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Article ; Online: Multiplex Immunosuppressant (ISD) Method for the Measurement of Cyclosporine A, Tacrolimus, Sirolimus/Rapamycin, and Everolimus in Whole Blood Using MassTrak™ Kit.

Zhang, Anqi / Conklin, Steven E

Methods in molecular biology (Clifton, N.J.)

2023 Volume 2737, Page(s) 307–318

Abstract: Cyclosporine A, everolimus, sirolimus, and tacrolimus are the most commonly used immunosuppressant drugs in organ transplant and auto-immune patients. The narrow therapeutic window of these immunosuppressant drugs requires close monitoring of drug blood ... ...

Abstract	Cyclosporine A, everolimus, sirolimus, and tacrolimus are the most commonly used immunosuppressant drugs in organ transplant and auto-immune patients. The narrow therapeutic window of these immunosuppressant drugs requires close monitoring of drug blood levels to ensure proper therapeutic response. A quick, robust high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was introduced for monitoring whole blood levels of these immunosuppressant drugs with the use of the MassTrak™ Immunosuppressant kit. The assay was carried out in 96-well plate format and requires a simple precipitation step; after which, the supernatant is subjected to liquid chromatography separation (2 min total run time) using a C18 Cartridge column. Identification and quantitation of cyclosporine A, everolimus, sirolimus, and tacrolimus was achieved by employing multiple reaction monitoring (MRM) in positive mode electrospray ionization (ESI). The method exhibits a linear measuring range from 10 to 1500 ng/mL (Cyclosporine A), 1.0-30.0 ng/mL (Everolimus), 1.0-26.0 ng/mL (Sirolimus), and 1.0-30.0 ng/mL (Tacrolimus) and has a within-run and between-run imprecision of <10%.
MeSH term(s)	Humans ; Immunosuppressive Agents ; Cyclosporine/chemistry ; Tacrolimus ; Everolimus ; Sirolimus ; Chromatography, Liquid/methods ; Tandem Mass Spectrometry/methods ; Drug Monitoring/methods
Chemical Substances	Immunosuppressive Agents ; Cyclosporine (83HN0GTJ6D) ; Tacrolimus (WM0HAQ4WNM) ; Everolimus (9HW64Q8G6G) ; Sirolimus (W36ZG6FT64)
Language	English
Publishing date	2023-12-01
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-3541-4_28
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Taking a step back from testing: Preanalytical considerations in molecular infectious disease diagnostics.

Conrad, Stephanie / Gant Kanegusuku, Anastasia / Conklin, Steven E

Clinical biochemistry

2022 Volume 115, Page(s) 22–32

Abstract: Recent studies evaluating the preanalytical factors that impact the outcome of nucleic-acid based methods for the confirmation of SARS-CoV-2 have illuminated the importance of identifying variables that promoted accurate testing, while using scarce ... ...

Abstract	Recent studies evaluating the preanalytical factors that impact the outcome of nucleic-acid based methods for the confirmation of SARS-CoV-2 have illuminated the importance of identifying variables that promoted accurate testing, while using scarce resources efficiently. The majority of laboratory errors occur in the preanalytical phase. While there are many resources identifying and describing mechanisms for main laboratory testing on automated platforms, there are fewer comprehensive resources for understanding important preanalytical and environmental factors that affect accurate molecular diagnostic testing of infectious diseases. This review identifies evidence-based factors that have been documented to impact the outcome of nucleic acid-based molecular techniques for the diagnosis of infectious diseases.
MeSH term(s)	Humans ; Clinical Laboratory Techniques/methods ; Specimen Handling ; COVID-19/diagnosis ; SARS-CoV-2 ; Pre-Analytical Phase ; COVID-19 Testing
Language	English
Publishing date	2022-12-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	390372-2
ISSN	1873-2933 ; 0009-9120
ISSN (online)	1873-2933
ISSN	0009-9120
DOI	10.1016/j.clinbiochem.2022.12.003
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Article ; Online: Advancements in the gold standard: Measuring steroid sex hormones by mass spectrometry.

Conklin, Steven E / Knezevic, Claire E

Clinical biochemistry

2020 Volume 82, Page(s) 21–32

Abstract: Sex hormones, such as testosterone and estrogens, play an essential role in regulating physiological and reproductive development throughout the lifetime of the individual. Although variation in levels of these hormones are observed throughout the ... ...

Abstract	Sex hormones, such as testosterone and estrogens, play an essential role in regulating physiological and reproductive development throughout the lifetime of the individual. Although variation in levels of these hormones are observed throughout the distinct stages in life, significant deviations from reference ranges can result in detrimental effects to the individual. Alterations, by either an increase or decrease, in hormone levels are associated with physiological changes, decreased reproductive capabilities, and increased risk for diseases. Hormone therapies (HTs) and assisted reproductive technologies (ARTs) are commonly used to address these factors. In addition to these treatments, gender-affirming therapies, an iteration of HTs, are also a prominent treatment for transgender individuals. Considering that the effectiveness of these treatments relies on achieving therapeutic hormone levels, monitoring of hormones has served as a way of assessing therapeutic efficay. The need for reliable methods to achieve this task has led to great advancements in methods for evaluating hormone concentrations in biological matrices. Although immunoassays are the more widely used method, mass spectrometry (MS)-based methods have proven to be more sensitive, specific, and reliable. Advances in MS technology and its applications for therapeutic hormone monitoring have been significant, hence integration of these methods in the clinical setting is desired. Here, we provide a general overview of HT and ART, and the immunoassay and MS-based methods currently utilized for monitoring sex hormones. Additionally, we highlight recent advances in MS-based methods and discuss future applications and considerations for MS-based hormone assays.
MeSH term(s)	Adult ; Chromatography, Liquid/methods ; Drug Monitoring/methods ; Drug Monitoring/trends ; Estrogen Replacement Therapy ; Female ; Gas Chromatography-Mass Spectrometry/methods ; Gas Chromatography-Mass Spectrometry/trends ; Gonadal Steroid Hormones/blood ; Gonadal Steroid Hormones/chemistry ; Gonadal Steroid Hormones/therapeutic use ; Humans ; Immunoassay/methods ; Male ; Middle Aged ; Reproductive Techniques, Assisted ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/trends ; Tandem Mass Spectrometry/methods ; Tandem Mass Spectrometry/trends ; Transgender Persons
Chemical Substances	Gonadal Steroid Hormones
Language	English
Publishing date	2020-03-21
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	390372-2
ISSN	1873-2933 ; 0009-9120
ISSN (online)	1873-2933
ISSN	0009-9120
DOI	10.1016/j.clinbiochem.2020.03.008
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Article ; Online: Therapeutic plasma exchange decreases plasma anti-SARS-CoV-2 spike IgG without increasing the proximate incidence of COVID-19.

Cone Sullivan, Jensyn / Conklin, Steven E / Conrad, Stephanie / Horowitz, Coby / Diethelm, Mark / Comenzo, Raymond

Journal of clinical apheresis

2023 Volume 38, Issue 6, Page(s) 721–726

Abstract: Background: Therapeutic plasma exchange (TPE) removes both pathologic and protective immunoglobulins (Ig). SARS-CoV-2 immunity is partially mediated by anti-SARS-CoV-2 spike antibodies (SAb), which impair viral host-cell invasion. Nonetheless, the ... ...

Abstract	Background: Therapeutic plasma exchange (TPE) removes both pathologic and protective immunoglobulins (Ig). SARS-CoV-2 immunity is partially mediated by anti-SARS-CoV-2 spike antibodies (SAb), which impair viral host-cell invasion. Nonetheless, the systematic effect of TPE on SAb concentration and SARS-CoV-2 immunity is unknown. Methods: Paired plasma waste specimens from the first (first-TPE) and last (last-TPE) TPE treatment were collected from 9 patients between July 21, 2021 and March 1, 2022. The effects of TPE on Ig levels were assessed by quantitatively comparing the SAb, total IgG, and total IgM levels first-/last-TPE treatment. Complementary qualitative assessment for these changes was achieved via protein electrophoresis (PEP) and immunofixation (IFE). A retrospective review was performed to investigate the incidence of new SARS-CoV-2 infections following TPE v. other treatment at the same outpatient apheresis/infusion center during the same time frame. Results: Median SAb levels between the first- and last-TPE waste specimens decreased significantly from 424.6 AU/mL to 17.0 AU/mL (P = 0.004). Concordantly, PEP and IFE analysis demonstrated broad Ig decreases. Cumulative incidence of subsequent COVID-19 diagnosis at 30, 90, and 180 days post-procedure did not differ between the TPE v. other treatment groups (n = 709 total patients). Conclusions: TPE significantly reduced SAb levels, a marker of SARS-CoV-2 immunity, but did not appear to provoke increased incidence of COVID-19 infections. Further investigation of the kinetics of TPE-mediated SAb decrease and post-TPE recovery are warranted.
MeSH term(s)	Humans ; Plasma Exchange ; Incidence ; COVID-19 Testing ; COVID-19/epidemiology ; COVID-19/therapy ; SARS-CoV-2 ; Immunoglobulin G ; Antibodies, Viral
Chemical Substances	Immunoglobulin G ; Antibodies, Viral
Language	English
Publishing date	2023-09-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	604912-6
ISSN	1098-1101 ; 0733-2459
ISSN (online)	1098-1101
ISSN	0733-2459
DOI	10.1002/jca.22087
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Zs.A 1831: Show issues

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Article ; Online: Comparative evaluation of blood collection tubes for clinical chemistry analysis.

Ayala-Lopez, Nadia / Conklin, Steven E / Tenney, Brandon J / Ness, Maryann / Marzinke, Mark A

Clinica chimica acta; international journal of clinical chemistry

2021 Volume 520, Page(s) 118–125

Abstract: Background: Routine chemistry testing is typically performed using serum or plasma to assess a patient's clinical status. At our institution, serum is the specimen type used. To reduce processing times, evaluation of plasma-based and rapid serum gel ... ...

Abstract	Background: Routine chemistry testing is typically performed using serum or plasma to assess a patient's clinical status. At our institution, serum is the specimen type used. To reduce processing times, evaluation of plasma-based and rapid serum gel separator tubes was performed. Methods: We compared the results of routine chemistry analytes collected in serum gel separator tubes (SST), plasma gel separator tubes (PST), rapid serum gel separator tubes (RST), and plasma tubes without gel separators (DGT). Result concordance was assessed at baseline (immediate testing after processing) and up to one week of refrigerated storage. Other parameters assessed were the susceptibility to hemolysis and lipemia interference, and changes in results after re-centrifugation. Percent changes were compared against the SST and evaluated according to established bias thresholds. Results: Total protein and potassium results at baseline in plasma-based tubes had percent changes from the SST that exceeded acceptability thresholds. Stability was significantly shortened for glucose, potassium, aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) when collected in the PST as compared to the SST. The RST was the least susceptible to hemolysis and lipemia interferents. Re-centrifugation affected the serum-based analysis of potassium. Conclusions: Plasma may reduce processing time at the expense of shortened sample stability and may require specimen source-specific reference intervals for potassium and total protein. The RST provides an alternate option to reduce processing time, while maintaining storage stability.
MeSH term(s)	Blood Specimen Collection ; Chemistry, Clinical ; Humans ; Plasma ; Potassium ; Serum
Chemical Substances	Potassium (RWP5GA015D)
Language	English
Publishing date	2021-05-25
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	80228-1
ISSN	1873-3492 ; 0009-8981
ISSN (online)	1873-3492
ISSN	0009-8981
DOI	10.1016/j.cca.2021.05.019
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Ud II Zs.173: Show issues

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Article ; Online: Polystyrene bead ingestion promotes adiposity and cardiometabolic disease in mice.

Zhao, Jingjing / Gomes, Daniel / Jin, Lexiao / Mathis, Steven P / Li, Xiaohong / Rouchka, Eric C / Bodduluri, Haribabu / Conklin, Daniel J / O'Toole, Timothy E

Ecotoxicology and environmental safety

2022 Volume 232, Page(s) 113239

Abstract: Vast amounts of plastic materials are produced in the modern world and despite recycling efforts, large amounts are disposed in water systems and landfills. Under these storage conditions, physical weathering and photochemical processes break down these ... ...

Abstract	Vast amounts of plastic materials are produced in the modern world and despite recycling efforts, large amounts are disposed in water systems and landfills. Under these storage conditions, physical weathering and photochemical processes break down these materials into smaller particles of the micro- and nano-scale. In addition, ecosystems can be contaminated with plastic particles which are manufactured in these size ranges for commercial purposes. Independent of source, microplastics are abundant in the environment and have found their way into water supplies and the food cycle where human exposure is inevitable. Nevertheless, the health consequences of microplastic ingestion, inhalation, or absorption are largely unknown. In this study we sought to determine if ingestion of microplastics promoted pre-clinical cardiovascular disease (CVD). To do this, we supplied mice with normal drinking water or that supplemented with polystyrene beads of two different sizes (0.5 µm and 5 µm) and two different doses (0.1 μg/ml and 1 μg/ml) each for 12 weeks and measured several indices of metabolism and glucose homeostasis. As early as 3 weeks of consumption, we observed an accelerated weight gain with a corresponding increase in body fat for some exposure groups versus the control mice. Some exposure groups demonstrated increased levels of fasting plasma glucose. Those mice consuming the smaller sized beads (0.5 µm) at the higher dose (1 μg/ml), had increased levels of fasting plasma insulin and higher homeostatic model assessment of insulin resistance (HOMA-IR) scores as well. This was accompanied by changes in the gut microbiome consistent with an obese phenotype. Using samples of perivascular adipose tissue collected from the same group, we observed changes in gene expression consistent with increased adipogenesis. These results suggest that ingestion of polystyrene beads promotes a cardiometabolic disease phenotype and thus may be an unrecognized risk factor for CVD.
MeSH term(s)	Adiposity ; Animals ; Cardiovascular Diseases/chemically induced ; Eating ; Ecosystem ; Mice ; Obesity ; Plastics/toxicity ; Polystyrenes/analysis
Chemical Substances	Plastics ; Polystyrenes
Language	English
Publishing date	2022-01-29
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	436536-7
ISSN	1090-2414 ; 0147-6513
ISSN (online)	1090-2414
ISSN	0147-6513
DOI	10.1016/j.ecoenv.2022.113239
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Article ; Online: Polystyrene bead ingestion promotes adiposity and cardiometabolic disease in mice

Jingjing Zhao / Daniel Gomes / Lexiao Jin / Steven P. Mathis / Xiaohong Li / Eric C. Rouchka / Haribabu Bodduluri / Daniel J. Conklin / Timothy E. O’Toole

Ecotoxicology and Environmental Safety, Vol 232, Iss , Pp 113239- (2022)

2022

Abstract	Vast amounts of plastic materials are produced in the modern world and despite recycling efforts, large amounts are disposed in water systems and landfills. Under these storage conditions, physical weathering and photochemical processes break down these materials into smaller particles of the micro- and nano-scale. In addition, ecosystems can be contaminated with plastic particles which are manufactured in these size ranges for commercial purposes. Independent of source, microplastics are abundant in the environment and have found their way into water supplies and the food cycle where human exposure is inevitable. Nevertheless, the health consequences of microplastic ingestion, inhalation, or absorption are largely unknown. In this study we sought to determine if ingestion of microplastics promoted pre-clinical cardiovascular disease (CVD). To do this, we supplied mice with normal drinking water or that supplemented with polystyrene beads of two different sizes (0.5 µm and 5 µm) and two different doses (0.1 μg/ml and 1 μg/ml) each for 12 weeks and measured several indices of metabolism and glucose homeostasis. As early as 3 weeks of consumption, we observed an accelerated weight gain with a corresponding increase in body fat for some exposure groups versus the control mice. Some exposure groups demonstrated increased levels of fasting plasma glucose. Those mice consuming the smaller sized beads (0.5 µm) at the higher dose (1 μg/ml), had increased levels of fasting plasma insulin and higher homeostatic model assessment of insulin resistance (HOMA-IR) scores as well. This was accompanied by changes in the gut microbiome consistent with an obese phenotype. Using samples of perivascular adipose tissue collected from the same group, we observed changes in gene expression consistent with increased adipogenesis. These results suggest that ingestion of polystyrene beads promotes a cardiometabolic disease phenotype and thus may be an unrecognized risk factor for CVD.
Keywords	Microplastics ; Polystyrene ; Cardiometabolic disease ; Obesity ; Gut microbiome ; Environmental pollution ; TD172-193.5 ; Environmental sciences ; GE1-350
Subject code	333
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Children's Oncology Group's 2023 blueprint for research: Behavioral science.

Embry, Leanne / Bingen, Kristin / Conklin, Heather M / Hardy, Steven / Jacola, Lisa M / Marchak, Jordan Gilleland / Paltin, Iris / Pelletier, Wendy / Devine, Katie A

Pediatric blood & cancer

2023 Volume 70 Suppl 6, Page(s) e30557

Abstract: ... of predictive factors (e.g., social determinants of health) and psychosocial outcomes, with overarching goals ...

Abstract	As survival rates for childhood cancer have improved, there has been increasing focus on identifying and addressing adverse impacts of cancer and its treatment on children and their families during treatment and into survivorship. The Behavioral Science Committee (BSC) of the Children's Oncology Group (COG), comprised of psychologists, neuropsychologists, social workers, nurses, physicians, and clinical research associates, aims to improve the lives of children with cancer and their families through research and dissemination of empirically supported knowledge. Key achievements of the BSC include enhanced interprofessional collaboration through integration of liaisons into other key committees within COG, successful measurement of critical neurocognitive outcomes through standardized neurocognitive assessment strategies, contributions to evidence-based guidelines, and optimization of patient-reported outcome measurement. The collection of neurocognitive and behavioral data continues to be an essential function of the BSC, in the context of therapeutic trials that are modifying treatments to maximize event-free survival, minimize adverse outcomes, and optimize quality of life. In addition, through hypothesis-driven research and multidisciplinary collaborations, the BSC will also begin to prioritize initiatives to expand the systematic collection of predictive factors (e.g., social determinants of health) and psychosocial outcomes, with overarching goals of addressing health inequities in cancer care and outcomes, and promoting evidence-based interventions to improve outcomes for all children, adolescents, and young adults with cancer.
MeSH term(s)	Adolescent ; Young Adult ; Child ; Humans ; Quality of Life ; Medical Oncology ; Neoplasms/therapy ; Neoplasms/psychology ; Behavioral Sciences ; Survival Rate
Language	English
Publishing date	2023-07-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2131448-2
ISSN	1545-5017 ; 1545-5009
ISSN (online)	1545-5017
ISSN	1545-5009
DOI	10.1002/pbc.30557
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Zs.A 1131: Show issues

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Article ; Online: Using multiple imputation of real-world data to estimate clinical remission in pediatric inflammatory bowel disease.

Zhang, Nanhua / Liu, Chunyan / Steiner, Steven J / Colletti, Richard B / Baldassano, Robert / Chen, Shiran / Cohen, Stanley / Kappelman, Michael D / Saeed, Shehzad / Conklin, Laurie S / Strauss, Richard / Volger, Sheri / King, Eileen / Lo, Kim Hung

Journal of comparative effectiveness research

2023 Volume 12, Issue 4, Page(s) e220136

Abstract: Aim: ...

Abstract	Aim:
MeSH term(s)	Humans ; Child ; Crohn Disease/drug therapy ; Reproducibility of Results ; Inflammatory Bowel Diseases ; Treatment Outcome ; Remission Induction
Language	English
Publishing date	2023-02-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2669725-7
ISSN	2042-6313 ; 2042-6305
ISSN (online)	2042-6313
ISSN	2042-6305
DOI	10.57264/cer-2022-0136
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Article ; Online: Contractile deficits in engineered cardiac microtissues as a result of MYBPC3 deficiency and mechanical overload.

Ma, Zhen / Huebsch, Nathaniel / Koo, Sangmo / Mandegar, Mohammad A / Siemons, Brian / Boggess, Steven / Conklin, Bruce R / Grigoropoulos, Costas P / Healy, Kevin E

Nature biomedical engineering

2018 Volume 2, Issue 12, Page(s) 955–967

Abstract: The integration of in vitro cardiac tissue models, human induced pluripotent stem cells (hiPSCs) and genome-editing tools allows for the enhanced interrogation of physiological phenotypes and recapitulation of disease pathologies. Here, using a cardiac ... ...

Abstract	The integration of in vitro cardiac tissue models, human induced pluripotent stem cells (hiPSCs) and genome-editing tools allows for the enhanced interrogation of physiological phenotypes and recapitulation of disease pathologies. Here, using a cardiac tissue model consisting of filamentous three-dimensional matrices populated with cardiomyocytes derived from healthy wild-type (WT) hiPSCs (WT hiPSC-CMs) or isogenic hiPSCs deficient in the sarcomere protein cardiac myosin-binding protein C (MYBPC3
MeSH term(s)	Calcium/metabolism ; Cardiomyopathy, Dilated/genetics ; Cardiomyopathy, Dilated/physiopathology ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Cells, Cultured ; E1A-Associated p300 Protein/metabolism ; GATA4 Transcription Factor/metabolism ; Gene Knockout Techniques ; Humans ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/metabolism ; Myocardial Contraction/genetics ; Myocardial Contraction/physiology ; Myocardium/metabolism ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/metabolism ; Sarcomeres/metabolism ; Stress, Mechanical ; Tissue Engineering
Chemical Substances	Carrier Proteins ; GATA4 Transcription Factor ; GATA4 protein, human ; myosin-binding protein C ; E1A-Associated p300 Protein (EC 2.3.1.48) ; EP300 protein, human (EC 2.3.1.48) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2018-09-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2157-846X
ISSN (online)	2157-846X
DOI	10.1038/s41551-018-0280-4
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