Enhancing the management of anorexia of ageing to counteract malnutrition : are physical activity guidelines optimal?

Funding Information: NJC and SERL receive funding from by The National Institute for Health Research (NIHR). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.Peer reviewedPublisher PD

Measurement of Heart Rate Using the Withings ScanWatch Device during Free-living Activities : Validation Study

Funding Information: This research is part of the Eastern Corridor Medical Engineering (ECME) project, which has been funded by European Union’s INTERREG VA programme, managed by the Special EU Programmes Body (SEUPB).Peer reviewedPublisher PD

Performance benchmarking microplate-immunoassays for quantifying target-specific cysteine oxidation reveals their potential for understanding redox-regulation and oxidative stress

The antibody-linked oxi-state assay (ALISA) for quantifying target-specific cysteine oxidation can benefit specialist and non-specialist users. Specialists can benefit from time-efficient analysis and high-throughput target and/or sample n-plex capacities. The simple and accessible “off-the-shelf” nature of ALISA brings the benefits of oxidative damage assays to non-specialists studying redox-regulation. Until performance benchmarking establishes confidence in the “unseen” microplate results, ALISA is unlikely to be widely adopted. Here, we implemented pre-set pass/fail criteria to benchmark ALISA by robustly evaluating immunoassay performance in diverse biological contexts. ELISA-mode ALISA assays were accurate, reliable, and sensitive. For example, the average inter-assay CV for detecting 20%- and 40%-oxidised PRDX2 or GAPDH standards was 4.6% (range: 3.6–7.4%). ALISA displayed target-specificity. Immunodepleting the target decreased the signal by ∼75%. Single-antibody formatted ALISA failed to quantify the matrix-facing alpha subunit of the mitochondrial ATP synthase. However, RedoxiFluor quantified the alpha subunit displaying exceptional performance in the single-antibody format. ALISA discovered that (1) monocyte-to-macrophage differentiation amplified PRDX2-specific cysteine oxidation in THP-1 cells and (2) exercise increased GAPDH-specific cysteine oxidation in human erythrocytes. The “unseen” microplate data were “seen-to-be-believed” via orthogonal visually displayed immunoassays like the dimer method. Finally, we established target (n = 3) and sample (n = 100) n-plex capacities in ∼4 h with 50–70 min hands-on time. Our work showcases the potential of ALISA to advance our understanding of redox-regulation and oxidative stress

Performance benchmarking microplate-immunoassays for quantifying target-specific cysteine oxidation reveals their potential for understanding redox-regulation and oxidative stress

The antibody-linked oxi-state assay (ALISA) for quantifying target-specific cysteine oxidation can benefit specialist and non-specialist users. Specialists can benefit from time-efficient analysis and high-throughput target and/or sample n-plex capacities. The simple and accessible “off-the-shelf” nature of ALISA brings the benefits of oxidative damage assays to non-specialists studying redox-regulation. Until performance benchmarking establishes confidence in the “unseen” microplate results, ALISA is unlikely to be widely adopted. Here, we implemented pre-set pass/fail criteria to benchmark ALISA by robustly evaluating immunoassay performance in diverse biological contexts. ELISA-mode ALISA assays were accurate, reliable, and sensitive. For example, the average inter-assay CV for detecting 20%- and 40%-oxidised PRDX2 or GAPDH standards was 4.6% (range: 3.6–7.4%). ALISA displayed target-specificity. Immunodepleting the target decreased the signal by ∼75%. Single-antibody formatted ALISA failed to quantify the matrix-facing alpha subunit of the mitochondrial ATP synthase. However, RedoxiFluor quantified the alpha subunit displaying exceptional performance in the single-antibody format. ALISA discovered that (1) monocyte-to-macrophage differentiation amplified PRDX2-specific cysteine oxidation in THP-1 cells and (2) exercise increased GAPDH-specific cysteine oxidation in human erythrocytes. The “unseen” microplate data were “seen-to-be-believed” via orthogonal visually displayed immunoassays like the dimer method. Finally, we established target (n = 3) and sample (n = 100) n-plex capacities in ∼4 h with 50–70 min hands-on time. Our work showcases the potential of ALISA to advance our understanding of redox-regulation and oxidative stress

Appetite, food intake, and gut hormone responses to glycomacropeptide protein ingestion in older adults: : A feasibility, acceptability, and pilot study

We would like express huge gratitude to our participants for taking part, and for making data collection such an enjoyable experience for the research team. We would like to thank our students Vicky Catterall, Beth Minion, Joe Ashworth, Monty Hardcastle, and Anna Brooks for supporting data collection. We also thank Agropur Ingredients (Eden Prairie, MN, USA) for providing GMP.Peer reviewe

Exercise decreases PP2A-specific reversible thiol oxidation in human erythrocytes:Implications for redox biomarkers

New readily accessible systemic redox biomarkers are needed to understand the biological roles reactive oxygen species (ROS) play in humans because overtly flawed, technically fraught, and unspecific assays severely hamper translational progress. The antibody-linked oxi-state assay (ALISA) makes it possible to develop valid ROS-sensitive target-specific protein thiol redox state biomarkers in a readily accessible microplate format. Here, we used a maximal exercise bout to disrupt redox homeostasis in a physiologically meaningful way to determine whether the catalytic core of the serine/threonine protein phosphatase PP2A is a candidate systemic redox biomarker in human erythrocytes. We reasoned that: constitutive oxidative stress (e.g., haemoglobin autoxidation) would sensitise erythrocytes to disrupted ion homeostasis as manifested by increased oxidation of the ion regulatory phosphatase PP2A. Unexpectedly, an acute bout of maximal exercise lasting ˜16 min decreased PP2A-specific reversible thiol oxidation (redox ratio, rest: 0.46; exercise: 0.33) without changing PP2A content (rest: 193 pg/ml; exercise: 191 pg/ml). The need for only 3-4 μl of sample to perform ALISA means PP2A-specific reversible thiol oxidation is a capillary-fingertip blood-compatible candidate redox biomarker. Consistent with biologically meaningful redox regulation, thiol reductant-inducible PP2A activity was significantly greater (+10%) at rest compared to exercise. We establish a route to developing new readily measurable protein thiol redox biomarkers for understanding the biological roles ROS play in humans

Explant analysis of AneuRx stent grafts: relationship between structural findings and clinical outcome

AbstractObjectiveWe reviewed the structural findings of explanted AneuRx stent grafts used to treat abdominal aortic aneurysms, and relate the findings to clinical outcome measures.MethodsWe reviewed data for all bifurcated AneuRx stent grafts explanted at surgery or autopsy and returned to the manufacturer from the US clinical trial and worldwide experience of more than 33,000 implants from 1996 to 2003. Devices implanted for more than 1 month with structural analysis are included in this article. Explant results were analyzed in relation to cause of explantation and pre-explant evidence of endoleak, enlargement, or device migration.ResultsOne hundred twenty explanted stent grafts, including 37 from the US clinical trial, were analyzed. Mean implant duration was 22 ± 13 months (range, 1-61 months). Structural abnormalities included stent fatigue fractures, fabric abrasion holes, and suture breaks. The mean number of nitinol stent strut fractures per explanted device was 3 ± 4, which represents less than 0.2% of the total number of stent struts in each device. The mean number of fabric holes per explanted device was 2 ± 3, with a median hole size of 0.5 mm2. Suture breaks were seen in most explanted devices, but composed less than 1.5% of the total number of sutures per device. “For cause” explants (n = 104) had a 10-month longer implant duration (P = .007) compared with “incidental” explants (n = 16). “For cause” explants had more fractures (3 ± 5; P = .005) and fabric holes (2 ± 3; P = .008) per device compared with “incidental” explants, but these differences were not significant (P = .3) when adjusted for duration of device implantation. Among clinical trial explants the number of fabric holes in grafts in patients with endoleak (2 ± 3 per device) was no different from those without endoleak (3 ± 4 per device; P = NS). The number of fatigue fractures or fabric holes was no different in grafts in clinical trial patients with pre-explant aneurysm enlargement compared with those without enlargement. Pre-explant stent-graft migration was associated with a greater number of stent strut fractures (5 ± 7 per device; P = .04) and fabric holes (3 ± 3 per bifurcation; P = .03) compared with explants without migration. Serial imaging studies revealed inadequate proximal, distal, or junctional device fixation as the probable cause of rupture or need for conversion to open surgery in 86% of “for cause” explants. Structural device abnormalities were usually remote from fixation sites, and no causal relationship between device findings and clinical outcome could be established.ConclusionsNitinol stent fatigue fractures, fabric holes, and suture breaks found in explanted AneuRx stent grafts do not appear to be related to clinical outcome measures. Longer term studies are needed to confirm these observations

Free-living Physical Activity and Executive Function : A Multi-Study Analysis of Age Groups and Times of Day

Acknowledgments The authors wish to thank all participants (and parents) for taking part in the studies. Additionally, we want to thank Merle Reuter and Ulrike Schwarz for their help in data collection and preparation of the AttentionGO project. We also thank the student assistants for their support in data collection in all studies. Further, we thank Patrick E. Shrout for his expert advice and valuable feedback on the first draft of the manuscript.Peer reviewedPublisher PD