Publications by authors named "Stuart Best"

31 Publications

Effects of salt intake on sympathetic neural and pressor responses to cold pressor test in premenopausal women with a history of normal pregnancy.

Am J Physiol Regul Integr Comp Physiol 2021 03 13;320(3):R307-R316. Epub 2021 Jan 13.

Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.

Excessive salt intake is considered a risk factor for the development of hypertension. Additionally, aberrant neurocirculatory responses to a cold stimulus are associated with an increased risk of hypertension. This study aimed to determine whether salt loading versus salt reduction would impact hemodynamic and sympathetic neural responses during the cold pressor test (CPT) in premenopausal women with a history of normal pregnancy. Nine healthy premenopausal women [42 ± 3 (SD) yr] were given a standardized isocaloric high-salt (HS; 250 mEq sodium/day) or low-salt (LS; 50 mEq sodium/day) diet for 1-wk each (∼2 mo apart with the order randomized), while water intake was ad libitum. Laboratory testing was performed following each HS and LS period in the mid-luteal phase of the menstrual cycle. Subjects were in the supine position and beat-by-beat blood pressure (BP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were continuously measured during 1-min baseline followed by 2-min CPT, and 3-min recovery. BP and HR increased during the CPT (both < 0.001); the responses were similar between HS and LS. MSNA increased during the CPT, but the increment (Δ) was greater during HS than LS (29 ± 6 vs. 15 ± 4 bursts/min; < 0.001). The transduction of MSNA for vasoconstriction during the CPT was lower in HS ( < 0.05). Thus, salt loading augments sympathetic neural reactivity to the cold stimulus with similar pressor responses compared with salt reduction, which may be attributed to the blunted neurovascular transduction-a compensatory mechanism for hemodynamic homeostasis in premenopausal women with a history of normal pregnancy.
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http://dx.doi.org/10.1152/ajpregu.00297.2020DOI Listing
March 2021

Salt intake impacts sympathetic neural control but not morning blood pressure surge in premenopausal women with a history of normal pregnancy.

Am J Physiol Heart Circ Physiol 2020 09 31;319(3):H571-H581. Epub 2020 Jul 31.

Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.

Salt intake may alter blood pressure (BP) regulation, but no study has investigated the impact of salt reduction versus salt loading on morning blood pressure surge (MBPS) and sympathetic neural control in premenopausal women with a history of normal pregnancy. Nine healthy women (42 ± 3 yr; mean ± SD) were given a low-salt diet (LS; 50 mEq sodium/day) and high-salt diet (HS; 250 mEq sodium/day) for 1 wk each (~2 mo apart with the order randomized), while water intake was ad libitum. Ambulatory BP at 24 h was measured, and the percent change in blood volume (BV) was calculated following LS and HS. MBPS was defined as the morning systolic BP (averaged for 2 h after wake-up) minus the lowest nocturnal systolic BP. Beat-by-beat BP, heart rate, and muscle sympathetic nerve activity (MSNA) were measured during supine rest. Signal averaging was used to characterize changes in beat-by-beat mean arterial pressure and total vascular conductance following spontaneous MSNA bursts to assess sympathetic vascular transduction. Ambulatory BP and MBPS (32 ± 7 vs. 26 ± 12 mmHg, = 0.208) did not differ between LS and HS. From LS to HS, BV increased by 4.3 ± 3.7% ( = 0.008). MSNA (30 ± 20 vs. 18 ± 13 bursts/100 heartbeats, = 0.005) was higher, whereas sympathetic vascular transduction was lower in LS than HS (both, < 0.01). Changes in MSNA from LS to HS were correlated to percent changes in BV ( = -0.673; = 0.047). Thus, salt intake affects sympathetic neural control but not MBPS in premenopausal women with a history of normal pregnancy. The underlying mechanisms remain unknown; however, alterations in sympathetic vascular transduction may, in part, contribute. This is the first study to demonstrate that MBPS and ambulatory BP were not affected by salt intake despite a significant change in sympathetic outflow in healthy premenopausal women with a history of normal pregnancy. This may be due to compensatory adaptations in MSNA and sympathetic vascular transduction during salt reduction versus salt loading.
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http://dx.doi.org/10.1152/ajpheart.00197.2020DOI Listing
September 2020

Arterial stiffness during whole-body passive heat stress in healthy older adults.

Physiol Rep 2019 05;7(9):e14094

Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, University of Texas Southwestern Medical Center, Dallas, Texas.

We tested the hypothesis that whole-body passive heat stress reduces arterial stiffness in older adults. At preheat stress (baseline) and when core temperature was elevated by 0.6 ± 0.2°C (mild) and 1.2 ± 0.3°C (moderate), arterial stiffness was measured in eight healthy younger (26 ± 5 years) and eight healthy older (70 ± 4 years) adults in the supine position. Arterial stiffness was estimated from carotid-to-femoral pulse wave velocity (cfPWV, applanation tonometry). cfPWV was higher at baseline in older adults (8.8 ± 2.3 m/sec vs. 5.6 ± 0.9 m/sec, P < 0.01) and this difference was maintained throughout passive heat stress (P < 0.01). cfPWV did not change (P ≥ 0.49) with passive heat stress in either younger (at moderate heat stress: 6.0 ± 1.0 m/sec) or older (at moderate heat stress: 8.5 ± 1.6 m/sec) adults. However, the influence of baseline cfPWV on the change in cfPWV during mild (r = -0.66, P = 0.04) and moderate (r = -0.87, P < 0.01) heat stress were inversely related in older adults, and the strength of these relations was not statistically different (P = 0.08). In younger adults, the influence of baseline cfPWV on the change in cfPWV during mild heat stress was also inversely related (r = -0.79, P = 0.01), while the strength of this relation was attenuated at moderate heat stress (r = -0.24, P = 0.30). Changes in arterial stiffness during passive heat stress in adults aged ≥65 year are likely dependent on the magnitude of baseline arterial stiffness and not necessarily age.
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http://dx.doi.org/10.14814/phy2.14094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503298PMC
May 2019

Role of Corin in Blood Pressure Regulation in Normotensive and Hypertensive Pregnancy.

Hypertension 2019 02;73(2):432-439

From the Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas (M.B.B., S.Y.P., J.-K.Y., M.H., Y.O., S.S.J., A.S.S., S.A.B., Q.F.).

Corin (an atrial natriuretic peptide-converting enzyme) represents a potential biomarker for gestational hypertensive disorders; yet, its role in blood pressure (BP) regulation throughout pregnancy remains unclear. We investigated the time course of change in blood corin content in relation to BP and sympathetic nerve activity throughout pregnancy. Forty-four women (29±0.9 years) participated. Following-term, 23 had low-risk (no personal history of gestational hypertensive disorders) normal pregnancies, 13 had high-risk (personal history of gestational hypertensive disorders) normal pregnancies, and 8 developed gestational hypertension. BP, heart rate, muscle sympathetic nerve activity, and serum corin were measured before pregnancy, during early (4-8 weeks) and late pregnancy (32-36 weeks), and postpartum (6-10 weeks). Overall, compared with prepregnancy, corin remained unchanged during early pregnancy, increased markedly during late pregnancy ( P<0.001), and returned to prepregnancy levels postpartum. In women who developed gestational hypertension, the change in corin from early to late pregnancy was greater than those with low-risk normal pregnancies (Δ971±134 versus Δ486±79 pg/mL; P<0.05). Throughout pregnancy, BP and muscle sympathetic nerve activity were augmented in women with gestational hypertension (all P<0.05). Finally, changes in corin from early to late pregnancy were related to all indices of BP ( R=0.454-0.551; all P<0.01) in late pregnancy, whereas burst frequency, burst incidence, and total muscle sympathetic nerve activity ( R=0.576-0.614; all P<0.001) in early pregnancy were related to changes in corin from early to late pregnancy. Corin plays a unique role in BP regulation throughout normotensive and, especially, hypertensive pregnancy and may represent a promising biomarker for determining women at high risk of adverse pregnancy outcome.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.12137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467519PMC
February 2019

A method for developing organisation-wide manual handling based physical employment standards in a military context.

J Sci Med Sport 2018 Nov 2;21(11):1162-1167. Epub 2018 Mar 2.

Land Division, Defence Science and Technology Group, Australia.

The benefit of job-related employment standards in physically demanding occupations are well known. A number of methodological frameworks have been established to guide the development of physical employment standards for single job functions. In the case of an organisation comprised of multiple and diverse employment specialisations, such as the Australian Army, it is impractical to develop unique employment standards for each occupation.

Objectives: To present an approach to organisational level physical employment standards development that seeks to retain occupationally specific task characteristics by applying a movement cluster approach.

Design: Structured methodological overview.

Methods: An outline of the research process used in performing job tasks analysis are presented, including the identification, quantification and characterisation, and verification of physically demanding manual handling tasks. The methodology used to filter task information collected from this job analyses to group manual handling tasks with similar characteristics (termed clusters), across a range of employment specialisations is given. Finally, we provide examples of test development based on these key manual handling clusters to develop a limited suite of tests with high content, criterion and face validity that may be implementable across a large organisation.

Results: Job task analysis was performed on 57 employment specialisations, identifying 458 tasks that were grouped into 10 movement based clusters. The rationalisation of criterion tasks through clustering informed the development of a limited suite of tests with high content, criterion and face validity that may be implementable across a large organisation.

Conclusion: This approach could be applied when developing physical employment standards across other multi-occupation organisations.
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http://dx.doi.org/10.1016/j.jsams.2018.02.008DOI Listing
November 2018

Physical, Physiological, and Dietary Comparisons Between Marine Corps Forces Special Operations Command Critical Skills Operators and Enablers.

Mil Med 2018 11;183(11-12):e341-e347

Sports Medicine Research Institute, College of Health Sciences, University of Kentucky, Lexington, KY.

Introduction: Tactical demands of a Marine Corps Forces Special Operations Command (MARSOC) Critical Skills Operator (CSO) require high levels of physical performance. During combat deployments, teams of CSOs are supplemented with enablers who specialize in mission-specific tasks. MARSOC CSOs and enablers serve alongside each other in extreme combat environments, often enduring the same physical demands, but the selection process for each group is very different. The purpose of this observational study was to quantify the physical, physiological, and dietary differences of MARSOC CSOs and enablers, as this may have a direct impact on tactical performance and provide important information to shape future research.

Materials And Methods: Fat free mass (FFM), fat mass (FM), fat mass index (FMI), fat free mass index (FFMI), anaerobic power (AP), anaerobic capacity (AC), aerobic capacity (VO2max), knee flexion (KF), knee extension (KE), trunk extension (TE), and trunk flexion (TF) isokinetic strength were collected. Dietary intake was collected using automated self-administered 24-hr dietary recalls (ASA24) for a subgroup of subjects.

Results: Testing on 164 male CSOs (age: 27.5 ± 3.8 yr, height: 178.7 ± 6.5 cm, mass: 85.7 ± 9.1 kg, and 7.6 ± 2.9 yr of military service) and 51 male enablers (age: 27.8 ± 5.4 yr, height: 178.4 ± 8.5 cm, mass: 83.8 ± 11.8 kg, and 7.9 ± 5.4 yr of military service) showed there were no significant differences for age, height, mass, or years of military service. (p > 0.05). CSOs demonstrated greater physiological performance in AP (W/kg) (p = 0.020), AC (W/kg) (p = 0.001), and VO2max (ml/kg/min) (p = 0.018). There were no significant differences in FM and FFM (p > 0.05), however CSOs demonstrated significantly higher FFMI (p = 0.011). CSOs also demonstrated greater KF (%BW) (p = 0.001), KE (%BW) (p = 0.001), TE (%BW) (p = 0.010), and TF (%BW) (p = 0.016). No differences in energy or macronutrient intake were observed in the subgroup.

Conclusions: MARSOC CSOs demonstrated significantly greater FFMI, AP, AC, VO2max, KF, KE, TE, and TF compared with enablers. Dietary intake was consistent between groups, but fueling concerns were identified for all personnel in the subgroup. These findings suggest the need for future studies to examine what physiological and strength thresholds are necessary to operate effectively as a member of a MSOT and determine the relationship between specific performance deficits and risk of injury. In addition, the integration of nutrition strategies that augment and optimize the performance of both CSOs and enablers may be beneficial.
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http://dx.doi.org/10.1093/milmed/usy049DOI Listing
November 2018

Left ventricular remodeling and arterial afterload in older women with uncontrolled and controlled hypertension.

Menopause 2018 05;25(5):554-562

Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, TX.

Objective: The prevalence of hypertension increases with advancing age in women. Blood pressure control is more difficult to achieve in older women, and despite well-controlled blood pressure, the cardiovascular mortality remains high. However, the underlying mechanisms are not understood.

Methods: Nineteen women with uncontrolled hypertension on drug treatment (70 ± 2 [SE] years, ambulatory awake blood pressure; 152 ± 2/84 ± 2 mm Hg), 19 with controlled hypertension (68 ± 1 years, 128 ± 2/71 ± 2 mm Hg), and 31 healthy normotensive women (68 ± 1 years, 127 ± 1/73 ± 1 mm Hg) were recruited. Participants were weaned from antihypertensive drugs and underwent 3 weeks of run-in before cardiac-vascular assessments. Left ventricular morphology was evaluated with cardiac magnetic resonance imaging. Arterial load and vascular stiffness were measured via ultrasound and applanation tonometry.

Results: Left ventricular mass normalized by body surface area was not different between hypertension groups (uncontrolled vs controlled: 50.0 ± 1.7 vs 51.8 ± 2.3 g/m), but it was lower in the normotensive group (41.7 ± 0.9 g/m; one-way analysis of variance [ANOVA] P = 0.004). Likewise, central pulse wave velocity was not different between hypertension groups (11.5 ± 0.6 vs 11.1 ± 0.5 m/s) and lower in the normotensive group (9.1 ± 0.3 m/s; 1-way ANOVA P = 0.0001). Total peripheral resistance was greater in uncontrolled hypertension (HTN) compared with normotensive group (2051 ± 323 vs 1719 ± 380 dyns/cm), whereas controlled HTN group (1925 ± 527 dyns/cm) was not different to either groups.

Conclusion: Regardless of current blood pressure control, hypertensive older women exhibited increased cardiac mass and arterial stiffness compared with normotensives. Future large-scale longitudinal studies are warranted to directly investigate the mechanisms for the high cardiovascular mortality among older hypertensive women with well-controlled blood pressure.
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http://dx.doi.org/10.1097/GME.0000000000001046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899015PMC
May 2018

Long-term effects of a renin inhibitor versus a thiazide diuretic on arterial stiffness and left ventricular diastolic function in elderly hypertensive patients.

Am J Physiol Regul Integr Comp Physiol 2017 Oct 19;313(4):R400-R409. Epub 2017 Jul 19.

Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas;

Arterial stiffness and cardiac function are important predictors of cardiovascular events in patients with hypertension, even with adequate blood pressure (BP) control. We evaluated whether a direct renin inhibitor, aliskiren, reduces arterial stiffness and modulates left ventricular function compared with a diuretic, hydrochlorothiazide, in elderly hypertensive patients. Twenty-one hypertensive patients [67 ± 14 (SD) yr] were randomly assigned to receive 6-mo aliskiren ( = 11) or hydrochlorothiazide ( = 10)-based therapy. We assessed β-stiffness of the local arteries, arterial elastance (), and echocardiographic variables, including early () and late () mitral inflow velocity, deceleration time of E, early (') and late (') diastolic mitral annular velocity, and left ventricular end-systolic elastance () before and after treatment. BP decreased similarly ( < 0.001) after both therapies. β-Stiffness of the carotid artery decreased after aliskiren but increased after hydrochlorothiazide treatment (aliskiren: 6.42 ± 2.34 pre vs. 5.07 ± 1.29 post; hydrochlorothiazide: 5.05 ± 1.78 vs. 7.25 ± 2.68, = 0.001 for interaction). β-Stiffness of the femoral and radial arteries were not different after either treatment. Different from aliskiren, decreased (73 ± 16 vs. 67 ± 14 cm/s, = 0.026), and the deceleration time was prolonged (218 ± 40 vs. 236 ± 35 ms, = 0.032) after hydrochlorothiazide therapy, whereas the /, and ' remained unchanged after both treatments. and decreased after aliskiren therapy (both < 0.05), whereas the / (ventricular-arterial coupling) was maintained after both treatments. Thus, aliskiren decreased the stiffness of carotid artery and left ventricular end-systolic elastance with maintenance of ventricular-arterial coupling without any effects on diastolic filling, while hydrochlorothiazide increased carotid arterial stiffness and slowed early diastolic filling in elderly hypertensive patients.
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http://dx.doi.org/10.1152/ajpregu.00125.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668614PMC
October 2017

Novel Bacterial Topoisomerase Inhibitors with Potent Broad-Spectrum Activity against Drug-Resistant Bacteria.

Antimicrob Agents Chemother 2017 05 24;61(5). Epub 2017 Apr 24.

Redx Pharma, Alderley Park, Cheshire, United Kingdom.

The novel bacterial topoisomerase inhibitor class is an investigational type of antibacterial inhibitor of DNA gyrase and topoisomerase IV that does not have cross-resistance with the quinolones. Here, we report the evaluation of the properties of a new series of this type of small molecule. Exemplar compounds selectively and potently inhibited the catalytic activities of DNA gyrase and topoisomerase IV but did not block the DNA breakage-reunion step. Compounds showed broad-spectrum inhibitory activity against a wide range of Gram-positive and Gram-negative pathogens, including biodefence microorganisms and No cross-resistance with fluoroquinolone-resistant and isolates was observed. Measured MIC values were 4 and 8 μg/ml against a panel of contemporary multidrug-resistant isolates of and , respectively. In addition, representative compounds exhibited greater antibacterial potency than the quinolones against obligate anaerobic species. Spontaneous mutation rates were low, with frequencies of resistance typically <10 against and at concentrations equivalent to 4-fold the MIC. Compound-resistant mutants that were isolated following serial passage were characterized by whole-genome sequencing and carried a single Arg38Leu amino acid substitution in the GyrA subunit of DNA gyrase. Preliminary safety data indicate that the series shows a promising therapeutic index and potential for low human ether-a-go-go-related gene (hERG) inhibition (50% inhibitory concentration [IC], >100 μM). In summary, the compounds' distinct mechanism of action relative to the fluoroquinolones, whole-cell potency, low potential for resistance development, and favorable safety profile warrant their continued investigation as potential broad-spectrum antibacterial agents.
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http://dx.doi.org/10.1128/AAC.02100-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5404544PMC
May 2017

Efficacy of brief behavioral counselling by allied health professionals to promote physical activity in people with peripheral arterial disease (BIPP): study protocol for a multi-center randomized controlled trial.

BMC Public Health 2016 11 9;16(1):1148. Epub 2016 Nov 9.

Queensland Research Centre for Peripheral Vascular Disease; College of Medicine and Dentistry, James Cook University, Townsville, QLD, 4811, Australia.

Background: Physical activity is recommended for people with peripheral arterial disease (PAD), and can improve walking capacity and quality of life; and reduce pain, requirement for surgery and cardiovascular events. This trial will assess the efficacy of a brief behavioral counselling intervention delivered by allied health professionals to improve physical activity in people with PAD.

Methods: This is a multi-center randomised controlled trial in four cities across Australia. Participants (N = 200) will be recruited from specialist vascular clinics, general practitioners and research databases and randomised to either the control or intervention group. Both groups will receive usual medical care, a written PAD management information sheet including advice to walk, and four individualised contacts from a protocol-trained allied health professional over 3 months (weeks 1, 2, 6, 12). The control group will receive four 15-min telephone calls with general discussion about PAD symptoms and health and wellbeing. The intervention group will receive behavioral counselling via two 1-h face-to-face sessions and two 15-min telephone calls. The counselling is based on the 5A framework and will promote interval walking for 3 × 40 min/week. Assessments will be conducted at baseline, and 4, 12 and 24 months by staff blinded to participant allocation. Objectively assessed outcomes include physical activity (primary), sedentary behavior, lower limb body function, walking capacity, cardiorespiratory fitness, event-based claudication index, vascular interventions, clinical events, cardiovascular function, circulating markers, and anthropometric measures. Self-reported outcomes include physical activity and sedentary behavior, walking ability, pain severity, and health-related quality of life. Data will be analysed using an intention-to-treat approach. An economic evaluation will assess whether embedding the intervention into routine care would likely be value for money. A cost-effectiveness analysis will estimate change in cost per change in activity indicators due to the intervention, and a cost-utility analysis will assess change in cost per quality-adjusted life year. A full uncertainty analysis will be undertaken, including a value of information analysis, to evaluate the economic case for further research.

Discussion: This trial will evaluate the efficacy and cost-effectiveness of a brief behavioral counselling intervention for a common cardiovascular disease with significant burden.

Trial Registration: ACTRN 12614000592640 Australian New Zealand Clinical Trials Registry. Registration Date 4 June 2014.
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http://dx.doi.org/10.1186/s12889-016-3801-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5103607PMC
November 2016

Sympathetic neural and cardiovascular responses during static handgrip exercise in women with a history of hypertensive pregnancy.

Clin Auton Res 2016 12 9;26(6):395-405. Epub 2016 Aug 9.

Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, 7232 Greenville Ave, Dallas, TX, 75231, USA.

Purpose: Women with a history of hypertensive pregnancy are at greater risk for future cardiovascular events; however, the mechanisms for this increased risk are unknown. Evidence suggests that an exercise stimulus unmasks latent hypertensive tendencies, identifying individuals at the greatest risk for developing cardiovascular disease. The current study examined the hypothesis that women with a hypertensive pregnancy history exhibit an augmented exercise pressor response.

Methods: Normotensive women with a history of healthy pregnancy (CON; n = 9) and hypertensive pregnancy (HP+; n = 12) were studied during the mid-luteal phase of the menstrual cycle. Heart rate (HR), systolic and diastolic blood pressure (SBP, DBP), and muscle sympathetic nerve activity (MSNA) were measured during a cold pressor test (CPT), and, following a sufficient period of recovery, during static handgrip to fatigue (SHG) and post-exercise circulatory arrest (PECA).

Results: The BP, HR, and MSNA responses to the CPT were similar between groups. The SBP response to SHG and PECA was similar between groups, but DBP and HR were significantly greater in HP+ women (both p < 0.05). MSNA burst frequency, but not burst incidence or total activity, tended to be elevated in HP+ women during the stressor (peak Δ from baseline 31 ± 13 vs. 23 ± 13 bursts/min; p for group = 0.06).

Conclusion: Despite no clinical signs of cardiovascular disease or hypertension, women with a history of hypertensive pregnancy display an enhanced cardiovascular reactivity to an exercise stimulus compared to women with a healthy pregnancy history. This response may be indicative of impaired cardiovascular control that precedes the clinical manifestation of hypertension or cardiovascular events.
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http://dx.doi.org/10.1007/s10286-016-0372-8DOI Listing
December 2016

Discovery and structure-activity relationships of a novel isothiazolone class of bacterial type II topoisomerase inhibitors.

Bioorg Med Chem Lett 2016 09 28;26(17):4179-83. Epub 2016 Jul 28.

Redx Pharma, Alderley Park, Cheshire SK10 4TG, United Kingdom.

There is an urgent and unmet medical need for new antibacterial drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. During the course of our wider efforts to discover and exploit novel mechanism of action antibacterials, we have identified a novel series of isothiazolone based inhibitors of bacterial type II topoisomerase. Compounds from the class displayed excellent activity against both Gram-positive and Gram-negative bacteria with encouraging activity against a panel of MDR clinical Escherichia coli isolates when compared to ciprofloxacin. Representative compounds also displayed a promising in vitro safety profile.
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http://dx.doi.org/10.1016/j.bmcl.2016.07.061DOI Listing
September 2016

Predicting Endurance Time in a Repetitive Lift and Carry Task Using Linear Mixed Models.

PLoS One 2016 5;11(7):e0158418. Epub 2016 Jul 5.

Centre for Human and Applied Physiology, Faculty of Health and Behavioural Sciences, University of Wollongong, Wollongong, Australia.

Objectives: Repetitive manual handling tasks account for a substantial portion of work-related injuries. However, few studies report endurance time in repetitive manual handling tasks. Consequently, there is little guidance to inform expected work time for repetitive manual handling tasks. We aimed to investigate endurance time and oxygen consumption of a repetitive lift and carry task using linear mixed models.

Methods: Fourteen male soldiers (age 22.4 ± 4.5 yrs, height 1.78 ± 0.04 m, body mass 76.3 ± 10.1 kg) conducted four assessment sessions that consisted of one maximal box lifting session and three lift and carry sessions. The relationships between carry mass (range 17.5-37.5 kg) and the duration of carry, and carry mass and oxygen consumption, were assessed using linear mixed models with random effects to account for between-subject variation.

Results: Results demonstrated that endurance time was inversely associated with carry mass (R2 = 0.24), with significant individual-level variation (R2 = 0.85). Normalising carry mass to performance in a maximal box lifting test improved the prediction of endurance time (R2 = 0.40). Oxygen consumption presented relative to total mass (body mass, external load and carried mass) was not significantly related to lift and carry mass (β1 = 0.16, SE = 0.10, 95%CI: -0.04, 0.36, p = 0.12), indicating that there was no change in oxygen consumption relative to total mass with increasing lift and carry mass.

Conclusion: Practically, these data can be used to guide work-rest schedules and provide insight into methods assessing the physical capacity of workers conducting repetitive manual handling tasks.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0158418PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933391PMC
July 2017

Efficacy of a Novel Tricyclic Topoisomerase Inhibitor in a Murine Model of Neisseria gonorrhoeae Infection.

Antimicrob Agents Chemother 2016 09 22;60(9):5592-4. Epub 2016 Aug 22.

Redx Pharma, Alderley Park, Cheshire, United Kingdom

There is an urgent need for new antibiotics to treat multidrug-resistant Neisseria gonorrhoeae In this report, the microbiology, in vivo pharmacokinetics, and efficacy of REDX05931, a representative novel tricyclic topoisomerase inhibitor, were evaluated. REDX05931 demonstrated high oral bioavailability in mice and reduced N. gonorrhoeae infection after a single dose in a mouse model of gonorrhea. These data support the potential of this series of small molecules as a new treatment for drug-resistant gonorrheal infections.
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http://dx.doi.org/10.1128/AAC.00913-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997832PMC
September 2016

Biological profiling of novel tricyclic inhibitors of bacterial DNA gyrase and topoisomerase IV.

J Antimicrob Chemother 2016 07 30;71(7):1905-13. Epub 2016 Mar 30.

Redx Pharma, BioHub, Alderley Park, Cheshire SK10 4TG, UK.

Objectives: The objective of this study was to characterize the in vitro and in vivo biological properties of a novel series of small-molecule bacterial type IIA topoisomerase inhibitors.

Methods: Bacterial susceptibility testing was performed by broth microdilution. Resistance frequencies were determined by plating bacteria onto agar containing test compound and enumerating mutants. Bacteria were passaged using subinhibitory concentrations of antibacterials to generate resistance. Target enzyme inhibition was determined by exposure to antibacterials and DNA; topoisomers were visualized by gel electrophoresis. Oral and intravenous pharmacokinetic profiles were determined in mice. In vivo efficacy was determined using a mouse model of septicaemia and thigh infection with MSSA and MRSA, respectively.

Results: Representative compounds REDX04139, REDX05604 and REDX05931 demonstrated in vitro potency against a range of Gram-positive and fastidious Gram-negative pathogens. Clinical isolate testing revealed REDX04139 and REDX05931 had MIC90 values of 0.25 and 0.5 mg/L, respectively, for MRSA and MIC90 values of 2 mg/L for streptococci. REDX04139 was bactericidal in vitro against Staphylococcus aureus at 8× MIC over 6 h. Pharmacokinetic profiling of REDX04139 and REDX05604 in mice revealed low clearance and excellent bioavailability (≥71%). REDX04139 provided 100% survival against S. aureus in a mouse septicaemia model, while REDX05604 reduced bacterial load by up to 3.7 log units in the MRSA mouse thigh infection model.

Conclusions: Redx Pharma has discovered a novel series of topoisomerase inhibitors that are being further developed for drug-resistant bacteria.
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http://dx.doi.org/10.1093/jac/dkw061DOI Listing
July 2016

Sympathetic Neural and Hemodynamic Responses During Cold Pressor Test in Elderly Blacks and Whites.

Hypertension 2016 May 28;67(5):951-8. Epub 2016 Mar 28.

From the Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas (Y.O., S.S.J., S.A.B., J.G.E., B.D.L., Q.F.); Departments of Internal Medicine (Y.O., S.S.J., S.A.B., B.A.-H., W.V., B.D.L., Q.F.) and Anesthesiology and Pain (J.M.H.), UT Southwestern Medical Center, Dallas, TX; Department of Special Care Dentistry, Matsumoto Dental University, Nagano, Japan (Y.O.); and Department of Biological Sciences, Northern Arizona University, Flagstaff (S.S.J.).

The sympathetic response during the cold pressor test (CPT) has been reported to be greater in young blacks than whites, especially in those with a family history of hypertension. Because blood pressure (BP) increases with age, we evaluated whether elderly blacks have greater sympathetic activation during CPT than age-matched whites. BP, heart rate, cardiac output, and muscle sympathetic nerve activity were measured during supine baseline, 2-minute CPT, and 3-minute recovery in 47 elderly (68 ± 7 [SD] years) volunteers (12 blacks and 35 whites). Baseline BP, heart rate, cardiac output, or muscle sympathetic nerve activity did not differ between races. Systolic and diastolic BP and heart rate increased during CPT (all P<0.001) with no racial differences (all P > 0.05). Cardiac output increased during CPT and ≤ 30 s of recovery in both groups, but was lower in blacks than whites. Muscle sympathetic nerve activity increased during CPT in both groups (both P<0.001); the increase in burst frequency was similar between groups, whereas the increase in total activity was smaller in blacks (P=0.030 for interaction). Peak change (Δ) in diastolic BP was correlated with Δ total activity at 1 minute into CPT in both blacks (r=0.78,P=0.003) and whites (r=0.43,P=0.009), whereas the slope was significantly greater in blacks (P=0.007). Thus, elderly blacks have smaller sympathetic and central hemodynamic (eg, cardiac output) responses, but a greater pressor response for a given sympathetic activation during CPT than elderly whites. This response may stem from augmented sympathetic vascular transduction, greater sympathetic activation to other vascular bed(s), or enhanced nonadrenergically mediated vasoconstriction in elderly blacks.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.115.06700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833636PMC
May 2016

A Box Lift and Place Assessment is Related to Performance of Several Military Manual Handling Tasks.

Mil Med 2016 Mar;181(3):258-64

Land Division, Defence Science and Technology Organisation, 506 Lorimer Street, Fishermans Bend, VIC 3207, Australia.

Soldiers undergo regular physical testing to assess their functional capacity. However, current physical tests, such as push-ups, sit-ups, and pull-ups, do not necessarily assess job-specific physical capability. This article assesses the utility of generic predictive tests and a task-related predictive test in predicting performance against four job-critical military manual handling tasks. The box lift and place test was found to be the superior predictor in performance of four job tasks; a pack lift and place (R(2) = 0.76), artillery gunner loading simulation (R(2) = 0.36), bombing up an M1 tank simulation, (R(2) = 0.47) and a bridge building simulation (R(2) = 0.63). Pull-ups and push-ups were poor predictors of performance in the majority of job tasks. Although the box lift and place had a larger correlation with the artillery gunner loading task than the generic assessment, it only accounted for 36% of the variance, indicating that a task simulation may be more appropriate to assess soldiers' capacity to perform this job task. These results support the use of a box lift and place rather than generic fitness tests for the evaluation of military manual handling tasks.
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http://dx.doi.org/10.7205/MILMED-D-15-00070DOI Listing
March 2016

Asian women have attenuated sympathetic activation but enhanced renal-adrenal responses during pregnancy compared to Caucasian women.

J Physiol 2015 Mar 26;593(5):1159-68. Epub 2015 Jan 26.

Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, TX, USA; University of Texas Southwestern Medical Center, Dallas, TX, USA.

Asians have a lower prevalence of hypertensive disorders of pregnancy than Caucasians. Since sympathetic overactivity and dysregulation of the renal-adrenal system (e.g. low aldosterone levels) have been found in preeclamptic women, we hypothesized that Asians have lower muscle sympathetic nerve activity (MSNA) and greater aldosterone concentrations during normal pregnancy than Caucasians. In a prospective study, blood pressure (BP), heart rate (HR), and MSNA were measured during supine and upright tilt (30 deg and 60 deg for 5 min each) in 9 Asians (32 ± 1 years (mean ± SEM)) and 12 Caucasians (29 ± 1 years) during pre-, early (≤8 weeks of gestation) and late (32-36 weeks) pregnancy, and post-partum (6-10 weeks after delivery). Supine MSNA increased with pregnancy in both groups (P < 0.001); it was significantly lower in Asians than Caucasians (14 ± 3 vs. 23 ± 3 bursts min(-1) and 16 ± 5 vs. 30 ± 3 bursts min(-1) in early and late pregnancy, respectively; P = 0.023). BP decreased during early pregnancy (P < 0.001), but was restored during late pregnancy. HR increased during pregnancy (P < 0.001) with no racial difference (P = 0.758). MSNA increased during tilting and it was markedly lower in Asians than Caucasians in late pregnancy (31 ± 6 vs. 49 ± 3 bursts min(-1) at 60 deg tilt; P = 0.003). Upright BP was lower in Asians, even in pre-pregnancy (P = 0.006), and this racial difference persisted during pregnancy. Direct renin and aldosterone increased during pregnancy (both P < 0.001); these hormones were greater in Asians (P = 0.086 and P = 0.014). Thus, Asians have less sympathetic activation but more upregulated renal-adrenal responses than Caucasians during pregnancy. These results may explain, at least in part, why Asian women are at low risk of hypertensive disorders in pregnancy.
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http://dx.doi.org/10.1113/jphysiol.2014.282277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358677PMC
March 2015

Heart rate recovery after maximal exercise is blunted in hypertensive seniors.

J Appl Physiol (1985) 2014 Dec 9;117(11):1302-7. Epub 2014 Oct 9.

Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas; and University of Texas Southwestern Medical Center, Dallas, Texas.

Abnormal heart rate recovery (HRR) after maximal exercise may indicate autonomic dysfunction and is a predictor for cardiovascular mortality. HRR is attenuated with aging and in middle-age hypertensive patients, but it is unknown whether HRR is attenuated in older-age adults with hypertension. This study compared HRR among 16 unmedicated stage 1 hypertensive (HTN) participants [nine men/seven women; 68 ± 5 (SD) yr; awake ambulatory blood pressure (BP) 149 ± 10/87 ± 7 mmHg] and 16 normotensive [control (CON)] participants (nine men/seven women; 67 ± 5 yr; 122 ± 4/72 ± 5 mmHg). HR, BP, oxygen uptake (V̇o2), cardiac output (Qc), and stroke volume (SV) were measured at rest, at two steady-state work rates, and graded exercise to peak during maximal treadmill exercise. During 6 min of seated recovery, the change in HR (ΔHR) was obtained every minute and BP every 2 min. In addition, HRR and R-R interval (RRI) recovery kinetics were analyzed using a monoexponential function, and the indexes (HRRI and RRII) were calculated. Maximum V̇o2, HR, Qc, and SV responses during exercise were not different between groups. ΔHR was significantly different (P < 0.001) between the HTN group (26 ± 8) and the CON group (36 ± 12 beats/min) after 1 min of recovery but less convincing at 2 min (P = 0.055). BP recovery was similar between groups. HRRI was significantly lower (P = 0.016), and there was a trend of lower RRII (P = 0.066) in the HTN group compared with the CON group. These results show that in older-age adults, HRR is attenuated further with the presence of hypertension, which may be attributable to an impairment of autonomic function.
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http://dx.doi.org/10.1152/japplphysiol.00395.2014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4254836PMC
December 2014

Plasma and lymphocyte Hsp72 responses to exercise in athletes with prior exertional heat illness.

Amino Acids 2014 Jun 17;46(6):1491-9. Epub 2014 Mar 17.

Exercise, Health and Performance Faculty Research Group, Faculty of Health Sciences, The University of Sydney, Lidcombe, P.O. Box 170, Sydney, NSW, 1825, Australia,

We investigated the effect of exercise in the heat on both intracellular and extracellular Hsp72 in athletes with a prior history of exertional heat illness (EHI). Two groups of runners, one consisting of athletes who had a previous history of EHI, and a control group (CON) of similar age (29.7 ± 1.2 and 29.1 ± 2 years CON vs. EHI) and fitness [maximal oxygen consumption [Formula: see text] 65.7 ± 2 and 64.5 ± 3 ml kg(-1) min(-1) CON vs. EHI] were recruited. Seven subjects in each group ran on a treadmill for 1 h at 72 % [Formula: see text] in warm conditions (30 °C, 40 % RH) reaching rectal temperatures of ~39.3 (CON) and ~39.2 °C (EHI). Blood was collected every 10 min during exercise and plasma was analysed for extracellular Hsp72. Intracellular Hsp72 levels were measured in both monocytes and lymphocytes before and immediately after the 60-min run, and then after 1 h recovery at an ambient temperature of 24 °C. Plasma Hsp72 increased from 1.18 ± 0.14 and 0.86 ± 0.08 ng/ml (CON vs. EHI) at rest to 4.56 ± 0.63 and 4.04 ± 0.45 ng/ml (CON vs. EHI, respectively) at the end of exercise (p < 0.001), with no difference between groups. Lymphocyte Hsp72 was lower in the EHI group at 60 min of exercise (p < 0.05), while monocyte Hsp72 was not different between groups. The results of the present study suggest that the plasma Hsp72 response to exercise in athletes with a prior history of EHI remained similar to that of the CON group, while the lymphocyte Hsp72 response was reduced.
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http://dx.doi.org/10.1007/s00726-014-1721-3DOI Listing
June 2014

Age and sex differences in muscle sympathetic nerve activity in relation to haemodynamics, blood volume and left ventricular size.

Exp Physiol 2014 Jun 17;99(6):839-48. Epub 2014 Jan 17.

Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, TX, USA UT Southwestern Medical Center, Dallas, TX, USA

We compared the effect of age- and sex-related differences in haemodynamics, blood volume (BV) and left ventricular (LV) size and mass on resting muscle sympathetic nerve activity (MSNA) in healthy, normotensive adults. Twenty young men (19-47 years old) and 20 young women (21-46 years old) as well as 15 older men (62-80 years old) and 15 older women (60-82 years old) were studied. Cardiac output (acetylene rebreathing), total peripheral resistance, forearm vascular resistance (FVR; venous occlusion plethysmography) and MSNA were measured during supine rest. Blood volume was calculated (CO rebreathing), and LV mass, end-diastolic (LVEDV) and end-systolic volumes (LVESV) were measured using magnetic resonance imaging. Cardiac index (P < 0.001 and P = 0.016), BV (both P < 0.001), LV mass (P < 0.001 and P = 0.002), LVEDV (P < 0.001 and P = 0.002) and LVESV (both P < 0.001) were lower in the older and female groups, respectively. Total peripheral resistance was significantly higher in the older (P < 0.001) and female groups (P = 0.014), but FVR was increased in the female groups (P = 0.048) only (age, P = 0.089). The MSNA was greater in the older groups (P < 0.001) only (sex, P = 0.228). Increased MSNA was shown to correlate with a decrease in BV (P = 0.004) in men only when adjusted for age (women, P = 0.133). There was a positive relation between MSNA and FVR (P = 0.020) in men but not women (P = 0.422). There were no significant relations between MSNA and LV mass, LVEDV or LVESV. The findings suggest that the increase in resting MSNA with age may be related to the decline in BV in men only, but it is unknown whether sex differences in sympathetic adrenergic vasoconstriction occur independently of these changes.
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http://dx.doi.org/10.1113/expphysiol.2013.077248DOI Listing
June 2014

Exercise-heat acclimation in young and older trained cyclists.

J Sci Med Sport 2014 Nov 31;17(6):677-82. Epub 2013 Oct 31.

Exercise Health and Performance Research Group, Faculty of Health Sciences, University of Sydney, Australia.

Objectives: The purpose of this study was to investigate the effect of age on the capacity to acclimatise to exercise-heat stress. This study hypothesised that age would not affect body temperature and heat loss effector responses to short-term exercise-heat acclimation in trained subjects.

Design: Seven young subjects (19-32 years) were matched with 7 older subjects (50-63 years). Subjects were highly trained but not specifically heat acclimated when they exercised for 60 min at 70%VO2max in hot-dry (35 °C, 40%RH) and thermoneutral (20 °C, 40%RH) conditions, pre and post 6 days of exercise-heat acclimation (70%VO2max, 35 °C, 40%RH).

Methods: Rectal temperature (Tr), skin temperature (Tsk), heart rate (HR), cutaneous vascular conductance (CVC) and whole body sweat loss (Msw) were measured during each testing session and Tr and HR were measured during each acclimation session.

Results: Tr, Tsk, %HRmax, CVC and Msw were similar across age groups both pre and post heat acclimation. Following heat acclimation relative decreases and increases in Tr and Msw, respectively, were similar in both subject groups. There was a significant reduction in heart rate (%HRmax) and increase in final CVC following the acclimation programme in the young group (all p < 0.05) but not the older group.

Conclusions: When comparing young and older well trained adults we found age affected the cardiovascular adaptation but not body temperature or whole body sweat loss to exercise-heat acclimation. These data suggest age does not affect the capacity to acclimatise to exercise-heat stress in highly trained adults undergoing short-term heat acclimation.
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http://dx.doi.org/10.1016/j.jsams.2013.10.243DOI Listing
November 2014

Effects of sex and hypertension subtype on haemodynamics and left ventricular diastolic function in older patients with stage 1 hypertension.

J Hypertens 2013 Nov;31(11):2282-9; discussion 2289

aThe University of Texas Southwestern Medical Center bInstitute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas, USA.

Background: Hypertension is associated with cardiovascular stiffening and left ventricular diastolic dysfunction, leading to comorbidities such as heart failure with preserved ejection fraction (HFpEF). It is unknown whether sex and hypertension subtype affect haemodynamics and left ventricular function in older individuals.

Methods: Ninety-five older patients with Stage 1 hypertension (ambulatory awake SBP135-159 mmHg) and 56 normotensive controls were enrolled. Patients were stratified prospectively into isolated systolic hypertension (ISH, DBP <85 mmHg) or systolic-diastolic hypertension (SDH, DBP ≥85 mmHg). Haemodynamics and Doppler variables including early filling (E) and averaged mitral annular (E'mean) velocities were measured during supine rest.

Results: Ambulatory awake blood pressures (BPs) were the highest in SDH, whereas supine SBP was similar in both hypertensive groups. No sex difference was observed in supine or ambulatory awake BPs in all groups. Stroke volume was similar among groups within the same sex, but smaller in women. Women exhibited faster E, slower E'mean and greater E/E'mean, whereas no group difference was observed in E within the same sex. In women, E'mean was significantly slower in SDH (5.9 ± 1.6 vs. 7.4 ± 1.1 cm/s, P < 0.01) and ISH (6.6 ± 1.6 cm/s, P = 0.07) than controls, resulting in the highest E/E'mean in SDH. In men, E'mean and E/E'mean were similar among the three groups.

Conclusion: These results suggest that elderly hypertensive women may have left ventricular early diastolic dysfunction and higher estimated filling pressure, consistent with their susceptibility to HFpEF. Women with SDH seemed to have more left ventricular diastolic dysfunction, which might be explained by the greater cumulative afterload when ambulatory.
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http://dx.doi.org/10.1097/HJH.0b013e3283649730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864621PMC
November 2013

Chronic renin inhibition lowers blood pressure and reduces upright muscle sympathetic nerve activity in hypertensive seniors.

J Physiol 2013 Dec 23;591(23):5913-22. Epub 2013 Sep 23.

Q. Fu: UT Southwestern Medical Center, Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, 7232 Greenville Avenue, Suite 435, Dallas, TX 75231, USA.

Cardiovascular risk remains high in patients with hypertension even with adequate blood pressure (BP) control. One possible mechanism may be sympathetic activation via the baroreflex. We tested the hypothesis that chronic inhibition of renin reduces BP without sympathetic activation, but diuresis augments sympathetic activity in elderly hypertensives. Fourteen patients with stage-I hypertension (66 ± 5 (SD) years) were treated with a direct renin inhibitor, aliskiren (n = 7), or a diuretic, hydrochlorothiazide (n = 7), for 6 months. Muscle sympathetic nerve activity (MSNA), BP, direct renin and aldosterone were measured during supine and a graded head-up tilt (HUT; 5 min 30° and 20 min 60°), before and after treatment. Sympathetic baroreflex sensitivity (BRS) was assessed. Both groups had similar BP reductions after treatment (all P < 0.01), while MSNA responses were different between hydrochlorothiazide and aliskiren (P = 0.006 pre/post × drug). Both supine and upright MSNA became greater after hydrochlorothiazide treatment (supine, 72 ± 18 post vs. 64 ± 15 bursts (100 beats)(-1) pre; 60° HUT, 83 ± 10 vs. 78 ± 13 bursts (100 beats)(-1); P = 0.002). After aliskiren treatment, supine MSNA remained unchanged (69 ± 13 vs. 64 ± 8 bursts (100 beats)(-1)), but upright MSNA was lower (74 ± 15 vs. 85 ± 10 bursts (100 beats)(-1); P = 0.012 for pre/post × posture). Direct renin was greater after both treatments (both P < 0.05), while upright aldosterone was greater after hydrochlorothiazide only (P = 0.002). The change in upright MSNA by the treatment was correlated with the change of aldosterone (r = 0.74, P = 0.002). Upright sympathetic BRS remained unchanged after either treatment. Thus, chronic renin inhibition may reduce upright MSNA through suppressed renin activity, while diuresis may evoke sympathetic activation via the upregulated renin-angiotensin-aldosterone system, without changing intrinsic sympathetic baroreflex function in elderly hypertensive patients.
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http://dx.doi.org/10.1113/jphysiol.2013.261362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3872761PMC
December 2013

On the relationship between discrete and repetitive lifting performance in military tasks.

J Strength Cond Res 2014 Mar;28(3):767-73

1Human Protection and Performance Division, Defense Science and Technology Organization, Fishermans Bend, Victoria, Australia; and 2Center for Musculoskeletal Research, Griffith University, Gold Coast, Queensland, Australia.

Military manual handling requirements range from discrete lifts to continuous and repetitive lifting tasks. For the military to introduce a discrete lifting assessment, the assessment must be predictive of the various submaximum lifting tasks personnel are required to perform. This study investigated the relationship between discrete and repetitive military lifting to assess the validity of implementing a discrete lifting test. Twenty-one soldiers from the Australian Army completed a whole-body box-lifting assessment as a one repetition maximum (1RM) and a series of submaximal lifting repetitions (% 1RM). Performance was measured between the number of lifting repetitions that could be performed at different intensities between 58 and 95% 1RM. A strong curvilinear relationship existed across the entire submaximal lifting range (r = 0.72, p ≤ 0.05). The model developed demonstrated a low predictive error (standard error of the estimate = 7.2% 1RM) with no differences detected in the relationship when comparing individuals of high and low strength. Findings support the use of a discrete functional lifting assessment in providing coverage of a broad range of military lifting tasks. Parallels can be drawn between the trend reported in the current study and weight-training exercises reported in the literature.
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http://dx.doi.org/10.1519/JSC.0b013e3182a364a6DOI Listing
March 2014

Recommendations on bioanalytical method stability implications of co-administered and co-formulated drugs by Global CRO Council for Bioanalysis (GCC).

Bioanalysis 2012 Sep;4(17):2117-26

Advion Bioanalytical Laboratories, Quintiles, NY, USA.

An open letter written by the Global CRO Council for Bioanalysis (GCC) describing the GCC survey results on stability data from co-administered and co-formulated drugs was sent to multiple regulatory authorities on 14 December 2011. This letter and further discussions at different GCC meetings led to subsequent recommendations on this topic of widespread interest within the bioanalytical community over the past 2 years.
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http://dx.doi.org/10.4155/bio.12.192DOI Listing
September 2012

The relationship between maximal lifting capacity and maximum acceptable lift in strength-based soldiering tasks.

J Strength Cond Res 2012 Jul;26 Suppl 2:S23-9

Center for Human and Applied Physiology, Faculty of Health and Behavioural Sciences, University of Wollongong, Australia.

Psychophysical assessments, such as the maximum acceptable lift, have been used to establish worker capability and set safe load limits for manual handling tasks in occupational settings. However, in military settings, in which task demand is set and capable workers must be selected, subjective measurements are inadequate, and maximal capacity testing must be used to assess lifting capability. The aim of this study was to establish and compare the relationship between maximal lifting capacity and a self-determined tolerable lifting limit, maximum acceptable lift, across a range of military-relevant lifting tasks. Seventy male soldiers (age 23.7 ± 6.1 years) from the Australian Army performed 7 strength-based lifting tasks to determine their maximum lifting capacity and maximum acceptable lift. Comparisons were performed to identify maximum acceptable lift relative to maximum lifting capacity for each individual task. Linear regression was used to identify the relationship across all tasks when the data were pooled. Strong correlations existed between all 7 lifting tasks (rrange = 0.87-0.96, p < 0.05). No differences were found in maximum acceptable lift relative to maximum lifting capacity across all tasks (p = 0.46). When data were pooled, maximum acceptable lift was equal to 84 ± 8% of the maximum lifting capacity. This study is the first to illustrate the strong and consistent relationship between maximum lifting capacity and maximum acceptable lift for multiple single lifting tasks. The relationship developed between these indices may be used to help assess self-selected manual handling capability through occupationally relevant maximal performance tests.
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http://dx.doi.org/10.1519/JSC.0b013e31825d7f5eDOI Listing
July 2012

Synthesis and SAR studies of novel 2-(6-aminomethylaryl-2-aryl-4-oxo-quinazolin-3(4H)-yl)acetamide vasopressin V1b receptor antagonists.

Bioorg Med Chem Lett 2011 Jun 13;21(12):3813-7. Epub 2011 Apr 13.

Department of Chemistry, MSD, Newhouse, Lanarkshire, UK.

Synthesis and structure-activity relationships (SAR) of a novel series of vasopressin V(1b) antagonists are described. 2-(6-Aminomethylaryl-2-aryl-4-oxo-quinazolin-3(4H)-yl)acetamide have been identified with low nanomolar affinity for the V(1b) receptor and good selectivity with respect to related receptors V(1a), V(2) and OT. Optimised compound 16 shows a good pharmacokinetic profile and activity in a mechanistic model of HPA dysfunction.
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http://dx.doi.org/10.1016/j.bmcl.2011.04.022DOI Listing
June 2011