Dementias and Microbiota Composition: Is Possible to Revert the Dementia Symptoms Reverting the Microbiota Composition?
NCT ID: NCT05943925
Last Updated: 2023-07-13
Study Results
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Basic Information
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UNKNOWN
240 participants
OBSERVATIONAL
2021-04-16
2025-02-01
Brief Summary
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Dementia is an umbrella term for several diseases, being Alzheimer's disease (AD) the most common form, contributing to 60-70% of cases. Other major forms include Lewy bodies Dementias (LBDs) and frontotemporal dementia (FTD).
The role of the gastrointestinal microbiota in human brain development and function is an area of increasing interest and research. A large number of studies suggest that the gut microbiota can influence the brain, cognition and behavior of the patients, and also modulate brain plasticity, modifying brain chemistry via various mechanisms like neural, immune and endocrine Within these last two years some studies have showed differences in the microbiota of the AD patients from healthy controls. In this sense, increasing number of studies, most of them in animal models, support the notion that probiotics have significant benefit in maintaining homeostasis of the Central Nervous System. And recent studies try to replicate this finding in AD patients with controversial results.
The main objective of DEM-BIOTA project is to improve the knowledge of the relationship between microbiota and dementia. DEM-BIOTA will explore the microbiota differences between dementias: AD, LBDs, that includes: Parkinson disease dementia (PDD) and Lewy Body Dementia (LBD) and FTD-behavioral variant, also in Mild Cognitive Impairment (MCI) to study the progression; in our context (Mediterranean diet and lifestyle) and characterize them in relation to neurocognitive and neuropsychiatric symptoms as well as patient functionality (dependency level). Moreover, the capacity of a probiotic compound in reverting or improving neurocognitive and neuropsychiatric symptoms and patient functionality in a sample of AD patients will be also studied.
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Detailed Description
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In the few studies already conducted, the patients included were diagnosticated of AD or it were included patients from all type of dementias. Even though AD is the most common type of dementia, there are more types of dementias that should be considered differentially as the features are significantly different. Given the diversity through the symptoms across dementias, a characterization of the gut microbiota of different types of dementia will be described, specifically, AD, LBDs: LBD and PDD separately, and FTD-behavioral variant. Furthermore, MCI subjects will be also studied in order to explore the microbiota changes before the onset of dementia (taking into account the high percentage of MCI that progress to dementia). These studies could reveal a risk factor compositional microbiota to develop dementia. The hypothesis is that microbiota will differ through different dementias and could be related to the feature symptoms of each one, being MCI subjects between healthy and dementia patients, in terms of microbiota composition.
As pointed out in the introduction, preclinical research shows that probiotics may improve cognitive performances in animal models with impaired cognition. However, data about the effects of probiotics on cognitive performance or psychopathological symptoms in humans are scarce and controversial. This lack of agreement could due to the differences in the population studied (young adults, elderly, healthy and clinic population, neurologic and psychiatric patients), the measures (different mood scales and different cognitive assessments), the probiotic compositions and the duration of treatment (from 3 weeks to 12 weeks). Considering the lack of knowledge about the probiotics potential treating dementia symptoms, dementia AD patients will be treated with a probiotic compound (a probiotic mixture already successful in improving cognitive impairment in AD patients, but only assessed by a cognitive screening and with no analysis of microbiota). The study will be conducted in an elderly group affected from AD, with a broad type of neuropsychological, neuropsychiatric and functional measures, and microbiota characterization at 12 and 24 weeks of treatment. An improvement of dementia symptoms due to probiotic consumption is expected, not only neuropsychological but also at a neuropsychiatric and functional level and these changes will be related to the changes of microbiota composition.
General objective: The main objective of DEM-BIOTA is to confirm the relationship between microbiota and dementia in our model of diet and lifestyle, improving the knowledge of the relationship between microbiota and dementias. This means to explore the possible differences between dementias in relation to microbiota in our context (Mediterranean diet and style of life) and characterize them in relation to neurocognitive and neuropsychiatric symptoms as well as patient functionality (dependency level). Moreover, the capacity of a probiotic compound in reverting or improving neurocognitive and neuropsychiatric symptoms and patient functionality will be studied.
This objective will be achieved through a multidisciplinary study considering microbiota composition and deep study of the dementia symptoms taking into account the personal characteristics of each patient. The final issue is to draw a relational map about the microbiota composition and dementia symptoms and the identification of the microbiota strains that are a risk factor of produce a deficit in metabolites. The project proposes to finally study how can a probiotic mixture improve AD symptoms, and study in deep the microbiota composition changes along with the changes (or not) of dementia symptoms.
This main objective will be carried out by combining our previous knowledge, partly of the collaboration with European Union partners, with data provided by literature on international studies on human population.
The aim match with the activities addressed in 1st Challenge identified in the Spanish Strategy for R+D+I Targeted to Societal Challenges "Health, Geographical change and Well-being": 1.1.2. Understanding disease; 1.2.1. Development of effective prevention and detection programs and improvement of disease propensity assessment.
1.3. SPECIFIC OBJECTIVES
1. \- Protocol revision and preparation. Revision of the all tests and scales, writing down all the protocols, alignment the study protocols with the hospitals' procedures, timetables, sample collection protocols, etc.
2. \- Study the microbiota composition (from stool samples of the patients) of AD patients in our context (Mediterranean lifestyle).
Describe the microbiota composition from AD patients in relation with their healthy controls.
To what extent does it differ from their controls and from the AD patient's composition of other countries?
3. \- Study microbiota composition differences (from stool samples of the patients) between some of the most known dementias: AD, PDD, LBD, FTD-behavioral variant
Describe and compare microbiota composition between some of the most known dementias: AD, PDD, LBD, FTD-behavioral variant.
Describe and compare microbiota composition between MCI patients and AD patients.
Describe and compare microbiota composition between MCI patients and PDD, LBD, FTD-behavioral variant patients.
Are there any relations between the microbiota composition of all experimental groups with neuropsychological, neuropsychiatric and functional characteristics present in these dementias and in these patients? All these relations could be modulated by life stressors and diet (adherence to Mediterranean diet)?
4. \- Study the effects of a probiotic compound in AD patients. In relation to AD symptoms: neuropsychological, neuropsychiatric and functional In relation to microbiota composition (analyzed from the stool samples of the patients) Until what extend and how the microbiota composition explains the AD symptoms? Can this probiotic compound improve the symptoms and is in general a good treatment/complement to the nowadays treatment?
5. \- Dissemination and formation. Dissemination of results at scientific (open access journals, congresses and other national and international meetings) and social level disclosure (newspapers, research group web, webs of the hospitals and Alzheimer association, conferences to general public, radio, television, etc.), as well as formation to patients, professionals and general public.
Conditions
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Study Design
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CASE_CONTROL
OTHER
Study Groups
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Healthy control group
The criteria for the recruitment will be:
Inclusion criteria: more than 60 years. Exclusion criteria: Significant neurology disease diagnosed, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the gastrointestinal (GI) tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day).
This control group were recruited from relatives of the patients enrolled or general population and interviewed at the hospital (relatives, University or their homes).
Neuropsychological, functional and neuropsychiatric assessment and stool sample.
No intervention
no intervention
Alzheimer Disease (AD)
The criteria for the recruitment will be:
Inclusion criteria: Alzheimer Disease (AD) diagnosed by the neurology service; more than 60 years.
Exclusion criteria: Comorbidity with other significant neurology disease, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the GI tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day).
Neuropsychological, functional and neuropsychiatric assessment and stool sample.
No intervention
no intervention
Mild Cognitive Impairment (MCI)- amnesic
The criteria for the recruitment will be:
Inclusion criteria: Mild Cognitive Impairment (MCI) amnesic, diagnosed by the neurology service; more than 60 years.
Exclusion criteria: Comorbidity with other significant neurology disease, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the gastrointestinal (GI) tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day).
Neuropsychological, functional and neuropsychiatric assessment and stool sample.
No intervention
no intervention
Parkinson Disease Dementia (PDD)
The criteria for the recruitment will be:
Inclusion criteria: Parkinson Disease Dementia (PDD) diagnosed by the neurology service; more than 60 years.
Exclusion criteria: Comorbidity with other significant neurology disease, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the gastrointestinal (GI) tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day).
Neuropsychological, functional and neuropsychiatric assessment and stool sample.
No intervention
no intervention
Lewy bodies dementia (LBD)
The criteria for the recruitment will be:
Inclusion criteria: Lewy Body Dementia (LBD) diagnosed by the neurology service; more than 60 years.
Exclusion criteria: Comorbidity with other significant neurology disease, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the gastrointestinal (GI) tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day).
Neuropsychological, functional and neuropsychiatric assessment and stool sample.
No intervention
no intervention
Frontotemporal Dementia (FTD)-behavioral variant
The criteria for the recruitment will be:
Inclusion criteria: Frontotemporal Dementia (FTD)-behavioral variant diagnosed by the neurology service; more than 60 years.
Exclusion criteria: Comorbidity with other significant neurology disease, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the gastrointestinal (GI) tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day).
Neuropsychological, functional and neuropsychiatric assessment and stool sample.
No intervention
no intervention
Alzheimer disease (AD)-control
Inclusion criteria: Alzheimer Disease (AD) diagnosed by the neurology service; more than 65 years. Exclusion criteria: Comorbidity with other significant neurology disease, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the gastrointestinal (GI) tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day).
Neuropsychological, functional and neuropsychiatric assessment and stool sample at basal, 12 weeks and 24 weeks.
Probiotic supplement
A total of 60 Alzheimer Disease (AD) patients will be recruited, 30 will ingest the probiotic mixture and 30 will ingest placebo (randomized assignment to the groups will be done). The experimental group will take the probiotic ingest daily: Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus fermentum (2 × 109 colony forming units (CFU)/g of each). This mixture of bacteria has been showed to have positive results with 12 weeks treatment.
Alzheimer disease (AD)-probiotic
Inclusion criteria: Alzheimer Disease (AD) diagnosed by the neurology service; more than 65 years. Exclusion criteria: Comorbidity with other significant neurology disease, infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample, corticosteroid use, immunosuppressors or immunostimulants treatment, illnesses of the gastrointestinal (GI) tract, large doses of commercial probiotics consumed (greater than or equal to 108 colony forming units (cfu) per organisms per day).
Neuropsychological, functional and neuropsychiatric assessment and stool sample at basal, 12 weeks and 24 weeks.
Probiotic supplement
A total of 60 Alzheimer Disease (AD) patients will be recruited, 30 will ingest the probiotic mixture and 30 will ingest placebo (randomized assignment to the groups will be done). The experimental group will take the probiotic ingest daily: Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus fermentum (2 × 109 colony forming units (CFU)/g of each). This mixture of bacteria has been showed to have positive results with 12 weeks treatment.
Interventions
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No intervention
no intervention
Probiotic supplement
A total of 60 Alzheimer Disease (AD) patients will be recruited, 30 will ingest the probiotic mixture and 30 will ingest placebo (randomized assignment to the groups will be done). The experimental group will take the probiotic ingest daily: Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus fermentum (2 × 109 colony forming units (CFU)/g of each). This mixture of bacteria has been showed to have positive results with 12 weeks treatment.
Eligibility Criteria
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Inclusion Criteria
* diagnosed by the neurology service (or healthy subjects, without any of these diagnostics).
* more than 60 years
Study 2-probiotic intervention,:
* AD diagnosed by the neurology service;
* more than 65 years.
Exclusion Criteria
* Comorbidity with other significant neurology disease,
* Infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample,
* corticosteroid use,
* immunosuppressors or immunostimulants treatment,
* illnesses of the Gastro Intestinal tract,
* large doses of commercial probiotics consumed (greater than or equal to 10 elevated to 8 colony forming unit per organisms per day).
Study 2-probiotic intervention:
* Comorbidity with other significant neurology disease,
* Infectious treatment with antibiotics in the previous 6 months prior to providing the stool sample,
* corticosteroid use,
* immunosuppressors or immunostimulants treatment,
* illnesses of the GI tract,
* large doses of commercial probiotics consumed (greater than or equal to 10 elevated to 8 cfu per organisms per day).
60 Years
ALL
Yes
Sponsors
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Ministerio de Ciencia e Innovación, Spain
OTHER_GOV
University Rovira i Virgili
OTHER
Responsible Party
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Margarita Torrente
Dr.
Principal Investigators
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Margarita Torrente, Dr
Role: PRINCIPAL_INVESTIGATOR
University Rovira i Virgili
Locations
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Dr. Margarita Torrente
Tarragona, , Spain
Countries
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Central Contacts
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Facility Contacts
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References
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Cabrera C, Vicens P, Torrente M. Modifiable Risk Factors for Dementia: The Role of Gut Microbiota. Curr Alzheimer Res. 2021;18(13):993-1009. doi: 10.2174/1567205018666211215152411.
Agahi A, Hamidi GA, Daneshvar R, Hamdieh M, Soheili M, Alinaghipour A, Esmaeili Taba SM, Salami M. Does Severity of Alzheimer's Disease Contribute to Its Responsiveness to Modifying Gut Microbiota? A Double Blind Clinical Trial. Front Neurol. 2018 Aug 15;9:662. doi: 10.3389/fneur.2018.00662. eCollection 2018.
Akbari E, Asemi Z, Daneshvar Kakhaki R, Bahmani F, Kouchaki E, Tamtaji OR, Hamidi GA, Salami M. Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial. Front Aging Neurosci. 2016 Nov 10;8:256. doi: 10.3389/fnagi.2016.00256. eCollection 2016.
Benton D, Williams C, Brown A. Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur J Clin Nutr. 2007 Mar;61(3):355-61. doi: 10.1038/sj.ejcn.1602546. Epub 2006 Dec 6.
Davari S, Talaei SA, Alaei H, Salami M. Probiotics treatment improves diabetes-induced impairment of synaptic activity and cognitive function: behavioral and electrophysiological proofs for microbiome-gut-brain axis. Neuroscience. 2013 Jun 14;240:287-96. doi: 10.1016/j.neuroscience.2013.02.055. Epub 2013 Mar 7.
Kelly JR, Allen AP, Temko A, Hutch W, Kennedy PJ, Farid N, Murphy E, Boylan G, Bienenstock J, Cryan JF, Clarke G, Dinan TG. Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects. Brain Behav Immun. 2017 Mar;61:50-59. doi: 10.1016/j.bbi.2016.11.018. Epub 2016 Nov 16.
Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A, Bisson JF, Rougeot C, Pichelin M, Cazaubiel M, Cazaubiel JM. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr. 2011 Mar;105(5):755-64. doi: 10.1017/S0007114510004319. Epub 2010 Oct 26.
Saji N, Niida S, Murotani K, Hisada T, Tsuduki T, Sugimoto T, Kimura A, Toba K, Sakurai T. Analysis of the relationship between the gut microbiome and dementia: a cross-sectional study conducted in Japan. Sci Rep. 2019 Jan 30;9(1):1008. doi: 10.1038/s41598-018-38218-7.
Tillisch K, Labus J, Kilpatrick L, Jiang Z, Stains J, Ebrat B, Guyonnet D, Legrain-Raspaud S, Trotin B, Naliboff B, Mayer EA. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology. 2013 Jun;144(7):1394-401, 1401.e1-4. doi: 10.1053/j.gastro.2013.02.043. Epub 2013 Mar 6.
Vogt NM, Kerby RL, Dill-McFarland KA, Harding SJ, Merluzzi AP, Johnson SC, Carlsson CM, Asthana S, Zetterberg H, Blennow K, Bendlin BB, Rey FE. Gut microbiome alterations in Alzheimer's disease. Sci Rep. 2017 Oct 19;7(1):13537. doi: 10.1038/s41598-017-13601-y.
Soldevila-Domenech N, Forcano L, Vintro-Alcaraz C, Cuenca-Royo A, Pinto X, Jimenez-Murcia S, Garcia-Gavilan JF, Nishi SK, Babio N, Gomis-Gonzalez M, Corella D, Sorli JV, Fernandez-Carrion R, Martinez-Gonzalez MA, Marti A, Salas-Salvado J, Castaner O, Fernandez-Aranda F, Torre R. Interplay between cognition and weight reduction in individuals following a Mediterranean Diet: Three-year follow-up of the PREDIMED-Plus trial. Clin Nutr. 2021 Sep;40(9):5221-5237. doi: 10.1016/j.clnu.2021.07.020. Epub 2021 Aug 5.
Buschke H. Cued recall in amnesia. J Clin Neuropsychol. 1984 Nov;6(4):433-40. doi: 10.1080/01688638408401233.
Buschke H, Kuslansky G, Katz M, Stewart WF, Sliwinski MJ, Eckholdt HM, Lipton RB. Screening for dementia with the memory impairment screen. Neurology. 1999 Jan 15;52(2):231-8. doi: 10.1212/wnl.52.2.231.
Dubois B, Slachevsky A, Litvan I, Pillon B. The FAB: a Frontal Assessment Battery at bedside. Neurology. 2000 Dec 12;55(11):1621-6. doi: 10.1212/wnl.55.11.1621.
Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189-98. doi: 10.1016/0022-3956(75)90026-6. No abstract available.
Goldberg D, Bridges K, Duncan-Jones P, Grayson D. Detecting anxiety and depression in general medical settings. BMJ. 1988 Oct 8;297(6653):897-9. doi: 10.1136/bmj.297.6653.897.
Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL. A new clinical scale for the staging of dementia. Br J Psychiatry. 1982 Jun;140:566-72. doi: 10.1192/bjp.140.6.566.
Pena-Casanova J, Quinones-Ubeda S, Gramunt-Fombuena N, Aguilar M, Casas L, Molinuevo JL, Robles A, Rodriguez D, Barquero MS, Antunez C, Martinez-Parra C, Frank-Garcia A, Fernandez M, Molano A, Alfonso V, Sol JM, Blesa R; NEURONORMA Study Team. Spanish Multicenter Normative Studies (NEURONORMA Project): norms for Boston naming test and token test. Arch Clin Neuropsychol. 2009 Jun;24(4):343-54. doi: 10.1093/arclin/acp039. Epub 2009 Aug 1.
Reisberg B. Functional assessment staging (FAST). Psychopharmacol Bull. 1988;24(4):653-9. No abstract available.
Reisberg B, Ferris SH, de Leon MJ, Crook T. The Global Deterioration Scale for assessment of primary degenerative dementia. Am J Psychiatry. 1982 Sep;139(9):1136-9. doi: 10.1176/ajp.139.9.1136.
REITAN RM. The relation of the trail making test to organic brain damage. J Consult Psychol. 1955 Oct;19(5):393-4. doi: 10.1037/h0044509. No abstract available.
Shulman KI. Clock-drawing: is it the ideal cognitive screening test? Int J Geriatr Psychiatry. 2000 Jun;15(6):548-61. doi: 10.1002/1099-1166(200006)15:63.0.co;2-u.
Sotos-Prieto M, Santos-Beneit G, Bodega P, Pocock S, Mattei J, Penalvo JL. VALIDATION OF A QUESTIONNAIRE TO MEASURE OVERALL MEDITERRANEAN LIFESTYLE HABITS FOR RESEARCH APPLICATION: THE MEDITERRANEAN LIFESTYLE INDEX (MEDLIFE). Nutr Hosp. 2015 Sep 1;32(3):1153-63. doi: 10.3305/nh.2015.32.3.9387.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Document Type: Informed Consent Form: study 1
Document Type: Informed Consent Form: study 2
Related Links
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Pena-Casanova J. (2019). Teoria e Interpretacion: Normalidad, Semiologia y Patologia Neuropsicologicas. Programa integrado de exploracion neuropsicologica. Test Barcelona-2. Masquelibros, S.L., Jaen. International Standrad Book Number: 978-84-120274-0-2.
Other Identifiers
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PID2019-103888RB-I00
Identifier Type: -
Identifier Source: org_study_id
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