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Article ; Online: Alternate typhoid toxin assembly evolved independently in the two

Chemello, Antonio J / Fowler, Casey C

2024 Volume 15, Issue 4, Page(s) e0340323

Abstract: AB: Importance: Typhoid toxin is an ... ...

Abstract	AB Importance: Typhoid toxin is an important
MeSH term(s)	Humans ; Typhoid Fever/microbiology ; Bacterial Toxins/genetics ; Bacterial Toxins/metabolism ; Salmonella/metabolism ; Salmonella typhi/genetics ; Virulence Factors/genetics ; Virulence Factors/metabolism
Chemical Substances	Bacterial Toxins ; Virulence Factors
Language	English
Publishing date	2024-03-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.03403-23
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Article ; Online: The endocannabinoid system - current implications for drug development.

Fowler, C J

Journal of internal medicine

2021 Volume 290, Issue 1, Page(s) 2–26

Abstract: In this review, the state of the art for compounds affecting the endocannabinoid (eCB) system is described with a focus on the treatment of pain. Amongst directly acting CB receptor ligands, clinical experience with ∆ ...

Abstract	In this review, the state of the art for compounds affecting the endocannabinoid (eCB) system is described with a focus on the treatment of pain. Amongst directly acting CB receptor ligands, clinical experience with ∆
MeSH term(s)	Cannabinoid Receptor Agonists/therapeutic use ; Chronic Pain/drug therapy ; Dronabinol/therapeutic use ; Drug Development ; Endocannabinoids/biosynthesis ; Endocannabinoids/metabolism ; Endocannabinoids/therapeutic use ; Humans ; Ligands ; Receptors, Cannabinoid/metabolism
Chemical Substances	Cannabinoid Receptor Agonists ; Endocannabinoids ; Ligands ; Receptors, Cannabinoid ; Dronabinol (7J8897W37S)
Language	English
Publishing date	2021-01-29
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	96274-0
ISSN	1365-2796 ; 0954-6820
ISSN (online)	1365-2796
ISSN	0954-6820
DOI	10.1111/joim.13229
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Article: The development of deep-ocean anoxia in a comprehensive ocean phosphorus model.

Donohue, J G / Florio, B J / Fowler, A C

GEM : international journal on geomathematics

2023 Volume 14, Issue 1, Page(s) 12

Abstract: We analyse a model of the phosphorus cycle in the ocean given by Slomp and Van Cappellen (Biogeosciences 4:155-171, 2007. 10.5194/bg-4-155-2007). This model contains four distinct oceanic boxes and includes relevant parts of the water, carbon and oxygen ... ...

Abstract	We analyse a model of the phosphorus cycle in the ocean given by Slomp and Van Cappellen (Biogeosciences 4:155-171, 2007. 10.5194/bg-4-155-2007). This model contains four distinct oceanic boxes and includes relevant parts of the water, carbon and oxygen cycles. We show that the model can essentially be solved analytically, and its behaviour completely understood without recourse to numerical methods. In particular, we show that, in the model, the carbon and phosphorus concentrations in the different ocean reservoirs are all slaved to the concentration of soluble reactive phosphorus in the deep ocean, which relaxes to an equilibrium on a time scale of 180,000 y, and we show that the deep ocean is either oxic or anoxic, depending on a critical parameter which we can determine explicitly. Finally, we examine how the value of this critical parameter depends on the physical parameters contained in the model. The presented methodology is based on tools from applied mathematics and can be used to reduce the complexity of other large, biogeochemical models. Supplementary information: The online version contains supplementary material available at 10.1007/s13137-023-00221-0.
Language	English
Publishing date	2023-05-30
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2564274-1
ISSN	1869-2680 ; 1869-2672
ISSN (online)	1869-2680
ISSN	1869-2672
DOI	10.1007/s13137-023-00221-0
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Article ; Online: Synthetic and Computational Design Insights toward Mimicking Protein Binding of Phosphate.

Fowler, Whitney C / Deng, Chuting / Teodoro, O Therese / de Pablo, Juan J / Tirrell, Matthew V

Bioconjugate chemistry

2024 Volume 35, Issue 3, Page(s) 300–311

Abstract: The unique and precise capabilities of proteins are renowned for their specificity and range of application. Effective mimicking of protein-binding offers enticing potential to direct their abilities toward useful applications, but it is nevertheless ... ...

Abstract	The unique and precise capabilities of proteins are renowned for their specificity and range of application. Effective mimicking of protein-binding offers enticing potential to direct their abilities toward useful applications, but it is nevertheless quite difficult to realize this characteristic of protein behavior in a synthetic material. Here, we design, synthesize, and evaluate experimentally and computationally a series of multicomponent phosphate-binding peptide amphiphile micelles to derive design insights into how protein binding behavior translates to synthetic materials. By inserting the Walker A P-loop binding motif into this peptide synthetic material, we successfully implemented the protein-binding design parameters of hydrogen-bonding and electrostatic interaction to bind phosphate completely and selectively in this highly tunable synthetic platform. Moreover, in this densely arrayed peptide environment, we use molecular dynamics simulations to identify an intriguing mechanistic shift of binding that is inaccessible in traditional proteins, introducing two corresponding new design elements─flexibility and minimization of the loss of entropy due to ion binding, in protein-analogous synthetic materials. We then translate these new design factors to
MeSH term(s)	Protein Binding ; Phosphates/chemistry ; Proteins/chemistry ; Peptides/chemistry ; Amino Acid Sequence ; Protein Conformation
Chemical Substances	Phosphates ; Proteins ; Peptides
Language	English
Publishing date	2024-02-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	1024041-x
ISSN	1520-4812 ; 1043-1802
ISSN (online)	1520-4812
ISSN	1043-1802
DOI	10.1021/acs.bioconjchem.3c00454
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Article: ENHANCE: a comparative prospective longitudinal study of cognitive outcomes after 3 years of hearing aid use in older adults.

Sarant, Julia Z / Busby, Peter A / Schembri, Adrian J / Fowler, Christopher / Harris, David C

Frontiers in aging neuroscience

2024 Volume 15, Page(s) 1302185

Abstract: Background: With an aging population, the prevalence of hearing loss and dementia are increasing rapidly. Hearing loss is currently considered the largest potentially modifiable risk factor for dementia. The effect of hearing interventions on cognitive ... ...

Abstract	Background: With an aging population, the prevalence of hearing loss and dementia are increasing rapidly. Hearing loss is currently considered the largest potentially modifiable risk factor for dementia. The effect of hearing interventions on cognitive function should therefore be investigated, as if effective, these may be successfully implemented to modify cognitive outcomes for older adults with hearing loss. Methods: This prospective longitudinal observational cohort study compared outcomes of a convenience sample of prospectively recruited first-time hearing aid users without dementia from an audiology center with those of community-living older adults participating in a large prospective longitudinal cohort study with/without hearing loss and/or hearing aids. All participants were assessed at baseline, 18 months, and 36 months using the same measures. Results: Participants were 160 audiology clinic patients (48.8% female patient; mean age 73.5 years) with mild-severe hearing loss, fitted with hearing aids at baseline, and 102 participants of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Aging (AIBL) (55.9% female patient; mean age 74.5 years). 18- and 36-month outcomes of subsets of the first participants to reach these points and complete the cognition assessment to date are compared. Primary comparative analysis showed cognitive stability for the hearing aid group while the AIBL group declined on working memory, visual attention, and psychomotor function. There was a non-significant trend for decline in visual learning for the AIBL group versus no decline for the hearing aid group. The hearing aid group showed significant decline on only 1 subtest and at a significantly slower rate than for the AIBL participants ( Conclusion: Hearing aid users demonstrated significantly better cognitive performance to 3 years post-fitting, suggesting that hearing intervention may delay cognitive decline/dementia onset in older adults. Further studies using appropriate measures of cognition, hearing, and device use, with longer follow-up, are required.
Language	English
Publishing date	2024-01-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2558898-9
ISSN	1663-4365
ISSN	1663-4365
DOI	10.3389/fnagi.2023.1302185
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Article ; Online: Effects of Stereotype-Focused Imagined Contact on Young Adults' Intentions for Intergenerational Interaction.

Fowler, Craig / Gasiorek, Jessica

The journals of gerontology. Series B, Psychological sciences and social sciences

2022

Abstract: Objectives: Face-to-face intergenerational contact is associated with more positive attitudes towards older adults. However, such contact can be difficult to achieve, and poor contact experiences can have negative consequences for intergenerational ... ...

Abstract	Objectives: Face-to-face intergenerational contact is associated with more positive attitudes towards older adults. However, such contact can be difficult to achieve, and poor contact experiences can have negative consequences for intergenerational relations. We examined whether mentally simulated intergenerational contact (which is more easily facilitated and controllable) could reduce young adults' inclinations to avoid intergenerational interactions by increasing their inclusion of the older outgroup in the self (IOS), and by enhancing their stereotypes of older adults' warmth and competence. Method: We conducted an online experiment with 373 young adults from the United States. Participants imagined talking with an older adult (aged 70-75) in circumstances intended to make salient either the older adult's warmth or their competence. Results: Both manipulations increased young adult participants' IOS with respect to older adults, which in turn predicted more positive assessments of older adults' warmth and competence. IOS, along with ratings of warmth and competence, inversely predicted the desire to avoid future interaction with older adults. Discussion: Findings indicate the viability of a simple and accessible intervention to improve intergenerational relations, which can be tailored to address different goals (e.g., encouraging intergenerational friendships vs. encouraging support for equal rights of older members of the workforce).
Language	English
Publishing date	2022-08-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	1223664-0
ISSN	1758-5368 ; 1079-5014
ISSN (online)	1758-5368
ISSN	1079-5014
DOI	10.1093/geronb/gbac119
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Article ; Online: How I do it: lateral canthal web revision-single Z-plasty technique.

Fowler, James / Moore, Corey C

Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale

2022 Volume 51, Issue 1, Page(s) 34

Abstract: Background: Lateral canthal webbing is a known complication of blepharoplasty, which occurs when the lateral aspect of the upper blepharoplasty incision is taken below the equator of the lateral canthus. Removing excessive eyelid skin laterally can also ...

Abstract	Background: Lateral canthal webbing is a known complication of blepharoplasty, which occurs when the lateral aspect of the upper blepharoplasty incision is taken below the equator of the lateral canthus. Removing excessive eyelid skin laterally can also result in a lateral canthal web. Currently, there is no standard approach for addressing this complication. Methods: Retrospective review of single surgeon practice between 2011 and 2019. All patients underwent revision surgery using the proposed single Z-plasty technique. Results: Twenty-three patients referred for lateral canthal web were included in the study. All patients had previous upper lid blepharoplasty, with the initial procedure occurring 8-63 months prior to the referral for revision. The majority of the blepharoplasties occurred in Ontario (n = 19), but some patients also underwent surgery in Alberta (n = 1), British Columbia (n = 1), and United States (n = 1). The initial surgeries were performed by a variety of specialities including plastic surgery (n = 16), otolaryngology (n = 4), ophthalmology (n = 2), and family medicine (n = 1). Following revision surgery using the single Z-plasty technique, all patients reported a subjective increase in functional and aesthetic satisfaction. No further revision surgery was required for any of these patients. Conclusion: The single Z-plasty technique is simple, robust, and could be easily incorporated into any cosmetic practice to address this complication of blepharoplasty.
MeSH term(s)	Blepharoplasty/methods ; Eyelids/surgery ; Humans ; Lacrimal Apparatus/surgery ; Reconstructive Surgical Procedures ; Reoperation
Language	English
Publishing date	2022-09-16
Publishing country	England
Document type	Journal Article
ZDB-ID	2434004-2
ISSN	1916-0216 ; 1916-0208 ; 0381-6605
ISSN (online)	1916-0216
ISSN	1916-0208 ; 0381-6605
DOI	10.1186/s40463-022-00585-7
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Article ; Online: BCL-2 inhibition in haematological malignancies: Clinical application and complications.

Fowler-Shorten, Dominic J / Hellmich, Charlotte / Markham, Matthew / Bowles, Kristian M / Rushworth, Stuart A

Blood reviews

2024 Volume 65, Page(s) 101195

Abstract: B-cell lymphoma-2 (BCL-2) family proteins are fundamental regulators of the intrinsic apoptotic pathway which modulate cellular fate. In many haematological malignancies, overexpression of anti-apoptotic factors (BCL-2, BCL-XL and MCL-1) circumvent ... ...

Abstract	B-cell lymphoma-2 (BCL-2) family proteins are fundamental regulators of the intrinsic apoptotic pathway which modulate cellular fate. In many haematological malignancies, overexpression of anti-apoptotic factors (BCL-2, BCL-XL and MCL-1) circumvent apoptosis. To address this cancer hallmark, a concerted effort has been made to induce apoptosis by inhibiting BCL-2 family proteins. A series of highly selective BCL-2 homology 3 (BH3) domain mimetics are in clinical use and in ongoing clinical trials for acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML), chronic lymphocytic leukaemia (CLL), and multiple myeloma (MM). These inhibitors serve as promising candidates, both as single agents or in combination therapy to improve patient outcomes. In other diseases such as follicular lymphoma, efficacy has been notably limited. There are also clinical problems with BCL-2 family inhibition, including drug resistance, disease relapse, tumour lysis syndrome, and clinically relevant cytopenias. Here, we provide a balanced view on both the clinical benefits of BCL-2 inhibition as well as the associated challenges.
MeSH term(s)	Humans ; Neoplasm Recurrence, Local/drug therapy ; Hematologic Neoplasms/metabolism ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use
Chemical Substances	Proto-Oncogene Proteins c-bcl-2 ; Antineoplastic Agents
Language	English
Publishing date	2024-03-21
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	639015-8
ISSN	1532-1681 ; 0268-960X
ISSN (online)	1532-1681
ISSN	0268-960X
DOI	10.1016/j.blre.2024.101195
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Article ; Online: Survey of current policy regarding the recognition and management of acute aortic syndrome in Great Britain.

Alawiye, Salma / Cooper, Graham / Fowler, Catherine / Reed, Matthew J

Emergency medicine journal : EMJ

2024 Volume 41, Issue 3, Page(s) 151–152

MeSH term(s)	Humans ; United Kingdom ; Aortic Dissection ; Acute Aortic Syndrome ; Acute Disease ; Emergency Service, Hospital
Language	English
Publishing date	2024-02-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2040124-3
ISSN	1472-0213 ; 1472-0205
ISSN (online)	1472-0213
ISSN	1472-0205
DOI	10.1136/emermed-2023-213376
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Article ; Online: Robot-Assisted Nasal Reconstruction: A Cadaveric Study.

Smith, Corey / Fowler, James / Ferreira, Louis / Moore, Corey

The Journal of craniofacial surgery

2023 Volume 34, Issue 4, Page(s) 1343–1346

Abstract: Objective: Manual contouring of cartilage for nasal reconstruction is tedious and time-consuming. The use of a robot could improve the speed and precision of the contouring process. This cadaveric study evaluates the efficiency and accuracy of a robot ... ...

Abstract	Objective: Manual contouring of cartilage for nasal reconstruction is tedious and time-consuming. The use of a robot could improve the speed and precision of the contouring process. This cadaveric study evaluates the efficiency and accuracy of a robot methodology for contouring the lower lateral cartilage of the nasal tip. Methods: An augmented robot with a spherical burring tool attached was utilized to carve 11 cadaveric rib cartilage specimens. In phase 1, the right lower lateral cartilage was harvested from a cadaveric specimen and used to define a carving path for each rib specimen. In phase 2, the cartilage remained in situ during the scanning and 3-dimensional modeling. The final carved specimens were compared with the preoperative plans through topographical accuracy analysis. The contouring times of the specimens were compared with 14 retrospectively reviewed cases (2017-2020) by an experienced surgeon. Results: Phase 1 root mean square error of 0.40±0.15 mm and mean absolute deviation of 0.33±0.13 mm. Phase 2 root mean square error of 0.43 mm and mean absolute deviation of 0.28 mm. The average carving time for the robot specimens was 14±3 minutes and 16 minutes for Phase 1 and Phase 2, respectively. The average manual carving by an experienced surgeon was 22±4 minutes. Conclusions: Robot-assisted nasal reconstruction is very precise and more efficient than manual contouring. This technique represents an exciting and innovative alternative for complex nasal reconstruction.
MeSH term(s)	Humans ; Robotics ; Rhinoplasty/methods ; Retrospective Studies ; Nose/surgery ; Cadaver
Language	English
Publishing date	2023-03-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	1159501-2
ISSN	1536-3732 ; 1049-2275
ISSN (online)	1536-3732
ISSN	1049-2275
DOI	10.1097/SCS.0000000000009272
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