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Article ; Online: Reframing the gender equity discussion in anaesthesiology: adopting best practices to promote physician retention and belonging.

Silver, Julie K / Feld, Lauren D / Clark Onwunyi, Varina R

2024

Language	English
Publishing date	2024-04-06
Publishing country	England
Document type	Editorial
ZDB-ID	80033-8
ISSN	1365-2044 ; 0003-2409
ISSN (online)	1365-2044
ISSN	0003-2409
DOI	10.1111/anae.16288
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Article ; Online: Structure of Nonstructural Protein 1 from SARS-CoV-2.

Clark, Lauren K / Green, Todd J / Petit, Chad M

Journal of virology

2021 Volume 95, Issue 4

Abstract: The periodic emergence of novel coronaviruses (CoVs) represents an ongoing public health concern with significant health and financial burdens worldwide. The most recent occurrence originated in the city of Wuhan, China, where a novel coronavirus (severe ...

Abstract	The periodic emergence of novel coronaviruses (CoVs) represents an ongoing public health concern with significant health and financial burdens worldwide. The most recent occurrence originated in the city of Wuhan, China, where a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) emerged causing severe respiratory illness and pneumonia. The continual emergence of novel coronaviruses underscores the importance of developing effective vaccines as well as novel therapeutic options that target either viral functions or host factors recruited to support coronavirus replication. The CoV nonstructural protein 1 (nsp1) has been shown to promote cellular mRNA degradation, block host cell translation, and inhibit the innate immune response to virus infection. Interestingly, deletion of the nsp1-coding region in infectious clones prevented the virus from productively infecting cultured cells. Because of nsp1's importance in the CoV life cycle, it has been highlighted as a viable target for both antiviral therapy and vaccine development. However, the fundamental molecular and structural mechanisms that underlie nsp1 function remain poorly understood, despite its critical role in the viral life cycle. Here, we report the high-resolution crystal structure of the amino globular portion of SARS-CoV-2 nsp1 (residues 10 to 127) at 1.77-Å resolution. A comparison of our structure with the SARS-CoV-1 nsp1 structure reveals how mutations alter the conformation of flexible loops, inducing the formation of novel secondary structural elements and new surface features. Paired with the recently published structure of the carboxyl end of nsp1 (residues 148 to 180), our results provide the groundwork for future studies focusing on SARS-CoV-2 nsp1 structure and function during the viral life cycle.
MeSH term(s)	Amino Acid Sequence ; COVID-19/virology ; Cell Line ; Crystallography, X-Ray ; Humans ; Protein Conformation ; SARS-CoV-2/chemistry ; SARS-CoV-2/genetics ; Sequence Alignment ; Viral Nonstructural Proteins/chemistry ; Viral Nonstructural Proteins/metabolism
Chemical Substances	NSP1 protein, SARS-CoV-2 ; Viral Nonstructural Proteins
Language	English
Publishing date	2021-01-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.02019-20
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Article ; Online: How often does homelessness precede criminal arrest in veterans? Results from the U.S. survey of prison inmates.

Elbogen, Eric B / DuBois, Chase M / Finlay, Andrea K / Clark, Sean / Kois, Lauren E / Wagner, H Ryan / Tsai, Jack

The American journal of orthopsychiatry

2023 Volume 93, Issue 6, Page(s) 486–493

Abstract: Research has shown links between homelessness and criminal legal involvement in military veterans. The present study aimed to determine the magnitude and directionality of this association by investigating the incidence of, and factors associated with, ... ...

Abstract	Research has shown links between homelessness and criminal legal involvement in military veterans. The present study aimed to determine the magnitude and directionality of this association by investigating the incidence of, and factors associated with, homelessness preceding criminal arrest among veterans. Data on incarcerated veterans (
MeSH term(s)	Humans ; Adolescent ; Criminals ; Veterans ; Prisons ; Prisoners ; Ill-Housed Persons ; Substance-Related Disorders/epidemiology
Language	English
Publishing date	2023-08-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	280031-7
ISSN	1939-0025 ; 0002-9432
ISSN (online)	1939-0025
ISSN	0002-9432
DOI	10.1037/ort0000693
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Article ; Online: GenPup-M: A novel validated owner-reported clinical metrology instrument for detecting early mobility changes in dogs.

Clark, Natasha L / Bates, Karl T / Harris, Lauren K / Tomlinson, Andrew W / Murray, Jane K / Comerford, Eithne J

PloS one

2023 Volume 18, Issue 12, Page(s) e0291035

Abstract: Objective: To use a previously validated veterinary clinical examination sheet, Liverpool Osteoarthritis in Dogs (LOAD) questionnaire, combined with kinetic and kinematic gait analysis in dogs with/without mobility problems to demonstrate the capacity ... ...

Abstract	Objective: To use a previously validated veterinary clinical examination sheet, Liverpool Osteoarthritis in Dogs (LOAD) questionnaire, combined with kinetic and kinematic gait analysis in dogs with/without mobility problems to demonstrate the capacity of a novel clinical metrology instrument ("GenPup-M") to detect canine mobility impairments. Design: Quantitative study. Animals: 62 dogs (31 with mobility impairments and 31 without mobility impairments). Procedure: The dogs' clinical history was obtained from owners and all dogs underwent a validated orthopaedic clinical examination. Mobility impairments were diagnosed in the mobility impaired group based on clinical history and orthopaedic examination. Owners were asked to complete GenPup-M along with a previously validated mobility questionnaire (Liverpool Osteoarthritis in Dogs (LOAD)) to identify construct validity. As a test of criterion validity, the correlation between instrument scores and the overall clinical examination scores, along with force-platform obtained peak vertical forces (PVF) were calculated. GenPup-M underwent internal consistency and factor analysis. Spatiotemporal parameters were calculated for dogs with/without mobility impairments to define the gait differences between these two groups. Results: Principal Component Analysis identified GenPup-M had two components with Eigenvalues >1 ("stiffness/ease of movement" and "willingness to be active/exercise"). Cronbach's α was used to test internal consistency of GenPup-M and was found to be "good" (0.87). There was a strong, positive correlation between GenPup-M and LOAD responses (r2 = 0.69, p<0.001) highlighting construct validity. Criterion validity was also shown when comparing GenPup-M to clinical examination scores (r2 = 0.74, p<0.001) and PVF (r2 = 0.43, p<0.001). Quantitative canine gait analysis showed that there were statistically significant differences between peak vertical forces (PVF) of mobility impaired and non-mobility impaired dogs (p<0.05). Analyses of PVF showed that non-mobility impaired dogs more evenly distributed their weight across all thoracic and pelvic limbs when compared to mobility impaired dogs. There were also consistent findings that mobility impaired dogs moved slower than non-mobility impaired dogs. Conclusion and clinical relevance: GenPup-M is a clinical metrology instrument (CMI) that can be completed by dog owners to detect all mobility impairments, including those that are early in onset, indicating the versatility of GenPup-M to assess dogs with and without mobility impairments. Results of the study found that GenPup-M positively correlated with all three objective measures of canine mobility and consequently showed criterion and construct validity. Owner-reported CMIs such as GenPup-M allow non-invasive scoring systems which veterinary surgeons and owners can use to allow communication and longitudinal assessment of a dog's mobility. It is anticipated that GenPup-M will be used by owners at yearly vaccinations/health checks, allowing identification of any subtle mobility changes, and enabling early intervention.
MeSH term(s)	Dogs ; Animals ; Dog Diseases/diagnosis ; Osteoarthritis/veterinary ; Surveys and Questionnaires ; Gait ; Pain Measurement/veterinary
Language	English
Publishing date	2023-12-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0291035
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Article: Structure of nonstructural protein 1 from SARS-CoV-2.

Clark, Lauren K / Green, Todd J / Petit, Chad M

bioRxiv : the preprint server for biology

2020

Abstract: The periodic emergence of novel coronaviruses (CoVs) represents an ongoing public health concern with significant health and financial burden worldwide. The most recent occurrence originated in the city of Wuhan, China where a novel coronavirus (SARS-CoV- ...

Abstract	The periodic emergence of novel coronaviruses (CoVs) represents an ongoing public health concern with significant health and financial burden worldwide. The most recent occurrence originated in the city of Wuhan, China where a novel coronavirus (SARS-CoV-2) emerged causing severe respiratory illness and pneumonia. The continual emergence of novel coronaviruses underscores the importance of developing effective vaccines as well as novel therapeutic options that target either viral functions or host factors recruited to support coronavirus replication. The CoV nonstructural protein 1 (nsp1) has been shown to promote cellular mRNA degradation, block host cell translation, and inhibit the innate immune response to virus infection. Interestingly, deletion of the nsp1-coding region in infectious clones prevented the virus from productively infecting cultured cells. Because of nsp1's importance in the CoV lifecycle, it has been highlighted as a viable target for both antiviral therapy and vaccine development. However, the fundamental molecular and structural mechanisms that underlie nsp1 function remain poorly understood, despite its critical role in the viral lifecycle. Here we report the high-resolution crystal structure of the amino, globular portion of SARS-CoV-2 nsp1 (residues 10 - 127) at 1.77Å resolution. A comparison of our structure with the SARS-CoV-1 nsp1 structure reveals how mutations alter the conformation of flexible loops, inducing the formation of novel secondary structural elements and new surface features. Paired with the recently published structure of the carboxyl end of nsp1 (residues 148 - 180), our results provide the groundwork for future studies focusing on SARS-CoV-2 nsp1 structure and function during the viral lifecycle. Importance: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent for the COVID-19 pandemic. One protein known to play a critical role in the coronavirus lifecycle is nonstructural protein1 (nsp1). As such, it has been highlighted in numerous studies as a target for both the development of antivirals and for the design of live-attenuated vaccines. Here we report the high-resolution crystal structure of nsp1 derived from SARS-CoV-2 at 1.77Å resolution. This structure will facilitate future studies focusing on understanding the relationship between structure and function for nsp1. In turn, understanding these structure-function relationships will allow nsp1 to be fully exploited as a target for both antiviral development and vaccine design.
Keywords	covid19
Language	English
Publishing date	2020-11-03
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.11.03.366757
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Article ; Online: Long-Term Effect of Salt Substitution for Cardiovascular Outcomes : A Systematic Review and Meta-Analysis.

Greenwood, Hannah / Barnes, Katelyn / Clark, Justin / Ball, Lauren / Albarqouni, Loai

Annals of internal medicine

2024

Abstract: Background: Salt substitution is a simple yet increasingly promising strategy to improve cardiovascular outcomes.: Purpose: To evaluate the long-term effects of salt substitution on cardiovascular outcomes.: Data sources: PubMed, EMBASE, Cochrane ... ...

Abstract	Background: Salt substitution is a simple yet increasingly promising strategy to improve cardiovascular outcomes. Purpose: To evaluate the long-term effects of salt substitution on cardiovascular outcomes. Data sources: PubMed, EMBASE, Cochrane CENTRAL, and CINAHL searched from inception to 23 August 2023. Trial registries, citation analysis, and hand-search were also done. Study selection: Randomized controlled trials (RCTs) comparing provision of or advice to use a salt substitute with no intervention or use of regular salt among adults for 6 months or longer in total study duration. Data extraction: Two authors independently screened articles, extracted data, and assessed risk of bias. Primary outcomes include mortality, major cardiovascular events (MACE), and adverse events at 6 months or greater. Secondary and post hoc outcomes include blood pressure, cause-specific mortality, and urinary excretion at 6 months or greater. Random-effects meta-analyses were done and certainty of effect estimates were assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Data synthesis: Of the 16 included RCTs, 8 reported on primary outcomes. Most ( Limitations: The evidence base is dominated by a single, large RCT. Most RCTs were from China or Taiwan and involved participants with higher-than-average cardiovascular risk; therefore, generalizability to other populations is very limited. Conclusion: Salt substitution may reduce all-cause or cardiovascular mortality, but the evidence for reducing cardiovascular events and for not increasing serious adverse events is uncertain, particularly for a Western population. The certainty of evidence is higher among populations at higher cardiovascular risk and/or following a Chinese diet. Primary funding source: National Health and Medical Research Council. (PROSPERO: CRD42022327566).
Language	English
Publishing date	2024-04-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	336-0
ISSN	1539-3704 ; 0003-4819
ISSN (online)	1539-3704
ISSN	0003-4819
DOI	10.7326/M23-2626
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Article ; Online: Pulse pressure and APOE ε4 dose interact to affect cerebral blood flow in older adults without dementia.

Edwards, Lauren / Thomas, Kelsey R / Weigand, Alexandra J / Edmonds, Emily C / Clark, Alexandra L / Brenner, Einat K / Banks, Sarah J / Gilbert, Paul E / Nation, Daniel A / Delano-Wood, Lisa / Bondi, Mark W / Bangen, Katherine J

Cerebral circulation - cognition and behavior

2024 Volume 6, Page(s) 100206

Abstract: This study assessed whether the effect of vascular risk on cerebral blood flow (CBF) varies by gene dose of apolipoprotein (APOE) ε4 alleles. 144 older adults without dementia from the Alzheimer's Disease Neuroimaging Initiative underwent arterial spin ... ...

Abstract	This study assessed whether the effect of vascular risk on cerebral blood flow (CBF) varies by gene dose of apolipoprotein (APOE) ε4 alleles. 144 older adults without dementia from the Alzheimer's Disease Neuroimaging Initiative underwent arterial spin labeling and T1-weighted MRI, APOE genotyping, fluorodeoxyglucose positron emission tomography (FDG-PET), lumbar puncture, and blood pressure (BP) assessment. Vascular risk was assessed using pulse pressure (systolic BP - diastolic BP). CBF was examined in six AD-vulnerable regions: entorhinal cortex, hippocampus, inferior temporal cortex, inferior parietal cortex, rostral middle frontal gyrus, and medial orbitofrontal cortex. Linear regressions tested the interaction between APOE ε4 dose and pulse pressure on CBF in each region, adjusting for age, sex, cognitive classification, antihypertensive medication use, FDG-PET, reference CBF region, and AD biomarker positivity. There was a significant interaction between pulse pressure and APOE ɛ4 dose on CBF in the entorhinal cortex, hippocampus, and inferior parietal cortex, such that higher pulse pressure was associated with lower CBF only among ε4 homozygous participants. These findings demonstrate that the association between pulse pressure and regional CBF differs by APOE ε4 dose, suggesting that targeting modifiable vascular risk factors may be particularly important for those genetically at risk for AD.
Language	English
Publishing date	2024-01-28
Publishing country	Netherlands
Document type	Journal Article
ISSN	2666-2450
ISSN (online)	2666-2450
DOI	10.1016/j.cccb.2024.100206
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Article ; Online: Risk factors for new-onset postpartum depression or anxiety symptoms during the COVID-19 pandemic.

Lewkowitz, Adam K / Schlichting, Lauren / Werner, Erika F / Vivier, Patrick M / Kahn, Linda G / Clark, Melissa A

American journal of obstetrics & gynecology MFM

2021 Volume 4, Issue 1, Page(s) 100502

MeSH term(s)	Anxiety/epidemiology ; COVID-19 ; Depression, Postpartum/diagnosis ; Depression, Postpartum/epidemiology ; Female ; Humans ; Pandemics ; Risk Factors ; SARS-CoV-2
Language	English
Publishing date	2021-10-09
Publishing country	United States
Document type	Letter
ISSN	2589-9333
ISSN (online)	2589-9333
DOI	10.1016/j.ajogmf.2021.100502
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Article ; Online: Service delivery approaches related to hearing aids in low- and middle-income countries or resource-limited settings: A systematic scoping review.

Dillard, Lauren K / Der, Carolina M / Laplante-Lévesque, Ariane / Swanepoel, De Wet / Thorne, Peter R / McPherson, Bradley / de Andrade, Victor / Newall, John / Ramos, Hubert D / Kaspar, Annette / Nieman, Carrie L / Clark, Jackie L / Chadha, Shelly

PLOS global public health

2024 Volume 4, Issue 1, Page(s) e0002823

Abstract: Hearing loss is an important global public health issue which can be alleviated through treatment with hearing aids. However, most people who would benefit from hearing aids do not receive them, in part due to challenges in accessing hearing aids and ... ...

Abstract	Hearing loss is an important global public health issue which can be alleviated through treatment with hearing aids. However, most people who would benefit from hearing aids do not receive them, in part due to challenges in accessing hearing aids and related services, which are most salient in low- and middle-income countries (LMIC) and other resource-limited settings. Innovative approaches for hearing aid service delivery can overcome many of the challenges related to access, including that of limited human resources trained to provide ear and hearing care. The purpose of this systematic scoping review is to synthesize evidence on service delivery approaches for hearing aid provision in LMIC and resource-limited settings. We searched 3 databases (PubMed, Scopus, Ovid MEDLINE) for peer-reviewed articles from 2000 to 2022 that focused on service delivery approaches related to hearing aids in LMIC or resource-limited settings. Fifteen peer-reviewed articles were included, which described hospital-based (3 studies), large-scale donation program (1 studies), community-based (7 studies), and remote (telehealth; 4 studies) service delivery approaches. Key findings are that hearing aid services can be successfully delivered in hospital- and community-based settings, and remotely, and that both qualified hearing care providers and trained non-specialists can provide quality hearing aid services. Service delivery approaches focused on community-based and remote care, and task sharing among qualified hearing care providers and trained non-specialists can likely improve access to hearing aids worldwide, thereby reducing the burden of untreated hearing loss.
Language	English
Publishing date	2024-01-24
Publishing country	United States
Document type	Journal Article
ISSN	2767-3375
ISSN (online)	2767-3375
DOI	10.1371/journal.pgph.0002823
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Article: Sex moderates the association between age and myelin water fraction in the cingulum and fornix among older adults without dementia.

Brenner, Einat K / Bangen, Katherine J / Clark, Alexandra L / Delano-Wood, Lisa / Evangelista, Nicole D / Edwards, Lauren / Sorg, Scott F / Jak, Amy J / Bondi, Mark W / Deoni, Sean C L / Lamar, Melissa

Frontiers in aging neuroscience

2023 Volume 15, Page(s) 1267061

Abstract: Background: Decreasing white matter integrity in limbic pathways including the fornix and cingulum have been reported in Alzheimer's disease (AD), although underlying mechanisms and potential sex differences remain understudied. We therefore sought to ... ...

Abstract	Background: Decreasing white matter integrity in limbic pathways including the fornix and cingulum have been reported in Alzheimer's disease (AD), although underlying mechanisms and potential sex differences remain understudied. We therefore sought to explore sex as a moderator of the effect of age on myelin water fraction (MWF), a measure of myelin content, in older adults without dementia ( Methods: Participants underwent neuropsychological evaluation and 3 T MRI at two research sites. Multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) quantified MWF in 3 Results: (1) There was a significant age by sex interaction on MWF of the fornix ( Conclusion: The current work adds to the literature by illuminating sex differences in age-related myelin decline using a measure sensitive to myelin and may help facilitate detection of AD risk for women.
Language	English
Publishing date	2023-12-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2558898-9
ISSN	1663-4365
ISSN	1663-4365
DOI	10.3389/fnagi.2023.1267061
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