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Article ; Online: Decellularization of the Human Liver to Generate Native Extracellular Matrix for Use in Automated Functional Assays with Stellate Cells.

Shepherd, Emma L / Northall, Ellie / Papakyriacou, Pantelitsa / Safranska, Karolina / Sorensen, Karen K / Lalor, Patricia F

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

2023 Volume 2669, Page(s) 233–244

Abstract: With the incidence of liver disease on the rise globally, increasing numbers of patients are presenting with advanced hepatic fibrosis and significant mortality risk. The demand far outstrips possible transplantation capacities, and thus there is an ... ...

Abstract	With the incidence of liver disease on the rise globally, increasing numbers of patients are presenting with advanced hepatic fibrosis and significant mortality risk. The demand far outstrips possible transplantation capacities, and thus there is an intense drive to develop new pharmacological therapies that stall or reverse liver scarring. Recent late-stage failures of lead compounds have highlighted the challenges of resolving fibrosis, which has developed and stabilized over many years and varies in nature and composition from individual to individual. Hence, preclinical tools are being developed in both the hepatology and tissue engineering communities to elucidate the nature, composition, and cellular interactions of the hepatic extracellular niche in health and disease. In this protocol, we describe strategies for decellularizing cirrhotic and healthy human liver specimens and show how these can be used in simple functional assays to detect the impact on stellate cell function. Our simple, small-scale approach is translatable to diverse lab settings and generates cell-free materials which could be used for a variety of in vitro analyses as well as a scaffold for repopulating with key hepatic cell populations.
MeSH term(s)	Humans ; Liver/physiology ; Liver Cirrhosis ; Liver Diseases ; Tissue Engineering/methods ; Extracellular Matrix ; Tissue Scaffolds
Language	English
Publishing date	2023-05-30
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-3207-9_14
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Article: The Contribution of Liver Sinusoidal Endothelial Cells to Clearance of Therapeutic Antibody.

James, Bethany H / Papakyriacou, Pantelitsa / Gardener, Matthew J / Gliddon, Louise / Weston, Christopher J / Lalor, Patricia F

Frontiers in physiology

2022 Volume 12, Page(s) 753833

Abstract: Many chronic inflammatory diseases are treated by administration of "biological" therapies in terms of fully human and humanized monoclonal antibodies or Fc fusion proteins. These tools have widespread efficacy and are favored because they generally ... ...

Abstract	Many chronic inflammatory diseases are treated by administration of "biological" therapies in terms of fully human and humanized monoclonal antibodies or Fc fusion proteins. These tools have widespread efficacy and are favored because they generally exhibit high specificity for target with a low toxicity. However, the design of clinically applicable humanized antibodies is complicated by the need to circumvent normal antibody clearance mechanisms to maintain therapeutic dosing, whilst avoiding development of off target antibody dependent cellular toxicity. Classically, professional phagocytic immune cells are responsible for scavenging and clearance of antibody
Language	English
Publishing date	2022-01-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2021.753833
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Article ; Online: Postexercise muscle glycogen synthesis with glucose, galactose, and combined galactose-glucose ingestion.

Podlogar, Tim / Shad, Brandon J / Seabright, Alex P / Odell, Oliver J / Lord, Samuel O / Civil, Rita / Salgueiro, Rafael B / Shepherd, Emma L / Lalor, Patricia F / Elhassan, Yasir S / Lai, Yu-Chiang / Rowlands, David S / Wallis, Gareth A

American journal of physiology. Endocrinology and metabolism

2023 Volume 325, Issue 6, Page(s) E672–E681

Abstract: Ingested galactose can enhance postexercise liver glycogen repletion when combined with glucose but effects on muscle glycogen synthesis are unknown. In this double-blind randomized study participants [7 men and 2 women; ... ...

Abstract	Ingested galactose can enhance postexercise liver glycogen repletion when combined with glucose but effects on muscle glycogen synthesis are unknown. In this double-blind randomized study participants [7 men and 2 women; V̇o
MeSH term(s)	Female ; Humans ; Male ; Blood Glucose ; Dietary Carbohydrates/pharmacology ; Eating/physiology ; Galactose ; Glucose ; Glycogen ; Insulin ; Muscle, Skeletal/physiology ; Double-Blind Method
Chemical Substances	Blood Glucose ; Dietary Carbohydrates ; Galactose (X2RN3Q8DNE) ; Glucose (IY9XDZ35W2) ; Glycogen (9005-79-2) ; Insulin
Language	English
Publishing date	2023-10-18
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603841-4
ISSN	1522-1555 ; 0193-1849
ISSN (online)	1522-1555
ISSN	0193-1849
DOI	10.1152/ajpendo.00127.2022
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Article ; Online: Mortality thresholds of juvenile trees to drought and heatwaves

Alexandra R. Lalor / Darin J. Law / David D. Breshears / Donald A. Falk / Jason P. Field / Rachel A. Loehman / F. Jack Triepke / Greg A. Barron-Gafford

Frontiers in Forests and Global Change, Vol

implications for forest regeneration across a landscape gradient

2023 Volume 6

Abstract: Tree loss is increasing rapidly due to drought- and heat-related mortality and intensifying fire activity. Consequently, the fate of many forests depends on the ability of juvenile trees to withstand heightened climate and disturbance anomalies. Extreme ... ...

Abstract	Tree loss is increasing rapidly due to drought- and heat-related mortality and intensifying fire activity. Consequently, the fate of many forests depends on the ability of juvenile trees to withstand heightened climate and disturbance anomalies. Extreme climatic events, such as droughts and heatwaves, are increasing in frequency and severity, and trees in mountainous regions must contend with these landscape-level climate episodes. Recent research focuses on how mortality of individual tree species may be driven by drought and heatwaves, but how juvenile mortality under these conditions would vary among species spanning an elevational gradient—given concurrent variation in climate, ecohydrology, and physiology–remains unclear. We address this knowledge gap by implementing a growth chamber study, imposing extreme drought with and without a compounding heatwave, for juveniles of five species that span a forested life zones in the Southwestern United States. Overall, the length of a progressive drought required to trigger mortality differed by up to 20 weeks among species. Inclusion of a heatwave hastened mean time to mortality for all species by about 1 week. Lower-elevation species that grow in warmer ambient conditions died earlier (Pinus ponderosa in 10 weeks, Pinus edulis in 14 weeks) than did higher-elevation species from cooler ambient conditions (Picea engelmannii and Pseudotsuga menziesii in 19 weeks, and Pinus flexilis in 30 weeks). When exposed to a heatwave in conjunction with drought, mortality advanced significantly only for species from cooler ambient conditions (Pinus flexilis: 2.7 weeks earlier; Pseudotsuga menziesii: 2.0 weeks earlier). Cooler ambient temperatures may have buffered against moisture loss during drought, resulting in longer survival of higher-elevation species despite expected drought tolerance of lower-elevation species due to tree physiology. Our study suggests that droughts will play a leading role in juvenile tree mortality and will most directly impact species at warmer climate ...
Keywords	climate change ; drought ; establishment ; forest regeneration ; heatwave ; landscape gradient ; Forestry ; SD1-669.5 ; Environmental sciences ; GE1-350
Subject code	590 ; 580
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article ; Online: Fasciola hepatica antioxidant and protease-inhibitor cocktail recombinant vaccines administered five times elicit potent and sustained immune responses in sheep but do not confer protection.

Cwiklinski, Krystyna / McEvoy, Amanda / López Corrales, Jesús / Jewhurst, Heather / Calvani, Nichola Eliza Davies / De Marco Verissimo, Carolina / Dorey, Amber Louise / Keane, Orla M / Dalton, John Pius / Lalor, Richard

Veterinary parasitology

2023 Volume 323, Page(s) 110049

Abstract: ... timepoints; two before experimental challenge with 60 F. hepatica metacercariae and three after infection ... in infected animals, no significant (P value >0.05) impact on weight gain was observed in this study ... However, these responses were not boosted by the challenge F. hepatica infection. A comparative analysis with previous ...

Abstract	Our laboratory's vaccine development strategy against the livestock parasite Fasciola hepatica centres around disrupting key biological processes by combining groups of antigens with similar/complementary functional actions into a single vaccine cocktail. In this study the focus was on antioxidant protein vaccines and a protease inhibitor vaccine aimed at disrupting the parasite's ability to defend against oxidative stress and protease-inhibitor balance, respectively. Two combinations of recombinantly expressed antioxidants were assessed, namely peroxiredoxin (rFhPrx), thioredoxin (rFhTrx) and thioredoxin-glutathione reductase (rFhTGR) (Group 1) and rFhPrx, rFhTrx, and two superoxide dismutases (rFhSOD1 and rFhSOD3) (Group 2). The protease inhibitor vaccine cocktail included representatives of each of the key secreted protease inhibitor families, namely a Kunitz-type inhibitor (rFhKT1), a serpin (rFhSrp1) and a stefin, (rFhStf1) (Group 3). The vaccine combinations were formulated in adjuvant Montanide 61VG administered at five timepoints; two before experimental challenge with 60 F. hepatica metacercariae and three after infection. The vaccine combinations did not reduce the liver fluke burden, and only Group 2 displayed a marginal reduction in egg viability (8.2%). Despite previous results showing an effect of liver fluke vaccines on overall weight gain in infected animals, no significant (P value >0.05) impact on weight gain was observed in this study. Antibodies were elicited against all the vaccine antigens within the cocktails and were maintained at high levels to the end of the trial, due to our strategy of continuing vaccine administration after infection. However, these responses were not boosted by the challenge F. hepatica infection. A comparative analysis with previous vaccine data using a protease inhibitor vaccine found no repeat of the promising outcomes associated with this vaccine, indicating that the addition of rFhSrp1 to the vaccine cocktail did not improve vaccine efficacy. Assessment of liver pathology across the two trials using a modified liver enzyme score (glutamate dehydrogenase to platelet ratio) at eight weeks post infection suggests an association with liver fluke burden above 45 flukes, which could be used to predict liver pathology in future trials. The results reported in this study highlight the ambiguousness in liver fluke vaccine development and the difficulty in obtaining consistent and repeatable protection. This work stresses the need for repetition of trials and the use of sufficiently sized groups to assess vaccine efficacy with adequate statistical power.
Language	English
Publishing date	2023-10-08
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	196831-2
ISSN	1873-2550 ; 0304-4017
ISSN (online)	1873-2550
ISSN	0304-4017
DOI	10.1016/j.vetpar.2023.110049
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Article ; Online: Hospital readmission risks in older adults following inpatient subacute care: A six-month follow-up study.

Lee, Den-Ching A / Williams, Cylie / Lalor, Aislinn F / Brown, Ted / Haines, Terry P

Archives of gerontology and geriatrics

2018 Volume 77, Page(s) 142–149

Abstract: Background: High rates of unplanned hospital readmissions are a burden on healthcare systems and individuals. This study examined factors at, and after initial hospital discharge and their associations with unplanned hospital readmission for older ... ...

Abstract	Background: High rates of unplanned hospital readmissions are a burden on healthcare systems and individuals. This study examined factors at, and after initial hospital discharge and their associations with unplanned hospital readmission for older adults up to six months post-discharge from subacute care. Methods: Older subacute care patients were surveyed prior to discharge, and assessed monthly post-discharge for six months. Data included the Geriatric Depression Scale, Phone-Fitt sub-scales, Friendship Scale, modified Lubben Social Network Scale, unplanned hospital readmission, self-reported physical capacity and falls in the last month were collected. Regression analyses were used to examine relationships between unplanned hospital readmission and variables that may predispose this outcome. Results: Participants (n = 311) completed the baseline assessment. N = 218 (70%) completed all at six-month post-discharge. Eighty-nine (29%) participants shared 143 readmissions. Those with cancer history (adjusted OR [95% CI]) (1.97 [1.15, 3.39]), neurological disease other than stroke (2.95 [1.32, 6.57]) and dependence on others to assist in bending tasks (1.94 [1.14, 3.29]) at initial discharge were associated with readmission within six months post-discharge. Those who fell in the last month (adjusted OR [robust 95% CI]) (2.28 [1.43, 3.64]), being less physical active (0.98 [0.96, 0.99]), and dependence on others in moving around residence (2.63 [1.37, 5.06]) after initial discharge were associated with a readmission in the next month within six months post-discharge. Conclusion: Trials investigating the effectiveness of strategies to reduce falls, build physical capacity, increase physical activity level, and connection with health care services after discharge to prevent readmission are warranted.
MeSH term(s)	Accidental Falls/statistics & numerical data ; Aged ; Cognitive Dysfunction/rehabilitation ; Female ; Follow-Up Studies ; Geriatric Assessment/methods ; Humans ; Inpatients ; Male ; Patient Discharge/trends ; Patient Readmission/trends ; Prospective Studies ; Subacute Care/statistics & numerical data ; Time Factors
Language	English
Publishing date	2018-05-09
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603162-6
ISSN	1872-6976 ; 0167-4943
ISSN (online)	1872-6976
ISSN	0167-4943
DOI	10.1016/j.archger.2018.05.005
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Article ; Online: Platelets: No longer bystanders in liver disease.

Chauhan, Abhishek / Adams, David H / Watson, Steve P / Lalor, Patricia F

Hepatology (Baltimore, Md.)

2016 Volume 64, Issue 5, Page(s) 1774–1784

Abstract: Growing lines of evidence recognize that platelets play a central role in liver homeostasis and pathobiology. Platelets have important roles at every stage during the continuum of liver injury and healing. These cells contribute to the initiation of ... ...

Abstract	Growing lines of evidence recognize that platelets play a central role in liver homeostasis and pathobiology. Platelets have important roles at every stage during the continuum of liver injury and healing. These cells contribute to the initiation of liver inflammation by promoting leukocyte recruitment through sinusoidal endothelium. They can activate effector cells, thus amplifying liver damage, and by modifying the hepatic cellular and cytokine milieu drive both hepatoprotective and hepatotoxic processes. Conclusion: In this review we summarize how platelets drive such pleiotropic actions and attempt to reconcile the paradox of platelets being both deleterious and beneficial to liver function; with increasingly novel methods of manipulating platelet function at our disposal, we highlight avenues for future therapeutic intervention in liver disease. (Hepatology 2016;64:1774-1784).
MeSH term(s)	Animals ; Blood Platelets/physiology ; Capillaries ; Cell Communication ; Endothelium, Vascular ; Forecasting ; Humans ; Liver/blood supply ; Liver/physiology ; Liver Cirrhosis/etiology ; Liver Diseases/blood ; Liver Diseases/etiology ; Liver Regeneration/physiology ; Myeloid Cells/physiology
Language	English
Publishing date	2016-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1002/hep.28526
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Article: Making and justifying health claims

Lalor, F. / Wall, P. G.

International journal of dairy technology

2013 Volume 66, Issue 3, Page(s) 321

Language	English
Document type	Article
ZDB-ID	1363788-5
ISSN	1364-727X
Database	Current Contents Nutrition, Environment, Agriculture

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Article ; Online: The relationship between discharge medications and falls in post-hospitalised older adults: A 6-month follow-up.

Lam, Kenneth / Lee, Den-Ching A / Lalor, Aislinn F / Stolwyk, Rene / Russell, Grant / Brown, Ted / McDermott, Fiona / Haines, Terry P

Australasian journal on ageing

2019 Volume 38, Issue 3, Page(s) 190–198

Abstract: Objective: To identify discharge medications, especially psychotropic medications that are associated with falls, amongst older adults within 6 months following hospitalisation.: Methods: Negative binomial regression was used to examine relationships ...

Abstract	Objective: To identify discharge medications, especially psychotropic medications that are associated with falls, amongst older adults within 6 months following hospitalisation. Methods: Negative binomial regression was used to examine relationships between discharge medications and falls in older post-hospitalised adults. Multiple regression that considered falls risk factors at discharge was performed. Results: Data for 267 participants showed that discharge medications were not independently associated with falls postdischarge after adjustment for other falls risk factors. Male gender (adjusted incidence rate ratio [95% confidence interval, CI]) 2.15 [1.36-3.40]), higher depression scores (1.14 [1.05-1.25]) and co-morbidity of neurological disease other than stroke (5.98 [3.08-11.60]) were independently associated with an increased rate of falls. Higher depression scores (1.20 [1.11-1.31]) and co-morbidity of cancer (1.97 [1.20-3.25]) were independently associated with an increased rate of injurious falls in the 6 months postdischarge. Conclusion: Falls prevention strategies, other than hospital discharge medication management in the postdischarge older adults, warrant investigation.
MeSH term(s)	Accidental Falls/prevention & control ; Age Factors ; Aged ; Aged, 80 and over ; Comorbidity ; Female ; Humans ; Male ; Medication Therapy Management ; Mental Health ; Patient Discharge ; Prospective Studies ; Protective Factors ; Risk Assessment ; Risk Factors ; Sex Factors ; Time Factors
Language	English
Publishing date	2019-02-25
Publishing country	Australia
Document type	Journal Article
ZDB-ID	1457406-8
ISSN	1741-6612 ; 0726-4240 ; 1440-6381
ISSN (online)	1741-6612
ISSN	0726-4240 ; 1440-6381
DOI	10.1111/ajag.12628
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Article ; Online: Ineligible, Unaware, or Uninterested? Associations Between Underrepresented Patient Populations and Retention in the Pathway to Cancer Clinical Trial Enrollment.

Caston, Nicole E / Lalor, Fallon / Wall, Jaclyn / Sussell, Jesse / Patel, Shilpen / Williams, Courtney P / Azuero, Andres / Arend, Rebecca / Liang, Margaret I / Rocque, Gabrielle B

JCO oncology practice

2022 Volume 18, Issue 11, Page(s) e1854–e1865

Abstract: Purpose: Cancer clinical trials can benefit current and future patients; however, Black patients, rural residents, and patients living in disadvantaged areas are often underrepresented. Using an adapted version of Unger and colleagues' model of the ... ...

Abstract	Purpose: Cancer clinical trials can benefit current and future patients; however, Black patients, rural residents, and patients living in disadvantaged areas are often underrepresented. Using an adapted version of Unger and colleagues' model of the process of clinical trial enrollment, we evaluated the relationship between underrepresented patient populations and trial end points. Methods: This retrospective study included 512 patients with breast or ovarian cancer who were prescribed a therapeutic drug at the University of Alabama at Birmingham from January 2017 to February 2020. Patient eligibility was assessed using open clinical trials. We estimated odds ratios and 95% CIs using logistic regression models to examine the relationship between underrepresented patient populations and trial enrollment end points: eligibility, interest, offer, enrollment, and declining enrollment. Results: Of the patients in our sample, 27% were Black, 18% were rural residents, and 19% lived in higher disadvantaged neighborhoods. In adjusted models, each comparison group had similar odds of being eligible for a clinical trial. Black versus White patients had 0.40 times the odds of interest in clinical trials and 0.56 times the odds of enrollment. Patients living in areas of higher versus lower disadvantage had 0.46 times the odds of enrolling and 3.40 times the odds of declining enrollment when offered. Conclusion: Eligibility did not drive clinical trial enrollment disparities in our sample; however, retention in the clinical trial enrollment process appears to vary by group. Additional work is needed to understand how interventions can be tailored to each population's specific needs.
MeSH term(s)	Humans ; Retrospective Studies ; Neoplasms/epidemiology ; Neoplasms/therapy ; Logistic Models ; Eligibility Determination ; Rural Population
Language	English
Publishing date	2022-09-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	3028198-2
ISSN	2688-1535 ; 2688-1527
ISSN (online)	2688-1535
ISSN	2688-1527
DOI	10.1200/OP.22.00359
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