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Article ; Online: Reply to: "Is Choosing Wisely Wise for Lobular Carcinoma in Patients Over 70 Years of Age? A National Cancer Database Analysis of Sentinel Node Practice Patterns.

Goldhaber, Nicole / O'Keefe, Thomas / Blair, Sarah

2023 Volume 31, Issue 3, Page(s) 1669–1670

MeSH term(s)	Humans ; Aged ; Aged, 80 and over ; Female ; Carcinoma, Lobular/pathology ; Sentinel Lymph Node/pathology ; Sentinel Lymph Node Biopsy ; Breast Neoplasms ; Axilla/pathology
Language	English
Publishing date	2023-11-28
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-023-14563-4
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Article ; Online: White-nose syndrome, winter duration, and pre-hibernation climate impact abundance of reproductive female bats.

Krueger, Sarah K / Williams, Sarah C / O'Keefe, Joy M / Zirkle, Gene A / Haase, Catherine G

PloS one

2024 Volume 19, Issue 4, Page(s) e0298515

Abstract: White-nose syndrome (WNS) is an infectious disease that disrupts hibernation in bats, leading to premature exhaustion of fat stores. Though we know WNS does impact reproduction in hibernating female bats, we are unsure how these impacts are exacerbated ... ...

Abstract	White-nose syndrome (WNS) is an infectious disease that disrupts hibernation in bats, leading to premature exhaustion of fat stores. Though we know WNS does impact reproduction in hibernating female bats, we are unsure how these impacts are exacerbated by local climate factors. We compiled data from four southeastern U.S. states and used generalized linear mixed effects models to compare effects of WNS, pre-hibernation climate variables, and winter duration on the number of reproductive females in species across the range of WNS susceptibility. We predicted we would see a decline in the number of reproductive females in WNS-susceptible species, with the effect exaggerated by longer winter durations and pre-hibernation climate variables that lead to reductions in foraging. We found that the number of reproductive females in WNS-susceptible species was positively correlated with pre-hibernation local climate conditions conducive to foraging; however, WNS-susceptible species experienced an overall decline with the presence of WNS and as winter duration increased. Our long-term dataset provides evidence that pre-hibernation climate, specifically favorable summer weather conditions for foraging, greatly influences the reproduction, regardless of WNS status.
MeSH term(s)	Animals ; Chiroptera/physiology ; Female ; Hibernation/physiology ; Seasons ; Reproduction/physiology ; Climate ; Mycoses/veterinary ; Mycoses/epidemiology ; White
Language	English
Publishing date	2024-04-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0298515
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Ascending aortic mass - a needle in a haystack.

Ratnaraj, Vignesh / Datta, Rachit / Scheuer, Sarah / Buratto, Edward / O'Keefe, Michael

ANZ journal of surgery

2023 Volume 93, Issue 5, Page(s) 1429–1430

MeSH term(s)	Humans ; Aorta/diagnostic imaging ; Mass Screening
Language	English
Publishing date	2023-01-05
Publishing country	Australia
Document type	Case Reports
ZDB-ID	2050749-5
ISSN	1445-2197 ; 1445-1433 ; 0004-8682
ISSN (online)	1445-2197
ISSN	1445-1433 ; 0004-8682
DOI	10.1111/ans.18266
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Article ; Online: An evidence-based approach to abnormal vision in the emergency department

O'Keefe, Kelly / Temple, Sarah

Emergency medicine practice

2020 Volume 22, Issue 4, Page(s) 1–28

Abstract: Patients present to the ED with visual disturbances that may be painful or painless and may include loss of visual acuity, field cuts, diplopia, and headache. A detailed history and complete ocular examination are essential to obtaining the correct ... ...

Abstract	Patients present to the ED with visual disturbances that may be painful or painless and may include loss of visual acuity, field cuts, diplopia, and headache. A detailed history and complete ocular examination are essential to obtaining the correct diagnosis and offering expedited treatment and referral. This review discusses the differential diagnosis for patients experiencing abnormal vision from a nontraumatic or minimally traumatic etiology, and reviews diagnostic and treatment strategies from an evidence-based perspective, including point-of-care ocular ultrasound. Management of the needs of special populations, such as patients with sickle cell disease, HIV, and those with a ventriculo-peritoneal shunt, is reviewed.
MeSH term(s)	Emergency Service, Hospital/organization & administration ; Humans ; Physical Examination/methods ; Vision Disorders/diagnosis ; Vision Disorders/physiopathology ; Vision Disorders/therapy ; Vision Tests/methods
Language	English
Publishing date	2020-04-01
Publishing country	United States
Document type	Journal Article
ISSN	1559-3908
ISSN (online)	1559-3908
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Membrane translocation at the ER: with a little help from my friends.

O'Keefe, Sarah / High, Stephen

The FEBS journal

2020 Volume 287, Issue 21, Page(s) 4607–4611

Abstract: The Sec61 complex is the proteinaceous pore through which one-third of mammalian polypeptides access the lumen of the endoplasmic reticulum (ER) during their translocation across, or insertion into, the ER membrane. N-terminal ER signal peptides mediate ... ...

Abstract	The Sec61 complex is the proteinaceous pore through which one-third of mammalian polypeptides access the lumen of the endoplasmic reticulum (ER) during their translocation across, or insertion into, the ER membrane. N-terminal ER signal peptides mediate polypeptide targeting to, and opening of, the Sec61 channel in a substrate-specific manner. Here, we discuss the recently defined features of ER signal peptides which necessitate the use of the accessory components Sec62 and Sec63 during the Sec61-mediated cotranslational translocation of newly synthesized secretory proteins.
MeSH term(s)	Animals ; Endoplasmic Reticulum/metabolism ; Humans ; Membrane Transport Proteins/genetics ; Membrane Transport Proteins/metabolism ; Protein Sorting Signals ; Protein Transport ; SEC Translocation Channels/genetics ; SEC Translocation Channels/metabolism ; Substrate Specificity
Chemical Substances	Membrane Transport Proteins ; Protein Sorting Signals ; SEC Translocation Channels ; SEC62 protein, human
Language	English
Publishing date	2020-04-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.15309
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Article ; Online: Characterization of Fluorescein Angiography Features in Pediatric Patients with Uveitis.

Hossain, Homaira Ayesha / Ye, Sarah / Ward, Laura / O'Keefe, Ghazala D

Ocular immunology and inflammation

2022 Volume 31, Issue 8, Page(s) 1635–1639

Abstract: Purpose: To characterize fluorescein angiography (FA) features in pediatric uveitis.: Methods: A retrospective cross-sectional study of pediatric uveitis patients in Atlanta, GA, who had FA imaging between May 2009 and August 2020.: Results: A ... ...

Abstract	Purpose: To characterize fluorescein angiography (FA) features in pediatric uveitis. Methods: A retrospective cross-sectional study of pediatric uveitis patients in Atlanta, GA, who had FA imaging between May 2009 and August 2020. Results: A total of 137 eyes of 88 patients were evaluated. The mean FA score in anterior uveitis was lower than that in other categories (p = .0093). The mean FA score in the clinically active group was higher than that in the clinically inactive group (p = .0057). The mean FA score in eyes 20/40 or better was lower than that in other categories (p = .0292). Worse visual acuity was associated with retinal vascular staining/leakage, retinal staining/pooling, and neovascularization elsewhere. Non-infectious uveitis more often demonstrated optic disc hyperfluorescence, retinal vascular staining/leakage, capillary leakage, and pinpoint leaks, while infectious uveitis more often demonstrated retinal staining/pooling. Conclusion: A standardized quantitative FA scoring system can be useful in the characterization of uveitis in pediatric patients.
MeSH term(s)	Humans ; Child ; Fluorescein Angiography/methods ; Retrospective Studies ; Cross-Sectional Studies ; Uveitis/diagnosis ; Uveitis, Anterior ; Tomography, Optical Coherence
Language	English
Publishing date	2022-07-25
Publishing country	England
Document type	Journal Article
ZDB-ID	1193873-0
ISSN	1744-5078 ; 0927-3948
ISSN (online)	1744-5078
ISSN	0927-3948
DOI	10.1080/09273948.2022.2091616
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Zs.A 4004: Show issues

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Article ; Online: Is Choosing Wisely Wise for Lobular Carcinoma in Patients Over 70 Years of Age? A National Cancer Database Analysis of Sentinel Node Practice Patterns.

Goldhaber, Nicole H / O'Keefe, Thomas / Kang, Jessica / Douglas, Sasha / Blair, Sarah L

Annals of surgical oncology

2023 Volume 30, Issue 10, Page(s) 6024–6032

Abstract: Background: Controversy continues in the treatment of breast cancer in women over 70 years of age. In 2016, the Society of Surgical Oncology recommended against routine use of sentinel lymph node biopsy (SLNBx) as part of the 'Choosing Wisely Campaign'. ...

Abstract	Background: Controversy continues in the treatment of breast cancer in women over 70 years of age. In 2016, the Society of Surgical Oncology recommended against routine use of sentinel lymph node biopsy (SLNBx) as part of the 'Choosing Wisely Campaign'. This study examines the oncologic safety of avoidance of routine SLNBx in patients over 70 years of age with invasive lobular carcinoma (ILC). Methods: The National Cancer Database was used to identify women with invasive ductal carcinoma (IDC) and ILC diagnosed between 2012 and 2020. Clinical and pathological staging, axillary staging, surgery type, and lymph node positivity between patients with IDC or ILC were compared. Results: Among women with T1 tumors, 85,949 (79.6%) patients with IDC and 12,761 (81.5%) patients with ILC underwent SLNBx (p < 0.001). Among patients who underwent SLNBx, those with IDC were more likely to have positive nodes (n = 7535, 8.8%) than those with ILC (n = 1041, 8.2%; p = 0.02). During the time interval of interest, for both IDC and ILC patients, the rate of axillary lymph node dissection decreased and rates of SLNBx or no axillary staging increased. On multivariate analysis, ILC histology was associated with use of SLNBx, but without nodal positivity. Conclusion: A trend de-escalation of axillary staging was identified in this study, however the majority of patients meeting the 'Choosing Wisely' criteria are still undergoing SLNBx. No increased risk of nodal positivity was identified among patients with ILC, suggesting that surgeons can continue to choose wisely and limit the use of SLNBx in women over 70 years of age with T1 ILC tumors.
MeSH term(s)	Humans ; Female ; Aged ; Aged, 80 and over ; Carcinoma, Lobular/surgery ; Carcinoma, Lobular/pathology ; Carcinoma, Ductal, Breast/surgery ; Carcinoma, Ductal, Breast/pathology ; Neoplasm Staging ; Breast Neoplasms/surgery ; Breast Neoplasms/pathology ; Sentinel Lymph Node/surgery ; Sentinel Lymph Node/pathology ; Lymphadenopathy
Language	English
Publishing date	2023-07-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-023-13886-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Biochemical and Biological Assays of Mycolactone-Mediated Inhibition of Sec61.

O'Keefe, Sarah / High, Stephen / Demangel, Caroline

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

2021 Volume 2387, Page(s) 163–181

Abstract: Mycobacterium ulcerans, the causative agent of Buruli ulcer disease, is unique among human pathogens in its capacity to produce mycolactone, a diffusible macrolide with immunosuppressive and cytotoxic properties. Recent studies have shown that ... ...

Abstract	Mycobacterium ulcerans, the causative agent of Buruli ulcer disease, is unique among human pathogens in its capacity to produce mycolactone, a diffusible macrolide with immunosuppressive and cytotoxic properties. Recent studies have shown that mycolactone operates by inhibiting the host membrane translocation complex (Sec61), with an unprecedented potency compared to previously identified Sec61 blockers. Mycolactone binding to the pore-forming subunit of Sec61 inhibits its capacity to transport nascent secretory and membrane proteins into the endoplasmic reticulum, leading to their cytosolic degradation by the ubiquitin:proteasome system. In T lymphocytes, Sec61 blockade by mycolactone manifests as a sharp decrease in the cell's ability to express homing receptors and release cytokines following activation. Sustained exposure of human cells to mycolactone typically generates proteotoxic stress responses in their cytosol and endoplasmic reticulum (ER), ultimately inducing apoptosis. Here we describe cell-free systems for studying Sec61-mediated protein translocation that allow the impact of mycolactone on the biogenesis of secretory and membrane proteins to be probed. We also describe biological assays of mycolactone-driven inhibition of Sec61 providing rapid and sensitive means to quantitatively assess the presence of the toxin in biological samples.
MeSH term(s)	Biological Assay ; Buruli Ulcer ; Humans ; Macrolides/pharmacology ; Membrane Proteins/metabolism ; SEC Translocation Channels
Chemical Substances	Macrolides ; Membrane Proteins ; SEC Translocation Channels ; mycolactone
Language	English
Publishing date	2021-10-13
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1779-3_16
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Membrane protein biogenesis at the ER: the highways and byways.

O'Keefe, Sarah / Pool, Martin R / High, Stephen

The FEBS journal

2021 Volume 289, Issue 22, Page(s) 6835–6862

Abstract: The Sec61 complex is the major protein translocation channel of the endoplasmic reticulum (ER), where it plays a central role in the biogenesis of membrane and secretory proteins. Whilst Sec61-mediated protein translocation is typically coupled to ... ...

Abstract	The Sec61 complex is the major protein translocation channel of the endoplasmic reticulum (ER), where it plays a central role in the biogenesis of membrane and secretory proteins. Whilst Sec61-mediated protein translocation is typically coupled to polypeptide synthesis, suggestive of significant complexity, an obvious characteristic of this core translocation machinery is its surprising simplicity. Over thirty years after its initial discovery, we now understand that the Sec61 complex is in fact the central piece of an elaborate jigsaw puzzle, which can be partly solved using new research findings. We propose that the Sec61 complex acts as a dynamic hub for co-translational protein translocation at the ER, proactively recruiting a range of accessory complexes that enhance and regulate its function in response to different protein clients. It is now clear that the Sec61 complex does not have a monopoly on co-translational insertion, with some transmembrane proteins preferentially utilising the ER membrane complex instead. We also have a better understanding of post-insertion events, where at least one membrane-embedded chaperone complex can capture the newly inserted transmembrane domains of multi-span proteins and co-ordinate their assembly into a native structure. Having discovered this array of Sec61-associated components and competitors, our next challenge is to understand how they act together in order to expand the range and complexity of the membrane proteins that can be synthesised at the ER. Furthermore, this diversity of components and pathways may open up new opportunities for targeted therapeutic interventions designed to selectively modulate protein biogenesis at the ER.
MeSH term(s)	Humans ; SEC Translocation Channels/genetics ; SEC Translocation Channels/chemistry ; Membrane Proteins/metabolism ; Endoplasmic Reticulum/metabolism ; Protein Transport/physiology ; Protein Processing, Post-Translational
Chemical Substances	SEC Translocation Channels ; Membrane Proteins
Language	English
Publishing date	2021-06-05
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.15905
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Article ; Online: Membrane protein biogenesis at the ER: the highways and byways

O'Keefe, Sarah / Pool, Martin R. / High, Stephen

The FEBS Journal. 2022 Nov., v. 289, no. 22 p.6835-6862

2022

Abstract: The Sec61 complex is the major protein translocation channel of the endoplasmic reticulum (ER), where it plays a central role in the biogenesis of membrane and secretory proteins. Whilst Sec61‐mediated protein translocation is typically coupled to ... ...

Abstract	The Sec61 complex is the major protein translocation channel of the endoplasmic reticulum (ER), where it plays a central role in the biogenesis of membrane and secretory proteins. Whilst Sec61‐mediated protein translocation is typically coupled to polypeptide synthesis, suggestive of significant complexity, an obvious characteristic of this core translocation machinery is its surprising simplicity. Over thirty years after its initial discovery, we now understand that the Sec61 complex is in fact the central piece of an elaborate jigsaw puzzle, which can be partly solved using new research findings. We propose that the Sec61 complex acts as a dynamic hub for co‐translational protein translocation at the ER, proactively recruiting a range of accessory complexes that enhance and regulate its function in response to different protein clients. It is now clear that the Sec61 complex does not have a monopoly on co‐translational insertion, with some transmembrane proteins preferentially utilising the ER membrane complex instead. We also have a better understanding of post‐insertion events, where at least one membrane‐embedded chaperone complex can capture the newly inserted transmembrane domains of multi‐span proteins and co‐ordinate their assembly into a native structure. Having discovered this array of Sec61‐associated components and competitors, our next challenge is to understand how they act together in order to expand the range and complexity of the membrane proteins that can be synthesised at the ER. Furthermore, this diversity of components and pathways may open up new opportunities for targeted therapeutic interventions designed to selectively modulate protein biogenesis at the ER.
Keywords	biogenesis ; endoplasmic reticulum ; membrane proteins ; monopoly ; polypeptides ; protein transport ; therapeutics
Language	English
Dates of publication	2022-11
Size	p. 6835-6862.
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	REVIEW
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.15905
Database	NAL-Catalogue (AGRICOLA)

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