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Article ; Online: Correction: Bringing Mechanical Context to Image-Based Measurements of Bone Integrity.

Loundagin, Lindsay L / Bredbenner, Todd L / Jepsen, Karl J / Edwards, W Brent

2023

Language	English
Publishing date	2023-10-14
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2186581-4
ISSN	1544-2241 ; 1544-1873
ISSN (online)	1544-2241
ISSN	1544-1873
DOI	10.1007/s11914-023-00829-z
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Article ; Online: Cognition and Amyloid-β in Older Veterans: Characterization and Longitudinal Outcomes of Data-Derived Phenotypes.

Thomas, Kelsey R / Clark, Alexandra L / Weigand, Alexandra J / Edwards, Lauren / Durazo, Alin Alshaheri / Membreno, Rachel / Luu, Britney / Rantins, Peter / Ly, Monica T / Rotblatt, Lindsay J / Bangen, Katherine J / Jak, Amy J

Journal of Alzheimer's disease : JAD

2024

Abstract: Background: Within older Veterans, multiple factors may contribute to cognitive difficulties. Beyond Alzheimer's disease (AD), psychiatric (e.g., PTSD) and health comorbidities (e.g., TBI) may also impact cognition.: Objective: This study aimed to ... ...

Abstract	Background: Within older Veterans, multiple factors may contribute to cognitive difficulties. Beyond Alzheimer's disease (AD), psychiatric (e.g., PTSD) and health comorbidities (e.g., TBI) may also impact cognition. Objective: This study aimed to derive subgroups based on objective cognition, subjective cognitive decline (SCD), and amyloid burden, and then compare subgroups on clinical characteristics, biomarkers, and longitudinal change in functioning and global cognition. Methods: Cluster analysis of neuropsychological measures, SCD, and amyloid PET was conducted on 228 predominately male Vietnam-Era Veterans from the Department of Defense-Alzheimer's Disease Neuroimaging Initiative. Cluster-derived subgroups were compared on baseline characteristics as well as 1-year changes in everyday functioning and global cognition. Results: The cluster analysis identified 3 groups. Group 1 (n = 128) had average-to-above average cognition with low amyloid burden. Group 2 (n = 72) had the lowest memory and language, highest SCD, and average amyloid burden; they also had the most severe PTSD, pain, and worst sleep quality. Group 3 (n = 28) had the lowest attention/executive functioning, slightly low memory and language, elevated amyloid and the worst AD biomarkers, and the fastest rate of everyday functioning and cognitive decline. Conclusions: Psychiatric and health factors likely contributed to Group 2's low memory and language performance. Group 3 was most consistent with biological AD, yet attention/executive function was the lowest score. The complexity of older Veterans' co-morbid conditions may interact with AD pathology to show attention/executive dysfunction (rather than memory) as a prominent early symptom. These results could have important implications for the implementation of AD-modifying drugs in older Veterans.
Language	English
Publishing date	2024-05-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-240077
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Article ; Online: Bringing Mechanical Context to Image-Based Measurements of Bone Integrity.

Loundagin, Lindsay L / Bredbenner, Todd L / Jepsen, Karl J / Edwards, W Brent

Current osteoporosis reports

2021 Volume 19, Issue 5, Page(s) 542–552

Abstract: Purpose of review: Image-based measurements of bone integrity are used to estimate failure properties and clinical fracture risk. This paper (1) reviews recent imaging studies that have enhanced our understanding of the mechanical pathways to bone ... ...

Abstract	Purpose of review: Image-based measurements of bone integrity are used to estimate failure properties and clinical fracture risk. This paper (1) reviews recent imaging studies that have enhanced our understanding of the mechanical pathways to bone fracture and (2) discusses the influence that inter-individual differences in image-based measurements may have on the clinical assessment of fracture risk RECENT FINDINGS: Increased tissue mineralization is associated with improved bone strength but reduced fracture toughness. Trabecular architecture that is important for fatigue resistance is less important for bone strength. The influence of porosity on bone failure properties is heavily dependent on pore location and size. The interaction of various characteristics, such as bone area and mineral content, can further complicate their influence on bone failure properties. What is beneficial for bone strength is not always beneficial for bone toughness or fatigue resistance. Additionally, given the large amount of imaging data that is clinically available, there is a need to develop effective translational strategies to better interpret non-invasive measurements of bone integrity.
MeSH term(s)	Absorptiometry, Photon ; Bone Density ; Fractures, Bone/diagnostic imaging ; Fractures, Bone/etiology ; Humans ; Porosity ; Tomography, X-Ray Computed
Language	English
Publishing date	2021-07-16
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2186581-4
ISSN	1544-2241 ; 1544-1873
ISSN (online)	1544-2241
ISSN	1544-1873
DOI	10.1007/s11914-021-00700-z
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Article ; Online: Twelve Months of Denosumab and/or Alendronate Is Associated With Improved Bone Fatigue Life, Microarchitecture, and Density in Ovariectomized Cynomolgus Monkeys.

Haider, Ifaz T / Loundagin, Lindsay L / Sawatsky, Andrew / Kostenuik, Paul J / Boyd, Steven K / Edwards, W Brent

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

2023 Volume 38, Issue 3, Page(s) 403–413

Abstract: Prolonged use of antiresorptives such as the bisphosphonate alendronate (ALN) and the RANKL inhibitor denosumab (DMAb) are associated with rare cases of atypical femoral fracture (AFF). The etiology of AFF is unclear, but it has been hypothesized that ... ...

Abstract	Prolonged use of antiresorptives such as the bisphosphonate alendronate (ALN) and the RANKL inhibitor denosumab (DMAb) are associated with rare cases of atypical femoral fracture (AFF). The etiology of AFF is unclear, but it has been hypothesized that potent osteoclast inhibitors may reduce bone fatigue resistance. The purpose of this study was to quantify the relationship between antiresorptive treatment and fatigue life (cycles to failure) in bone from ovariectomized cynomolgus monkeys. We analyzed humeral bone from 30 animals across five treatment groups. Animals were treated for 12 months with subcutaneous (sc) vehicle (VEH), sc DMAb (25 mg/kg/month), or intravenous (iv) ALN (50 μg/kg/month). Another group received 6 months VEH followed by 6 months DMAb (VEH-DMAb), and the final group received 6 months ALN followed by 6 months DMAb (ALN-DMAb). A total of 240 cortical beam samples were cyclically tested in four-point bending at 80, 100, 120, or 140 MPa peak stress. High-resolution imaging and density measurements were performed to evaluate bone microstructure and composition. Samples from the ALN (p = 0.014), ALN-DMAb (p = 0.008), and DMAb (p < 0.001) groups illustrated higher fatigue-life measurements than VEH. For example, at 140 MPa the VEH group demonstrated a median ± interquartile range (IQR) fatigue life of 1987 ± 10593 cycles, while animals in the ALN, ALN-DMAb, and DMAb groups survived 9850 ± 13648 (+395% versus VEH), 10493 ± 16796 (+428%), and 14495 ± 49299 (+629%) cycles, respectively. All antiresorptive treatment groups demonstrated lower porosity, smaller pore size, greater pore spacing, and lower number of canals versus VEH (p < 0.001). Antiresorptive treatment was also associated with greater apparent density, dry density, and ash density (p ≤ 0.03). We did not detect detrimental changes following antiresorptive treatments that would explain their association with AFF. In contrast, 12 months of treatment may have a protective effect against fatigue fractures. © 2022 American Society for Bone and Mineral Research (ASBMR).
MeSH term(s)	Animals ; Alendronate/pharmacology ; Denosumab/pharmacology ; Macaca fascicularis ; Bone Density ; Bone and Bones ; Bone Diseases ; Bone Density Conservation Agents/pharmacology
Chemical Substances	Alendronate (X1J18R4W8P) ; Denosumab (4EQZ6YO2HI) ; Bone Density Conservation Agents
Language	English
Publishing date	2023-01-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632783-7
ISSN	1523-4681 ; 0884-0431
ISSN (online)	1523-4681
ISSN	0884-0431
DOI	10.1002/jbmr.4758
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Article ; Online: Single-cell mapping of regenerative and fibrotic healing responses after musculoskeletal injury.

Tower, Robert J / Bancroft, Alec C / Chowdary, Ashish R / Barnes, Spencer / Edwards, Nicole J / Pagani, Chase A / Dawson, Lindsay A / Levi, Benjamin

Stem cell reports

2022 Volume 17, Issue 10, Page(s) 2334–2348

Abstract: After injury, a cascade of events repairs the damaged tissue, including expansion and differentiation of the progenitor pool and redeposition of matrix. To guide future wound regeneration strategies, we compared single-cell sequencing of regenerative ( ... ...

Abstract	After injury, a cascade of events repairs the damaged tissue, including expansion and differentiation of the progenitor pool and redeposition of matrix. To guide future wound regeneration strategies, we compared single-cell sequencing of regenerative (third phalangeal element [P3]) and fibrotic (second phalangeal element [P2]) digit tip amputation (DTA) models as well as traumatic heterotopic ossification (HO; aberrant). Analyses point to a common initial response to injury, including expansion of progenitors, redeposition of matrix, and activation of transforming growth factor β (TGF-β) and WNT pathways. Surprisingly, fibrotic P2 DTA showed greater transcriptional similarity to HO than to regenerative P3 DTA, suggesting that gene expression more strongly correlates with healing outcome than with injury type or cell origin. Differential analysis and immunostaining revealed altered activation of inflammatory pathways, such as the complement pathway, in the progenitor cells. These data suggests that common pathways are activated in response to damage but are fine tuned within each injury. Modulating these pathways may shift the balance toward regenerative outcomes.
MeSH term(s)	Amputation, Surgical ; Bone and Bones/injuries ; Cell Differentiation ; Humans ; Musculoskeletal System/injuries ; Ossification, Heterotopic ; Regeneration ; Transforming Growth Factor beta
Chemical Substances	Transforming Growth Factor beta
Language	English
Publishing date	2022-09-22
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	2720528-9
ISSN	2213-6711 ; 2213-6711
ISSN (online)	2213-6711
ISSN	2213-6711
DOI	10.1016/j.stemcr.2022.08.011
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Article ; Online: Regional White Matter Hyperintensities Relate to Specific Cognitive Abilities in Older Adults Without Dementia.

Membreno, Rachel / Thomas, Kelsey R / Calcetas, Amanda T / Edwards, Lauren / Bordyug, Maria / Showell, Maya / Stanfill, Morgan / Brenner, Einat K / Walker, Kayla S / Rotblatt, Lindsay J / Brickman, Adam M / Edmonds, Emily C / Bangen, Katherine J

Alzheimer disease and associated disorders

2023 Volume 37, Issue 4, Page(s) 303–309

Abstract: Introduction: White matter hyperintensities (WMHs) are magnetic resonance imaging markers of small vessel cerebrovascular disease that are associated with cognitive decline and clinical Alzheimer disease. Previous studies have often focused on global or ...

Abstract	Introduction: White matter hyperintensities (WMHs) are magnetic resonance imaging markers of small vessel cerebrovascular disease that are associated with cognitive decline and clinical Alzheimer disease. Previous studies have often focused on global or total WMH; less is known about associations of regional WMHs and cognitive abilities among older adults without dementia. Methods: A total of 610 older adults with normal cognition (n=302) or mild cognitive impairment (n=308) from the Alzheimer's Disease Neuroimaging Initiative underwent neuropsychological testing and magnetic resonance imaging. Linear regression models examined associations between regional WMH volumes and cognition, adjusting for age, sex, education, apolipoprotein E ε4 allele frequency, and pulse pressure. Results: Among all participants, greater regional WMH volume in all lobes was associated with poorer performance on memory and speed/executive functioning. Among participants with normal cognition, greater temporal and occipital WMH volumes were associated with poorer memory, whereas no regional WMH volumes were associated with speed/executive function. Discussion: Results show that greater regional WMH volume relates to poorer cognitive functioning-even among those with normal cognition. Together with results from previous studies, our findings raise the possibility that WMH may be a useful therapeutic target and/or important effect modifier in treatment or prevention dementia trials.
MeSH term(s)	Humans ; Aged ; White Matter ; Cognition ; Cognitive Dysfunction ; Executive Function ; Alzheimer Disease
Language	English
Publishing date	2023-11-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1002700-2
ISSN	1546-4156 ; 0893-0341
ISSN (online)	1546-4156
ISSN	0893-0341
DOI	10.1097/WAD.0000000000000585
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Article ; Online: Population Genomics of Legionella longbeachae and Hidden Complexities of Infection Source Attribution.

Bacigalupe, Rodrigo / Lindsay, Diane / Edwards, Giles / Fitzgerald, J Ross

Emerging infectious diseases

2017 Volume 23, Issue 5, Page(s) 750–757

Abstract: Legionella longbeachae is the primary cause of legionellosis in Australasia and Southeast Asia and an emerging pathogen in Europe and the United States; however, our understanding of the population diversity of L. longbeachae from patient and ... ...

Abstract	Legionella longbeachae is the primary cause of legionellosis in Australasia and Southeast Asia and an emerging pathogen in Europe and the United States; however, our understanding of the population diversity of L. longbeachae from patient and environmental sources is limited. We analyzed the genomes of 64 L. longbeachae isolates, of which 29 were from a cluster of legionellosis cases linked to commercial growing media in Scotland in 2013 and 35 were non-outbreak-associated isolates from Scotland and other countries. We identified extensive genetic diversity across the L. longbeachae species, associated with intraspecies and interspecies gene flow, and a wide geographic distribution of closely related genotypes. Of note, we observed a highly diverse pool of L. longbeachae genotypes within compost samples that precluded the genetic establishment of an infection source. These data represent a view of the genomic diversity of L. longbeachae that will inform strategies for investigating future outbreaks.
MeSH term(s)	Australia/epidemiology ; Cluster Analysis ; Computational Biology/methods ; Gene Flow ; Genetic Variation ; Genome, Bacterial ; Genomics/methods ; High-Throughput Nucleotide Sequencing ; Humans ; Legionella longbeachae/classification ; Legionella longbeachae/genetics ; Legionellosis/epidemiology ; Legionellosis/microbiology ; New Zealand/epidemiology ; Phylogeny ; Plasmids/genetics ; RNA, Bacterial ; RNA, Ribosomal, 16S ; Recombination, Genetic ; Scotland/epidemiology ; Serogroup ; United States/epidemiology
Chemical Substances	RNA, Bacterial ; RNA, Ribosomal, 16S
Language	English
Publishing date	2017-04-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	1380686-5
ISSN	1080-6059 ; 1080-6040
ISSN (online)	1080-6059
ISSN	1080-6040
DOI	10.3201/eid2305.161165
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Article ; Online: A Resident-Driven Quality Initiative for Reducing Opioid Prescribing in Patients Undergoing Elective General Surgery Procedures, With Long-Term Follow-Up

Ryan Lamm / Megan Lundgren / Adrienne Christopher / Jacob Woodroof / Lindsay Edwards / Christopher Kustera / Charles J. Yeo / Kristin M. Noonan / Harish Lavu / Caitlyn Costanzo / Scott Cowan

Patient Safety, Vol 5, Iss

2023 Volume 3

Abstract: Background The opioid epidemic has been declared a public health emergency in the United States—and major news outlets have labeled operating rooms as “unintended gateways.” In response to this emergency, our academic institution sought to decrease our ...

Abstract	# Background The opioid epidemic has been declared a public health emergency in the United States—and major news outlets have labeled operating rooms as “unintended gateways.” In response to this emergency, our academic institution sought to decrease our contribution to the potential diversion pool—the opioids surgeons prescribe to patients which go unused. # Methods Patients undergoing common surgical procedures between August 2017 and March 2018 were identified. Patients were contacted by phone and consented, and opioid use data was collected. The potential diversion pool was calculated as pills prescribed minus pills consumed for each patient and procedure, and subgroup analysis was performed to correlate the number of opioid pills taken within 24 hours before hospital discharge to the number taken after discharge. # Results Surveys were completed for 357 patients. Overall, 6,831 of the 12,061 tablets prescribed were unused (57%). Patients who took 7 or more doses of oral opioids in the last 24 hours before discharge had significantly fewer (30%) pills remaining compared to patients who took 0–6 doses (68% remaining). Ninety-nine of 111 patients (89%) who took 0 tablets 24 hours prior to discharge left with an opioid prescription, creating a diversion pool of 2,419 pills remaining out of 3,353 prescribed (72%). Based on a 95% confidence interval of procedural opioid consumption, prescribing guidelines were created within a toolkit designed to set preoperative expectations, promote use of nonopioid analgesics, and provide opioid disposal information. We have continued to track our data, with low opioid prescribing patterns. # Conclusion Surgical departments can develop opioid reduction toolkits aimed at reducing the potential diversion pool of opioids in our communities. Such toolkits have a sustained positive impact.
Keywords	Medicine ; R
Subject code	616
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	Patient Safety Authority
Document type	Article ; Online
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Article ; Online: Declining muscle NAD

Aflatounian, Ali / Paris, Valentina Rodriguez / Richani, Dulama / Edwards, Melissa C / Cochran, Blake J / Ledger, William L / Gilchrist, Robert B / Bertoldo, Michael J / Wu, Lindsay E / Walters, Kirsty A

Molecular metabolism

2022 Volume 65, Page(s) 101583

Abstract: Polycystic ovary syndrome (PCOS) is a common endocrine disorder, defined by reproductive and endocrine abnormalities, with metabolic dysregulation including obesity, insulin resistance and hepatic steatosis. Recently, it was found that skeletal muscle ... ...

Abstract	Polycystic ovary syndrome (PCOS) is a common endocrine disorder, defined by reproductive and endocrine abnormalities, with metabolic dysregulation including obesity, insulin resistance and hepatic steatosis. Recently, it was found that skeletal muscle insulin sensitivity could be improved in obese, post-menopausal, pre-diabetic women through treatment with nicotinamide mononucleotide (NMN), a precursor to the prominent redox cofactor nicotinamide adenine dinucleotide (NAD
MeSH term(s)	Animals ; Dihydrotestosterone/metabolism ; Female ; Humans ; Hyperandrogenism/metabolism ; Insulin Resistance/physiology ; Lipids ; Metabolic Syndrome/metabolism ; Mice ; Muscle, Skeletal/metabolism ; NAD/metabolism ; Nicotinamide Mononucleotide/metabolism ; Obesity/metabolism ; Polycystic Ovary Syndrome/metabolism
Chemical Substances	Lipids ; Dihydrotestosterone (08J2K08A3Y) ; NAD (0U46U6E8UK) ; Nicotinamide Mononucleotide (1094-61-7)
Language	English
Publishing date	2022-09-09
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2708735-9
ISSN	2212-8778 ; 2212-8778
ISSN (online)	2212-8778
ISSN	2212-8778
DOI	10.1016/j.molmet.2022.101583
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Article ; Online: Validation of International Classification of Diseases criteria to identify severe influenza hospitalizations.

Snyder, Brittney M / Patterson, Megan F / Gebretsadik, Tebeb / Wu, Pingsheng / Ding, Tan / Lee, Rees L / Edwards, Kathryn M / Somerville, Lindsay A / Braciale, Thomas J / Ortiz, Justin R / Hartert, Tina V

Influenza and other respiratory viruses

2022 Volume 16, Issue 3, Page(s) 371–375

Abstract: In this cohort study of hospitalized patients with linked medical record data, we developed International Classification of Diseases (ICD) criteria that accurately identified laboratory-confirmed, severe influenza hospitalizations (positive predictive ... ...

Abstract	In this cohort study of hospitalized patients with linked medical record data, we developed International Classification of Diseases (ICD) criteria that accurately identified laboratory-confirmed, severe influenza hospitalizations (positive predictive value [PPV] 80%, 95% confidence interval [CI] 71-87%), which we validated through medical record documentation. These criteria identify patients with clinically important influenza illness outcomes to inform evaluation of preventive and therapeutic interventions and public health policy recommendations.
MeSH term(s)	Cohort Studies ; Hospitalization ; Humans ; Influenza, Human/diagnosis ; Influenza, Human/epidemiology ; Influenza, Human/therapy ; International Classification of Diseases ; Predictive Value of Tests
Language	English
Publishing date	2022-01-04
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2274538-5
ISSN	1750-2659 ; 1750-2640
ISSN (online)	1750-2659
ISSN	1750-2640
DOI	10.1111/irv.12931
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