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Article ; Online: Oral Ingestion of an Iron-Containing Hand Warmer in a Pediatric Patient.

Hardin, Jeremy R / Suzuki, Emi / Seltzer, Justin A / Suhandynata, Raymond T / Sivagnanam, Mamata / Lasoff, Daniel R

2024 Volume 35, Issue 1, Page(s) 70–73

Abstract: Hand warmer packets are common products used to provide a portable, nonflammable heat source via the exothermic oxidation of iron. We present the first reported case of pediatric hand warmer packet ingestion in a three-year-old male who developed an ... ...

Abstract	Hand warmer packets are common products used to provide a portable, nonflammable heat source via the exothermic oxidation of iron. We present the first reported case of pediatric hand warmer packet ingestion in a three-year-old male who developed an elevated serum iron concentration (peak 335 ug/dL) and gastrointestinal injury after ingesting the contents of a HOTHANDS hand warmer packet. He was treated with endoscopic gastric foreign body removal and lavage, as well as proton-pump inhibitors and whole bowel irrigation. Hand warmer packs contain reduced elemental iron powder, which has been shown to have a more favorable safety profile when compared to iron salts. The mechanism of toxicity for reduced iron is unknown, though it is thought to be due to conversion to more toxic iron ions in an acidic environment. While the current adult literature suggests that ingestion of a single hand warmer packet is without significant risk, our case demonstrates that even a partial ingestion carries a significant risk of both iron toxicity and direct gastrointestinal caustic injury in a young child. This case demonstrates the need for multidisciplinary care and consideration of urgent endoscopic foreign body removal and gastric lavage followed by whole bowel irrigation to mitigate the potential of severe iron toxicity.
MeSH term(s)	Child, Preschool ; Humans ; Male ; Abdominal Injuries ; Eating ; Foreign Bodies/therapy ; Hand ; Iron ; Thoracic Injuries ; Upper Extremity
Chemical Substances	Iron (E1UOL152H7)
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	1238909-2
ISSN	1545-1534 ; 1080-6032
ISSN (online)	1545-1534
ISSN	1080-6032
DOI	10.1177/10806032231222373
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Zs.A 3025: Show issues

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Article: Phosphate-binding pocket on cyclin B governs CDK substrate phosphorylation and mitotic timing.

Ng, Henry Y / Adly, Armin N / Whelpley, Devon H / Suhandynata, Raymond T / Zhou, Huilin / Morgan, David O

bioRxiv : the preprint server for biology

2024

Abstract: Cell cycle progression is governed by complexes of the cyclin-dependent kinases (CDKs) and their regulatory subunits cyclin and Cks1. CDKs phosphorylate hundreds of substrates, often at multiple sites. Multisite phosphorylation depends on Cks1, which ... ...

Abstract	Cell cycle progression is governed by complexes of the cyclin-dependent kinases (CDKs) and their regulatory subunits cyclin and Cks1. CDKs phosphorylate hundreds of substrates, often at multiple sites. Multisite phosphorylation depends on Cks1, which binds initial priming phosphorylation sites to promote secondary phosphorylation at other sites. Here, we describe a similar role for a recently discovered phosphate-binding pocket (PP) on B-type cyclins. Mutation of the PP in Clb2, the major mitotic cyclin of budding yeast, alters bud morphology and delays the onset of anaphase. Using phosphoproteomics
Language	English
Publishing date	2024-02-29
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.28.582599
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Article ; Online: Comparison of two highly sensitive benzodiazepine immunoassay lab developed tests for urine drug testing in clinical specimens.

Lund, Kyle / Menlyadiev, Marlen / Lee, Kyunghoon / Kelner, Michael J / Fitzgerald, Robert L / Suhandynata, Raymond T

Journal of mass spectrometry and advances in the clinical lab

2023 Volume 28, Page(s) 91–98

Abstract: Background: The VALID Act is a legislative effort that, if enacted, would alter the regulatory requirements of laboratory developed tests (LDTs) used for clinical testing in the United States. Benzodiazepines, which are primarily excreted into urine as ... ...

Abstract	Background: The VALID Act is a legislative effort that, if enacted, would alter the regulatory requirements of laboratory developed tests (LDTs) used for clinical testing in the United States. Benzodiazepines, which are primarily excreted into urine as glucuronidated metabolites such as lorazepam, cross-react poorly with FDA-cleared immunoassays, leading to false-negatives. This shortfall can be addressed with LDTs created by adding glucuronidase to the immunoassay reagents producing "high sensitivity" assays that detect glucuronidated metabolites. Methods: Precision and stability of two high-sensitivity (HS) benzodiazepine immunoassays from Roche and Thermo Scientific were evaluated using manufacturer-supplied quality control (QC) material and glucuronidated QC material. The immunoassays were directly compared to an LC-MS/MS LDT benzodiazepine assay to determine clinical sensitivity/specificity using urine specimens (n = 82 for Thermo Scientific; n = 265 for Roche). The clinical impact of the HS LDT immunoassay was determined by analyzing clinical testing results 60 days before and after its implementation. Results: The precision and clinical sensitivity/specificity of the HS-Thermo Scientific and HS-Roche benzodiazepine assays were acceptable. The reagent stability of the HS-Thermo Scientific immunoassay was poor, whereas the HS-Roche immunoassay was stable. After implementation of the HS-Roche benzodiazepine immunoassay as an LDT, there was a 30-fold increase Conclusions: We demonstrate the development and validation of an immunoassay LDT with improved sensitivity for glucuronidated benzodiazepines. This LDT can detect glucuronidated benzodiazepines in clinical urine specimens and is stable for 60 days. Importantly, we were able to validate the immunoassay as an LDT by utilizing an LC-MS/MS LDT.
Language	English
Publishing date	2023-03-01
Publishing country	Netherlands
Document type	Journal Article
ISSN	2667-145X
ISSN (online)	2667-145X
DOI	10.1016/j.jmsacl.2023.02.010
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Article ; Online: Evaluating the performance of the Roche FEN2 fentanyl immunoassay and its clinical implementation: The role of LDT-based mass spectrometry testing.

Menlyadiev, Marlen / Suhandynata, Raymond T / Lund, Kyle / Kelner, Michael J / Fitzgerald, Robert L

Journal of mass spectrometry and advances in the clinical lab

2023 Volume 28, Page(s) 105–113

Abstract: Introduction: While laboratory-developed tests (LDTs) using liquid chromatography tandem mass spectrometry (LC-MS/MS) are widely employed to support the development of FDA-cleared drug immunoassays, their significance in the clinical implementation and ... ...

Abstract	Introduction: While laboratory-developed tests (LDTs) using liquid chromatography tandem mass spectrometry (LC-MS/MS) are widely employed to support the development of FDA-cleared drug immunoassays, their significance in the clinical implementation and evaluation of such assays is often overlooked. This paper reports on the important role of LC-MS/MS LDTs in demonstrating improved performance of the Roche FEN2 fentanyl immunoassay compared with the Thermo DRI fentanyl immunoassay. Methods: The FEN2 assay was implemented according to the manufacturer's instructions and its performance was compared to the existing DRI assay using LC-MS/MS as a reference. Clinical sensitivity and specificity were determined using 250 consecutive random patient specimens. Spiking experiments were conducted to determine cross-reactivity with 31 fentanyl analogs. Select DRI false-positive samples were analyzed by the FEN2 assay via time-of-flight mass spectrometry method (LC-QTOF). Results: The FEN2 assay showed improved clinical sensitivity compared to the DRI (98% vs 61%) in 250 consecutive patient samples due to its ability to detect norfentanyl. It also showed better clinical specificity by correctly classifying select DRI false-positive results. Upon implementation in clinical practice, the FEN2 resulted in a higher screening positivity rate than the DRI (17.3% vs 13.3%) and a greater LC-MS/MS confirmation rate of immunoassay-positive samples (96.8% vs 88.8%, respectively). Conclusion: The use of LC-MS/MS LDTs demonstrated that the FEN2 assay has greater clinical sensitivity and is less prone to false-positives than the DRI assay. These findings support the use of FEN2 in routine clinical practice and emphasize the role of mass spectrometry-based LDTs in clinical toxicology testing.
Language	English
Publishing date	2023-03-09
Publishing country	Netherlands
Document type	Journal Article
ISSN	2667-145X
ISSN (online)	2667-145X
DOI	10.1016/j.jmsacl.2023.02.009
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Article ; Online: Pharmacokinetics, Fecal Output, and Grimace Scores in Rabbits Given Long-acting Buprenorphine or Fentanyl for Postsurgical Analgesia.

Farkas, Michelle R / Dorn, Shanelle / Muller, Liam / Singh, Vikram Pal / Sepulveda, Yadira J / Suhandynata, Raymond T / Momper, Jeremiah D / Masuda, Koichi / Richter, Philip J

Journal of the American Association for Laboratory Animal Science : JAALAS

2024

Abstract: The New Zealand white rabbit ( ...

Abstract	The New Zealand white rabbit (
Language	English
Publishing date	2024-03-15
Publishing country	United States
Document type	Journal Article
ISSN	2769-6677
ISSN (online)	2769-6677
DOI	10.30802/AALAS-JAALAS-23-000074
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Article ; Online: Variable Delta-9-Tetrahydrocannabinol Pharmacokinetics and Pharmacodynamics After Cannabis Smoking in Regular Users.

Liyanage, Marlon / Nikanjam, Mina / Capparelli, Edmund V / Suhandynata, Raymond T / Fitzgerald, Robert L / Marcotte, Thomas D / Grant, Igor / Momper, Jeremiah D

Therapeutic drug monitoring

2023 Volume 45, Issue 5, Page(s) 689–696

Abstract: Background: Despite its federally restricted status, cannabis is widely used medicinally and recreationally. The pharmacokinetics (PK) and central nervous system (CNS) effects of tetrahydrocannabinol (THC), the major psychoactive cannabinoid, are not ... ...

Abstract	Background: Despite its federally restricted status, cannabis is widely used medicinally and recreationally. The pharmacokinetics (PK) and central nervous system (CNS) effects of tetrahydrocannabinol (THC), the major psychoactive cannabinoid, are not well understood. The objective of this study was to develop a population PK model of inhaled THC, including sources of variability, and to conduct an exploratory analysis of potential exposure-response relationships. Methods: Regular adult cannabis users smoked a single cannabis cigarette containing 5.9% THC (Chemovar A) or 13.4% THC (Chemovar B) ad libitum. THC concentrations in whole blood were measured and used to develop a population PK model to identify potential factors contributing to interindividual variability in THC PK and to describe THC disposition. Relationships between model-predicted exposure and heart rate, change in composite driving score on a driving simulator, and perceived highness were evaluated. Results: From the 102 participants, a total of 770 blood THC concentrations were obtained. A two-compartment structural model adequately fit the data. Chemovar and baseline THC (THC BL ) were found to be significant covariates for bioavailability, with Chemovar A having better THC absorption. The model predicted that heavy users-those with the highest THC BL -would have significantly higher absorption than those with lighter previous use. There was a statistically significant relationship between exposure and heart rate, and exposure and perceived highness. Conclusions: THC PK is highly variable and related to baseline THC concentrations and different chemovars. The developed population PK model showed that heavier users had higher THC bioavailability. To better understand the factors affecting THC PK and dose-response relationships, future studies should incorporate a wide range of doses, multiple routes of administration, and different formulations relevant to typical community use.
MeSH term(s)	Adult ; Humans ; Marijuana Smoking ; Dronabinol/pharmacokinetics ; Cannabis/chemistry ; Cannabinoids/pharmacokinetics ; Biological Availability
Chemical Substances	Dronabinol (7J8897W37S) ; Cannabinoids
Language	English
Publishing date	2023-05-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	424443-6
ISSN	1536-3694 ; 0163-4356
ISSN (online)	1536-3694
ISSN	0163-4356
DOI	10.1097/FTD.0000000000001104
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Zs.A 1503: Show issues

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Article: Bacterial antiviral defense pathways encode eukaryotic-like ubiquitination systems.

Chambers, Lydia R / Ye, Qiaozhen / Cai, Jiaxi / Gong, Minheng / Ledvina, Hannah E / Zhou, Huilin / Whiteley, Aaron T / Suhandynata, Raymond T / Corbett, Kevin D

bioRxiv : the preprint server for biology

2023

Abstract: Ubiquitination and related pathways play crucial roles in protein homeostasis, signaling, and innate ... ...

Abstract	Ubiquitination and related pathways play crucial roles in protein homeostasis, signaling, and innate immunity
Language	English
Publishing date	2023-09-26
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.09.26.559546
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Article ; Online: Qua-Alluding to the Past: A Case of Methaqualone Analog Ingestion.

Lund, Kyle / Srihari, Priya / Suhandynata, Raymond T / Schwartz, Kristy / Fitzgerald, Robert L / Kreshak, Allyson A

Journal of analytical toxicology

2021

Abstract: Methaqualone, known previously under the brand name Quaalude, is a Schedule I sedative hypnotic drug that may cause neurotoxicity in overdose, characterized by somnolence, hyperreflexia and muscular hyperactivity. We present a case of a 21-year-old male ... ...

Abstract	Methaqualone, known previously under the brand name Quaalude, is a Schedule I sedative hypnotic drug that may cause neurotoxicity in overdose, characterized by somnolence, hyperreflexia and muscular hyperactivity. We present a case of a 21-year-old male who reportedly ingested methaqualone in addition to insufflation of street cocaine. He subsequently developed hypoxia, hyperreflexia, myoclonus, and altered mental status. His laboratory results were notable for the presence of methemoglobinemia, which was most likely due to a cocaine contaminant. Laboratory analysis of the alleged methaqualone pills identified the substance as SL-164, a dichlorinated methaqualone analog. Urine toxicology results were positive for SL-164 (and presumed metabolites) as well as for cocaine and tetrahydrocannabinol metabolites. The patient was treated with supplemental oxygen and a benzodiazepine (lorazepam) and observed in the Emergency Department (ED) until his symptoms resolved. This case highlights current community access to methaqualone analogs. The case also focuses on laboratory techniques used to identify the methaqualone analog.
Language	English
Publishing date	2021-09-21
Publishing country	England
Document type	Journal Article
ZDB-ID	752391-9
ISSN	1945-2403 ; 0146-4760
ISSN (online)	1945-2403
ISSN	0146-4760
DOI	10.1093/jat/bkab103
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Zs.A 1333: Show issues

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Article ; Online: Shared and distinct roles of Esc2 and Mms21 in suppressing genome rearrangements and regulating intracellular sumoylation.

Suhandynata, Raymond T / Gao, Yong-Qi / Zhou, Ann L / Yang, Yusheng / Wang, Pang-Che / Zhou, Huilin

PloS one

2021 Volume 16, Issue 2, Page(s) e0247132

Abstract: Protein sumoylation, especially when catalyzed by the Mms21 SUMO E3 ligase, plays a major role in suppressing duplication-mediated gross chromosomal rearrangements (dGCRs). How Mms21 targets its substrates in the cell is insufficiently understood. Here, ... ...

Abstract	Protein sumoylation, especially when catalyzed by the Mms21 SUMO E3 ligase, plays a major role in suppressing duplication-mediated gross chromosomal rearrangements (dGCRs). How Mms21 targets its substrates in the cell is insufficiently understood. Here, we demonstrate that Esc2, a protein with SUMO-like domains (SLDs), recruits the Ubc9 SUMO conjugating enzyme to specifically facilitate Mms21-dependent sumoylation and suppress dGCRs. The D430R mutation in Esc2 impairs its binding to Ubc9 and causes a synergistic growth defect and accumulation of dGCRs with mutations that delete the Siz1 and Siz2 E3 ligases. By contrast, esc2-D430R does not appreciably affect sensitivity to DNA damage or the dGCRs caused by the catalytically inactive mms21-CH. Moreover, proteome-wide analysis of intracellular sumoylation demonstrates that esc2-D430R specifically down-regulates sumoylation levels of Mms21-preferred targets, including the nucleolar proteins, components of the SMC complexes and the MCM complex that acts as the catalytic core of the replicative DNA helicase. These effects closely resemble those caused by mms21-CH, and are relatively unaffected by deleting Siz1 and Siz2. Thus, by recruiting Ubc9, Esc2 facilitates Mms21-dependent sumoylation to suppress the accumulation of dGCRs independent of Siz1 and Siz2.
MeSH term(s)	Amino Acid Sequence ; Cell Cycle Proteins/chemistry ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; DNA Damage ; DNA Replication ; Down-Regulation ; Mutagenesis ; Protein Binding ; Protein Domains ; Protein Stability ; Proteomics ; SUMO-1 Protein/chemistry ; SUMO-1 Protein/genetics ; SUMO-1 Protein/metabolism ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/chemistry ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Sequence Alignment ; Sumoylation ; Ubiquitin-Conjugating Enzymes/chemistry ; Ubiquitin-Conjugating Enzymes/metabolism ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism
Chemical Substances	Cell Cycle Proteins ; Esc2 protein, S cerevisiae ; Mms21 protein, S cerevisiae ; SUMO-1 Protein ; Saccharomyces cerevisiae Proteins ; Siz2 protein, S cerevisiae ; Ubiquitin-Conjugating Enzymes (EC 2.3.2.23) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Siz1 protein, S cerevisiae (EC 6.3.2.-) ; ubiquitin-conjugating enzyme UBC9 (EC 6.3.2.-)
Language	English
Publishing date	2021-02-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0247132
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Article ; Online: Driving Under the Influence of Cannabis: Impact of Combining Toxicology Testing with Field Sobriety Tests.

Fitzgerald, Robert L / Umlauf, Anya / Hubbard, Jacqueline A / Hoffman, Melissa A / Sobolesky, Philip M / Ellis, Shannon E / Grelotti, David J / Suhandynata, Raymond T / Huestis, Marilyn A / Grant, Igor / Marcotte, Thomas D

Clinical chemistry

2023 Volume 69, Issue 7, Page(s) 724–733

Abstract: Background: Cannabis is increasingly used both medically and recreationally. With widespread use, there is growing concern about how to identify cannabis-impaired drivers.: Methods: A placebo-controlled randomized double-blinded protocol was ... ...

Abstract	Background: Cannabis is increasingly used both medically and recreationally. With widespread use, there is growing concern about how to identify cannabis-impaired drivers. Methods: A placebo-controlled randomized double-blinded protocol was conducted to study the effects of cannabis on driving performance. One hundred ninety-one participants were randomized to smoke ad libitum a cannabis cigarette containing placebo or delta-9-tetrahydrocannabinol (THC) (5.9% or 13.4%). Blood, oral fluid (OF), and breath samples were collected along with longitudinal driving performance on a simulator (standard deviation of lateral position [SDLP] and car following [coherence]) over a 5-hour period. Law enforcement officers performed field sobriety tests (FSTs) to determine if participants were impaired. Results: There was no relationship between THC concentrations measured in blood, OF, or breath and SDLP or coherence at any of the timepoints studied (P > 0.05). FSTs were significant (P < 0.05) for classifying participants into the THC group vs the placebo group up to 188 minutes after smoking. Seventy-one minutes after smoking, FSTs classified 81% of the participants who received active drug as being impaired. However, 49% of participants who smoked placebo (controls) were also deemed impaired at this same timepoint. Combining a 2 ng/mL THC cutoff in OF with positive findings on FSTs reduced the number of controls classified as impaired to zero, 86 minutes after smoking the placebo. Conclusions: Requiring a positive toxicology result in addition to the FST observations substantially improved the classification accuracy regarding possible driving under the influence of THC by decreasing the percentage of controls classified as impaired.
MeSH term(s)	Humans ; Cannabis ; Dronabinol ; Driving Under the Influence ; Marijuana Smoking ; Hallucinogens ; Cannabinoid Receptor Agonists ; Automobile Driving
Chemical Substances	Dronabinol (7J8897W37S) ; Hallucinogens ; Cannabinoid Receptor Agonists
Language	English
Publishing date	2023-05-26
Publishing country	England
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80102-1
ISSN	1530-8561 ; 0009-9147
ISSN (online)	1530-8561
ISSN	0009-9147
DOI	10.1093/clinchem/hvad054
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