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Glycine supplementation can partially restore oxidative stress-associated glutathione deficiency in ageing cats
- Avika Ruparell, Janet E. Alexander, Ryan Eyre, Laura Carvell-Miller, Y. Becca Leung, Samantha J. M. Evans, Lucy J. Holcombe, Martina Heer, Phillip Watson
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- Journal:
- British Journal of Nutrition , First View
- Published online by Cambridge University Press:
- 29 February 2024, pp. 1-15
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Intracellular levels of glutathione, the major mammalian antioxidant, are reported to decline with age in several species. To understand whether ageing affects circulating glutathione levels in cats, blood was sampled from two age groups, < 3 years and > 9 years. Further, to determine whether dietary supplementation with glutathione precursor glycine (GLY) affects glutathione concentrations in senior cats (> 8 years), a series of free GLY inclusion level dry diets were fed. Subsequently, a 16-week GLY feeding study was conducted in senior cats (> 7 years), measuring glutathione, and markers of oxidative stress. Whole blood and erythrocyte total, oxidised and reduced glutathione levels were significantly decreased in senior cats, compared with their younger counterparts (P ≤ 0·02). The inclusion level study identified 1·5 % free GLY for the subsequent dry diet feeding study. Significant increases in erythrocyte total and reduced glutathione were observed between senior cats fed supplemented and control diets at 4 weeks (P ≤ 0·03; maximum difference of 1·23 µM). Oxidative stress markers were also significantly different between groups at 8 (P = 0·004; difference of 0·68 nG/ml in 8-hydroxy-2'-deoxyguanosine) and 12 weeks (P ≤ 0·049; maximum difference of 0·62 nG/mG Cr in F2-isoprostane PGF2α). Senior cats have lower circulating glutathione levels compared with younger cats. Feeding senior cats a complete and balanced dry diet supplemented with 1·5 % free GLY for 12 weeks elevated initial erythrocyte glutathione and altered markers of oxidative stress. Dietary supplementation with free GLY provides a potential opportunity to restore age-associated reduction in glutathione in cats.
The Implementation of a Prehospital Whole Blood Transfusion Program and Early Results
- Charles Coyle, Tony Zitek, Paul E. Pepe, Madonna Stotsenburg, Kenneth A. Scheppke, Peter Antevy, Richard Giroux, David A. Farcy
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- Journal:
- Prehospital and Disaster Medicine / Volume 38 / Issue 4 / August 2023
- Published online by Cambridge University Press:
- 26 June 2023, pp. 513-517
- Print publication:
- August 2023
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Introduction:
In far-forward combat situations, the military challenged dogma by using whole blood transfusions (WBTs) rather than component-based therapy. More recently, some trauma centers have initiated WBT programs with reported success. There are a few Emergency Medical Service (EMS) systems that are using WBTs, but the vast majority are not. Given the increasing data supporting the use of WBTs in the prehospital setting, more EMS systems are likely to consider or begin WBT programs in the future.
Objective:A prehospital WBT program was recently implemented in Palm Beach County, Florida (USA). This report will discuss how the program was implemented, the obstacles faced, and the initial results.
Methods:This report describes the process by which a prehospital WBT program was implemented by Palm Beach County Fire Rescue and the outcomes of the initial case series of patients who received WBTs in this system. Efforts to initiate the prehospital WBT program for this system began in 2018. The program had several obstacles to overcome, with one of the major obstacles being the legal team’s perception of potential liability that might occur with a new prehospital blood transfusion program. This obstacle was overcome through education of local elected officials regarding the latest scientific evidence in favor of prehospital WBTs with potential life-saving benefits to the community. After moving past this hurdle, the program went live on July 6, 2022. The initial indications for transfusion of cold-stored, low titer, leukoreduced O+ whole blood in the prehospital setting included traumatic injuries with systolic blood pressure (SBP) < 70mmHg or SBP < 90mmHg plus heart rate (HR) > 110 beats per minute.
Findings:From the date of onset through December 31, 2022, Palm Beach County Fire Rescue transported a total of 881 trauma activation patients, with 20 (2.3%) receiving WBT. Overall, nine (45%) of the patients who had received WBTs so far remain alive. No adverse events related to transfusion were identified following WBT administration. A total of 18 units of whole blood reached expiration of the unit’s shelf life prior to transfusion.
Conclusion:Despite a number of logistical and legal obstacles, Palm Beach County Fire Rescue successfully implemented a prehospital WBT program. Other EMS systems that are considering a prehospital WBT program should review the included protocol and the barriers to implementation that were faced.
Epidemiological and Accounting Analysis of Ground Ambulance Whole Blood Transfusion
- Julian G. Mapp, Eric A. Bank, Lesley A. Osborn, Michael L. Stringfellow, David W. Reininger, Christopher J. Winckler, Prehospital Research and Innovation in Military and Expeditionary Environments (PRIME2) Group
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- Journal:
- Prehospital and Disaster Medicine / Volume 35 / Issue 1 / February 2020
- Published online by Cambridge University Press:
- 18 December 2019, pp. 98-103
- Print publication:
- February 2020
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Introduction:
In October 2017, the American Association of Blood Bankers (AABB; Bethesda, Maryland USA) approved a petition to allow low-titer group O whole blood as a standard product without the need for a waiver. Around that time, a few Texas, USA-based Emergency Medical Services (EMS) systems incorporated whole blood into their ground ambulances. The purpose of this project was to describe the epidemiology of ground ambulance patients that received a prehospital whole blood transfusion. The secondary aim of this project was to report an accounting analysis of these ground ambulance prehospital whole blood programs.
Methods:The dataset came from the Harris County Emergency Service District 48 Fire Department (HCESD 48; Harris County, Texas USA) and San Antonio Fire Department (SAFD; San Antonio, Texas USA) whole blood Quality Assurance/Quality Improvement (QA/QI) databases from September 2017 through December 2018. The primary outcome of this study was the prehospital transfusion indication. The secondary outcome was the projected cost per life saved during the first 10 years of the prehospital whole blood initiative.
Results:Of 58 consecutive prehospital whole blood administrations, the team included all 58 cases. Hemorrhagic shock from a non-traumatic etiology accounted for 46.5% (95% CI, 34.3%-59.2%) of prehospital whole blood recipients. In the non-traumatic hemorrhagic shock cohort, gastrointestinal hemorrhage was the underlying etiology of hemorrhagic shock in 66.7% (95% CI, 47.8%-81.4%) of prehospital whole blood transfusion recipients. The projected average cost to save a life in Year 10 was US$5,136.51 for the combined cohort, US$4,512.69 for HCESD 48, and US$5,243.72 for SAFD EMS.
Conclusion:This retrospective analysis of ground ambulance patients that receive prehospital whole blood transfusion found that non-traumatic etiology accounted for 46.5% (95% CI, 34.3%-59.2%) of prehospital whole blood recipients. Additionally, the accounting analysis suggests that by Year 10 of a ground ambulance whole blood transfusion program, the average cost to save a life will be approximately US$5,136.51.
Whole blood transcriptome analysis in bipolar disorder reveals strong lithium effect
- Catharine E. Krebs, Anil P.S. Ori, Annabel Vreeker, Timothy Wu, Rita M. Cantor, Marco P. M. Boks, Rene S. Kahn, Loes M. Olde Loohuis, Roel A. Ophoff
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- Journal:
- Psychological Medicine / Volume 50 / Issue 15 / November 2020
- Published online by Cambridge University Press:
- 07 October 2019, pp. 2575-2586
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Background
Bipolar disorder (BD) is a highly heritable mood disorder with complex genetic architecture and poorly understood etiology. Previous transcriptomic BD studies have had inconsistent findings due to issues such as small sample sizes and difficulty in adequately accounting for confounders like medication use.
MethodsWe performed a differential expression analysis in a well-characterized BD case-control sample (Nsubjects = 480) by RNA sequencing of whole blood. We further performed co-expression network analysis, functional enrichment, and cell type decomposition, and integrated differentially expressed genes with genetic risk.
ResultsWhile we observed widespread differential gene expression patterns between affected and unaffected individuals, these effects were largely linked to lithium treatment at the time of blood draw (FDR < 0.05, Ngenes = 976) rather than BD diagnosis itself (FDR < 0.05, Ngenes = 6). These lithium-associated genes were enriched for cell signaling and immune response functional annotations, among others, and were associated with neutrophil cell-type proportions, which were elevated in lithium users. Neither genes with altered expression in cases nor in lithium users were enriched for BD, schizophrenia, and depression genetic risk based on information from genome-wide association studies, nor was gene expression associated with polygenic risk scores for BD.
ConclusionsThese findings suggest that BD is associated with minimal changes in whole blood gene expression independent of medication use but emphasize the importance of accounting for medication use and cell type heterogeneity in psychiatric transcriptomic studies. The results of this study add to mounting evidence of lithium's cell signaling and immune-related mechanisms.