Thermoregulatory responses to combined moderate heat stress and hypoxia

Objective: The aim of this study was to examine the cutaneous vascular and sudomotor responses to combined moderate passive heat stress and normobaric hypoxia. Method: Thirteen healthy young males, dressed in a water-perfused suit, underwent passive heating (Δcore temperature ~0.7 °C) twice (NORMOXIA; 20.9% O2 and HYPOXIA; 13% O2). Chest and forearm skin blood flow (SkBF; laser Doppler flux), local sweat rate (SR; capacitance hygrometry) and core (intestinal pill) and skin temperatures, were recorded. Results: HYPOXIA reduced baseline oxygen saturation (98±1 vs. 89±6%, P<0.001) and elevated chest (P=0.03) and forearm SkBF (P=0.03) and HR (64±9 vs. 69±8 beats.min-1, P<0.01). During heating, mean body temperature (T ̅BODY) thresholds for SkBF (P=0.41) and SR (P=0.28) elevations were not different between trials. The SkBF: T ̅BODY linear sensitivity during the initial phase of heating was lower at the Chest (P=0.035) but not different at the forearm (P=0.17) during HYPOXIA. With increasing levels of heating chest SkBF was not different (P=0.55) but forearm SkBF was lower on the forearm (P<0.01) during HYPOXIA. Chest (P=0.85) and forearm (P=0.79) SR:T ̅BODY linear sensitivities were not different between trials. Conclusion: Whilst sudomotor responses and the initiation of cutaneous blood flow elevations are unaffected, hypoxia differentially effects regional SkBF responses during moderate passive heating

Impact of eight weeks of repeated ischaemic preconditioning on brachial artery and cutaneous microcirculatory function in healthy males

Background Ischaemic preconditioning has well-established cardiac and vascular protective effects. Short interventions (one week) of daily ischaemic preconditioning episodes improve conduit and microcirculatory function. This study examined whether a longer (eight weeks) and less frequent (three per week) protocol of repeated ischaemic preconditioning improves vascular function. Methods Eighteen males were randomly allocated to either ischaemic preconditioning (22.4 ± 2.3 years, 23.7 ± 3.1 kg/m2) or a control intervention (26.0 ± 4.8 years, 26.4 ± 1.9 kg/m2). Brachial artery endothelial-dependent (FMD), forearm cutaneous microvascular function and cardiorespiratory fitness were assessed at zero, two and eight weeks. Results A greater improvement in FMD was evident following ischaemic preconditioning training compared with control at weeks 2 (2.24% (0.40, 4.08); p=0.02) and 8 (1.11% (0.13, 2.10); p=0.03). Repeated ischaemic preconditioning did not change cutaneous microcirculatory function or fitness. Conclusions These data indicate that a feasible and practical protocol of regular ischaemic preconditioning episodes improves endothelial function in healthy individuals within two weeks, and these effects persist following repeated ischaemic preconditioning for eight weeks

Cardiorespiratory Fitness Modulates The Acute Flow-Mediated Dilation Response Following High-Intensity But Not Moderate-Intensity Exercise In Elderly Men.

Impaired endothelial function is observed with ageing and with low cardiorespiratory fitness (VO2peak) whilst improvements in both are suggested to be reliant on higher-intensity exercise in the elderly. This may be due to the flow-mediated dilation (FMD) response to acute exercise of varying intensity. We examined the hypothesis that exercise-intensity alters the FMD response in healthy elderly adults, and would be modulated by VO2peak Forty-seven elderly men were stratified into lower- (VO2peak = 24.3±2.9 ml.kg(-1)min(-1), n=27) and higher-fit groups (VO2peak = 35.4±5.5 ml.kg(-1)min(-1), n=20) after a test of cycling peak power output (PPO). In randomised order, participants undertook 27 min moderate-intensity continuous (MICE; 40% PPO) or high-intensity interval cycling exercise (HIIE; 70% PPO), or no-exercise control. Brachial FMD was assessed at rest, 10 and 60 min after exercise. In control, FMD reduced in both groups (P=0.05). FMD increased after MICE in both groups [increase of 0.86 % (95% CI, 0.17 to 1.56), P=0.01], and normalised after 60 min. In the lower-fit, FMD reduced after HIIE [reduction of 0.85 % (95% CI, 0.12 to 1.58), P=0.02), and remained decreased at 60 min (P=0.05). In the higher-fit FMD was unchanged immediately after HIIE and increased after 60 min [increase of 1.52 % (95% CI, 0.41 to 2.62), P<0.01], which was correlated with VO2peak (r =0.41; P<0.01). Exercise-intensity alters the FMD response in elderly adults, and VO2peak modulates the FMD response following HIIE, but not MICE. The sustained decrease in FMD in the lower-fit may represent a signal for vascular adaptation or endothelial fatigue

Foot kinematics in patients with two patterns of pathological plantar hyperkeratosis

Background: The Root paradigm of foot function continues to underpin the majority of clinical foot biomechanics practice and foot orthotic therapy. There are great number of assumptions in this popular paradigm, most of which have not been thoroughly tested. One component supposes that patterns of plantar pressure and associated hyperkeratosis lesions should be associated with distinct rearfoot, mid foot, first metatarsal and hallux kinematic patterns. Our aim was to investigate the extent to which this was true. Methods: Twenty-seven subjects with planter pathological hyperkeratosis were recruited into one of two groups. Group 1 displayed pathological plantar hyperkeratosis only under metatarsal heads 2, 3 and 4 (n = 14). Group 2 displayed pathological plantar hyperkeratosis only under the 1st and 5th metatarsal heads (n = 13). Foot kinematics were measured using reflective markers on the leg, heel, midfoot, first metatarsal and hallux. Results: The kinematic data failed to identify distinct differences between these two groups of subjects, however there were several subtle (generally <3°) differences in kinematic data between these groups. Group 1 displayed a less everted heel, a less abducted heel and a more plantarflexed heel compared to group 2, which is contrary to the Root paradigm. Conclusions: There was some evidence of small differences between planter pathological hyperkeratosis groups. Nevertheless, there was too much similarity between the kinematic data displayed in each group to classify them as distinct foot types as the current clinical paradigm proposes

Population-based analysis of ocular Chlamydia trachomatis in trachoma-endemic West African communities identifies genomic markers of disease severity.

BACKGROUND: Chlamydia trachomatis (Ct) is the most common infectious cause of blindness and bacterial sexually transmitted infection worldwide. Ct strain-specific differences in clinical trachoma suggest that genetic polymorphisms in Ct may contribute to the observed variability in severity of clinical disease. METHODS: Using Ct whole genome sequences obtained directly from conjunctival swabs, we studied Ct genomic diversity and associations between Ct genetic polymorphisms with ocular localization and disease severity in a treatment-naïve trachoma-endemic population in Guinea-Bissau, West Africa. RESULTS: All Ct sequences fall within the T2 ocular clade phylogenetically. This is consistent with the presence of the characteristic deletion in trpA resulting in a truncated non-functional protein and the ocular tyrosine repeat regions present in tarP associated with ocular tissue localization. We have identified 21 Ct non-synonymous single nucleotide polymorphisms (SNPs) associated with ocular localization, including SNPs within pmpD (odds ratio, OR = 4.07, p* = 0.001) and tarP (OR = 0.34, p* = 0.009). Eight synonymous SNPs associated with disease severity were found in yjfH (rlmB) (OR = 0.13, p* = 0.037), CTA0273 (OR = 0.12, p* = 0.027), trmD (OR = 0.12, p* = 0.032), CTA0744 (OR = 0.12, p* = 0.041), glgA (OR = 0.10, p* = 0.026), alaS (OR = 0.10, p* = 0.032), pmpE (OR = 0.08, p* = 0.001) and the intergenic region CTA0744-CTA0745 (OR = 0.13, p* = 0.043). CONCLUSIONS: This study demonstrates the extent of genomic diversity within a naturally circulating population of ocular Ct and is the first to describe novel genomic associations with disease severity. These findings direct investigation of host-pathogen interactions that may be important in ocular Ct pathogenesis and disease transmission

The impact of exercise and thermal training interventions on thermoregulatory and cardiovascular function in young and post-menopausal females

The female reproductive hormone oestrogen influences cardiovascular and thermoregulatory control. A dramatic decline in oestrogen during the menopause causes cardiovascular and thermoregulatory dysfunction resulting in hot flushes (HFs). HFs consist of feelings of intense heat with rapid increases in cutaneous vasodilation and sweating that severely affect quality of life and increase cardiovascular disease risk. Treatment using hormone replacement therapy for HFs is contraindicated in some symptomatic females meaning an alternative strategy is warranted. Exercise training may reduce HFs; however no study to date has examined the physiological mechanisms that cause changes in the frequency and severity of HFs following a period of exercise training. Exercise training is known to enhance thermoregulatory efficiency via an earlier core temperature onset for cutaneous vasodilation and sweating in pre-menopausal females. Exercise training is also known to positively impact vascular function in the conduit, cutaneous and cerebral vessels and thus can also decrease cardiovascular risk in symptomatic post-menopausal females. Heat acclimation interventions target the same thermoregulatory and cardiovascular physiological mechanisms, and may also be beneficial. The primary aim of this thesis was to (i) examine whether exercise training reduces objectively measured HFs via improving cardiovascular and thermoregulatory dysfunction in symptomatic post-menopausal females, and to (ii) assess the efficacy of an exercise-independent stimulus in improving thermoregulatory and cardiovascular function in pre-menopausal females.Twenty-one symptomatic post-menopausal females completed a 16-week exercise training intervention (n=14, 52±4y, 29±6 kg/m2) or a no-exercise control intervention (n=7, 52±6y, 30±7 kg/m2). Cardiorespiratory fitness (VO2peak) and brachial artery endothelial function was assessed using flow-mediated dilation (FMD). Participants underwent a passive heat stress in a water-perfused suit (~48ºC) to obtain core temperature thresholds and sensitivities for cutaneous vascular conductance (CVC) and sweat rate at two sites (chest and forearm). Middle cerebral artery velocity (MCAv) was measured at rest and throughout the heat stress. All measurements were repeated following the intervention period. HFs reduced by 39 HF•wk (95% CI= 31, 47) following exercise training compared to no change in control. HF-severity reduced by 101 (AU) (95% CI= 80, 121) following exercise training compared to no change in control. VO2peak and FMD improved (P0.05). This was accompanied by a reduction in chest skin blood flow of 26 AU (95% CI, 21, 30; P=0.01) during HFs following exercise training compared to no change in control (P=0.10). MCAv was attenuated by 3.4 cm/s (95% CI, 0.7, 5.1; P<0.001) during a HF following exercise training compared to control [0.6 cm/s (95% CI, -0.7, 1.8; P=0.93)].Eighteen pre-menopausal females (25±8y) were assigned to 3x30-min of cycling exercise (70% HRmax) or warm water immersion (42ºC) to the level of the sternum for 8-weeks. FMD (P=0.003) and VO2peak (P<0.001) improved following both interventions. Core body temperature reduced by 0.14ºC (95% CI, 0.04, 0.23; P=0.004) following both interventions. Sweat rate mean body temperature thresholds at the chest and forearm occurred 0.10ºC (95% CI=-0.14, 0.33, P<0.001) and 0.19ºC (0.12, 0.23ºC, P<0.001) earlier following the interventions, alongside an increase in sweat rate sensitivity of 1.18 mg•cm2•min-1 (95% CI= 0.68, 1.67; P<0.001) following water immersion compared to 0.28 mg•cm2•min-1 (95% CI= 0.23, 0.78) following exercise training. CVC core temperature thresholds occurred ~0.20ºC earlier at the chest and forearm (P<0.001). Resting MCAv was 2.30 cm/s (95% CI=1.20, 3.34; P<0.001) higher, with decreases in MCAv attenuated during heat stress, following both interventions.The findings from this thesis suggest that reductions in the frequency and severity of HFs with exercise training are mediated by improvements in thermoregulatory function, alongside cerebral, conduit and cutaneous adaptation. This coincided with objective reductions in HF severity following exercise training, with attenuation in the physiological perturbations observed during an acute HF. Consequently, interventions that target thermoregulatory function may be useful in reducing post-menopausal HFs. In keeping with the exercise mediated physiological changes, warm water immersion training also elicits similar favourable thermoregulatory, conduit- and cerebrovascular adaptations to a period of moderate intensity exercise training in pre-menopausal females. Immersion therapy may therefore be applicable to HF-symptomatic post-menopausal females

Effective Theory Approach to the Spontaneous Breakdown of Lorentz Invariance

We generalize the coset construction of Callan, Coleman, Wess and Zumino to theories in which the Lorentz group is spontaneously broken down to one of its subgroups. This allows us to write down the most general low-energy effective Lagrangian in which Lorentz invariance is non-linearly realized, and to explore the consequences of broken Lorentz symmetry without having to make any assumptions about the mechanism that triggers the breaking. We carry out the construction both in flat space, in which the Lorentz group is a global spacetime symmetry, and in a generally covariant theory, in which the Lorentz group can be treated as a local internal symmetry. As an illustration of this formalism, we construct the most general effective field theory in which the rotation group remains unbroken, and show that the latter is just the Einstein-aether theory.Comment: 45 pages, no figures

Hybrid Equation/Agent-Based Model of Ischemia-Induced Hyperemia and Pressure Ulcer Formation Predicts Greater Propensity to Ulcerate in Subjects with Spinal Cord Injury

Pressure ulcers are costly and life-threatening complications for people with spinal cord injury (SCI). People with SCI also exhibit differential blood flow properties in non-ulcerated skin. We hypothesized that a computer simulation of the pressure ulcer formation process, informed by data regarding skin blood flow and reactive hyperemia in response to pressure, could provide insights into the pathogenesis and effective treatment of post-SCI pressure ulcers. Agent-Based Models (ABM) are useful in settings such as pressure ulcers, in which spatial realism is important. Ordinary Differential Equation-based (ODE) models are useful when modeling physiological phenomena such as reactive hyperemia. Accordingly, we constructed a hybrid model that combines ODEs related to blood flow along with an ABM of skin injury, inflammation, and ulcer formation. The relationship between pressure and the course of ulcer formation, as well as several other important characteristic patterns of pressure ulcer formation, was demonstrated in this model. The ODE portion of this model was calibrated to data related to blood flow following experimental pressure responses in non-injured human subjects or to data from people with SCI. This model predicted a higher propensity to form ulcers in response to pressure in people with SCI vs. non-injured control subjects, and thus may serve as novel diagnostic platform for post-SCI ulcer formation. © 2013 Solovyev et al

The paradox of productivity: agricultural productivity promotes food system inefficiency

The principal policy focus for food has been to increase agricultural productivity and to liberalize markets allowing globalized trade. This focus has led to huge growth in the supply of agricultural produce, more calories becoming available, and price declining. The availability of cheaper calories increasingly underpins diets creating malnourishment through obesity, and global competition incentivizes producers who can produce the most, cheaply, typically with environmental damage. We propose re-focusing, away from yields per unit input, to the food system's overall productivity and efficiency-the number of people that can be fed healthily and sustainably per unit input. Since the Second World War, and particularly in recent decades, the over-Arching rationale of agricultural and food trade policy has been that by increasing the productivity of agriculture and efficiency of its markets, trade will drive down food prices, drive up choices and food availability: implicitly defining more available and cheaper food as the route to achieving the international public good of global food security. Here we hypothesize that a focus on increasing availability of food, and lowering food prices through focusing on agricultural productivity and trade does reduce prices and increases availability, but also encourages the externalization of costs on health and environment, and instead of providing public goods arguably represents market failure. In other words, a focus on increasing agricultural yields and efficiency decreases the efficiency of the food system through incentivizing externalization of costs. The focus should rather be on the efficiency of the food system to deliver profits, healthy diets and a healthy planet. Reframing the productivity argument towards the efficiency of the food system provides a clear route to reducing market failure, improving public health and sustainability