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1.
Soc Work Public Health ; 39(4): 368-378, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38459705

ABSTRACT

The impact of HIV-related stigma on social workers, clinicians, counselors, and advocates working in organizations serving people living with HIV (PLWH), is rarely considered. Professionals experience "courtesy stigma" when working with or on behalf of PLWH, regardless of their personal HIV status. PubMed, Medline, and PsycInfo databases, along with a review of relevant reference lists and referrals, identified 13 studies addressing this phenomenon. Although limited, this brief review suggests that members of the HIV workforce do indeed face challenges that compromise their personal and professional well-being as a result of courtesy stigma. Addressing stigma among professionals is necessary to support the health of those working in the field, and to avoid undermining the efforts of this important workforce. More research is needed to understand the perceptions and experiences of courtesy stigma and how this stigma may adversely impact the psychological well-being, social functioning, and professional practice of HIV professionals.


Subject(s)
HIV Infections , Social Stigma , Humans , Social Workers , HIV Infections/psychology
2.
Aust Crit Care ; 37(2): 288-294, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37537123

ABSTRACT

BACKGROUND: Intensive care unit (ICU) nurses are exposed to critical incidents daily at their workplace, which may have long-term physical and psychological impacts. Despite the growing evidence supporting clinical debriefing in health care to prevent these impacts, a scarcity of literature exists to support its use in the adult intensive care setting. OBJECTIVES: The objective of this study was to explore nurses' perceptions of clinical debriefing after critical incidents in an adult ICU. METHODS: A qualitative descriptive design was utilised. Thematic analysis of data from individual semistructured interviews with six ICU nurses was undertaken. FINDINGS: In this study, two themes were identified. Firstly, participants valued hot debriefing after critical incidents for the key reasons of having an opportunity to reflect on and learn from a critical incident and reduce normalisation of stressful situations. Secondly, when logistical factors such as communication, timing, and location were not considered, the attendance at debriefings was negatively influenced. Participants identified that ICU nurses commonly prioritised patient tasks over attending a debrief; therefore, teamwork and flexibility with logistics was crucial. CONCLUSIONS: Hot debriefing, of a short duration and close to the time of the event, was valued and played an important role in staff wellbeing and self-care, contributing to preventing self-blame and normalisation of stressful situations. A clearer definition of the term along with greater recognition of types of events that could be considered critical incidents is required for staff support after critical incidents in the complex intensive care setting.


Subject(s)
Critical Care Nursing , Nurses , Nursing Staff, Hospital , Adult , Humans , Nursing Staff, Hospital/psychology , Intensive Care Units , Qualitative Research
3.
J Opt Soc Am A Opt Image Sci Vis ; 39(11): 2026-2034, 2022 Nov 01.
Article in English | MEDLINE | ID: mdl-36520699

ABSTRACT

The effects of time-varying measurement noise on transmission matrix acquisition processes are considered for the first time, to our knowledge. Dominant noise sources are discussed, and the noise properties of a typical interferometer system used for characterizing a multimode fiber transmission matrix are quantified. It is demonstrated that an appropriate choice of measurement basis allows a more accurate transmission matrix to be more quickly obtained in the presence of measurement noise. Finally, it is shown that characterizing the noise figure of the experimental system allows the inverse transmission matrix to be constructed with an ideal amount of regularization, which can in turn be used for optimal image acquisition.

4.
Biosensors (Basel) ; 12(11)2022 Nov 10.
Article in English | MEDLINE | ID: mdl-36354508

ABSTRACT

(1) Background: During a cochlear implant insertion, the mechanical trauma can cause residual hearing loss in up to half of implantations. The forces on the cochlea during the insertion can lead to this mechanical trauma but can be highly variable between subjects which is thought to be due to differing anatomy, namely of the scala tympani. This study presents a systematic investigation of the influence of different geometrical parameters of the scala tympani on the cochlear implant insertion force. The influence of these parameters on the insertion forces were determined by testing the forces within 3D-printed, optically transparent models of the scala tympani with geometric alterations. (2) Methods: Three-dimensional segmentations of the cochlea were characterised using a custom MATLAB script which parametrised the scala tympani model, procedurally altered the key shape parameters (e.g., the volume, vertical trajectory, curvature, and cross-sectional area), and generated 3D printable models that were printed using a digital light processing 3D printer. The printed models were then attached to a custom insertion setup that measured the insertion forces on the cochlear implant and the scala tympani model during a controlled robotic insertion. (3) Results: It was determined that the insertion force is largely unaffected by the overall size, curvature, vertical trajectory, and cross-sectional area once the forces were normalised to an angular insertion depth. A Capstan-based model of the CI insertion forces was developed and matched well to the data acquired. (4) Conclusion: By using accurate 3D-printed models of the scala tympani with geometrical alterations, it was possible to demonstrate the insensitivity of the insertion forces to the size and shape of the scala tympani, after controlling for the angular insertion depth. This supports the Capstan model of the cochlear implant insertion force which predicts an exponential growth of the frictional force with an angular insertion depth. This concludes that the angular insertion depth, rather than the length of the CI inserted, should be the major consideration when evaluating the insertion force and associated mechanical trauma caused by cochlear implant insertion.


Subject(s)
Cochlear Implantation , Cochlear Implants , Humans , Scala Tympani/surgery , Cochlear Implantation/methods , Cochlea/anatomy & histology , Cochlea/surgery , Mechanical Phenomena
5.
Front Vet Sci ; 9: 898325, 2022.
Article in English | MEDLINE | ID: mdl-36268043

ABSTRACT

Feedlot performance and carcass characteristics of tropical beef steers backgrounded on buffel grass (Cenchrus ciliaris) only or buffel grass oversown with desmanthus (Desmanthus spp. ; 11.5% initial sward botanical composition) were evaluated. It was hypothesized that tropical beef cattle steers backgrounded on buffel grass only or buffel grass oversown with desmanthus with similar backgrounding growth performance will not differ in feedlot growth performance and carcass quality. Three hundred and twelve Bos indicus × Bos taurus tropical composite steers, 20-23 months old and weighing 413 ± 24 kg, previously backgrounded on buffel grass only or buffel-desmanthus mixed pastures for 147 days were finished on a concentrate diet in the feedlot for 110 days before slaughter. Buffel-desmanthus backgrounded steers had a slightly higher average daily gain (ADG; 1.8 kg/day) than the buffel grass backgrounded steers that had 1.7 kg/day ADG (p < 0.01). However, the final live weight and dry matter intake were not different (p ≥ 0.59). All the carcass traits measured were not different (p ≥ 0.18). Only 4% buffel grass and 8% buffel-desmanthus backgrounded steers fell short of the Meat Standards Australia (MSA) index, a level that is within the 4-9% reported for cattle produced in Queensland and slaughtered between July 2019 and June 2020. These findings indicate that desmanthus can be used to background beef cattle in northern Australia vertosol soil regions, where there is a paucity of adapted pasture legumes, with no negative impact on feedlot performance and carcass quality. The hypothesis that tropical beef cattle steers backgrounded on buffel grass only pastures or buffel grass oversown with desmanthus with similar backgrounding growth performance will have similar feedlot growth performance and carcass quality was accepted.

6.
Appl Opt ; 61(15): 4315-4321, 2022 May 20.
Article in English | MEDLINE | ID: mdl-36256291

ABSTRACT

A complex-valued transmission matrix describing a scattering medium can be constructed from a sequence of many interferometric measurements. A major challenge in such experiments is to correct for rapid phase drift of the optical system during the data acquisition process, especially when the phase drifts significantly between consecutive measurements. Therefore, a new method is presented where the exact phase drift between two measurements is characterized and corrected using a single additional measurement. This approach removes the need to continuously track the phase and significantly relaxes the phase stability requirements of the interferometer, allowing transmission matrices to be constructed in the presence of fast and erratic phase drift.

7.
ACS Nano ; 16(11): 18009-18017, 2022 Nov 22.
Article in English | MEDLINE | ID: mdl-36162100

ABSTRACT

We present a high-throughput method for identifying and characterizing individual nanowires and for automatically designing electrode patterns with high alignment accuracy. Central to our method is an optimized machine-readable, lithographically processable, and multi-scale fiducial marker system─dubbed LithoTag─which provides nanostructure position determination at the nanometer scale. A grid of uniquely defined LithoTag markers patterned across a substrate enables image alignment and mapping in 100% of a set of >9000 scanning electron microscopy (SEM) images (>7 gigapixels). Combining this automated SEM imaging with a computer vision algorithm yields location and property data for individual nanowires. Starting with a random arrangement of individual InAs nanowires with diameters of 30 ± 5 nm on a single chip, we automatically design and fabricate >200 single-nanowire devices. For >75% of devices, the positioning accuracy of the fabricated electrodes is within 2 pixels of the original microscopy image resolution. The presented LithoTag method enables automation of nanodevice processing and is agnostic to microscopy modality and nanostructure type. Such high-throughput experimental methodology coupled with data-extensive science can help overcome the characterization bottleneck and improve the yield of nanodevice fabrication, driving the development and applications of nanostructured materials.

8.
Adv Nutr ; 13(6): 2329-2340, 2022 12 22.
Article in English | MEDLINE | ID: mdl-36056917

ABSTRACT

Aspartame (Asp) and acesulfame-K (Ace-K) are nonnutritive sweeteners (NNSs) commonly used in combination to replace added sugars in reduced- or low-calorie foods and beverages. Despite Asp/Ace-K blends having negligible calories, their effects on appetite have not been reviewed systematically. We therefore undertook a systematic review and meta-analysis of the metabolic effects of Asp/Ace-K blends on energy intake (EI), subjective appetite scores, blood glucose, and the incretin hormones glucose-dependent insulinotropic peptide and glucagon-like peptide. MEDLINE, Web of Science, and Cochrane CENTRAL databases (Embase, PubMed, and CINAHL) were searched (May 2021) for randomized controlled trials (RCTs). Human RCTs using Asp/Ace-K blends compared with sugar and water controls were included, whereas isolated cell and animal studies were excluded. An overall 4829 publications were identified and 8 studies, including 274 participants, were retrieved for review. The Asp/Ace-K group's EI was significantly reduced compared with sugar [mean difference (MD): -196.56 kcal/meal; 95% CI: -332.01, -61.11 kcal/meal; P = 0.004] and water (MD: -213.42 kcal/meal; 95% CI: -345.4, -81.44 kcal/meal; P = 0.002). Meta-analysis of subjective appetite scores and incretins could not be undertaken due to inconsistencies in data reporting and insufficient data, respectively, but of the 4 studies identified, no differences were observed between Asp/Ace-K blends and controls. The Asp/Ace-K group's blood glucose was nonsignificantly reduced compared with sugar (MD: -1.48 mmol/L; 95% CI: -3.26, 0.3 mmol/L; P = 0.1) and water (MD: -0.08 mmol/L; 95% CI: -0.62, 0.47 mmol/L; P = 0.78). Lower EI in participants who were predominantly healthy and assigned to Asp/Ace-K blends could not be reliably attributed to changes in subjective appetite scores. Blood glucose and incretins were also generally not affected by Asp/Ace-K blends when compared with controls. Additional short- and long-term RCTs using NNSs and sugars at dietarily relevant levels are needed. This trial was registered at the International Prospective Register of Systematic Reviews (PROSPERO: CRD42017061015).


Subject(s)
Appetite , Aspartame , Animals , Humans , Aspartame/pharmacology , Blood Glucose/metabolism , Randomized Controlled Trials as Topic , Sweetening Agents/pharmacology
9.
J Opt Soc Am A Opt Image Sci Vis ; 39(3): 392-400, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35297422

ABSTRACT

Iterative Fourier transform algorithms are widely used for hologram generation for phase-modulating spatial light modulators. In this paper, we introduce a new technique called the "intermediate domain," which decomposes the Fourier transforms used into multiple subtransforms, the combination of which can offer major performance benefits over traditional approaches. To demonstrate this, we introduce ID-GS, an implementation of the intermediate domain technique for possibly the best known hologram generation algorithm, Gerchberg-Saxton. We discuss the performance of this across a wide range of configurations with a focus on computational performance.

10.
Nanotheranostics ; 6(3): 306-321, 2022.
Article in English | MEDLINE | ID: mdl-35223382

ABSTRACT

Lanthanide-based beta-tricalcium phosphate (ß-TCP) upconversion nanoparticles are exploited as a non-viral vector for imaging guided-gene therapy by virtue of their unique optical properties and multi-modality imaging ability, high transfection efficiency, high biocompatibility, dispersibility, simplicity of synthesis and surface modification. Ytterbium and thulium-doped ß-TCP nanoparticles (ßTCPYbTm) are synthesized via co-precipitation method, coated with polyethylenimine (PEI) and functionalized with a nuclear-targeting peptide (TAT). Further, in vitro studies revealed that the nanotheranostic carriers are able to transfect cells with the plasmid eGFP at a high efficiency, with approximately 60% of total cells producing the fluorescent green protein. The optimized protocol developed comprises the most efficient ßTCPYbTm/PEI configuration, the amount and the order of assembly of ßTCPYbTm:PEI, TAT, plasmid DNA and the culturing conditions. With having excellent dispersibility and high chemical affinity toward nucleic acid, calcium ions released from ßTCPYbTm:PEI nanoparticles can participate in delivering nucleic acids and other therapeutic molecules, overcoming the nuclear barriers and improving the transfection efficacy. Equally important, the feasibility of the upconversion multifunctional nanovector to serve as an effective contrast agent for imaging modality, capable of converting low-energy light to higher-energy photons via a multi-photons mechanism, endowing greater unique luminescent properties, was successfully demonstrated.


Subject(s)
Lanthanoid Series Elements , Nanoparticles , Calcium Phosphates , Genetic Therapy/methods , HeLa Cells , Humans , Nanoparticles/chemistry , Precision Medicine
11.
Toxicon X ; 12: 100081, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34522881

ABSTRACT

Snakebite incidence at least partly depends on the biology of the snakes involved. However, studies of snake biology have been largely neglected in favour of anthropic factors, with the exception of taxonomy, which has been recognised for some decades to affect the design of antivenoms. Despite this, within-species venom variation and the unpredictability of the correlation with antivenom cross-reactivity has continued to be problematic. Meanwhile, other aspects of snake biology, including behaviour, spatial ecology and activity patterns, distribution, and population demography, which can contribute to snakebite mitigation and prevention, remain underfunded and understudied. Here, we review the literature relevant to these aspects of snakebite and illustrate how demographic, spatial, and behavioural studies can improve our understanding of why snakebites occur and provide evidence for prevention strategies. We identify the large gaps that remain to be filled and urge that, in the future, data and relevant metadata be shared openly via public data repositories so that studies can be properly replicated and data used in future meta-analyses.

12.
Appl Opt ; 60(4): A313-A322, 2021 Feb 01.
Article in English | MEDLINE | ID: mdl-33690384

ABSTRACT

Spatial light modulators (SLMs) are key research tools in several contemporary applied optics research domains. In this paper, we present the argument that an open platform for interacting with SLMs would dramatically increase their accessibility to researchers. We introduce HoloBlade, an open-hardware implementation of an SLM driver-stack, and provide a detailed exposition of HoloBlade's architecture, key components, and detailed design. An optical verification rig is constructed to demonstrate that HoloBlade can provide Fourier imaging capability in a 4f system. Finally, we discuss HoloBlade's future development roadmap and the opportunities that it presents as a research tool for applied optics.

13.
Adv Simul (Lond) ; 6(1): 6, 2021 Mar 04.
Article in English | MEDLINE | ID: mdl-33663603

ABSTRACT

This article describes an operational framework for implementing translational simulation in everyday practice. The framework, based on an input-process-output model, is developed from a critical review of the existing translational simulation literature and the collective experience of the authors' affiliated translational simulation services. The article describes how translational simulation may be used to explore work environments and/or people in them, improve quality through targeted interventions focused on clinical performance/patient outcomes, and be used to design and test planned infrastructure or interventions. Representative case vignettes are used to show how the framework can be applied to real world healthcare problems, including clinical space testing, process development, and culture. Finally, future directions for translational simulation are discussed. As such, the article provides a road map for practitioners who seek to address health service outcomes using translational simulation.

14.
Europace ; 22(5): 1-13, May., 2020. tabela, ilustração
Article in English | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1100489

ABSTRACT

The field of observational studies or "real world studies" is in rapid development with many new techniques introduced and increased understanding of traditional methods. For this reason, the current paper provides an overview of current methods with focus on new techniques. Some highlights can be emphasized: We provide an overview of sources of data for observational studies. There is an overview of sources of bias and confounding. Next There is an overview of causal inference techniques that are increasingly used. The most commonly used techniques for statistical modelling are reviewed with focus on the important distinction of risk versus prediction. The final section provides examples of common problems with reporting observational data.


Subject(s)
Arrhythmias, Cardiac/epidemiology , Atrial Fibrillation/epidemiology , Observational Study
15.
BMJ Open ; 10(1): e034399, 2020 01 21.
Article in English | MEDLINE | ID: mdl-31969369

ABSTRACT

INTRODUCTION: Arterial stiffness and left ventricular (LV) hypertrophy are the key markers of hypertensive target organ damage (TOD) associated with increased cardiovascular morbidity and mortality. We have previously shown that dietary inorganic nitrate supplementation lowers blood pressure (BP) in hypertension, however, whether this approach might also improve markers of hypertensive TOD is unknown. In this study, we will investigate whether daily dietary inorganic nitrate administration reduces LV mass and improves measures of arterial stiffness. METHODS AND DESIGN: NITRATE-TOD is a double-blind, randomised, single-centre, placebo-controlled phase II trial aiming to enrol 160 patients with suboptimal BP control on one or more antihypertensives. Patients will be randomised to receive 4 months once daily dose of either nitrate-rich beetroot juice or nitrate-deplete beetroot juice (placebo). The primary outcomes are reduction in LV mass and reduction in pulse wave velocity (PWV) and central BP.The study has a power of 95% for detecting a 9 g LV mass change by cardiovascular MRI (~6% change for a mildly hypertrophied heart of 150 g). For PWV, we have a power of >95% for detecting a 0.6 m/s absolute change. For central systolic BP, we have a>90% power to detect a 5.8 mm Hg difference in central systolic BP.Secondary end points include change in ultrasound flow-mediated dilation, change in plasma nitrate and nitrite concentration and change in BP. ETHICS AND DISSEMINATION: The study was approved by the London-City and East Research Ethics Committee (10/H0703/98). Trial results will be published according to the Consolidated Standards of Reporting Trials statement and will be presented at conferences and reported in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03088514.


Subject(s)
Blood Pressure/drug effects , Hypertension/drug therapy , Nitrates/therapeutic use , Vascular Stiffness/drug effects , Adolescent , Adult , Aged , Aged, 80 and over , Dietary Supplements , Double-Blind Method , Female , Humans , Hypertension/physiopathology , Male , Middle Aged , Pulse Wave Analysis , United Kingdom , Young Adult
16.
OSA Contin ; 3(10): 2660-2679, 2020 Oct 15.
Article in English | MEDLINE | ID: mdl-34222834

ABSTRACT

Non-interferometric approaches to quantitative phase imaging could enable its application in low-cost, miniaturised settings such as capsule endoscopy. We present two possible architectures and both analyse and mitigate the effect of sensor misalignment on phase imaging performance. This is a crucial step towards determining the feasibility of implementing phase imaging in a capsule device. First, we investigate a design based on a folded 4f correlator, both in simulation and experimentally. We demonstrate a novel technique for identifying and compensating for axial misalignment and explore the limits of the approach. Next, we explore the implications of axial and transverse misalignment, and of manufacturing variations on the performance of a phase plate-based architecture, identifying a clear trade-off between phase plate resolution and algorithm convergence time. We conclude that while the phase plate architecture is more robust to misalignment, both architectures merit further development with the goal of realising a low-cost, compact system for applying phase imaging in capsule endoscopy.

17.
J Opt Soc Am A Opt Image Sci Vis ; 36(12): 2068-2075, 2019 Dec 01.
Article in English | MEDLINE | ID: mdl-31873381

ABSTRACT

We present an algorithm for generating high-quality holograms for computer generated holography: holographic predictive search. This approach is presented as an alternative to traditional holographic search algorithms such as direct search (DS) and simulated annealing (SA). We first introduce the current search-based methods and then introduce an analytical model of the underlying Fourier elements. This is used to make prescient judgments regarding the next iteration of the algorithm. This approach is developed for the case of phase-modulating devices with phase-sensitive reconstructions. When compared to conventional iterative approaches such as DS and SA on a multiphase device, holographic predictive search offered a fivefold improvement in quality as well as up to a 10-fold improvement in convergence time. This comes at the cost of an increased iteration overhead.

18.
J Opt Soc Am A Opt Image Sci Vis ; 36(9): 1456-1462, 2019 Sep 01.
Article in English | MEDLINE | ID: mdl-31503837

ABSTRACT

Traditional search algorithms for computer hologram generation such as Direct Search and Simulated Annealing offer some of the best hologram qualities at convergence when compared to rival approaches. Their slow generation times and high processing power requirements mean, however, that they see little use in performance critical applications. This paper presents the novel sorted pixel selection (SPS) modification for holographic search algorithms that offers mean square error reductions in the range of 14.7-19.2% for the test images used. SPS operates by substituting a weighted search selection procedure for traditional random pixel selection processes. While small, the improvements seen are observed consistently across a wide range of test cases and require limited overhead for implementation.

19.
Int J Obes (Lond) ; 43(12): 2370-2380, 2019 12.
Article in English | MEDLINE | ID: mdl-31152154

ABSTRACT

BACKGROUND: Elevated circulating levels of the divergent transforming growth factor-beta (TGFb) family cytokine, growth differentiation factor 15 (GDF15), acting through its CNS receptor, glial-derived neurotrophic factor receptor alpha-like (GFRAL), can cause anorexia and weight loss leading to anorexia/cachexia syndrome of cancer and other diseases. Preclinical studies suggest that administration of drugs based on recombinant GDF15 might be used to treat severe obesity. However, the role of the GDF15-GFRAL pathway in the physiological regulation of body weight and metabolism is unclear. The critical site of action of GFRAL in the CNS has also not been proven beyond doubt. To investigate these two aspects, we have inhibited the actions of GDF15 in mice started on high-fat diet (HFD). METHODS: The actions of GDF15 were inhibited using two methods: (1) Groups of 8 mice under HFD had their endogenous GDF15 neutralised by monoclonal antibody treatment, (2) Groups of 15 mice received AAV-shRNA to knockdown GFRAL at its hypothesised major sites of action, the hindbrain area postrema (AP) and the nucleus of the solitary tract (NTS). Metabolic measurements were determined during both experiments. CONCLUSIONS: Treating mice with monoclonal antibody to GDF15 shortly after commencing HFD results in more rapid gain of body weight, adiposity and hepatic lipid deposition than the control groups. This is accompanied by reduced glucose and insulin tolerance and greater expression of pro-inflammatory cytokines in adipose tissue. Localised AP and NTS shRNA-GFRAL knockdown in mice commencing HFD similarly caused an increase in body weight and adiposity. This effect was in proportion to the effectiveness of GFRAL knockdown, indicated by quantitative analysis of hindbrain GFRAL staining. We conclude that the GDF15-GFRAL axis plays an important role in resistance to obesity in HFD-fed mice and that the major site of action of GDF15 in the CNS is GFRAL-expressing neurons in the AP and NTS.


Subject(s)
Adiposity , Glial Cell Line-Derived Neurotrophic Factor Receptors , Growth Differentiation Factor 15 , Rhombencephalon , Adiposity/genetics , Adiposity/physiology , Animals , Area Postrema/cytology , Area Postrema/metabolism , Area Postrema/physiology , Body Weight/physiology , Diet, High-Fat , Glial Cell Line-Derived Neurotrophic Factor Receptors/genetics , Glial Cell Line-Derived Neurotrophic Factor Receptors/metabolism , Growth Differentiation Factor 15/genetics , Growth Differentiation Factor 15/metabolism , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Neurons/cytology , Neurons/metabolism , Neurons/physiology , Obesity/metabolism , Rhombencephalon/cytology , Rhombencephalon/metabolism , Rhombencephalon/physiology , Solitary Nucleus/cytology , Solitary Nucleus/metabolism , Solitary Nucleus/physiology
20.
Metabolomics ; 14(1): 8, 2018 01.
Article in English | MEDLINE | ID: mdl-30104954

ABSTRACT

Introduction: The effects of exercise on the heart and its resistance to disease are well-documented. Recent studies have identified that exercise-induced resistance to arrhythmia is due to the preservation of mitochondrial membrane potential. Objectives: To identify novel metabolic changes that occur parallel to these mitochondrial alterations, we performed non-targeted metabolomics analysis on hearts from sedentary and exercise-trained rats challenged with isolated heart ischemia-reperfusion injury (I/R). Methods: Eight-week old Sprague-Dawley rats were treadmill trained 5 days/week for 6 weeks (exercise duration and intensity progressively increased to 1 h at 30 m/min up a 10.5% incline, 75-80% VO2max). The recovery of pre-ischemic function for sedentary rat hearts was 28.8 ± 5.4% (N = 12) compared to exercise trained hearts, which recovered 51.9% ± 5.7 (N = 14) (p < 0.001). Results: Non-targeted GC-MS metabolomics analysis of (1) sedentary rat hearts; (2) exercise-trained rat hearts; (3) sedentary rat hearts challenged with global ischemia-reperfusion (I/R) injury; and (4) exercise-trained rat hearts challenged with global I/R (10/group) revealed 15 statistically significant metabolites between groups by ANOVA using Metaboanalyst (p < 0.001). Enrichment analysis of these metabolites for pathway-associated metabolic sets indicated a > 10-fold enrichment for ammonia recycling and protein biosynthesis. Subsequent comparison of the sedentary hearts post-I/R and exercise-trained hearts post-I/R further identified significant differences in three metabolites (oleic acid, pantothenic acid, and campesterol) related to pantothenate and CoA biosynthesis (p ≤ 1.24E-05, FDR ≤ 5.07E-4). Conclusions: These studies shed light on novel mechanisms in which exercise-induced cardioprotection occurs in I/R that complement both the mitochondrial stabilization and antioxidant mechanisms recently described. These findings also link protein synthesis and protein degradation (protein quality control mechanisms) with exercise-linked cardioprotection and mitochondrial susceptibility for the first time in cardiac I/R.


Subject(s)
Membrane Potential, Mitochondrial/physiology , Mitochondrial Membranes/physiology , Reperfusion Injury/metabolism , Animals , Coronary Artery Disease/metabolism , Disease Models, Animal , Gas Chromatography-Mass Spectrometry/methods , Heart/physiopathology , Ischemia/metabolism , Male , Metabolome/physiology , Metabolomics/methods , Mitochondria, Heart/metabolism , Myocardial Ischemia/metabolism , Myocardial Reperfusion , Myocardial Reperfusion Injury/metabolism , Myocardium/metabolism , Physical Conditioning, Animal/physiology , Rats , Rats, Sprague-Dawley , Sedentary Behavior
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