Heart rate and oxygen uptake relationship: a comparison of loaded marching and running in women

Heart rate (beats · min^–1;f _c) measured during marching with a load is often used to predict the oxygen cost (1·min^–1; VO₂) of the activity. The prediction comes from thef _c/VO₂ relationship determined from laboratory measures off _c and VO₂ during treadmill running. Studies in men have suggested that this may not be appropriate although this has yet to be examined in women. This study, therefore, compared thef _c/VO₂ relationship between loaded marching and maximal running protocols in women. Sixteen female subjects [mean (SD), age 21.9 (2.3) years, height 6 (0.06) m, weight 62.6 (7.6) kg] had theirf _c (from three-lead chest electrodes) and VO₂ measured first during standard treadmill run protocols, and again 1 week later during loaded marching protocols. The slopes and intercepts determined from linear regression off _c on VO₂ for each individual for each protocol were compared as were the maximalf _c(f _cmax), VO₂ and ratings of perceived exertion (RPE) from the last work period of each protocol in pairedt-tests. The VO₂ slopes (P < 0.01) and intercepts (P < 0.05) differed significantly between loaded marching and running.f _cmax for loaded marching were 90% off _cmax for running (P < 0.01) and VO₂ for loaded marching were 80% of those for running (P < 0.01). However, RPE at the final levels for the two protocols were not significantly different. The data suggest that in women the VO₂ relationships for loaded marching and for running are different. This difference is similar to that found in men when speed is held constant and the load and gradient are varied. The results suggest that it would be erroneous to usef _c and VO₂ measured during running protocols in the laboratory to estimate energy expenditure and work intensity during loaded marching in the filed.     

Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19

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Backpack load affects lower limb muscle activity patterns of female hikers during prolonged load carriage

This study investigated the effect of prolonged load carriage on lower limb muscle activity displayed by female recreational hikers. Electromyography (EMG) signals from vastus lateralis (VL), biceps femoris (BF), semitendinosus (ST), tibialis anterior (TA) and gastrocnemius (GM) were recorded for fifteen female hikers carrying four loads (0%, 20%, 30% and 40% body weight (BW)) over 8 km. Muscle burst duration, muscle burst onset relative to initial contact and integrated EMG signals (iEMG) were calculated to evaluate muscle activity, whereas the shift in mean power frequency (MPF) was used to evaluate muscle fatigue. Increased walking distance significantly decreased the MPF of TA; decreased the iEMG for VL, ST and GM; and shortened VL muscle burst duration. Furthermore, carrying 20–40% BW loads significantly increased VL and GM iEMG and increased BF muscle burst duration, whereas a 40% BW load caused a later VL muscle burst onset. The differences observed in muscle activity with increased load mass seem to be adjustments aimed at maintaining balance and attenuating the increased loads placed on the lower limbs during gait. Based on the changes in muscle activity, a backpack load limit of 30% BW may reduce the risk of lower limb injury for female hikers during prolonged walking.     

Spatiotemporal and kinematic changes in gait while carrying an energy harvesting assault pack system

Soldiers are fielded with a variety of equipment including battery powered electronic devices. An energy harvesting assault pack (EHAP) was developed to provide a power source to recharge batteries and reduce the quantity and load of extra batteries carried into the field. Little is known about the biomechanical implications of carrying a suspended-load energy harvesting system compared to the military standard assault pack (AP). Therefore, the goal of this study was to determine the impact of pack type and load magnitude on spatiotemporal and kinematic parameters while walking at 1.34 m/s on an instrumented treadmill at decline, level, and incline grades. There was greater forward trunk lean while carrying the EHAP and the heavy load (decline: p < 0.001; level: p = 0.009; incline: p = 0.003). As load increased from light to heavy, double support stance time was longer (decline: p = 0.012; level: p < 0.001; incline: p < 0.001), strides were shorter (incline: p = 0.013), and knee flexion angle at heel strike was greater (decline: p = 0.033; level: p = 0.035; incline: p = 0.005). When carrying the EHAP, strides (decline: p = 0.007) and double support stance time (incline: p = 0.006) was longer, the knee was more flexed at heel strike (level: p = 0.014; incline: p < 0.001) and there was a smaller change in knee flexion during weight acceptance (decline: p = 0.0013; level: p = 0.007; incline: p = 0.0014). Carrying the EHAP elicits changes to gait biomechanics compared to carrying the standard AP. Understanding how load-suspension systems influence loaded gait biomechanics are warranted before transitioning these systems into military or recreational environments.     

Persistence of infection in mice inoculated intranasally with Cryptococcus neoformans

Cryptococcus neoformans was instilled intranasally into mice which were periodically sacrificed to determine the course of infection. Cryptococci persisted within the nasal passages throughout the 90 day study. Extranasal dissemination began 14–28 days after instillation and was still demonstrable 90 days post-exposure. Ten percent mortality was observed in mice receiving 10⁶ cryptococci, while no mortality was observed in mice exposed to 10³ or 10⁴ cryptococci. Our research suggests that nasal colonization with C. neoformans can precede pulmonary and systemic cryptococcosis by weeks or months.     

Intranasal Microemulsion of Sildenafil Citrate: In Vitro Evaluation and In Vivo Pharmacokinetic Study in Rabbits

The purpose of the present study was to prepare intranasal delivery system of sildenafil citrate and estimate its relative bioavailability after nasal administration in rabbits to attain rapid onset of action with good efficacy at lower doses. Sildenafil citrate saturated solubility was determined in different solvents, cosolvents, and microemulsion systems. For nasal application, sildenafil citrate was formulated in two different systems: the first was a cosolvent system (S3) of benzyl alcohol/ethanol/water/Transcutol/taurodeoxy cholate/Tween 20 (0.5:16.8:47.7:15.9:1:18.1% w/w). The second was a microemulsion system (ME6) containing Oleic acid: Labrasol/Transcutol/water (8.33:33.3:16.66:41.66% w/w). The prepared systems were characterized in relation to their clarity, particle size, viscosity, pH, and nasal ciliotoxicity. In vivo pharmacokinetic performance of the selected system ME6 (with no nasal ciliotoxicity) was evaluated in a group of six rabbits in a randomized crossover study and compared to the marketed oral tablets. The targeted solubility (>20 mg/ml) of sildenafil citrate was achieved with cosolvent systems S1, S3, and S5 and with microemulsion systems ME3–ME6. The saturated solubility of sildenafil citrate in cosolvent system S3 and microemulsion system ME6 were 22.98 ± 1.26 and 23.79 ± 1.16 mg/ml, respectively. Microemulsion formulation ME6 showed shorter t _max (0.75 h) and higher AUC_(0-∞) (1,412.42 ng h/ml) compared to the oral tablets which showed t _max equals 1.25 h and AUC_(0-∞) of 1,251.14 ng h/ml after administration to rabbits at dose level of 5 mg/kg. The relative bioavailability was 112.89%. In conclusion, the nasal absorption of sildenafil citrate microemulsion was found to be fast, indicating the potential of nasal delivery instead of the conventional oral administration of such drug.     

ELLIPSE Study: A Phase 1 study evaluating the tolerance of bevacizumab nasal spray in the treatment of epistaxis in hereditary hemorrhagic telangiectasia

Background: Hereditary hemorrhagic telangiectasia (HHT) is a dominantly inherited genetic vascular disorder in which epistaxis is the most frequent manifestation, responsible for high morbidity. Management of this symptom has no standard, and local treatments are often aggressive. Their efficacy is variable and has not been proven. Anti-angiogenic drugs, such as bevacizumab, are a new treatment strategy. Its systemic administration in patients with HHT improves liver damage-related symptoms and epistaxis. To limit the systemic adverse effects of bevacizumab and to ease administration, a local administration seems suitable. Primary objective: To evaluate the tolerance of increasing doses of bevacizumab administered as a nasal spray in patients with HHT-related epistaxis. Secondary objectives were to study the bioavailability and efficacy of bevacizumab against epistaxis when given as a nasal spray. Methodology: Phase 1, randomized, double-blind, placebo-controlled, monocentric study performed sequentially (dose escalation) on 5 groups of 8 patients. Each group was made up of 6 verum and 2 placebos. Five increasing doses of bevacizumab nasal spray (25 mg/mL) were evaluated: 12.5, 25, 50, 75 and 100 mg. Results: A total of 40 patients were included between October 2011 and October 2012. Bevacizumab nasal spray was well tolerated in all patients and the drug was not detected in their serum. No dose limiting toxicity was observed. No efficacy was observed at any dose in this study. Conclusion: Based on these results, bevacizumab nasal spray is a safe treatment of epistaxis in HHT. However, a randomized Phase 2 study is needed to determine its efficacy. Trial Registration: ClinicalTrials.gov Identifier #{"type":"clinical-trial","attrs":{"text":"NCT01507480","term_id":"NCT01507480"}}NCT01507480     

Diurnal Variation in the Symptoms of Colds and Influenza

The present research examined diurnal variation in the severity of symptoms of experimentally-induced colds and influenza. Nasal secretion was greatest in the morning, decreased over the day, and then showed a slight increase in the late evening. Colds did not change the average temperature, nor did they alter the temperature rhythm. Similar, negative results were found with alertness ratings.

Influenza B illnesses produced an increase in nasal secretion and systemic effects. The average temperature increased during this illness and subjects reported that they felt more drowsy. Diurnal variation in the severity of local and central symptoms was observed, with nasal secretion and the temperature increase being greatest in the early morning. These results have important implications for the assessment and treatment of the illnesses.