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2. High Cellular Monocyte Activation in People Living With Human Immunodeficiency Virus on Combination Antiretroviral Therapy and Lifestyle-Matched Controls Is Associated With Greater Inflammation in Cerebrospinal Fluid

Author

Booiman, Thijs, Wit, Ferdinand W., Maurer, Irma, De Francesco, Davide, Sabin, Caroline A., Harskamp, Agnes M., Prins, Maria, Garagnani, Paolo, Pirazzini, Chiara, Franceschi, Claudio, Fuchs, Dietmar, Gisslén, Magnus, Winston, Alan, Reiss, Peter, Kootstra, Neeltje A., Reiss, P., Wit, F. W. N. M., Schouten, J., Kooij, K. W., van Zoest, R. A., Elsenga, B. C., Janssen, F. R., Heidenrijk, M., Zikkenheiner, W., van der Valk, M., Kootstra, N. A., Booiman, T., Harskamp-Holwerda, A. M., Boeser-Nunnink, B., Maurer, I., Mangas Ruiz, M. M., Girigorie, A. F., Villaudy, J., Frankin, E., Pasternak, A., Berkhout, B., van der Kuyl, T., Portegies, P., Schmand, B. A., Geurtsen, G. J., ter Stege, J. A., Klein Twennaar, M., Majoie, C. B. L. M., Caan, M. W. A., Su, T., Weijer, K., Bisschop, P. H. L. T., Kalsbeek, A., Wezel, M., Visser, I., Ruhé, H. G., Franceschi, C., Garagnani, P., Pirazzini, C., Capri, M., Dall’Olio, F., Chiricolo, M., Salvioli, S., Hoeijmakers, J., Pothof, J., Prins, M., Martens, M., Moll, S., Berkel, J., Totté, M., Kovalev, S., Gisslén, M., Fuchs, D., Zetterberg, H., Winston, A., Underwood, J., McDonald, L., Stott, M., Legg, K., Lovell, A., Erlwein, O., Doyle, N., Kingsley, C., Sharp, D. J., Leech, R., Cole, J. H., Zaheri, S., Hillebregt, M. M. J., Ruijs, Y. M. C., Benschop, D. P., Burger, D., de Graaff-Teulen, M., Guaraldi, G., Bürkle, A., Sindlinger, T., Moreno-Villanueva, M., Keller, A., Sabin, C., de Francesco, D., Libert, C., and Dewaele, S.

Published
2017
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4. Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment

Author

Underwood, Jonathan, De Francesco, Davide, Cole, James H, Caan, Matthan W A, van Zoest, Rosan A, Schmand, Ben A, Sharp, David J, Sabin, Caroline A, Reiss, Peter, Winston, Alan Coolaboratori: Reiss P, Wit FWNM, Schouten J, Kooij KW, van Zoest RA, Elsenga BC, Janssen FR, Heidenrijk M, Zikkenheiner W, van der Valk M, Kootstra NA, Harskamp-Holwerda AM, Maurer I, Mangas Ruiz MM, Girigorie AF, Villaudy J, Frankin E, Pasternak A, Berkhout B, van der Kuyl T, Portegies P, Schmand BA, Geurtsen GJ, Ter Stege JA, Klein Twennaar M, Majoie CBLM, Caan MWA, Su T, Weijer K, Bisschop PHLT, Kalsbeek A, Wezel M, Visser I, Ruhé HG, Franceschi C, Garagnani P, Pirazzini C, Capri M, Dall'Olio F, Chiricolo M, Salvioli S, Hoeijmakers J, Pothof J, Prins M, Martens M, Moll S, Berkel J, Totté M, Kovalev S, Gisslén M, Fuchs D, Zetterberg H, Winston A, Underwood J, McDonald L, Stott M, Legg K, Lovell A, Erlwein O, Doyle N, Kingsley C, Sharp DJ, Leech R, Cole JH, Zaheri S, Hillebregt MMJ, Ruijs YMC, Benschop DP, Burger D, de Graaff-Teulen M, Guaraldi G, Bürkle A, Sindlinger T, Moreno-Villanueva M, Keller A, Sabin C, de Francesco D, Libert C, Dewaele S, Boffito M, Mallon P, Post F, Sachikonye M, Anderson J, Asboe D, Garvey L, Pozniak A, Vera J, Williams I, Campbell L, Yurdakul S, Okumu S, Pollard L, Otiko D, Phillips L, Laverick R, Fisher M, Clarke A, Bexley A, Richardson C, Macken A, Ghavani-Kia B, Maher J, Byrne M, Flaherty A, Mguni S, Clark R, Nevin-Dolan R, Pelluri S, Johnson M, Ngwu N, Hemat N, Jones M, Carroll A, Whitehouse A, Burgess L, Babalis D, Higgs C, Seah E, Fletcher S, Anthonipillai M, Moyes A, Deats K, Syed I, Matthews C., Underwood, Jonathan, De Francesco, Davide, Cole, James H, Caan, Matthan W A, van Zoest, Rosan A, Schmand, Ben A, Sharp, David J, Sabin, Caroline A, Reiss, Peter, Winston, Alan Coolaboratori: Reiss P, Wit FWNM, Schouten J, Kooij KW, van Zoest RA, Elsenga BC, Janssen FR, Heidenrijk M, Zikkenheiner W, van der Valk M, Kootstra NA, Harskamp-Holwerda AM, Maurer I, Mangas Ruiz MM, Girigorie AF, Villaudy J, Frankin E, Pasternak A, Berkhout B, van der Kuyl T, Portegies P, Schmand BA, Geurtsen GJ, Ter Stege JA, Klein Twennaar M, Majoie CBLM, Caan MWA, Su T, Weijer K, Bisschop PHLT, Kalsbeek A, Wezel M, Visser I, Ruhé HG, Franceschi C, Garagnani P, Pirazzini C, Capri M, Dall'Olio F, Chiricolo M, Salvioli S, Hoeijmakers J, Pothof J, Prins M, Martens M, Moll S, Berkel J, Totté M, Kovalev S, Gisslén M, Fuchs D, Zetterberg H, Winston A, Underwood J, McDonald L, Stott M, Legg K, Lovell A, Erlwein O, Doyle N, Kingsley C, Sharp DJ, Leech R, Cole JH, Zaheri S, Hillebregt MMJ, Ruijs YMC, Benschop DP, Burger D, de Graaff-Teulen M, Guaraldi G, Bürkle A, Sindlinger T, Moreno-Villanueva M, Keller A, Sabin C, de Francesco D, Libert C, Dewaele S, Boffito M, Mallon P, Post F, Sabin C, Sachikonye M, Winston A, Anderson J, Asboe D, Boffito M, Garvey L, Mallon P, Post F, Pozniak A, Sabin C, Sachikonye M, Vera J, Williams I, Winston A, Post F, Campbell L, Yurdakul S, Okumu S, Pollard L, Williams I, Otiko D, Phillips L, Laverick R, Fisher M, Clarke A, Vera J, Bexley A, Richardson C, Mallon P, Macken A, Ghavani-Kia B, Maher J, Byrne M, Flaherty A, Anderson J, Mguni S, Clark R, Nevin-Dolan R, Pelluri S, Johnson M, Ngwu N, Hemat N, Jones M, Carroll A, Whitehouse A, Burgess L, Babalis D, Winston A, Garvey L, Underwood J, Stott M, McDonald L, Boffito M, Asboe D, Pozniak A, Higgs C, Seah E, Fletcher S, Anthonipillai M, Moyes A, Deats K, Syed I, Matthews C., Molecular Genetics, Biomedical Engineering and Physics, Radiology and Nuclear Medicine, ACS - Atherosclerosis & ischemic syndromes, ACS - Diabetes & metabolism, ACS - Microcirculation, AMS - Restoration & Development, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Neurovascular Disorders, Graduate School, AII - Infectious diseases, APH - Aging & Later Life, Medical Psychology, Amsterdam Neuroscience - Neurodegeneration, Global Health, Infectious diseases, APH - Mental Health, APH - Methodology, Commission of the European Communities, Imperial College Healthcare NHS Trust- BRC Funding, and National Institute for Health Research

Subjects
Multivariate statistics, medicine.medical_specialty, COmorBidity in Relation to AIDS (COBRA) Collaboration and the Pharmacokinetic and clinical Observations in PePle over fiftY (POPPY) Study Group, Immunology, Human immunodeficiency virus (HIV), Audiology, medicine.disease_cause, Microbiology, 03 medical and health sciences, 0302 clinical medicine, multivariate, SDG 3 - Good Health and Well-being, Neuroimaging, Medicine and Health Sciences, medicine, Major Article, OLDER-PEOPLE, 030212 general & internal medicine, VALIDITY, Cognitive impairment, cognitive impairment, Science & Technology, neuroimaging, SCORES, business.industry, Biology and Life Sciences, HIV, MEN, Cognition, Mental health, White matter microstructure, PREVALENCE, 3. Good health, Infectious Diseases, Oncology, REGISTRATION, business, Life Sciences & Biomedicine, Neurocognitive, 030217 neurology & neurosurgery
Abstract

Background The optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts. Methods Differences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria. Results The prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05). There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker. Conclusion Different methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach., We have previously described a novel multivariate method (NMM) with theoretical statistical advantages over existing methods, which we assessed here in 3 cohorts of people living with HIV. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status.

Published
2019

5. Comprehensive microRNA profiling in B-cells of human centenarians by massively parallel sequencing

Author

Gombar Saurabh, Jung Hwa, Dong Feng, Calder Brent, Atzmon Gil, Barzilai Nir, Tian Xiao-Li, Pothof Joris, Hoeijmakers Jan HJ, Campisi Judith, Vijg Jan, and Suh Yousin

Subjects
MicroRNA, Centenarians, Aging, Life span, Massively parallel sequencing, Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and play a critical role in development, homeostasis, and disease. Despite their demonstrated roles in age-associated pathologies, little is known about the role of miRNAs in human aging and longevity. Results We employed massively parallel sequencing technology to identify miRNAs expressed in B-cells from Ashkenazi Jewish centenarians, i.e., those living to a hundred and a human model of exceptional longevity, and younger controls without a family history of longevity. With data from 26.7 million reads comprising 9.4 × 108 bp from 3 centenarian and 3 control individuals, we discovered a total of 276 known miRNAs and 8 unknown miRNAs ranging several orders of magnitude in expression levels, a typical characteristics of saturated miRNA-sequencing. A total of 22 miRNAs were found to be significantly upregulated, with only 2 miRNAs downregulated, in centenarians as compared to controls. Gene Ontology analysis of the predicted and validated targets of the 24 differentially expressed miRNAs indicated enrichment of functional pathways involved in cell metabolism, cell cycle, cell signaling, and cell differentiation. A cross sectional expression analysis of the differentially expressed miRNAs in B-cells from Ashkenazi Jewish individuals between the 50th and 100th years of age indicated that expression levels of miR-363* declined significantly with age. Centenarians, however, maintained the youthful expression level. This result suggests that miR-363* may be a candidate longevity-associated miRNA. Conclusion Our comprehensive miRNA data provide a resource for further studies to identify genetic pathways associated with aging and longevity in humans.

Published
2012
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