Evaluation of Work Efficiency in Structural Firefighters.

ABSTRACT: Langford, EL, Bergstrom, HC, Lanham, S, Eastman, AQ, Best, S, Ma, X, Mason, MR, and Abel, MG. Evaluation of work efficiency in structural firefighters. J Strength Cond Res 37(12): 2457-2466, 2023-To perform occupational tasks safely and effectively, firefighters (FF) must work quickly and consume air provided by the self-contained breathing apparatus (SCBA) efficiently. However, most literature only factors work rate into performance, neglecting the inherent time limitation imposed by the SCBA. The purpose of this article was to (a) evaluate the reliability and variability in a "work efficiency" (WE) performance metric reflective of both work rate and air consumption; (b) explore the relationship between WE and established measures of metabolic strain; and (c) identify fitness, anthropometric, and demographic correlates of WE. About 79 structural FF completed an air consumption drill while breathing through an SCBA. Self-paced work duration and air consumption were entered into the WE equation. A subsample of FF (n = 44) completed another randomized trial while breathing through a portable gas analyzer. Anthropometric and fitness data were collected separately. Correlations were performed between WE vs. fitness, anthropometric, demographic, and metabolic outcomes. Multiple linear regression was used to identify the strongest predictors of WE. WE was reliable (intraclass correlation coefficient = 0.71) and yielded inter-FF variability {0.79 ± 0.25 ([lb·in-2·min]-1) × 104; coefficient of variation = 31.6%}. WE was positively correlated to oxygen consumption (V̇O2) (L·minute-1, mL·kg-1·minute-1) and tidal volume and negatively correlated to V̇E/V̇O2 and respiratory frequency. Height, upper-body endurance, and aerobic endurance were identified as the strongest predictors of WE (adjusted R2 = 0.59, RMSE = 0.16). WE is a reliable and occupationally relevant method to assess FF performance because it accounts for work rate and air consumption. Firefighters may enhance WE through a training intervention focused on improving metabolic tolerance, upper-body endurance, and aerobic endurance.

Implementation of High Intensity Interval Training and Autoregulatory Progressive Resistance Exercise in a Law Enforcement Training Academy.

The purpose of this investigation was to assess the feasibility and efficacy of implementing autoregulatory progressive resistance exercise (APRE) and high intensity interval training (HIIT) methodologies to improve physical fitness and occupational physical ability in police cadets. Two law enforcement academy classes were stratified into a standard care academy training cohort (SC; n=32, m=27, f=5) and a high performance cohort (HP; n=31; m=27, f=4) that utilized APRE and HIIT methodologies during a 17-week academy training program. Demographic, internal loading parameters, anthropometric, fitness outcomes (i.e., 1.5-mile run, 1-repetition maximum bench press, sit-up repetitions, push-up repetitions, & 300m run) and timed completion of a occupation physical ability test (OPAT) were collected at three academy time points (entrance, mid-point and exit). Mixed factor (time vs. group) repeated measures ANOVA were used to evaluate the effects of the training intervention on performance outcomes. Significance was set at p<0.05. Both groups demonstrated significant improvements in all fitness outcomes except the OPAT from entrance to exit tests (p<0.05). The HP experienced greater improvements in push-up performance compared to the SC (p<0.001). OPAT time decreased in both groups from entrance to midpoint, but significantly increased from baseline to exit (p<.05). Despite similar inter-group fitness improvements, the HP reported lower session RPE values (p<0.01), indicating fitness adaptations occurred at a lower internal load. This study demonstrated the feasibility of successfully implementing APRE and HIIT methodologies within a cadet population. Furthermore, these methodologies produced similar improvements in cadet fitness and occupational performance at a lower internal load.

Posture-related changes in sympathetic baroreflex sensitivity during normal pregnancy.

Normal pregnancy is associated with vast adjustments in cardiovascular autonomic control. Sympathetic baroreflex sensitivity has been reported to be attenuated during pregnancy in animal models, but most studies in humans are cross-sectional and findings from longitudinal case studies are inconclusive. It remains unclear how sympathetic baroreflex sensitivity is altered longitudinally during pregnancy within an individual in different body postures. Therefore, this study examined the impact of posture on sympathetic baroreflex sensitivity in 24 normal-weight normotensive pregnant women. Spontaneous sympathetic baroreflex sensitivity was assessed during early (6-11 weeks) and late (32-36 weeks) pregnancy and 6-10 weeks postpartum in the supine posture and graded head-up tilt (30° and 60°). In addition, data from the postpartum period were compared with (and no different to) 18 age-matched non-pregnant women to confirm that the postpartum period was reflective of a non-pregnant condition (online supplement). When compared with postpartum (-3.8 ± 0.4 bursts/100 heartbeats/mmHg), supine sympathetic baroreflex sensitivity was augmented during early pregnancy (-5.9 ± 0.4 bursts/100 heartbeats/mmHg, P < 0.001). However, sympathetic baroreflex sensitivity at 30° or 60° head-up tilt was not different between any phase of gestation (P > 0.05). When compared to supine, sympathetic baroreflex sensitivity at 60° head-up tilt was significantly blunted during early (Δ2.0 ± 0.7 bursts/100 heartbeats/mmHg, P = 0.024) and late (Δ1.5 ± 0.6 bursts/100 heartbeats/mmHg, P = 0.049) pregnancy but did not change postpartum (Δ0.4 ± 0.6 bursts/100 heartbeats/mmHg, P = 1.0). These data show that time-course changes in sympathetic baroreflex sensitivity are dependent on the posture it is examined in and provides a foundation of normal blood pressure regulation during pregnancy for future studies in women at risk for adverse pregnancy outcomes.

Quadriceps electromyography during flywheel-based inertial training (FIT) and dynamic constant external resistance (DCER) squats at similar tempo.

Flywheel-based iso-inertial training (FIT) has been purported to provide enhanced adaptations to muscle overload compared to dynamic constant external resistance (DCER), but previous studies have not controlled for exercise intensity. We compared quadriceps electromyography (EMG) amplitude between FIT- and DCER-squats with similar tempo. Eleven (5 M and 6F) resistance-trained participants completed sets of five maximal velocity FIT (0.025 kg∙m2) and DCER (55 ± 15 %1RM) squats. Sagittal plane knee joint angles and surface EMG activity of the vastus lateralis (VL), vastus medialis (VM) and rectus femoris (RF) were measured. Repetition time and peak knee angles were similar between FIT and DCER squats. Mean knee angular velocity during the concentric (122.2 ± 23.6 vs. 108.9 ± 22.9, p = 0.022, Cohen's D: 0.820), but not eccentric, phase was significantly greater during FIT. Peak VM (210.4 ± 49.3 vs. 177.5 ± 56.3 %MVIC, p = 0.001; Cohen's D: 1.416), but not VL or RF, EMG amplitude was significantly greater in FIT compared to DCER. Mean EMG amplitude was significantly (p < 0.001) greater during the concentric than the eccentric phase for the VL and VM but not RF. Mean EMG amplitude was not significantly different between modes during either the concentric or eccentric phase. Quadriceps EMG amplitude is largely similar between FIT and DCER squats when matched for movement velocity.

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

There is an increasingly urgent and unmet medical need for novel antibiotic drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. Novel bacterial type II topoisomerase inhibitors (NBTIs) are of high interest due to limited cross-resistance with fluoroquinolones, however analogues with Gram-negative activity often suffer from hERG channel inhibition. A novel series of bicyclic-oxazolidinone inhibitors of bacterial type II topoisomerase were identified which display potent broad-spectrum anti-bacterial activity, including against MDR strains, along with an encouraging in vitro safety profile. In vivo proof of concept was achieved in a A. baumannii mouse thigh infection model.

Impact of high-salt versus low-salt intake on the response of sympathetic baroreflex sensitivity to orthostasis in women with a history of normal pregnancy.

Previous studies have demonstrated that sympathetic baroreflex sensitivity (BRS) increases during orthostatic stress in humans. We recently showed that dietary salt intake affects sympathetic neural control in healthy premenopausal women. This study aimed to determine whether salt loading versus salt reduction would impact sympathetic BRS during orthostasis in premenopausal women with a history of normal pregnancy. Nine healthy women [42 ± 3 (SD) yr] were given a standardized isocaloric high-salt (250 mEq sodium/day) or low-salt (50 mEq sodium/day) diet for 1 wk each (∼2 mo apart with the order randomized), whereas water intake was ad libitum. Laboratory testing was performed following each high- and low-salt period in the midluteal phase of the menstrual cycle. Hemodynamics and muscle sympathetic nerve activity (MSNA) were measured at baseline (supine; 2 min) and during a graded head-up tilt (30° for 5 min and 60° for 20 min). Sympathetic BRS was assessed during baseline and head-up tilt. Hemodynamics were not different between salt conditions during baseline or tilt. Both supine and upright MSNA indices were lower in high salt than low salt (all P < 0.05), however, there was no interaction effect (P = 0.507-0.996). On moving from supine to upright, sympathetic BRS remained unchanged in high salt but increased in low salt (P = 0.028 for interaction). Thus, salt loading diminishes the responsiveness of sympathetic BRS during orthostasis compared with salt reduction in healthy premenopausal women with prior normal pregnancy. Whether this is one underlying mechanism for salt-induced development of hypertension during ambulation remains to be determined.

Predictors of Work Efficiency in Structural Firefighters.

OBJECTIVE: Develop a novel work efficiency (WE) metric to quantify firefighter physical ability and identify correlates of WE. METHODS: Physical fitness and anthropometric measurements were taken on 19 male firefighters. Firefighters performed a timed maximal effort simulated fireground test (SFGT). WE was quantified as: (1/[Air depletion × SFGT completion time]) × 10,000. Regression analyses were used to identify predictors of WE. RESULTS: WE was significantly correlated to age, relative body fat, fat mass, occupational experience, jump height, inverted row repetitions, relative bench press and squat strength, treadmill time to exhaustion, relative ventilatory threshold, and relative peak oxygen consumption. Treadmill time to exhaustion and relative lower body strength accounted for the greatest variance in WE (R2 = 0.72, root mean square error = 0.07). CONCLUSION: Aerobic endurance and relative lower body strength were related to an occupationally-specific assessment of firefighter physical ability.

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

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 P < 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; P < 0.001). The transduction of MSNA for vasoconstriction during the CPT was lower in HS (P < 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.

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

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, P = 0.208) did not differ between LS and HS. From LS to HS, BV increased by 4.3 ± 3.7% (P = 0.008). MSNA (30 ± 20 vs. 18 ± 13 bursts/100 heartbeats, P = 0.005) was higher, whereas sympathetic vascular transduction was lower in LS than HS (both, P < 0.01). Changes in MSNA from LS to HS were correlated to percent changes in BV (r = -0.673; P = 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.NEW & NOTEWORTHY 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.

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

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.

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

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.

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

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.

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

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.

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

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 ±â€Š2 [SE] years, ambulatory awake blood pressure; 152 ±â€Š2/84 ±â€Š2 mm Hg), 19 with controlled hypertension (68 ±â€Š1 years, 128 ±â€Š2/71 ±â€Š2 mm Hg), and 31 healthy normotensive women (68 ±â€Š1 years, 127 ±â€Š1/73 ±â€Š1 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 ±â€Š1.7 vs 51.8 ±â€Š2.3 g/m), but it was lower in the normotensive group (41.7 ±â€Š0.9 g/m; one-way analysis of variance [ANOVA] P = 0.004). Likewise, central pulse wave velocity was not different between hypertension groups (11.5 ±â€Š0.6 vs 11.1 ±â€Š0.5 m/s) and lower in the normotensive group (9.1 ±â€Š0.3 m/s; 1-way ANOVA P = 0.0001). Total peripheral resistance was greater in uncontrolled hypertension (HTN) compared with normotensive group (2051 ±â€Š323 vs 1719 ±â€Š380 dyns/cm), whereas controlled HTN group (1925 ±â€Š527 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.

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

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 (n = 11) or hydrochlorothiazide (n = 10)-based therapy. We assessed ß-stiffness of the local arteries, arterial elastance (Ea), and echocardiographic variables, including early (E) and late (A) mitral inflow velocity, deceleration time of E, early (E') and late (A') diastolic mitral annular velocity, and left ventricular end-systolic elastance (Ees) before and after treatment. BP decreased similarly (P < 0.001) after both therapies. ß-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, P = 0.001 for interaction). ß-Stiffness of the femoral and radial arteries were not different after either treatment. Different from aliskiren, E decreased (73 ± 16 vs. 67 ± 14 cm/s, P = 0.026), and the deceleration time was prolonged (218 ± 40 vs. 236 ± 35 ms, P = 0.032) after hydrochlorothiazide therapy, whereas the E/A, and E' remained unchanged after both treatments. Ea and Ees decreased after aliskiren therapy (both P < 0.05), whereas the Ea/Ees (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.

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

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 in vitro properties of a new series of this type of small molecule. Exemplar compounds selectively and potently inhibited the catalytic activities of Escherichia coli 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 Mycobacterium tuberculosis No cross-resistance with fluoroquinolone-resistant Staphylococcus aureus and E. coli isolates was observed. Measured MIC90 values were 4 and 8 µg/ml against a panel of contemporary multidrug-resistant isolates of Acinetobacter baumannii and E. coli, 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 <10-8 against E. coli and A. baumannii at concentrations equivalent to 4-fold the MIC. Compound-resistant E. coli 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 in vitro 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 [IC50], >100 µM). In summary, the compounds' distinct mechanism of action relative to the fluoroquinolones, whole-cell potency, low potential for resistance development, and favorable in vitro safety profile warrant their continued investigation as potential broad-spectrum antibacterial agents.

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.

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.

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

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.

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

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.

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

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 (ß1 = 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.