Publications by authors named "Kyle Bartholomew"

4 Publications

  • Page 1 of 1

Augmenting the Activity of Macrolide Adjuvants against .

ACS Med Chem Lett 2020 Sep 12;11(9):1723-1731. Epub 2020 Aug 12.

Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.

Approximately 1.7 million Americans develop hospital associated infections each year, resulting in more than 98,000 deaths. One of the main contributors to such infections is the Gram-negative pathogen . Recently, it was reported that aryl 2-aminoimidazole (2-AI) compounds potentiate macrolide antibiotics against a highly virulent strain of , AB5075. The two lead compounds in that report increased clarithromycin (CLR) potency against AB5075 by 16-fold, lowering the minimum inhibitory concentration (MIC) from 32 to 2 μg/mL at a concentration of 10 μM. Herein, we report a structure-activity relationship study of a panel of derivatives structurally inspired by the previously reported aryl 2-AI leads. Substitutions around the core phenyl ring yielded a lead that potentiates clarithromycin by 64- and 32-fold against AB5075 at 10 and 7.5 μM, exceeding the dose response of the original lead. Additional probing of the amide linker led to the discovery of two urea containing adjuvants that suppressed clarithromycin resistance in AB5075 by 64- and 128-fold at 7.5 μM. Finally, the originally reported adjuvant was tested for its ability to suppress the evolution of resistance to clarithromycin over the course of nine consecutive days. At 30 μM, the parent compound reduced the CLR MIC from 512 to 2 μg/mL, demonstrating that the original lead remained active against a more CLR resistant strain of AB5075.
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http://dx.doi.org/10.1021/acsmedchemlett.0c00276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488284PMC
September 2020

Retrospective analysis of complications associated with retrobulbar bupivacaine in dogs undergoing enucleation surgery.

Vet Anaesth Analg 2020 Sep 6;47(5):588-594. Epub 2020 May 6.

Department of Biostatistics and Medical Informatics, University of Wisconsin - Madison, Madison, WI, USA.

Objective: To investigate complications associated with, and without, bupivacaine retrobulbar local anesthesia in dogs undergoing unilateral enucleation surgery.

Study Design: Retrospective, observational study.

Animals: A total of 167 dogs underwent unilateral enucleation surgery via a transpalpebral approach.

Methods: Records from 167 dogs that underwent unilateral enucleation surgery that did (RB) or did not (NB) include retrobulbar bupivacaine anesthesia were reviewed, including anesthetic record, daily physical examination records, surgery report, patient discharge report and patient notes within 14 days of the surgery. Specific complications and severity were compared between RB and NB using the Wilcoxon rank-sum test. A 'complication burden' (0-5) comprising five prespecified complications was assigned and tested using rank-sum procedures. Statistical significance was set to 0.05.

Results: Group RB included 97 dogs and group NB 70 dogs. Dogs in NB had a 17.0 percentage points (points) greater risk for a postoperative recovery complication (38.6% versus 21.6%; 95% confidence interval: 3.0-30.6 points; p = 0.017). There was inconclusive evidence that dogs in group RB had a lower risk of requiring perioperative anticholinergic administration (12.4% versus 22.9%; 10.5 points; p = 0.073). Other complications were similar between groups RB and NB with risks that differed by <10 points. The risk of hemorrhage was similar between groups RB (22.7%) and NB (20.0%) with no significant difference in the level of severity (p = 0.664).

Conclusions And Clinical Relevance: In this retrospective study, the use of retrobulbar bupivacaine for enucleation surgery in dogs was not associated with an increased risk of major or minor complications.
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http://dx.doi.org/10.1016/j.vaa.2020.04.007DOI Listing
September 2020

The intergenerational transmission of partnering.

PLoS One 2018 13;13(11):e0205732. Epub 2018 Nov 13.

Pay Tel, Greensboro, NC, United States of America.

As divorce and cohabitation dissolution in the US have increased, partnering has expanded to the point that sociologists describe a merry-go-round of partners in American families. Could one driver of the increase in the number of partners be an intergenerational transmission of partnering? We discuss three theoretical perspectives on potential mechanisms that would underlie an intergenerational transmission of partnering: the transmission of economic hardship, the transmission of marriageable characteristics and relationship skills, and the transmission of relationship commitment. Using the National Longitudinal Survey of Youth 1979 Child and Young Adult study (NLSY79 CYA) and their mothers in the National Longitudinal Survey of Youth 1979 (NLSY79), we examined the intergenerational transmission of partnering, including both marital and cohabitating unions, using prospective measures of family and economic instability as well as exploiting sibling data to try to identify potential mechanisms. Even after controlling for maternal demographic characteristics and socioeconomic factors, the number of maternal partners was positively associated with offspring's number of partners. Hybrid sibling Poisson regression models that examined sibling differential experiences of maternal partners indicated that there were no differences between siblings who witnessed more or fewer maternal partners. Overall, results suggested that the transmission of poor marriageable characteristics and relationship skills from mother to child may warrant additional attention as a potential mechanism through which the number of partners continues across generations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0205732PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233917PMC
April 2019

A Two-Input Fluorescent Logic Gate for Glutamate and Zinc.

ACS Chem Neurosci 2017 06 6;8(6):1159-1162. Epub 2017 Mar 6.

Department of Chemistry, University of Missouri , 601 South College Avenue, Columbia, Missouri 65211, United States.

The direct visualization of neurotransmitters is a continuing problem in neuroscience; however, functional fluorescent sensors for organic analytes are still rare. Herein, we describe a fluorescent sensor for glutamate and zinc ions. The sensor acts as a fluorescent logic gate, giving a turn-off response to glutamate or zinc ion alone. The combination of analytes produces a large increase in fluorescence. This type of sensor will aid in the study of neurotransmission, in this case, for neurons that copackage high concentrations of zinc and glutamate.
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http://dx.doi.org/10.1021/acschemneuro.6b00420DOI Listing
June 2017