Publications by authors named "Holdsworth D"

High cardiac sympathetic drive and release of the sympathetic cotransmitter neuropeptide Y (NPY) are significant features of congestive heart failure (CHF), in which resting venous NPY levels are known to be associated with mortality. However, whether circulating NPY levels increase during exercise in CHF when they are already elevated is controversial. We sought to establish the dynamics of circulating NPY levels in CHF patients treated with contemporary medical therapy and devices in relationship to indices of performance linked to long-term prognosis.

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Introduction: Abnormal cardiorespiratory symptoms and investigative findings in service personnel typically result in prolonged investigation and occupational restriction. This analysis aimed to assess the impact of the xford ilitary Cardiopulmonary xercise Testing linic (OMEC), which investigates such symptoms and findings, on occupational recommendations.

Methods: A service evaluation was conducted on all OMEC attendances over a 5-year period.

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Nonclinical QTc studies can augment clinical QTc assessments in regulatory submissions provided they are of sufficient quality and sensitivity. Both the statistical performance and species translation play a role in determining the sensitivity of the model. The current analyses examine the effects of dofetilide or vehicle on the QT interval in nonhuman primate (NHP; n = 16) using a one-step estimated marginal means method where both treatment and animal ID are used in regression models to avoid a separate rate correction step, in comparison to other commonly utilized methods.

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Background: Given the increasing interest in dietary interventions to improve cardiovascular health, this trial assessed the impact of fortified eggs (FE) versus nonegg supplemented diet and time-restricted eating (TRE) versus usual care diet on cardiovascular biomarkers.

Methods: The study was a unblinded, 2-by-2 factorial design, which randomized patients, with either a prior cardiovascular event or 2 cardiovascular risk factors, to FE or a nonegg supplemented diet and TRE or usual care diet. Patients randomized to FE were instructed to consume at least 12 FE/week (with eggs provided); those on a nonegg supplemented diet restricted egg consumption to <2 eggs/week.

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Calcium sulfate is an established carrier for localized drug delivery, but a means to non-invasively measure drug release, which would improve our understanding of localized delivery, remains an unmet need. We aim to quantitatively estimate the diffusion-controlled release of small molecules loaded into a calcium sulfate carrier through a gadobutrol-based contrast agent, which acts as a surrogate small molecule. A central cylindrical core made of calcium sulfate, either alone or within a metal scaffold, is loaded with contrast agents that release into agar.

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Accurate body temperature measurement is essential for monitoring and managing safety during outdoor activities. Physical activities are an essential consideration for public health, with sports taking up an important proportion of these. Athletes' performances can be directly affected by body temperature fluctuations, with overheating or hypothermia posing serious health risks.

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Porous metallic prosthesis components can now be manufactured using additive manufacturing techniques, and may prove beneficial for promoting bony ingrowth, for accommodating drug delivery systems, and for reducing stress shielding. Using finite element modeling techniques, 36 scenarios (three porous stems, three bone densities, and four held arm positions) were analysed to assess the viability of porous humeral stems for use in total shoulder arthroplasty, and their resulting mechanobiological impact on the surrounding humerus bone. All three porous stems were predicted to experience stresses below the yield strength of Ti6Al4V (880 MPa) and to be capable of withstanding more than 10 million cycles of each loading scenario before failure.

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Background: Concerns have arisen that anterior cruciate ligament reconstruction (ACLR) with lateral extra-articular tenodesis (LET) may accelerate the development of posttraumatic osteoarthritis in the lateral compartment of the knee.

Purpose/hypothesis: The purpose of this study was to evaluate whether the augmentation of ACLR with LET affects the quality of lateral compartment articular cartilage on magnetic resonance imaging (MRI) at 2 years postoperatively. We hypothesized that there would be no difference in T1rho and T2 relaxation times when comparing ACLR alone with ACLR + LET.

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Study Design: Diagnostic test study.

Objective: To determine the reliability and validity or diagnostic accuracy of two previously described endplate structural defect (EPSD) assessment methods.

Summary Of Background Data: Studies of EPSD may further the understanding of pathoanatomic mechanisms underlying back pain.

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Hydrogels are three-dimensional (3D) water-swellable polymeric matrices that are used extensively in tissue engineering and drug delivery. Hydrogels can be conformed into any desirable shape using 3D bio-printing, making them suitable for personalized treatment. Among the different 3D bio-printing techniques, digital light processing (DLP)-based printing offers the advantage of quickly fabricating high resolution structures, reducing the chances of cell damage during the printing process.

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Background: Since the COVID-19 pandemic, post-COVID syndrome (persistent symptoms/complications lasting >12 weeks) continues to pose medical and economic challenges. In military personnel, where optimal fitness is crucial, prolonged limitations affecting their ability to perform duties has occupational and psychological implications, impacting deployability and retention. Research investigating post-COVID syndrome exercise capacity and cardiopulmonary effects in military personnel is limited.

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Introduction: Fusion pacing requires correct timing of left ventricular pacing to right ventricular activation, although it is unclear whether this is maintained when atrioventricular (AV) conduction changes during exercise. We used cardiopulmonary exercise testing (CPET) to compare cardiac resynchronization therapy (CRT) using fusion pacing or fixed AV delays (AVD).

Methods: Patients 6 months post-CRT implant with PR intervals < 250 ms performed two CPET tests, using either the SyncAV™ algorithm or fixed AVD of 120 ms in a double-blinded, randomized, crossover study.

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Introduction: COVID-19 infection can precede, in a proportion of patients, a prolonged syndrome including fatigue, exercise intolerance, mood and cognitive problems. This study aimed to describe the profile of fatigue-related, exercise-related, mood-related and cognitive-related outcomes in a COVID-19-exposed group compared with controls.

Methods: 113 serving UK Armed Forces participants were followed up at 5, 12 (n=88) and 18 months (n=70) following COVID-19.

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Whether a compound prolongs cardiac repolarization independent of changes in beat rate is a critical question in drug research and development. Current practice is to resolve this in two steps. First, the QT interval is corrected for the influence of rate and then statistical significance is tested.

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Porous additively-manufactured structures could have a niche in orthopaedic implants, due to their potential to reduce stiffness (stress-shielding), improve bony ingrowth, and potential to house reservoirs of drug-eluting non-structural biomaterials. Computer aided design and finite element (FE) modelling plays an important role in the design of porous structured biomedical implants; however it is important to validate both their static and fatigue behaviours using experimental testing. This study compared the mechanical behaviors of titanium cylindrical gyroid structures of varying porosities using physical testing of additively manufactured prototypes and FE models.

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The cardiovascular safety pharmacology (SP) study conducted to satisfy ICH S7A and S7B has commonly used a cross-over study design where each animal receives all treatments. In an increasing number of cases, cross-over designs are not possible and parallel studies have to be used. These can seldom be as large as 8 animals/treatment to match an n = 8 cross-over.

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The protist genus Gromia was first described in 1835 by Dujardin and while gromiids are prominent in the marine environment, Gromia oviformis was, for a long time, the only valid species regularly recorded. To date, 16 species that are morphologically and/or genetically distinct have been described. While recent studies are documenting their diversity and their ecological importance, G.

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Study Design: A descriptive, cross-sectional cadaver study.

Objective: This study aimed to provide a thorough depiction of vertebral endplate defects classified based on their morphologic features and reported with respect to size, location, and prevalence in the human cadaveric spines of older adults.

Summary Of Background Data: Back pain has been associated with vertebral endplate defects; however, findings have been inconsistent.

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Pain experiences in patients with knee osteoarthritis (OA) may be influenced differently by OA risk factors, reducing the translatability of preclinical research into the clinic. Our objective was to contrast evoked pain patterns after exposure to different OA risk factors including acute joint trauma, chronic instability, or obesity/metabolic syndrome using rat models of experimental knee OA. We tested longitudinal patterns of evoked pain behaviors (knee pressure pain threshold and hindpaw withdrawal threshold) in young male rats exposed to different OA-inducing risk factors including (1) nonsurgical joint trauma (impact-induced anterior cruciate ligament (ACL) rupture); (2) surgical joint destabilization (ACL + medial meniscotibial ligament transection); and (3) high fat/sucrose (HFS) diet-induced obesity.

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Background: Significant numbers of individuals struggle to return to work following acute coronavirus disease 2019 (COVID-19). The UK Military developed an integrated medical and occupational pathway (Defence COVID-19 Recovery Service, DCRS) to ensure safe return to work for those with initially severe disease or persistent COVID-19 sequalae. Medical deployment status (MDS) is used to determine ability to perform job role without restriction ('fully deployable', FD) or with limitations ('medically downgraded', MDG).

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Infection is a major complication associated with orthopedic implants. It often involves the development of biofilms on metal substrates, which act as barriers to the host's immune system and systemic antibiotic treatment. The current standard of treatment is revision surgery, often involving the delivery of antibiotics through incorporation into bone cements.

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The number of animals used in a nonhuman primate (NHP) in vivo QTc assessment conducted as part of the safety pharmacology (SP) studies on a potential new drug is relatively small (4-8 subjects). The number is much smaller than the number of healthy volunteers in a conventional thorough QT (TQT) study (40-60 volunteers). How is it possible that such small studies could offer an equivalent sensitivity in an integrated nonclinical and clinical cardiac repolarization risk assessment? This study provided the opportunity to empirically demonstrate in a large number of NHPs the performance of a nonclinical evaluation at a similar size to a TQT study.

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Detailed characterisation of cardiopulmonary limitations in patients post-COVID-19 is currently limited, particularly in elite athletes. A male elite distance runner in his late 30s experienced chest pain following confirmed COVID-19. He underwent cardiopulmonary exercise testing (CPET) at 5 months postacute illness.

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Failure to recover following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may have a profound impact on individuals who participate in high-intensity/volume exercise as part of their occupation/recreation. The aim of this study was to describe the longitudinal cardiopulmonary exercise function, fatigue, and mental health status of military-trained individuals (up to 12-mo postinfection) who feel recovered, and those with persistent symptoms from two acute disease severity groups (hospitalized and community-managed), compared with an age-, sex-, and job role-matched control. Eighty-eight participants underwent cardiopulmonary functional tests at baseline (5 mo following acute illness) and 12 mo; 25 hospitalized with persistent symptoms (hospitalized-symptomatic), 6 hospitalized and recovered (hospitalized-recovered); 28 community-managed with persistent symptoms (community-symptomatic); 12 community-managed, now recovered (community-recovered), and 17 controls.

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Background: The COVID-19 pandemic has led to significant morbidity and mortality, with the former impacting and limiting individuals requiring high physical fitness, including sportspeople and emergency services.

Methods: Observational cohort study of 4 groups: hospitalised, community illness with on-going symptoms (community-symptomatic), community illness now recovered (community-recovered) and comparison. A total of 113 participants (aged 39 ± 9, 86% male) were recruited: hospitalised (n = 35), community-symptomatic (n = 34), community-recovered (n = 18) and comparison (n = 26), approximately five months following acute illness.

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