sciences , University of Porto , Porto , Portugal
| | | | - Lauren Harper
- e Western Health and Social Care Trust, Rivendell, Tyrone & Fermanagh Hospital , Omagh , UK
| | - Erich Kasten
- f Department of Psychology , MSH University of Applied Sciences & Medical University , Hamburg , Germany
| | - Sara Mondini
- g Department of General Psychology , University of Padova , Padova , Italy
| | - Bengt Persson
- h Department of Psychology , Linnaeus University , Växjö , Sweden
| | - Nataliya Varako
- i Research Center of Neurology, Lomonosov Moscow State University , Moscow , Russia
| | - Erik Hessen
- j Department of Psychology , University of Oslo , Oslo , Norway.,k Department of Neurology , Akershus University Hospital , Oslo , Norway
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Khimchenko A, Bikis C, Pacureanu A, Hieber SE, Thalmann P, Deyhle H, Schweighauser G, Hench J, Frank S, Müller‐Gerbl M, Schulz G, Cloetens P, Müller B. Hard X-Ray Nanoholotomography: Large-Scale, Label-Free, 3D Neuroimaging beyond Optical Limit. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2018; 5:1700694. [PMID: 29938163 PMCID: PMC6010902 DOI: 10.1002/advs.201700694] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Revised: 02/17/2018] [Indexed: 05/22/2023]
Abstract
There have been great efforts on the nanoscale 3D probing of brain tissues to image subcellular morphologies. However, limitations in terms of tissue coverage, anisotropic resolution, stain dependence, and complex sample preparation all hinder achieving a better understanding of the human brain functioning in the subcellular context. Herein, X-ray nanoholotomography is introduced as an emerging synchrotron radiation-based technology for large-scale, label-free, direct imaging with isotropic voxel sizes down to 25 nm, exhibiting a spatial resolution down to 88 nm. The procedure is nondestructive as it does not require physical slicing. Hence, it allows subsequent imaging by complementary techniques, including histology. The feasibility of this 3D imaging approach is demonstrated on human cerebellum and neocortex specimens derived from paraffin-embedded tissue blocks. The obtained results are compared to hematoxylin and eosin stained histological sections and showcase the ability for rapid hierarchical neuroimaging and automatic rebuilding of the neuronal architecture at the level of a single cell nucleolus. The findings indicate that nanoholotomography can complement microscopy not only by large isotropic volumetric data but also by morphological details on the sub-100 nm level, addressing many of the present challenges in brain tissue characterization and probably becoming an important tool in nanoanatomy.
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Affiliation(s)
- Anna Khimchenko
- Biomaterials Science Center (BMC)Department of Biomedical EngineeringUniversity of Basel4123AllschwilSwitzerland
| | - Christos Bikis
- Biomaterials Science Center (BMC)Department of Biomedical EngineeringUniversity of Basel4123AllschwilSwitzerland
| | - Alexandra Pacureanu
- ID16A‐NI Nano‐Imaging BeamlineEuropean Synchrotron Radiation Facility (ESRF)38043GrenobleFrance
| | - Simone E. Hieber
- Biomaterials Science Center (BMC)Department of Biomedical EngineeringUniversity of Basel4123AllschwilSwitzerland
| | - Peter Thalmann
- Biomaterials Science Center (BMC)Department of Biomedical EngineeringUniversity of Basel4123AllschwilSwitzerland
| | - Hans Deyhle
- Biomaterials Science Center (BMC)Department of Biomedical EngineeringUniversity of Basel4123AllschwilSwitzerland
| | - Gabriel Schweighauser
- Institute of PathologyDepartment of NeuropathologyBasel University Hospital4056BaselSwitzerland
| | - Jürgen Hench
- Institute of PathologyDepartment of NeuropathologyBasel University Hospital4056BaselSwitzerland
| | - Stephan Frank
- Institute of PathologyDepartment of NeuropathologyBasel University Hospital4056BaselSwitzerland
| | - Magdalena Müller‐Gerbl
- Musculoskeletal Research GroupDepartment of BiomedicineUniversity of Basel4056BaselSwitzerland
| | - Georg Schulz
- Biomaterials Science Center (BMC)Department of Biomedical EngineeringUniversity of Basel4123AllschwilSwitzerland
| | - Peter Cloetens
- ID16A‐NI Nano‐Imaging BeamlineEuropean Synchrotron Radiation Facility (ESRF)38043GrenobleFrance
| | - Bert Müller
- Biomaterials Science Center (BMC)Department of Biomedical EngineeringUniversity of Basel4123AllschwilSwitzerland
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Hessen E, Hokkanen L, Ponsford J, van Zandvoort M, Watts A, Evans J, Haaland KY. Core competencies in clinical neuropsychology training across the world. Clin Neuropsychol 2017; 32:642-656. [PMID: 29214891 DOI: 10.1080/13854046.2017.1413210] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
OBJECTIVE This work aimed to review main competency requirements from training models in countries with well-established specialties in clinical neuropsychology and to extract core competencies that likely will apply to clinical neuropsychologists regardless of regional and cultural context. METHOD We reviewed standards for post-graduate training in clinical neuropsychology from countries in Europe, Australia, and North America based on existing literature, presentations at international conferences, and from description of the training models from national psychological or neuropsychological associations. RESULTS Despite differences, the reviewed models share similar core competencies considered necessary for a specialty in clinical neuropsychology: (1) In-depth knowledge of general psychology including clinical psychology (post-graduate level), ethical, and legal standards. (2) Expert knowledge about clinically relevant brain-behavioral relationships. (3) Comprehensive knowledge about, and skills in, related clinical disciplines. (4) In-depth knowledge about and skills in neuropsychological assessment, including decision-making and diagnostic competency according to current classification of diseases. (5) Competencies in the area of diversity and culture in relation to clinical neuropsychology. (6) Communication competency of neuropsychological findings and test results to relevant and diverse audiences. (7) Knowledge about and skills in psychological and neuropsychological intervention, including treatment and rehabilitation. CONCLUSIONS All the models have undergone years of development in accordance with requirements of national health care systems in different parts of the world. Despite differences, the common core competency requirements across different regions of the world suggest generalizability of these competencies. We hope this summary can be useful as countries with less established neuropsychology training programs develop their models.
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Affiliation(s)
- Erik Hessen
- a Department of Psychology , University of Oslo , Oslo , Norway
| | - Laura Hokkanen
- b Faculty of Medicine, Department of Psychology and Logopedics , University of Helsinki , Helsinki , Finland
| | - Jennie Ponsford
- c School of Psychological Sciences , Monash University , Melbourne , Australia
| | | | - Ann Watts
- e Entabeni Hospital , Durban , South Africa
| | - Jonathan Evans
- f Institute of Health & Wellbeing , University of Glasgow , Glasgow , UK
| | - Kathleen Y Haaland
- g Department of Psychiatry and Behavioral Sciences , University of New Mexico , Albuquerque , NM , USA
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Kim YS, Yoon BE. Altered GABAergic Signaling in Brain Disease at Various Stages of Life. Exp Neurobiol 2017; 26:122-131. [PMID: 28680297 PMCID: PMC5491580 DOI: 10.5607/en.2017.26.3.122] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2017] [Revised: 05/06/2017] [Accepted: 05/15/2017] [Indexed: 01/21/2023] Open
Abstract
In the healthy brain, gamma-aminobutyric acid (GABA) is regulated by neurons and glia. This begs the question: what happens in the malfunctioning brain? There are many reasons why diseases occur, including genetic mutations, systemic problems, and environmental influences. There are also many ways in which GABA can become dysregulated, such as through alterations in its synthesis or release, and changes in systems that respond to it. Notably, dysregulation of GABA can have a large impact on the brain. To date, few reviews have examined brain diseases in which dysregulation of GABA is implicated as an underlying factor. Accordingly, the time is ripe for investigating alterations in GABAergic signaling that may play a role in changes in neuronal activity observed in the major brain disorders that occur during various stages of life. This review is meant to provide a better understanding of the role of GABA in brain health and contributor to social problems from a scientific perspective.
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Affiliation(s)
- Yoo Sung Kim
- Department of Molecular Biology, Dankook University, Cheonan 31116, Korea
| | - Bo-Eun Yoon
- Department of Molecular Biology, Dankook University, Cheonan 31116, Korea
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Ellul P, Boyer L, Groc L, Leboyer M, Fond G. Interleukin-1 β-targeted treatment strategies in inflammatory depression: toward personalized care. Acta Psychiatr Scand 2016; 134:469-484. [PMID: 27744648 DOI: 10.1111/acps.12656] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/21/2016] [Indexed: 12/15/2022]
Abstract
OBJECTIVES It is unknown whether a cytokine signature may help the identification of subgroup of patient who would respond to personalized treatment. As interleukin-1 beta (Il-1β) seems to play a major role in mood disorder, a systematic review and meta-analysis of its potential role in major depressive disorder (MDD) was carried out. METHODS A systematic search was performed to identify appropriate MDD vs. control studies pertaining to Il-1β. Methodological quality and possible moderators were also assessed. RESULTS A total of 1922 studies were identified, and 53 articles were selected. Results showed an association between increased blood IL-1β and MDD in high-quality studies only. No association with age was found. No IL-1β gene-related polymorphisms has been associated with MDD. No effect of antidepressant on IL-1β level has been found, although the antidepressants investigated were various. Qualitative analyses indicate that MDD coupled to a history of childhood trauma may be a subgroup for IL-1β -targeted therapies. No difference in studies utilizing a stimulation method has been identified to date. CONCLUSIONS The present work has confirmed IL-1β as a biological marker of interest for innovative MDD treatments. However, further studies are needed to clarify the patients with MDD who may benefit from these therapies.
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Affiliation(s)
- P Ellul
- INSERM U955, eq15 Translational Psychiatry team, Paris Est University, DHU Pe-PSY, Pôle de Psychiatrie et d'addictologie des Hôpitaux Universitaires H Mondor, Créteil, France
| | - L Boyer
- EA 3279 Research Unit - Public Health: Chronic Diseases and Quality of Life, Aix-Marseille University, Marseille, France
| | - L Groc
- CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, Bordeaux University, Bordeaux, France
| | - M Leboyer
- INSERM U955, eq15 Translational Psychiatry team, Paris Est University, DHU Pe-PSY, Pôle de Psychiatrie et d'addictologie des Hôpitaux Universitaires H Mondor, Créteil, France.,Fondation FondaMental, Créteil, France
| | - G Fond
- INSERM U955, eq15 Translational Psychiatry team, Paris Est University, DHU Pe-PSY, Pôle de Psychiatrie et d'addictologie des Hôpitaux Universitaires H Mondor, Créteil, France.,Fondation FondaMental, Créteil, France
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Hughes T, Hansson L, Sønderby IE, Athanasiu L, Zuber V, Tesli M, Song J, Hultman CM, Bergen SE, Landén M, Melle I, Andreassen OA, Djurovic S. A Loss-of-Function Variant in a Minor Isoform of ANK3 Protects Against Bipolar Disorder and Schizophrenia. Biol Psychiatry 2016; 80:323-330. [PMID: 26682468 DOI: 10.1016/j.biopsych.2015.09.021] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2015] [Revised: 09/10/2015] [Accepted: 09/24/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND Ankyrin-3 (ANK3) was one of the first genes to reach significance in a bipolar disorder genome-wide association study. Many subsequent association studies confirmed this finding and implicated this gene in schizophrenia. However, the exact nature of the role of ANK3 in the pathophysiology remains elusive. In particular, the specific isoforms involved and the nature of the imbalance are unknown. METHODS We genotyped a Norwegian sample of 402 patients with bipolar disorder, 293 patients with schizophrenia, and 330 healthy control subjects genome-wide with the Illumina Human Exome BeadChip. We performed allelic association tests at the genome-wide and gene levels and found a significantly associated single nucleotide polymorphism in a splice site of ANK3. We replicated this finding in two other samples and studied the functional effect of this single nucleotide polymorphism by performing quantitative polymerase chain reaction on the affected exon junction in complementary DNA from blood total RNA. RESULTS The splice site single nucleotide polymorphism (rs41283526) is located in an alternatively spliced exon of ANK3 and has a strong and significant protective effect against bipolar disorder (odds ratio = .31) and schizophrenia (odds ratio = .21). The minor allele of rs41283526 is a loss-of-function variant that disables the correct splicing of the transcript. Data from the BrainSpan human developmental transcriptome show that the exon bearing this variant is expressed only in a minor isoform of ANK3, the transcription of which is initiated in early adolescence. CONCLUSIONS Our results suggest that an elevated expression of this transcript starting in adolescence may be an important factor in the pathophysiology of schizophrenia and bipolar disorder.
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Affiliation(s)
- Timothy Hughes
- Department of Medical Genetics, Oslo; NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo.
| | - Lars Hansson
- Department of Medical Genetics, Oslo; NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo
| | - Ida E Sønderby
- Department of Medical Genetics, Oslo; NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo
| | - Lavinia Athanasiu
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo; NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo
| | - Verena Zuber
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo; NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo; Prostate Cancer Research Group, Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo
| | - Martin Tesli
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo; NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo
| | - Jie Song
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm
| | - Christina M Hultman
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm
| | - Sarah E Bergen
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm
| | - Mikael Landén
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
| | - Ingrid Melle
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo; NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway
| | | | - Srdjan Djurovic
- Department of Medical Genetics, Oslo; NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway
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Bigler ED. Systems Biology, Neuroimaging, Neuropsychology, Neuroconnectivity and Traumatic Brain Injury. Front Syst Neurosci 2016; 10:55. [PMID: 27555810 PMCID: PMC4977319 DOI: 10.3389/fnsys.2016.00055] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2016] [Accepted: 06/08/2016] [Indexed: 01/03/2023] Open
Abstract
The patient who sustains a traumatic brain injury (TBI) typically undergoes neuroimaging studies, usually in the form of computed tomography (CT) and magnetic resonance imaging (MRI). In most cases the neuroimaging findings are clinically assessed with descriptive statements that provide qualitative information about the presence/absence of visually identifiable abnormalities; though little if any of the potential information in a scan is analyzed in any quantitative manner, except in research settings. Fortunately, major advances have been made, especially during the last decade, in regards to image quantification techniques, especially those that involve automated image analysis methods. This review argues that a systems biology approach to understanding quantitative neuroimaging findings in TBI provides an appropriate framework for better utilizing the information derived from quantitative neuroimaging and its relation with neuropsychological outcome. Different image analysis methods are reviewed in an attempt to integrate quantitative neuroimaging methods with neuropsychological outcome measures and to illustrate how different neuroimaging techniques tap different aspects of TBI-related neuropathology. Likewise, how different neuropathologies may relate to neuropsychological outcome is explored by examining how damage influences brain connectivity and neural networks. Emphasis is placed on the dynamic changes that occur following TBI and how best to capture those pathologies via different neuroimaging methods. However, traditional clinical neuropsychological techniques are not well suited for interpretation based on contemporary and advanced neuroimaging methods and network analyses. Significant improvements need to be made in the cognitive and behavioral assessment of the brain injured individual to better interface with advances in neuroimaging-based network analyses. By viewing both neuroimaging and neuropsychological processes within a systems biology perspective could represent a significant advancement for the field.
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Affiliation(s)
- Erin D. Bigler
- Department of Psychology, Neuroscience Center, Brigham Young UniversityProvo, UT, USA
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Shorvon S. Neurology Worldwide. Neurology 2016. [DOI: 10.1002/9781118486160.ch1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
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Wagner CJ, Metzger FG, Sievers C, Marschall U, L'hoest H, Stollenwerk B, Stock S. Depression-related treatment and costs in Germany: Do they change with comorbidity? A claims data analysis. J Affect Disord 2016; 193:257-66. [PMID: 26773923 DOI: 10.1016/j.jad.2015.12.068] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Revised: 12/07/2015] [Accepted: 12/26/2015] [Indexed: 10/22/2022]
Abstract
BACKGROUND Existing diverse bottom-up estimations of direct costs associated with depression in Germany motivated a detailed patient-level analysis of depression-related treatment (DRT), -costs (DRC) and Comorbidity. METHODS A large sickness fund's claims data was used to retrospectively identify patients aged 18-65 years with new-onset depression treatment between January 1st and February 15th 2010, and follow them until December 31st 2010, describe DRT, estimate associated DRC, and predict DRC with a generalised linear model. RESULTS A total of 18,139 patients were analysed. Mean direct DRC were €783. Predictors of DRC regarding psychiatric comorbidities were: "Delusion, psychotic disorders and personality disorders" (DRC-ratio 1.72), "Alcohol/drug addiction" (1.82), "abuse of alcohol/drugs" (1.57). Predictors of DRC regarding medical comorbidities were: "Rheumatoid arthritis" (0.77), "atherosclerosis" (0.65), "pregnancy" (0.66), and "Osteoarthritis" (1.87). Of all patients, 60.8% received their most intense/specialised DRT from a general practitioner, a medical specialist (23.7%), a psychotherapist (8.0%), a medical specialist and psychotherapist (2.9%), or in hospital (4.6%). Serious psychiatric comorbidity nearly tripled depression-related hospitalisation rates. LIMITATIONS Seasonal affective disorder and missing psychiatric outpatient clinic data must be considered. CONCLUSIONS Estimated DRC are significantly below the assessment of the German national guideline. Differing definitions of observation period and cost attribution might explain differing German DRC results. Signs of hospital psychiatric comorbidity bias indicate overestimation of hospital DRC. Identified associations of DRC with certain medical diseases in older adults warrant further research. Up to one quarter of patients with severe depression diagnosis might lack specialist treatment.
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Affiliation(s)
- Christoph J Wagner
- Institute for Health Economics and Clinical Epidemiology, Cologne University Hospital, Germany.
| | - Florian G Metzger
- Department of Psychiatry and Psychotherapy and Geriatric Center, Tuebingen University Hospital, Germany
| | - Christoph Sievers
- BARMER GEK Statutory Health Insurance Fund, Headquarters, 42285 Wuppertal, Germany
| | - Ursula Marschall
- BARMER GEK Statutory Health Insurance Fund, Headquarters, 42285 Wuppertal, Germany
| | - Helmut L'hoest
- BARMER GEK Statutory Health Insurance Fund, Headquarters, 42285 Wuppertal, Germany
| | - Bjoern Stollenwerk
- Institute of Health Economics and Health Care Management, Helmholtz Zentrum Muenchen, Germany
| | - Stephanie Stock
- Institute for Health Economics and Clinical Epidemiology, Cologne University Hospital, Germany
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Effects of the Financial Crisis on Psychotropic Drug Consumption in a Cohort from a Semi-Urban Region in Catalonia, Spain. PLoS One 2016; 11:e0148594. [PMID: 26872210 PMCID: PMC4752355 DOI: 10.1371/journal.pone.0148594] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Accepted: 01/21/2016] [Indexed: 01/20/2023] Open
Abstract
Purpose Evidence of whether the recent economic crisis has or has not had an effect on psychotropic drug consumption is very scarce. Our objective was to determine if there had in fact been an increase in psychotropic drug use as a result of the financial crisis. Methods In our study a retrospective cohort (between January 1, 2005, and December 31, 2012) was made up of individuals from the general population in a region in the northeast of Catalonia, Spain. We specified a generalized linear mixed model along with combined ‘selection on observables’ as (propensity scoring) matching and ‘selection on unobservables’ as (random coefficient) the panel data model methods, and performed inferences using a Bayesian framework. Results In the period following the economic crisis (post 2009), there was an increase in the consumption of psychotropic drugs which was significantly higher among those who had already been consuming psychotropic drugs prior to 2009 and those most likely to be unemployed. The increase was of greater significance when consumption was measured by the number of drugs being taken, rather than by the defined daily dose (DDD), with the greatest increase occurring in 2011; the very year in which Spain was most affected by the crisis. Conclusions Once the financial crisis had ended, there was an increase in the severity, rather than the intensity, of mental health disorders in individuals who had already had disorders before the crisis. This increase occurred in those most likely to be unemployed, and the severity was accentuated in the toughest year of the economic crisis.
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Akintunde JK, Oboh G. Subchronic exposure to leachate activates key markers linked with neurological disorder in Wistar male rat. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2015; 22:18541-18553. [PMID: 26362636 DOI: 10.1007/s11356-015-5327-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2014] [Accepted: 08/27/2015] [Indexed: 06/05/2023]
Abstract
The linking of various environmental chemicals exposure to neurodegenerative disorders is current. This study was undertaken to elucidate the toxic effects and the underlying biochemical mechanism of leachate obtained from Elewi Odo municipal battery recycling site (EOMABRL) using key markers of neuronal damage in rat via an oral route. Analysis of the concentrations of heavy metals showed that lead, cadmium, nickel, chromium, manganese, and iron were higher than the acceptable limits set by the regulatory authority-the World Health Organization. Whereas, copper, zinc, and cobalt were lower than permissible limits. EOMABRL was administered at 0, 20, 40, 60, 80, and 100% concentrations to adult male rats for 60 days. An in vitro study was also carried out in the cerebellum to assess cholinesterase biochemistry assays. Following exposure, brain was collected to determine the antioxidant status. EOMABRL administration significantly increased superoxide dismutase (SOD) and catalase (CAT) activities, and a sequential decrease in reduced glutathione (GSH) level with a concomitant increase in the accumulation of hydrogen peroxide (H2O2) and malondialdehyde (MDA) level was observed, when compared with the control. The treated rat had a significant (P < 0.05) increase in the activities of acetycholinesterase (AChE) and butyrylcholinesterase (BuChE). Taken together, these findings conclude that some possible mechanisms by which EOMABRL elicits neuronal disorder in male rat could be through the activation of AChE and BuChE and induction of oxidative stress with necrosis of neuronal cells.
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Affiliation(s)
- J K Akintunde
- Functional Foods, Nutraceuticals and Phytomedicine Research Laboratory, Department of Biochemistry, Federal University of Technology, P.M.B. 704, Akure, 340001, Nigeria.
- Drug Metabolism and Molecular Environmental Toxicology Research Laboratory, Biochemistry Unit, Department of Biosciences and Biotechnology, College of Pure and Applied Sciences, Kwara State University, Malete, P.M.B. 1530, Ilorin, Nigeria.
| | - G Oboh
- Functional Foods, Nutraceuticals and Phytomedicine Research Laboratory, Department of Biochemistry, Federal University of Technology, P.M.B. 704, Akure, 340001, Nigeria.
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González-Quintanilla V, Toriello M, Palacio E, González-Gay MA, Castillo J, Montes S, Martínez-Nieto R, Fernandez J, Rojo A, Gutiérrez S, Pons E, Oterino A. Systemic and cerebral endothelial dysfunction in chronic migraine. A case-control study with an active comparator. Cephalalgia 2015; 36:552-60. [PMID: 26395894 DOI: 10.1177/0333102415607857] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2015] [Accepted: 08/30/2015] [Indexed: 01/03/2023]
Abstract
BACKGROUND AND OBJECTIVE Unlike migraine and migraine with aura, little information exists regarding chronic migraine (CM) as a risk factor for cardiovascular disease. In this study we aim to determine whether an association between CM and endothelial dysfunction exists. METHODS Individuals 18 years and older diagnosed with episodic migraine (EM) and CM according to ICHD criteria were studied. After an overnight fast and abstinence from vasoactive drugs, ultrasound studies were performed and blood samples taken from patients and matched controls according to internationally agreed on protocols. RESULTS A total of 113 individuals were enrolled (35 CM, 37 EM, 41 controls). CM patients had a lower percentage of flow-mediated vasodilation (FMD; difference of means = 5.03%; p = 1.0E-6) and breath-holding index (BHI; difference of means 0.754; p = 2.0E-6), as well as increased carotid intima media thickness (cIMT; difference of means = 0.128 mm; p = 7.0E-5) than controls. The EM patients and controls comparison found similar, but less pronounced, differences: decreased BHI (p = 0.031), and increased cIMT (p = 0.028). Fibrinogen (r = 0.277; p = 0.006), C-reactive protein (r = 0.288; p = 0.003), and erythrocyte rate sedimentation (r = 0.298; p = 0.002) also correlated with cIMT, and inversely with BHImV and FMD. CONCLUSIONS Migraine is associated with systemic and cerebral endothelial dysfunction demonstrated by ultrasound studies and biological markers. The degree of these changes was strongly associated with the severity of migraine. Our data indicate that migraine may be a cerebral disorder with systemic endothelial damage.
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Affiliation(s)
| | - María Toriello
- Service of Neurology, Hospital Universitario Marqués de Valdecilla, IDIVAL, Spain
| | - Enrique Palacio
- Service of Neurology, Hospital Universitario Marqués de Valdecilla, IDIVAL, Spain
| | - Miguel A González-Gay
- Service of Rheumatology, Hospital Universitario Marqués de Valdecilla, IDIVAL, Spain
| | - Jesús Castillo
- Health Service of Camargo Costa, Servicio Cántabro de Salud, Spain
| | - Silvia Montes
- Health Service of Camargo Costa, Servicio Cántabro de Salud, Spain
| | | | - Jenifer Fernandez
- Service of Neurology, Hospital Universitario Marqués de Valdecilla, IDIVAL, Spain
| | - Alvaro Rojo
- Service of Neurology, Hospital Universitario Marqués de Valdecilla, IDIVAL, Spain
| | - Silvia Gutiérrez
- Service of Neurology, Hospital Universitario Marqués de Valdecilla, IDIVAL, Spain
| | - Enar Pons
- Service of Neurology, Hospital Universitario Marqués de Valdecilla, IDIVAL, Spain
| | - Agustín Oterino
- Service of Neurology, Hospital Universitario Marqués de Valdecilla, IDIVAL, Spain
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Camus S, Ko WKD, Pioli E, Bezard E. Why bother using non-human primate models of cognitive disorders in translational research? Neurobiol Learn Mem 2015; 124:123-9. [PMID: 26135120 DOI: 10.1016/j.nlm.2015.06.012] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Accepted: 06/23/2015] [Indexed: 01/24/2023]
Abstract
Although everyone would agree that successful translation of therapeutic candidates for central nervous disorders should involve non-human primate (nhp) models of cognitive disorders, we are left with the paucity of publications reporting either the target validation or the actual preclinical testing in heuristic nhp models. In this review, we discuss the importance of nhps in translational research, highlighting the advances in technological/methodological approaches for 'bridging the gap' between preclinical and clinical experiments. In this process, we acknowledge that nhps remain a vital tool for the investigation of complex cognitive functions, given their resemblance to humans in aspects of behaviour, anatomy and physiology. The recent improvements made for a suitable nhp model in cognitive research, including new surrogates of disease and application of innovative methodological approaches, are continuous strides for reaching efficient translation for human benefit. This will ultimately aid the development of innovative treatments against the current and future threat of neurological and psychiatric disorders to the global population.
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Affiliation(s)
| | - Wai Kin D Ko
- Motac Neuroscience Ltd, Manchester, United Kingdom
| | - Elsa Pioli
- Motac Neuroscience Ltd, Manchester, United Kingdom
| | - Erwan Bezard
- Motac Neuroscience Ltd, Manchester, United Kingdom; Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France
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Andreassen OA, Harbo HF, Wang Y, Thompson WK, Schork AJ, Mattingsdal M, Zuber V, Bettella F, Ripke S, Kelsoe JR, Kendler KS, O'Donovan MC, Sklar P, The Psychiatric Genomics Consortium (PGC) Bipolar Disorder and Schizophrenia Work Groups 16, The International Multiple Sclerosis Genetics Consortium (IMSGC), McEvoy LK, Desikan RS, Lie BA, Djurovic S, Dale AM. Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder: differential involvement of immune-related gene loci. Mol Psychiatry 2015; 20:207-14. [PMID: 24468824 PMCID: PMC4356743 DOI: 10.1038/mp.2013.195] [Citation(s) in RCA: 163] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2013] [Revised: 11/13/2013] [Accepted: 11/25/2013] [Indexed: 12/11/2022]
Abstract
Converging evidence implicates immune abnormalities in schizophrenia (SCZ), and recent genome-wide association studies (GWAS) have identified immune-related single-nucleotide polymorphisms (SNPs) associated with SCZ. Using the conditional false discovery rate (FDR) approach, we evaluated pleiotropy in SNPs associated with SCZ (n=21,856) and multiple sclerosis (MS) (n=43,879), an inflammatory, demyelinating disease of the central nervous system. Because SCZ and bipolar disorder (BD) show substantial clinical and genetic overlap, we also investigated pleiotropy between BD (n=16,731) and MS. We found significant genetic overlap between SCZ and MS and identified 21 independent loci associated with SCZ, conditioned on association with MS. This enrichment was driven by the major histocompatibility complex (MHC). Importantly, we detected the involvement of the same human leukocyte antigen (HLA) alleles in both SCZ and MS, but with an opposite directionality of effect of associated HLA alleles (that is, MS risk alleles were associated with decreased SCZ risk). In contrast, we found no genetic overlap between BD and MS. Considered together, our findings demonstrate genetic pleiotropy between SCZ and MS and suggest that the MHC signals may differentiate SCZ from BD susceptibility.
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Affiliation(s)
- O A Andreassen
- NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
- Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA
| | - H F Harbo
- Department of Neurology, Oslo University Hospital, Ullevål, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Y Wang
- NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
- Multimodal Imaging Laboratory, University of California at San Diego, La Jolla, CA, USA
- Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA
| | - W K Thompson
- Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA
| | - A J Schork
- Multimodal Imaging Laboratory, University of California at San Diego, La Jolla, CA, USA
- Cognitive Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA
- Center for Human Development, University of California at San Diego, La Jolla, CA, USA
| | - M Mattingsdal
- NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Sørlandet Hospital, Kristiansand, Norway
| | - V Zuber
- NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
- Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, Norway
| | - F Bettella
- NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
| | - S Ripke
- Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
- Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - J R Kelsoe
- Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA
| | - K S Kendler
- Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
| | - M C O'Donovan
- MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Heath Park, Cardiff, UK
| | - P Sklar
- The Division of Psychiatric Genetics and Genomics, Mount Sinai School of Medicine, New York, NY, USA
| | - The Psychiatric Genomics Consortium (PGC) Bipolar Disorder and Schizophrenia Work Groups16
- NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
- Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA
- Department of Neurology, Oslo University Hospital, Ullevål, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Multimodal Imaging Laboratory, University of California at San Diego, La Jolla, CA, USA
- Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA
- Cognitive Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA
- Center for Human Development, University of California at San Diego, La Jolla, CA, USA
- Sørlandet Hospital, Kristiansand, Norway
- Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, Norway
- Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
- Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
- MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Heath Park, Cardiff, UK
- The Division of Psychiatric Genetics and Genomics, Mount Sinai School of Medicine, New York, NY, USA
- PGC co-authors are listed separately in Supplementary Information
- Department of Radiology, University of California, San Diego, La Jolla, CA, USA
- Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway
| | - The International Multiple Sclerosis Genetics Consortium (IMSGC)
- NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
- Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA
- Department of Neurology, Oslo University Hospital, Ullevål, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Multimodal Imaging Laboratory, University of California at San Diego, La Jolla, CA, USA
- Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA
- Cognitive Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA
- Center for Human Development, University of California at San Diego, La Jolla, CA, USA
- Sørlandet Hospital, Kristiansand, Norway
- Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, Norway
- Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
- Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
- MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Heath Park, Cardiff, UK
- The Division of Psychiatric Genetics and Genomics, Mount Sinai School of Medicine, New York, NY, USA
- PGC co-authors are listed separately in Supplementary Information
- Department of Radiology, University of California, San Diego, La Jolla, CA, USA
- Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway
| | - L K McEvoy
- Multimodal Imaging Laboratory, University of California at San Diego, La Jolla, CA, USA
- Department of Radiology, University of California, San Diego, La Jolla, CA, USA
| | - R S Desikan
- Multimodal Imaging Laboratory, University of California at San Diego, La Jolla, CA, USA
- Department of Radiology, University of California, San Diego, La Jolla, CA, USA
| | - B A Lie
- Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway
| | - S Djurovic
- NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
- Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway
| | - A M Dale
- Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA
- Multimodal Imaging Laboratory, University of California at San Diego, La Jolla, CA, USA
- Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA
- Department of Radiology, University of California, San Diego, La Jolla, CA, USA
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Tohka J. Partial volume effect modeling for segmentation and tissue classification of brain magnetic resonance images: A review. World J Radiol 2014; 6:855-864. [PMID: 25431640 PMCID: PMC4241492 DOI: 10.4329/wjr.v6.i11.855] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2014] [Revised: 09/03/2014] [Accepted: 09/24/2014] [Indexed: 02/06/2023] Open
Abstract
Quantitative analysis of magnetic resonance (MR) brain images are facilitated by the development of automated segmentation algorithms. A single image voxel may contain of several types of tissues due to the finite spatial resolution of the imaging device. This phenomenon, termed partial volume effect (PVE), complicates the segmentation process, and, due to the complexity of human brain anatomy, the PVE is an important factor for accurate brain structure quantification. Partial volume estimation refers to a generalized segmentation task where the amount of each tissue type within each voxel is solved. This review aims to provide a systematic, tutorial-like overview and categorization of methods for partial volume estimation in brain MRI. The review concentrates on the statistically based approaches for partial volume estimation and also explains differences to other, similar image segmentation approaches.
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Scholten AC, Haagsma JA, Panneman MJM, van Beeck EF, Polinder S. Traumatic brain injury in the Netherlands: incidence, costs and disability-adjusted life years. PLoS One 2014; 9:e110905. [PMID: 25343447 PMCID: PMC4208832 DOI: 10.1371/journal.pone.0110905] [Citation(s) in RCA: 70] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2014] [Accepted: 09/20/2014] [Indexed: 11/26/2022] Open
Abstract
OBJECTIVE Traumatic brain injury (TBI) is a major cause of death and disability, leading to great personal suffering and huge costs to society. Integrated knowledge on epidemiology, economic consequences and disease burden of TBI is scarce but essential for optimizing healthcare policy and preventing TBI. This study aimed to estimate incidence, cost-of-illness and disability-adjusted life years (DALYs) of TBI in the Netherlands. METHODS This study included data on all TBI patients who were treated at an Emergency Department (ED - National Injury Surveillance System), hospitalized (National Medical Registration), or died due to their injuries in the Netherlands between 2010-2012. Direct healthcare costs and indirect costs were determined using the incidence-based Dutch Burden of Injury Model. Disease burden was assessed by calculating years of life lost (YLL) owing to premature death, years lived with disability (YLD) and DALYs. Incidence, costs and disease burden were stratified by age and gender. RESULTS TBI incidence was 213.6 per 100,000 person years. Total costs were €314.6 (USD $433.8) million per year and disease burden resulted in 171,200 DALYs (on average 7.1 DALYs per case). Men had highest mean costs per case (€19,540 versus €14,940), driven by indirect costs. 0-24-year-olds had high incidence and disease burden but low economic costs, whereas 25-64-year-olds had relatively low incidence but high economic costs. Patients aged 65+ had highest incidence, leading to considerable direct healthcare costs. 0-24-year-olds, men aged 25-64 years, traffic injury victims (especially bicyclists) and home and leisure injury victims (especially 0-5-year-old and elderly fallers) are identified as risk groups in TBI. CONCLUSIONS The economic and health consequences of TBI are substantial. The integrated approach of assessing incidence, costs and disease burden enables detection of important risk groups in TBI, development of prevention programs that target these risk groups and assessment of the benefits of these programs.
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Affiliation(s)
- Annemieke C. Scholten
- Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Juanita A. Haagsma
- Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands
| | | | - Ed F. van Beeck
- Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Suzanne Polinder
- Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands
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Abstract
Brain diseases represent a considerable social and economic burden in Europe. With yearly costs of about 800 billion euros and an estimated 179 million people afflicted in 2010, brain diseases are an unquestionable emergency and a grand challenge for neuroscientists.
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Affiliation(s)
- Monica DiLuca
- Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milano, Italy.
| | - Jes Olesen
- Department of Neurology N39, University of Copenhagen, Glostrup, 2600, Denmark.
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Kuo A, Smith MT. Theoretical and practical applications of the intracerebroventricular route for CSF sampling and drug administration in CNS drug discovery research: A mini review. J Neurosci Methods 2014; 233:166-71. [DOI: 10.1016/j.jneumeth.2014.06.006] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2014] [Revised: 06/06/2014] [Accepted: 06/09/2014] [Indexed: 12/12/2022]
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Fond G, Hamdani N, Kapczinski F, Boukouaci W, Drancourt N, Dargel A, Oliveira J, Le Guen E, Marlinge E, Tamouza R, Leboyer M. Effectiveness and tolerance of anti-inflammatory drugs' add-on therapy in major mental disorders: a systematic qualitative review. Acta Psychiatr Scand 2014; 129:163-79. [PMID: 24215721 DOI: 10.1111/acps.12211] [Citation(s) in RCA: 124] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/20/2013] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To provide a systematic review of the literature regarding the efficacy of anti-inflammatory drugs in three major mental disorders [major depressive disorder (MDD), schizophrenia and bipolar disorders]. METHOD Four databases were explored, without any year or language restrictions. The baseline search paradigm was limited to open-labelled clinical and randomized controlled trials (RCTs). RESULTS Four major classes of anti-inflammatory drugs were identified, namely polyunsaturated fatty acids (PUFAs), cyclooxygenase (COX) inhibitors, anti-TNFalpha and minocycline. Effectiveness and benefit/risk ratio of each class in MDD, bipolar disorders and schizophrenia was detailed when data were available. Several meta-analyses indicated effectiveness of PUFAs in MDD with a good tolerance profile. One meta-analysis indicated that COX-2 specific inhibitors showed effectiveness in schizophrenia. Anti-TNFalpha showed important effectiveness in resistant MDD with blood inflammatory abnormalities. Minocycline showed effectiveness in schizophrenia. CONCLUSION Polyunsaturated fatty acids seem to have the best benefit/risk ratio profile but proved their effectiveness only in MDD. A number of anti-inflammatory drugs are available as adjunct treatment for treatment-resistant patients with MDD, schizophrenia and bipolar disorder. If used with caution regarding their possible side-effects, they may be reasonable therapeutic alternatives for resistant symptomatology.
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Affiliation(s)
- G Fond
- Pôle de psychiatrie des hôpitaux universitaires H Mondor, University Paris Est-Créteil, INSERM U955, Eq Psychiatrie Génétique, Fondation FondaMental Fondation de coopération scientifique en santé mentale, Créteil, France
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Le HH, Hodgkins P, Postma MJ, Kahle J, Sikirica V, Setyawan J, Erder MH, Doshi JA. Economic impact of childhood/adolescent ADHD in a European setting: the Netherlands as a reference case. Eur Child Adolesc Psychiatry 2014; 23:587-98. [PMID: 24166532 PMCID: PMC4077218 DOI: 10.1007/s00787-013-0477-8] [Citation(s) in RCA: 86] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2013] [Accepted: 09/24/2013] [Indexed: 11/22/2022]
Abstract
Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent psychiatric disorder in children/adolescents. This study reviews available European-based studies of ADHD-related costs and applies the findings to the Netherlands to estimate annual national costs for children/adolescents from a societal perspective. A systematic literature search was conducted for primary studies in Europe, published January 1, 1990 through April 23, 2013. Per-person cost estimates were converted to 2012 Euros and used to estimate annual national ADHD-related costs based on the Dutch 2011 census, ADHD prevalence rates, family composition, and employment rates. Seven studies met the inclusion criteria. The average total ADHD-related costs ranged from €9,860 to 14,483 per patient and annual national costs were between €1,041 and €1,529 million (M). The largest cost category was education (€648 M), representing 62 and 42 % of the low- and high-value overall national estimates, respectively. By comparison, ADHD patient healthcare costs ranged between €84 M (8 %) and €377 M (25 %), and social services costs were €4.3 M (0.3-0.4 %). While the majority of the costs were incurred by ADHD patients themselves, €161 M (11-15 %) was healthcare costs to family members that were attributable to having an ADHD child/adolescent. In addition, productivity losses of family members were €143-€339 M (14-22 %). Despite uncertainties because of the small number of studies identified and the wide range in the national cost estimates, our results suggest that ADHD imposes a significant economic burden on multiple public sectors in Europe. The limited number of European-based studies examining the economic burden of ADHD highlights the need for more research in this area.
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Affiliation(s)
- Hoa H. Le
- PharmacoEpidemiology & PharmacoEconomics, University of Groningen, Antonius Deusinglaan 1, 9713 Groningen, The Netherlands
| | - Paul Hodgkins
- Global Health Economics and Outcomes Research, Shire, 725 Chesterbrook Boulevard, Wayne, PA 19087 USA
| | - Maarten J. Postma
- PharmacoEpidemiology & PharmacoEconomics, University of Groningen, Antonius Deusinglaan 1, 9713 Groningen, The Netherlands
| | - Jennifer Kahle
- BPS International, 3830 Valley Centre #705 PMB503, San Diego, CA 92130 USA
| | - Vanja Sikirica
- Global Health Economics and Outcomes Research, Shire, 725 Chesterbrook Boulevard, Wayne, PA 19087 USA
| | - Juliana Setyawan
- Global Health Economics and Outcomes Research, Shire, 725 Chesterbrook Boulevard, Wayne, PA 19087 USA
| | - M. Haim Erder
- Global Health Economics and Outcomes Research, Shire, 725 Chesterbrook Boulevard, Wayne, PA 19087 USA
| | - Jalpa A. Doshi
- General Internal Medicine, University of Pennsylvania, 1222 Blockley Hall, Philadelphia, PA 19104-6021 USA
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Thomas S, Pai N, Dawes K, Wilson C, Williams V. Updating medical school psychiatry curricula to meet projected mental health needs. Australas Psychiatry 2013; 21:578-82. [PMID: 23996665 DOI: 10.1177/1039856213500092] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
OBJECTIVE In view of the growing disease burden of mental disorders, we consider the pressing need to update medical school psychiatry education to better equip doctors to recognise and treat these conditions. Key challenges to the delivery of medical school mental health curricula, and possible directions for reform, are reviewed with the aims of stimulating collaboration and enhancing the efficiency across schools. CONCLUSIONS In Australia, medical school expansion provides opportunities to prepare many training doctors to meet growing mental health care needs. Despite this, published reviews of practice and curriculum models are notably lacking. Australia, unlike other countries, has yet to agree on a core curriculum in medical school psychiatry, with practices varying widely between schools. Curricula should equip doctors to better recognise and treat common mental disorders during early stages, as well as preparing some for specialist psychiatry training. High-quality, multidisciplinary teaching in varied clinical settings may boost teaching resources. Additionally, medical education provides opportunities to better equip doctors to take care of their own mental health. Key challenges are to achieve a consensus on core curricula across Australian medical schools, and an appropriate proportion of medical school curriculum time for mental disorders, relative to their complexity and large disease burden.
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Affiliation(s)
- Susan Thomas
- Lecturer in Mental Health and Behavioural Sciences, Graduate School of Medicine, University of Wollongong, Wollongong, NSW, Australia
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Birngruber T, Ghosh A, Perez-Yarza V, Kroath T, Ratzer M, Pieber TR, Sinner F. Cerebral open flow microperfusion: A newin vivotechnique for continuous measurement of substance transport across the intact blood-brain barrier. Clin Exp Pharmacol Physiol 2013; 40:864-71. [DOI: 10.1111/1440-1681.12174] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2013] [Revised: 08/09/2013] [Accepted: 09/11/2013] [Indexed: 11/28/2022]
Affiliation(s)
- Thomas Birngruber
- Joanneum Research GmbH; HEALTH-Institute for Biomedicine and Health Sciences; Graz Austria
| | - Arijit Ghosh
- Department of Internal Medicine; Division of Endocrinology and Metabolism; Medical University of Graz; Graz Austria
| | - Veronica Perez-Yarza
- Department of Internal Medicine; Division of Endocrinology and Metabolism; Medical University of Graz; Graz Austria
| | - Thomas Kroath
- Joanneum Research GmbH; HEALTH-Institute for Biomedicine and Health Sciences; Graz Austria
| | - Maria Ratzer
- Joanneum Research GmbH; HEALTH-Institute for Biomedicine and Health Sciences; Graz Austria
| | - Thomas R Pieber
- Joanneum Research GmbH; HEALTH-Institute for Biomedicine and Health Sciences; Graz Austria
- Department of Internal Medicine; Division of Endocrinology and Metabolism; Medical University of Graz; Graz Austria
| | - Frank Sinner
- Joanneum Research GmbH; HEALTH-Institute for Biomedicine and Health Sciences; Graz Austria
- Department of Internal Medicine; Division of Endocrinology and Metabolism; Medical University of Graz; Graz Austria
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