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Article ; Online: Relationship of Muscle Apolipoprotein E Expression with Markers of Cellular Stress, Metabolism, and Blood Biomarkers in Cognitively Healthy and Impaired Older Adults.

Johnson, Chelsea N / McCoin, Colin S / Kueck, Paul J / Hawley, Amelia G / John, Casey S / Thyfault, John P / Swerdlow, Russell H / Geiger, Paige C / Morris, Jill K

Journal of Alzheimer's disease : JAD

2023 Volume 92, Issue 3, Page(s) 1027–1035

Abstract: Background: Individuals with mild cognitive impairment (MCI) have reduced lipid-stimulated mitochondrial respiration in skeletal muscle. A major risk factor for Alzheimer's disease (AD), the apolipoprotein E4 (APOE4) allele, is implicated in lipid ... ...

Abstract	Background: Individuals with mild cognitive impairment (MCI) have reduced lipid-stimulated mitochondrial respiration in skeletal muscle. A major risk factor for Alzheimer's disease (AD), the apolipoprotein E4 (APOE4) allele, is implicated in lipid metabolism and is associated with metabolic and oxidative stress that can result from dysfunctional mitochondria. Heat shock protein 72 (Hsp72) is protective against these stressors and is elevated in the AD brain. Objective: Our goal was to characterize skeletal muscle ApoE and Hsp72 protein expression in APOE4 carriers in relationship to cognitive status, muscle mitochondrial respiration and AD biomarkers. Methods: We analyzed previously collected skeletal muscle tissue from 24 APOE4 carriers (60y+) who were cognitively healthy (CH, n = 9) or MCI (n = 15). We measured ApoE and Hsp72 protein levels in muscle and phosphorylated tau181 (pTau181) levels in plasma, and leveraged previously collected data on APOE genotype, mitochondrial respiration during lipid oxidation, and VO2 max. Results: Muscle ApoE (p = 0.013) and plasma pTau181 levels (p < 0.001) were higher in MCI APOE4 carriers. Muscle ApoE positively correlated with plasma pTau181 in all APOE4 carriers (R2 = 0.338, p = 0.003). Hsp72 expression negatively correlated with ADP (R2 = 0.775, p = <0.001) and succinate-stimulated respiration (R2 = 0.405, p = 0.003) in skeletal muscle of MCI APOE4 carriers. Plasma pTau181 negatively tracked with VO2 max in all APOE4 carriers (R2 = 0.389, p = 0.003). Analyses were controlled for age. Conclusion: This work supports a relationship between cellular stress in skeletal muscle and cognitive status in APOE4 carriers.
MeSH term(s)	Humans ; Aged ; Apolipoprotein E4/genetics ; HSP72 Heat-Shock Proteins ; Apolipoproteins E/genetics ; Alzheimer Disease/genetics ; Cognitive Dysfunction/genetics ; Muscles ; Biomarkers ; Apolipoprotein E3/genetics
Chemical Substances	Apolipoprotein E4 ; HSP72 Heat-Shock Proteins ; Apolipoproteins E ; Biomarkers ; Apolipoprotein E3
Language	English
Publishing date	2023-02-10
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-221192
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Article: Red cell exchange in sickle cell disease.

Swerdlow, Paul S

Hematology. American Society of Hematology. Education Program

2006 , Page(s) 48–53

Abstract: Red cell exchange transfusions remain an effective but possibly underutilized therapy in the acute and chronic treatment of sickle cell disease. In sickle cell disease, increased blood viscosity can cause complications when the hemoglobin exceeds 10 g/dL ...

Abstract	Red cell exchange transfusions remain an effective but possibly underutilized therapy in the acute and chronic treatment of sickle cell disease. In sickle cell disease, increased blood viscosity can cause complications when the hemoglobin exceeds 10 g/dL even if this is due to simple transfusion. Red cell exchange can provide needed oxygen carrying capacity while reducing the overall viscosity of blood. Acute red cell exchange is useful in acute infarctive stroke, in acute chest and the multi-organ failure syndromes, the right upper quadrant syndrome, and possibly priapism. Neither simple or exchange transfusions are likely to hasten resolution of an acute pain episode.
MeSH term(s)	Anemia, Sickle Cell/therapy ; Blood Viscosity ; Erythrocyte Transfusion/methods ; Exchange Transfusion, Whole Blood/methods ; Female ; Humans ; Male ; Multiple Organ Failure/therapy ; Priapism/therapy ; Stroke/therapy
Language	English
Publishing date	2006
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1520-4391
ISSN	1520-4391
DOI	10.1182/asheducation-2006.1.48
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Article ; Online: A Mitochondrial Biomarker-Based Study of S-Equol in Alzheimer's Disease Subjects: Results of a Single-Arm, Pilot Trial.

Wilkins, Heather M / Mahnken, Jonathan D / Welch, Paul / Bothwell, Rebecca / Koppel, Scott / Jackson, Richard L / Burns, Jeffrey M / Swerdlow, Russell H

Journal of Alzheimer's disease : JAD

2017 Volume 59, Issue 1, Page(s) 291–300

Abstract: ... whether an ERβ agonist could improve mitochondrial function in actual AD subjects, we administered S-equol (10 mg ... activity before initiating S-equol (lead-in), after two weeks of S-equol (active treatment), and two weeks ... after stopping S-equol (wash-out). Because the intra-individual variation of this enzyme across samples ...

Abstract	Reductions in bioenergetic fluxes, mitochondrial enzyme activities, and mitochondrial number are observed in Alzheimer's disease (AD). Preclinical work indicates estrogen pathway signaling by either estrogen or selective β estrogen receptor (ERβ) agonists benefits these parameters. To assess whether an ERβ agonist could improve mitochondrial function in actual AD subjects, we administered S-equol (10 mg twice daily) to 15 women with AD and determined the platelet mitochondria cytochrome oxidase (COX) activity before initiating S-equol (lead-in), after two weeks of S-equol (active treatment), and two weeks after stopping S-equol (wash-out). Because the intra-individual variation of this enzyme across samples taken at different times was unknown we used a nonparametric, single-arm, dichotomous endpoint that classified subjects whose active treatment COX activity exceeded the average of their lead-in and wash-out measures as positive responders. Eleven positive responses were observed (p < 0.06). The implications of this finding on our null hypothesis (that S-equol does not influence platelet mitochondria COX activity) are discussed. To our knowledge, this is the first time a direct mitochondrial target engagement biomarker has been utilized in an AD clinical study.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/drug therapy ; Alzheimer Disease/genetics ; Alzheimer Disease/pathology ; Apolipoprotein E4/genetics ; Electron Transport Complex IV/metabolism ; Equol/administration & dosage ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Mitochondria/drug effects ; Mitochondria/enzymology ; Phytoestrogens/administration & dosage ; Pilot Projects ; Treatment Outcome
Chemical Substances	Apolipoprotein E4 ; Phytoestrogens ; Equol (531-95-3) ; Electron Transport Complex IV (EC 1.9.3.1)
Language	English
Publishing date	2017-05-26
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-170077
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Article: Use of humans in biomedical experimentation

Swerdlow, Paul S

Scientific integrity : text and cases in responsible conduct of research

2005

Institution	United States
Author's details	Paul S. Swerdlow
MeSH term(s)	Human Experimentation/ethics ; Embryo Research/legislation & jurisprudence ; Ethics Committees, Research ; Fetal Research/legislation & jurisprudence ; Human Experimentation/legislation & jurisprudence ; Informed Consent ; Internationality ; Privacy/legislation & jurisprudence ; Research Subjects ; Vulnerable Populations
Keywords	United States ; Biomedical and Behavioral Research
Language	English
Size	p. 91-126.
Publisher	ASM Press
Publishing place	Washington, DC
Document type	Article
ISBN	1555813186 ; 9781555813185
Database	Catalogue of the US National Library of Medicine (NLM)

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Article ; Online: Genetic subgroups inform on pathobiology in adult and pediatric Burkitt lymphoma.

Thomas, Nicole / Dreval, Kostiantyn / Gerhard, Daniela S / Hilton, Laura K / Abramson, Jeremy S / Ambinder, Richard F / Barta, Stefan / Bartlett, Nancy L / Bethony, Jeffrey / Bhatia, Kishor / Bowen, Jay / Bryan, Anthony C / Cesarman, Ethel / Casper, Corey / Chadburn, Amy / Cruz, Manuela / Dittmer, Dirk P / Dyer, Maureen A / Farinha, Pedro /

Gastier-Foster, Julie M / Gerrie, Alina S / Grande, Bruno M / Greiner, Timothy / Griner, Nicholas B / Gross, Thomas G / Harris, Nancy L / Irvin, John D / Jaffe, Elaine S / Henry, David / Huppi, Rebecca / Leal, Fabio E / Lee, Michael S / Martin, Jean Paul / Martin, Marie-Reine / Mbulaiteye, Sam M / Mitsuyasu, Ronald / Morris, Vivian / Mullighan, Charles G / Mungall, Andrew J / Mungall, Karen / Mutyaba, Innocent / Nokta, Mostafa / Namirembe, Constance / Noy, Ariela / Ogwang, Martin D / Omoding, Abraham / Orem, Jackson / Ott, German / Petrello, Hilary / Pittaluga, Stefania / Phelan, James D / Ramos, Juan Carlos / Ratner, Lee / Reynolds, Steven J / Rubinstein, Paul G / Sissolak, Gerhard / Slack, Graham / Soudi, Shaghayegh / Swerdlow, Steven H / Traverse-Glehen, Alexandra / Wilson, Wyndham H / Wong, Jasper / Yarchoan, Robert / ZenKlusen, Jean C / Marra, Marco A / Staudt, Louis M / Scott, David W / Morin, Ryan D

Blood

2023 Volume 141, Issue 8, Page(s) 904–916

Abstract: Burkitt lymphoma (BL) accounts for most pediatric non-Hodgkin lymphomas, being less common but significantly more lethal when diagnosed in adults. Much of the knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), ... ...

Abstract	Burkitt lymphoma (BL) accounts for most pediatric non-Hodgkin lymphomas, being less common but significantly more lethal when diagnosed in adults. Much of the knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), leaving its relationship to adult BL (aBL) and other adult lymphomas not fully explored. We sought to more thoroughly identify the somatic changes that underlie lymphomagenesis in aBL and any molecular features that associate with clinical disparities within and between pBL and aBL. Through comprehensive whole-genome sequencing of 230 BL and 295 diffuse large B-cell lymphoma (DLBCL) tumors, we identified additional significantly mutated genes, including more genetic features that associate with tumor Epstein-Barr virus status, and unraveled new distinct subgroupings within BL and DLBCL with 3 predominantly comprising BLs: DGG-BL (DDX3X, GNA13, and GNAI2), IC-BL (ID3 and CCND3), and Q53-BL (quiet TP53). Each BL subgroup is characterized by combinations of common driver and noncoding mutations caused by aberrant somatic hypermutation. The largest subgroups of BL cases, IC-BL and DGG-BL, are further characterized by distinct biological and gene expression differences. IC-BL and DGG-BL and their prototypical genetic features (ID3 and TP53) had significant associations with patient outcomes that were different among aBL and pBL cohorts. These findings highlight shared pathogenesis between aBL and pBL, and establish genetic subtypes within BL that serve to delineate tumors with distinct molecular features, providing a new framework for epidemiologic, diagnostic, and therapeutic strategies.
MeSH term(s)	Child ; Humans ; Adult ; Burkitt Lymphoma/pathology ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Lymphoma, Large B-Cell, Diffuse/pathology ; Mutation
Language	English
Publishing date	2023-02-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2022016534
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Article ; Online: Proceedings from the Albert Charitable Trust Inaugural Workshop on 'Understanding the Acute Effects of Exercise on the Brain'.

Brain plasticity (Amsterdam, Netherlands)

2022 Volume 8, Issue 2, Page(s) 153–168

Abstract: An inaugural workshop supported by "The Leo and Anne Albert Charitable Trust," was held October 4-7, 2019 in Scottsdale, Arizona, to focus on the effects of exercise on the brain and to discuss how physical activity may prevent or delay the onset of ... ...

Abstract	An inaugural workshop supported by "The Leo and Anne Albert Charitable Trust," was held October 4-7, 2019 in Scottsdale, Arizona, to focus on the effects of exercise on the brain and to discuss how physical activity may prevent or delay the onset of aging-related neurodegenerative conditions. The Scientific Program Committee (led by Dr. Jeff Burns) assembled translational, clinical, and basic scientists who research various aspects of the effects of exercise on the body and brain, with the overall goal of gaining a better understanding as to how to delay or prevent neurodegenerative diseases. In particular, research topics included the links between cardiorespiratory fitness, the cerebrovasculature, energy metabolism, peripheral organs, and cognitive function, which are all highly relevant to understanding the effects of acute and chronic exercise on the brain. The Albert Trust workshop participants addressed these and related topics, as well as how other lifestyle interventions, such as diet, affect age-related cognitive decline associated with Alzheimer's and other neurodegenerative diseases. This report provides a synopsis of the presentations and discussions by the participants, and a delineation of the next steps towards advancing our understanding of the effects of exercise on the aging brain.
Language	English
Publishing date	2022-12-20
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2827963-3
ISSN	2213-6312 ; 2213-6312
ISSN (online)	2213-6312
ISSN	2213-6312
DOI	10.3233/BPL-220146
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Article ; Online: Flow cytometric immunophenotyping of cerebrospinal fluid specimens.

Craig, Fiona E / Ohori, N Paul / Gorrill, Timothy S / Swerdlow, Steven H

American journal of clinical pathology

2011 Volume 135, Issue 1, Page(s) 22–34

Abstract: Flow cytometric immunophenotyping (FCI) is recommended in the evaluation of cerebrospinal fluid (CSF) specimens for hematologic neoplasms. This study reviewed FCI of CSF specimens collected for primary diagnosis (n = 77) and follow-up for known ... ...

Abstract	Flow cytometric immunophenotyping (FCI) is recommended in the evaluation of cerebrospinal fluid (CSF) specimens for hematologic neoplasms. This study reviewed FCI of CSF specimens collected for primary diagnosis (n = 77) and follow-up for known malignancy (n = 153). FCI was positive in 11 (4.8%) of 230 specimens: acute myeloid leukemia, 6; precursor B-acute lymphoblastic leukemia, 2; B-cell lymphoma, 2; and T-cell lymphoma, 1. Positive results were obtained in low-cellularity specimens, including 2 with fewer than 100 events in the population of interest. FCI was indeterminate in 19 (8.3%) of 230 specimens, including 3 with only sparse events, 8 with possible artifact (apparent lack of staining, nonspecific or background staining, and aspirated air), and 8 with phenotypic findings considered insufficient for diagnosis. Indeterminate specimens were often limited by low cellularity and lacked normal cell populations to evaluate for appropriate staining. FCI may be of value in low-cellularity CSF specimens, although the results should be interpreted with caution.
MeSH term(s)	Acute Disease ; Cerebrospinal Fluid/immunology ; Flow Cytometry/methods ; Humans ; Immunophenotyping/methods ; Leukemia, Myeloid, Acute/cerebrospinal fluid ; Leukemia, Myeloid, Acute/diagnosis ; Leukemia, Myeloid, Acute/immunology ; Lymphoma, B-Cell/cerebrospinal fluid ; Lymphoma, B-Cell/diagnosis ; Lymphoma, B-Cell/immunology ; Lymphoma, T-Cell/cerebrospinal fluid ; Lymphoma, T-Cell/diagnosis ; Lymphoma, T-Cell/immunology ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/cerebrospinal fluid ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/immunology
Language	English
Publishing date	2011-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2944-0
ISSN	1943-7722 ; 0002-9173
ISSN (online)	1943-7722
ISSN	0002-9173
DOI	10.1309/AJCPANA7ER1ABMZI
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Book ; Online: Infectious disease surveillance needs for the United States

Lipsitch, Marc / Bassett, Mary T. / Brownstein, John S. / Elliott, Paul / Eyre, David / Grabowski, M. Kate / Hay, James A. / Johansson, Michael / Kissler, Stephen M. / Larremore, Daniel B. / Layden, Jennifer / Lessler, Justin / Lynfield, Ruth / MacCannell, Duncan / Madoff, Lawrence C. / Metcalf, C. Jessica E. / Meyers, Lauren A. / Ofori, Sylvia K. / Quinn, Celia /

Bento, Ana I. Ramos / Reich, Nick / Riley, Steven / Rosenfeld, Roni / Samore, Matthew H. / Sampath, Rangarajan / Slayton, Rachel B. / Swerdlow, David L. / Truelove, Shaun / Varma, Jay K. / Grad, Yonatan H.

lessons from COVID-19

2023

Abstract: ... to support decision making during a pandemic, drawing on the lessons of COVID-19 in the U.S., while looking ... to jurisdictions in the U.S. and beyond to learn lessons about the value of specific data types. In this report ...

Abstract	The COVID-19 pandemic has highlighted the need to upgrade systems for infectious disease surveillance and forecasting and modeling of the spread of infection, both of which inform evidence-based public health guidance and policies. Here, we discuss requirements for an effective surveillance system to support decision making during a pandemic, drawing on the lessons of COVID-19 in the U.S., while looking to jurisdictions in the U.S. and beyond to learn lessons about the value of specific data types. In this report, we define the range of decisions for which surveillance data are required, the data elements needed to inform these decisions and to calibrate inputs and outputs of transmission-dynamic models, and the types of data needed to inform decisions by state, territorial, local, and tribal health authorities. We define actions needed to ensure that such data will be available and consider the contribution of such efforts to improving health equity.
Keywords	Computer Science - Computers and Society ; Physics - Physics and Society ; Quantitative Biology - Populations and Evolution
Subject code	306
Publishing date	2023-11-22
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Thalidomide and its analogs for hemoglobinopathies: two birds with one stone?

Kutlar, Abdullah / Meiler, Steffen / Swerdlow, Paul / Knight, Robert

Expert review of hematology

2012 Volume 5, Issue 1, Page(s) 9–11

MeSH term(s)	Animals ; Hemoglobinopathies/drug therapy ; Humans ; Mice ; Thalidomide/analogs & derivatives ; Thalidomide/therapeutic use
Chemical Substances	Thalidomide (4Z8R6ORS6L)
Language	English
Publishing date	2012-02
Publishing country	England
Document type	Editorial
ZDB-ID	2516804-6
ISSN	1747-4094 ; 1747-4086
ISSN (online)	1747-4094
ISSN	1747-4086
DOI	10.1586/ehm.11.77
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Article ; Online: Systematic literature review of the impact and effectiveness of monovalent meningococcal C conjugated vaccines when used in routine immunization programs.

Tin Tin Htar, Myint / Jackson, Sally / Balmer, Paul / Serra, Lidia Cristina / Vyse, Andrew / Slack, Mary / Riera-Montes, Margarita / Swerdlow, David L / Findlow, Jamie

BMC public health

2020 Volume 20, Issue 1, Page(s) 1890

Abstract: Background: Monovalent meningococcal C conjugate vaccine (MCCV) was introduced into the routine immunization program in many countries in Europe and worldwide following the emergence of meningococcal serogroup C (MenC) in the late 1990s. This systematic ...

Abstract	Background: Monovalent meningococcal C conjugate vaccine (MCCV) was introduced into the routine immunization program in many countries in Europe and worldwide following the emergence of meningococcal serogroup C (MenC) in the late 1990s. This systematic literature review summarizes the immediate and long-term impact and effectiveness of the different MCCV vaccination schedules and strategies employed. Methods: We conducted a systematic literature search for peer-reviewed, scientific publications in the databases of MEDLINE (via PubMed), LILACS, and SCIELO. We included studies from countries where MCCV have been introduced in routine vaccination programs and studies providing the impact and effectiveness of MCCV published between 1st January 2001 and 31st October 2017. Results: Forty studies were included in the review; 30 studies reporting impact and 17 reporting effectiveness covering 9 countries (UK, Spain, Italy, Canada, Brazil, Australia, Belgium, Germany and the Netherlands). Following MCCV introduction, significant and immediate reduction of MenC incidence was consistently observed in vaccine eligible ages in all countries with high vaccine uptake. The reduction in non-vaccine eligible ages (especially population > 65 years) through herd protection was generally observed 3-4 years following introduction. Vaccine effectiveness (VE) was mostly assessed through screening methods and ranged from 38 to 100%. The VE was generally highest during the first year after vaccination and waned over time. The VE was better maintained in countries employing catch-up campaigns in older children and adolescents, compared to routine infant only schedules. Conclusions: MCCV were highly effective, showing a substantial and sustained decrease in MenC invasive meningococcal disease. The epidemiology of meningococcal disease is in constant transition, and some vaccination programs now include adolescents and higher valent vaccines due to the recent increase in cases caused by serogroups not covered by MCCV. Continuous monitoring of meningococcal disease is essential to understand disease evolution in the setting of different vaccination programs.
MeSH term(s)	Adolescent ; Aged ; Australia ; Belgium ; Brazil ; Canada ; Child ; Europe ; Germany ; Humans ; Immunization Programs ; Infant ; Italy ; Meningococcal Infections/epidemiology ; Meningococcal Infections/prevention & control ; Meningococcal Vaccines ; Netherlands ; Spain ; Vaccination ; Vaccines, Conjugate
Chemical Substances	Meningococcal Vaccines ; Vaccines, Conjugate
Language	English
Publishing date	2020-12-09
Publishing country	England
Document type	Journal Article ; Systematic Review
ZDB-ID	2041338-5
ISSN	1471-2458 ; 1471-2458
ISSN (online)	1471-2458
ISSN	1471-2458
DOI	10.1186/s12889-020-09946-1
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