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Article ; Online: Discovery of an adjuvant that resensitizes polymyxin B-resistant bacteria.

Mahdavi, Michael / Findlay, Brandon L

2023 Volume 97, Page(s) 117541

Abstract: Infections caused by antibiotic-resistant bacteria are a major threat to health, increasing mortality rates and straining health systems worldwide. Adjuvants targeted to beta-lactamase function are able to resensitize bacteria to beta-lactam antibiotics, ...

Abstract	Infections caused by antibiotic-resistant bacteria are a major threat to health, increasing mortality rates and straining health systems worldwide. Adjuvants targeted to beta-lactamase function are able to resensitize bacteria to beta-lactam antibiotics, but there is comparatively little research into the use of adjuvants against other resistance phenotypes. In this study, we performed a high-throughput screen of 74 natural products to identify adjuvants that synergized with antibiotics to eradicate resistant Gram-negative bacteria. From this, we identified six adjuvant hits which restored growth inhibition when combined with the relevant antibiotic, and pursued a lead candidate, perforone, which possessed selective adjuvant activity in combination with polymyxin B against polymyxin-resistant Escherichia coli cells. These results suggest that pairing adjuvants with antibiotics could be a useful general intervention against resistant bacteria, helping to mitigate the effects of antimicrobial resistance.
MeSH term(s)	Polymyxin B/pharmacology ; Anti-Bacterial Agents/pharmacology ; Polymyxins/pharmacology ; Bacteria ; Gram-Negative Bacteria ; Escherichia coli ; Adjuvants, Pharmaceutic/pharmacology ; Microbial Sensitivity Tests ; Drug Resistance, Multiple, Bacterial
Chemical Substances	Polymyxin B (J2VZ07J96K) ; Anti-Bacterial Agents ; Polymyxins ; Adjuvants, Pharmaceutic
Language	English
Publishing date	2023-12-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1161284-8
ISSN	1464-3391 ; 0968-0896
ISSN (online)	1464-3391
ISSN	0968-0896
DOI	10.1016/j.bmc.2023.117541
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Article ; Online: Fitness Costs of Antibiotic Resistance Impede the Evolution of Resistance to Other Antibiotics.

Chowdhury, Farhan R / Findlay, Brandon L

ACS infectious diseases

2023 Volume 9, Issue 10, Page(s) 1834–1845

Abstract: Antibiotic resistance is a major threat to global health, claiming the lives of millions every year. With a nearly dry antibiotic development pipeline, novel strategies are urgently needed to combat resistant pathogens. One emerging strategy is the use ... ...

Abstract	Antibiotic resistance is a major threat to global health, claiming the lives of millions every year. With a nearly dry antibiotic development pipeline, novel strategies are urgently needed to combat resistant pathogens. One emerging strategy is the use of sequential antibiotic therapy, postulated to reduce the rate at which antibiotic resistance evolves. Here, we use the soft agar gradient evolution (SAGE) system to carry out high-throughput in vitro bacterial evolution against antibiotic pressure. We find that evolution of resistance to the antibiotic chloramphenicol (CHL) severely affects bacterial fitness, slowing the rate at which resistance to the antibiotics nitrofurantoin and streptomycin emerges. In vitro acquisition of compensatory mutations in the CHL-resistant cells markedly improves fitness and nitrofurantoin adaptation rates but fails to restore rates to wild-type levels against streptomycin. Genome sequencing reveals distinct evolutionary paths to resistance in fitness-impaired populations, suggesting resistance trade-offs in favor of mitigation of fitness costs. We show that the speed of bacterial fronts in SAGE plates is a reliable indicator of adaptation rates and evolutionary trajectories to resistance. Identification of antibiotics whose mutational resistance mechanisms confer stable impairments may help clinicians prescribe sequential antibiotic therapies that are less prone to resistance evolution.
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Nitrofurantoin ; Drug Resistance, Bacterial ; Streptomycin ; Mutation ; Bacteria/genetics
Chemical Substances	Anti-Bacterial Agents ; Nitrofurantoin (927AH8112L) ; Streptomycin (Y45QSO73OB)
Language	English
Publishing date	2023-09-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2373-8227
ISSN (online)	2373-8227
DOI	10.1021/acsinfecdis.3c00156
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Article ; Online: In Reply to the Letter to the Editor Regarding "Systematic Review of Research, Mentorship, and Career Resources for Medical Students Pursuing Neurosurgical Training".

Carter, Ashley / Findlay, Matthew C / Earl, Emma Rose / Khan, Majid / Bauer, Sawyer / Farsi, Koorosh / Lucke-Wold, Brandon / Karsy, Michael

World neurosurgery

2024 Volume 182, Page(s) 236

MeSH term(s)	Humans ; Career Choice ; Education, Medical, Undergraduate ; Mentors ; Students, Medical ; Systematic Reviews as Topic ; Neurosurgery/education
Language	English
Publishing date	2024-02-08
Publishing country	United States
Document type	Letter
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2023.11.097
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Article ; Online: High Failure Rates in Prisoners Undergoing Spine Fusion Surgery.

Findlay, Matthew C / Kim, Robert B / Sherrod, Brandon A / Mazur, Marcus D

World neurosurgery

2023 Volume 172, Page(s) e396–e405

Abstract: Objective: The medical literature on prisoner health care is limited, despite data showing that prisoners experience high rates of physical and mental health challenges. We compared clinical outcomes for prisoners undergoing spine fusion with comparable ...

Abstract	Objective: The medical literature on prisoner health care is limited, despite data showing that prisoners experience high rates of physical and mental health challenges. We compared clinical outcomes for prisoners undergoing spine fusion with comparable nonincarcerated patients and determined what factors were implicated in differences in outcomes. Methods: Prisoners who underwent spinal fusion in 2011-2021 were retrospectively compared with an age-, sex-, and procedure-matched 3:1 control group of nonincarcerated spinal fusion patients. Fusion failure was confirmed by lack of bridging bone between vertebrae on CT or radiographic images >1 year postoperatively or evidence of instrumentation failure with resultant >2 mm of translation on flexion/extension radiographs. Results: Twenty-seven identified prisoners were compared with 81 nonincarcerated controls. Ten prisoners and 6 controls experienced nonunion (37% vs. 7%, P < 0.01). Rates of risk factors for nonunion, such as smoking history, elevated body mass index, chronic steroid use, diabetes mellitus, previous spine surgery, and levels fused, were not significantly different between prisoners and controls. Among prisoners, those with nonunion were younger (45 vs. 53 years, P = 0.03), had greater body mass index (34 vs. 29, P = 0.02), and were more likely to undergo reoperation (30% vs. 0%, P = 0.02). Multivariate analysis revealed that prisoners carry a 9.62 increased odds of nonunion compared with controls. Conclusions: This is one of few studies investigating health care outcomes in prisoners. We found they had a significantly higher rate of nonunion than matched control patients from the general population treated at the same hospital, suggesting additional measures may be necessary postoperatively to support fusion in prisoners.
MeSH term(s)	Humans ; Retrospective Studies ; Risk Factors ; Diskectomy/methods ; Reoperation ; Radiography ; Spinal Fusion/methods ; Treatment Outcome
Language	English
Publishing date	2023-01-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2023.01.038
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Zs.A 1159: Show issues

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Article ; Online: Emerging Treatments for Subarachnoid Hemorrhage.

Findlay, Matthew C / Kundu, Mrinmoy / Nelson, Jayson R / Cole, Kyril L / Winterton, Candace / Tenhoeve, Samuel / Lucke-Wold, Brandon

CNS & neurological disorders drug targets

2024

Abstract: The current landscape of therapeutic strategies for subarachnoid hemorrhage (SAH), a significant adverse neurological event commonly resulting from the rupture of intracranial aneurysms, is rapidly evolving. Through an in-depth exploration of the natural ...

Abstract	The current landscape of therapeutic strategies for subarachnoid hemorrhage (SAH), a significant adverse neurological event commonly resulting from the rupture of intracranial aneurysms, is rapidly evolving. Through an in-depth exploration of the natural history of SAH, historical treatment approaches, and emerging management modalities, the present work aims to provide a broad overview of the shifting paradigms in SAH care. By synthesizing the historical management protocols with contemporary therapeutic advancements, patient-specific treatment plans can be individualized and optimized to deliver outstanding care for the best possible SAH-related outcomes.
Language	English
Publishing date	2024-02-22
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	2228394-8
ISSN	1996-3181 ; 1871-5273
ISSN (online)	1996-3181
ISSN	1871-5273
DOI	10.2174/0118715273279212240130065713
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Zs.A 5892: Show issues

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Article ; Online: Innovative Discoveries in Neurosurgical Treatment of Neurodegenerative Diseases: A Narrative Review.

Findlay, Matthew C / Khan, Majid / Kundu, Mrinmoy / Johansen, Chase M / Lucke-Wold, Brandon

Current Alzheimer research

2023 Volume 20, Issue 6, Page(s) 394–402

Abstract: Neurodegenerative diseases (NDDs) encapsulate conditions in which neural cell populations are perpetually degraded and nervous system function destroyed. Generally linked to increased age, the proportion of patients diagnosed with a NDD is growing as ... ...

Abstract	Neurodegenerative diseases (NDDs) encapsulate conditions in which neural cell populations are perpetually degraded and nervous system function destroyed. Generally linked to increased age, the proportion of patients diagnosed with a NDD is growing as human life expectancies rise. Traditional NDD therapies and surgical interventions have been limited. However, recent breakthroughs in understanding disease pathophysiology, improved drug delivery systems, and targeted pharmacologic agents have allowed innovative treatment approaches to treat NDDs. A common denominator for administering these new treatment options is the requirement for neurosurgical skills. In the present narrative review, we highlight exciting and novel preclinical and clinical discoveries being integrated into NDD care. We also discuss the traditional role of neurosurgery in managing these neurodegenerative conditions and emphasize the critical role of neurosurgery in effectuating these newly developed treatments.
MeSH term(s)	Humans ; Neurodegenerative Diseases/surgery ; Neurosurgical Procedures
Language	English
Publishing date	2023-10-05
Publishing country	United Arab Emirates
Document type	Review ; Journal Article
ZDB-ID	2205170-3
ISSN	1875-5828 ; 1567-2050
ISSN (online)	1875-5828
ISSN	1567-2050
DOI	10.2174/1567205020666230911125646
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Zs.A 6235: Show issues

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Article ; Online: Modeling Meningiomas: Optimizing Treatment Approach.

Khan, Majid / Hanna, Chadwin / Findlay, Matthew / Lucke-Wold, Brandon / Karsy, Michael / Jensen, Randy L

Neurosurgery clinics of North America

2023 Volume 34, Issue 3, Page(s) 479–492

Abstract: Preclinical meningioma models offer a setting to test molecular mechanisms of tumor development and targeted treatment options but historically have been challenging to generate. Few spontaneous tumor models in rodents have been established, but cell ... ...

Abstract	Preclinical meningioma models offer a setting to test molecular mechanisms of tumor development and targeted treatment options but historically have been challenging to generate. Few spontaneous tumor models in rodents have been established, but cell culture and in vivo rodent models have emerged along with artificial intelligence, radiomics, and neural networks to differentiate the clinical heterogeneity of meningiomas. We reviewed 127 studies using PRISMA guideline methodology, including laboratory and animal studies, that addressed preclinical modeling. Our evaluation identified that meningioma preclinical models provide valuable molecular insight into disease progression and effective chemotherapeutic and radiation approaches for specific tumor types.
MeSH term(s)	Animals ; Humans ; Meningioma/therapy ; Meningeal Neoplasms/therapy ; Artificial Intelligence ; Disease Progression
Language	English
Publishing date	2023-04-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1196855-2
ISSN	1558-1349 ; 1042-3680
ISSN (online)	1558-1349
ISSN	1042-3680
DOI	10.1016/j.nec.2023.02.014
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Article ; Online: Subtemporal Approach for the Treatment of Ruptured and Unruptured Distal Basilar Artery Aneurysms: Is There a Contemporary Use?

Findlay, Matthew C / Bounajem, Michael T / Kim, Robert B / Henson, J Curran / Azab, Mohammed A / Cutler, Christopher B / Khan, Majid / Brandon, Cameron / Budohoski, Karol P / Rennert, Robert C / Couldwell, William T

Operative neurosurgery (Hagerstown, Md.)

2024

Abstract: Background and objectives: Distal basilar artery aneurysms (DBAs) are high-risk lesions for which endovascular treatment is preferred because of their deep location, yet indications for open clipping nonetheless remain. The subtemporal approach allows ... ...

Abstract	Background and objectives: Distal basilar artery aneurysms (DBAs) are high-risk lesions for which endovascular treatment is preferred because of their deep location, yet indications for open clipping nonetheless remain. The subtemporal approach allows for early proximal control and direct visualization of critical posterior perforating arteries, especially for posterior-projecting aneurysms. Our objective was to describe our clinical experience with the subtemporal approach for clipping DBAs in the evolving endovascular era. Methods: This was a retrospective, single-institution case series of patients with DBAs treated with microsurgery over a 21-year period (2002-2023). Demographic, clinical, and surgical data were collected for analysis. Results: Twenty-seven patients underwent clipping of 11 ruptured and 16 unruptured DBAs with a subtemporal approach (24 female; mean age 53 years). Ten patients had expanded craniotomies for treatment of additional aneurysms. The aneurysm occlusion rate was 100%. Good neurological outcomes as defined by the modified Rankin Scale score ≤2 and Glasgow Outcome Scale score ≥4 were achieved in 21/27 patients (78%). Two patients died before hospital discharge, one from vasospasm-induced strokes and another from an intraoperative myocardial infarction. Conclusion: These results demonstrate that microsurgical clip ligation of DBAs using the subtemporal approach remains a viable option for complex lesions not amenable to endovascular management.
Language	English
Publishing date	2024-05-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2767575-0
ISSN	2332-4260 ; 2332-4252
ISSN (online)	2332-4260
ISSN	2332-4252
DOI	10.1227/ons.0000000000001185
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Article ; Online: In Reply to the Letter to the Editor Regarding "Systematic Review of Research, Mentorship, and Career Resources for Medical Students Pursuing Neurosurgical Training".

Carter, Ashley / Findlay, Matthew C / Earl, Emma Rose / Khan, Majid / Bauer, Sawyer / Farsi, Koorosh / Lucke-Wold, Brandon / Karsy, Michael

World neurosurgery

2023 Volume 180, Page(s) 264

MeSH term(s)	Humans ; Career Choice ; Education, Medical, Undergraduate ; Mentors ; Students, Medical
Language	English
Publishing date	2023-12-19
Publishing country	United States
Document type	Letter
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2023.09.043
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Article ; Online: The Chemical Ecology of Predatory Soil Bacteria.

Findlay, Brandon L

ACS chemical biology

2016 Volume 11, Issue 6, Page(s) 1502–1510

Abstract: The study of natural products is entering a renaissance, driven by the discovery that the majority of bacterial secondary metabolites are not produced under standard laboratory conditions. Understanding the ecological role of natural products is key to ... ...

Abstract	The study of natural products is entering a renaissance, driven by the discovery that the majority of bacterial secondary metabolites are not produced under standard laboratory conditions. Understanding the ecological role of natural products is key to efficiently directing our screening efforts, and to ensuring that each screen efficiently captures the full biosynthetic repertoire of the producing organisms. Myxobacteria represent one of the most common and diverse groups of bacteria, with roughly 2500 strains publically available. Fed largely through predation, the myxobacteria have developed a large repertoire of natural products that target other microorganisms, including bacteria and fungi. Many of these interactions can be observed in predation assays, providing direct evidence for environmental interactions. With a focus on Myxococcus xanthus, this review will highlight how recent advances in myxobacteria are revealing the chemical ecology of bacterial natural products.
MeSH term(s)	Anti-Bacterial Agents/metabolism ; Antibiosis/physiology ; Biofilms ; Biological Products/isolation & purification ; Biological Products/metabolism ; Ecology ; Electron Transport ; Lipoxygenase Inhibitors/metabolism ; Lysine/analogs & derivatives ; Lysine/metabolism ; Macrolides/metabolism ; Myxococcus xanthus/metabolism ; Quorum Sensing ; Secondary Metabolism ; Siderophores/metabolism ; Soil Microbiology
Chemical Substances	Anti-Bacterial Agents ; Biological Products ; Lipoxygenase Inhibitors ; Macrolides ; Siderophores ; carolacton ; myxochelin A (120243-02-9) ; Myxococcus xanthus antibiotic TA (60616-99-1) ; Lysine (K3Z4F929H6)
Language	English
Publishing date	2016--17
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1554-8937
ISSN (online)	1554-8937
DOI	10.1021/acschembio.6b00176
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