Δευτέρα, 17 Σεπτεμβρίου 2018

Genotypic Resistance to Quinolone and Tetracycline in Salmonella Dublin Strains Isolated from Humans and Animals in Brazil

Microbial Drug Resistance, Ahead of Print.


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An Efficient Genome Editing Strategy To Generate Putative Null Mutants in Caenorhabditis elegans Using CRISPR/Cas9

Null mutants are essential for analyzing gene function. Here, we describe a simple and efficient method to generate Caenorhabditis elegans null mutants using CRISPR/Cas9 and short single stranded DNA oligo repair templates to insert a universal 43-nucleotide-long knock-in cassette (STOP-IN) into the early exons of target genes. This STOP-IN cassette has stop codons in all three reading frames and leads to frameshifts, which will generate putative null mutations regardless of the reading frame of the insertion position in exons. The STOP-IN cassette also contains an exogenous Cas9 target site that allows further genome editing and provides a unique sequence that simplifies the identification of successful insertion events via PCR. As a proof of concept, we inserted the STOP-IN cassette right at a Cas9 target site in aex-2 to generate new putative null alleles by injecting preassembled Cas9 ribonucleoprotein and a short synthetic single stranded DNA repair template containing the STOP-IN cassette and two ~35-nucleotide-long homology arms identical to the sequences flanking the Cas9 cut site. We showed that these new aex-2 alleles phenocopied an existing loss-of-function allele of aex-2. We further showed that the new aex-2 null alleles could be reverted back to the wild-type sequence by targeting the exogenous Cas9 cut site included in the STOP-IN cassette and providing a single stranded wild-type DNA repair oligo. We applied our STOP-IN method to generate new putative null mutants for 20 additional genes, including three pharyngeal muscle-specific genes (clik-1, clik-2, and clik-3), and reported a high insertion rate (46%) based on the animals we screened. We showed that null mutations of clik-2 cause recessive lethality with a severe pumping defect and clik-3 null mutants have a mild pumping defect, while clik-1 is dispensable for pumping. We expect that the knock-in method using the STOP-IN cassette will facilitate the generation of new null mutants to understand gene function in C. elegans and other genetic model organisms.



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Contents



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Editorial Board



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Dual-task training of children with neuromotor disorders during robot-assisted gait therapy: prerequisites of patients and influence on leg muscle activity

Walking in daily life is complex entailing various prerequisites such as leg strength, trunk stability or cognitive and motor dual task (DT) activities. Conventional physiotherapy can be complemented with robo...

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Indeterminate biliary strictures differential diagnosis: back to the future



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Focus on Pancreatic Cancer



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Effects of resveratrol on regulation on UCP2 and cardiac function in diabetic rats

Abstract

Mitochondrial dysfunction is essential in the development and prognosis of diabetic cardiomyopathy (DCM). Resveratrol (RES) is thought as a mitochondrial protector. In this study, we hypothesized that RES may ameliorate mitochondrial function and consequently improve cardiac function in diabetic rats, and uncoupling protein 2 (UCP2) was involved in the protective effects of RES on DCM. Thirty rats were divided into three groups: normal control, DCM, and DCM+RES groups. DCM was induced by high-fat diet and streptozotocin (STZ) intraperitoneal injection, the rats in DCM+RES group received RES gavage for 16 weeks. RES improved the insulin resistance, and reduced the level of triglyceride, cholesterol, and low density lipoprotein cholesterol (LDLc) in DCM rats (all P < 0.05). Echocardiographic and hemodynamic studies revealed that RES treatment reversed the impaired diastolic and systolic cardiac function in DCM rats. Meanwhile, RES improved myocardial structural disorder and fibrosis, reserved mitochondrial membrane potential level (P < 0.05), and suppressed myocardial apoptosis in DCM rats (P < 0.05). Myocardial mitochondrial respiratory enzyme activities were improved by RES treatment in DCM rats (P < 0.05), accompanied with attenuated reactive oxygen species (ROS) generation (P < 0.05). The expression of UCP2 was further increased by RES treatment both in the myocardium of DCM rats (P < 0.05) and in the H9c2 cardiomyocytes incubated with high-glucose (P < 0.05). The protective effects of RES on high glucose-induced ROS generation, MPTP opening, Cyto c release, and cell apoptosis were all blunted by inhibiting the expression of UCP2 (all P < 0.05). In conclusion, RES treatment improved cardiac function and inhibited cardiomyocyte apoptosis, involving in ameliorating mitochondrial function in diabetic rats. UCP2 mediated the protective effects of RES on diabetic hearts.



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Indeterminate biliary strictures differential diagnosis: back to the future



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Focus on Pancreatic Cancer



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Optical probing of acetylcholine receptors on neurons in the medial habenula with a novel caged nicotine drug analogue

The Journal of Physiology, Volume 0, Issue ja, -Not available-.


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Medic Mindset Podcast: Thinking about tachycardia

Host Ginger Locke interviews Dr. Katherine Remick about how a differential diagnosis and patient history can differentiate between SVT and sinus tachycardia

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Medic Mindset Podcast: Thinking about tachycardia

Host Ginger Locke interviews Dr. Katherine Remick about how a differential diagnosis and patient history can differentiate between SVT and sinus tachycardia

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Bristol Hospital selects ESO Health Data Exchange to improve community health and safety

Greater insight and sharing of information between EMS agencies and Emergency Departments creates continuity in patient care records and timeliness of treatment options.

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Effective dose of remifentanil for intubation in children



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Medic Mindset Podcast: How to become an EMS ‘lifer’

Mitigate the effects a career in EMS can take to nurture your career longevity in EMS

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Response of rainbow trout’s ( Oncorhynchus mykiss ) hypothalamus to glucose and oleate assessed through transcription factors BSX, ChREBP, CREB, and FoxO1

Abstract

We aimed to obtain information regarding mechanisms that link glucose- and fatty acid-sensing systems to expression of neuropeptides that regulate food intake in the fish brain. We assessed the relative expression and protein levels of the transcription factors BSX, ChREBP, FoxO1, and CREB in the hypothalamus of rainbow trout (Oncorhynchus mykiss) treated for 6 h with either glucose or oleate in vivo (intra-cerebroventricular treatment with 1 µl 100 g− 1 body weight of 40 µg glucose or 1 µmol oleate) or in vitro (incubation with 4–8 mM glucose or 100–500 µM oleate). BSX levels decreased after oleate treatment for mRNA (10% in vitro and 47% in vivo) and protein (25%), while minor changes occurred after glucose treatment. CREB values generally decreased after glucose or oleate treatment for mRNA (50% in vivo) as well as the phosphorylation status of protein (80%). Foxo1 mRNA levels increased in vivo with glucose (129%) and decreased in vivo with oleate (60%), and protein phosphorylation status increased with glucose (in vivo) and oleate. mRNA values of chrebpα decreased in response to glucose and oleate, while protein levels decreased with oleate and increased with glucose. The results support the association of several transcription factors with metabolic control of food intake in fish.



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Nextivity introduces Cel-Fi GO RED FirstNet Booster

New smart signal booster delivers strong in-building cellular coverage for the nation's public safety network on bands 12 and 14 to ensure coverage during emergencies. SAN DIEGO - [Mobile World Congress Americas, Booth #S.2938] - Nextivity Inc. today introduced the Cel-Fi GO RED FirstNet Booster. The smart signal booster amplifies FirstNet service inside buildings, ensuring that first...

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Delayed parasympathetic reactivation and sympathetic withdrawal following maximal cardiopulmonary exercise testing (CPET) in hypoxia

Abstract

Purpose

This study investigated the effects of acute hypoxic exposure on post-exercise cardiac autonomic modulation following maximal cardiopulmonary exercise testing (CPET).

Methods

Thirteen healthy men performed CPET and recovery in normoxia (N) and normobaric hypoxia (H) (FiO2 = 13.4%, ≈ 3500 m). Post-exercise cardiac autonomic modulation was assessed during recovery (300 s) through the analysis of fast-phase and slow-phase heart rate recovery (HRR) and heart rate variability (HRV) indices.

Results

Both short-term, T30 (mean difference (MD) 60.0 s, 95% CI 18.2–101.8, p = 0.009, ES 1.01), and long-term, HRRt (MD 21.7 s, 95% CI 4.1–39.3, p = 0.020, ES 0.64), time constants of HRR were higher in H. Fast-phase (30 and 60 s) and slow-phase (300 s) HRR indices were reduced in H either when expressed in bpm or in percentage of HRpeak (p < 0.05). Chronotropic reserve recovery was lower in H than in N at 30 s (MD − 3.77%, 95% CI − 7.06 to − 0.49, p = 0.028, ES − 0.80) and at 60 s (MD − 7.23%, 95% CI − 11.45 to − 3.01, p = 0.003, ES − 0.81), but not at 300 s (p = 0.436). Concurrently, Ln-RMSSD was reduced in H at 60 and 90 s (p < 0.01) but not at other time points during recovery (p > 0.05).

Conclusions

Affected fast-phase, slow-phase HRR and HRV indices suggested delayed parasympathetic reactivation and sympathetic withdrawal after maximal exercise in hypoxia. However, a similar cardiac autonomic recovery was re-established within 5 min after exercise cessation. These findings have several implications in cardiac autonomic recovery interpretation and in HR assessment in response to high-intensity hypoxic exercise.



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Effects of repeated long-duration water immersions on skeletal muscle performance in well-trained male divers

Abstract

Purpose

The objective of this study was to examine the effects of repeated long-duration water immersions (WI)s at 1.35 atmospheres absolute (ATA) on neuromuscular performance in load bearing and non-load bearing muscle groups.

Methods

During a dive week (DW), fifteen well-trained male divers completed five consecutive 6-h resting dives with 18-h surface intervals while breathing compressed air at 1.35 ATA. Skeletal muscle performance assessments occurred immediately before and after each WI, and 24 and 72 h after the final WI. Exercise assessments included maximum voluntary isometric contraction (MVIC), maximal isokinetic (IK) contraction, maximum handgrip strength (MHG). Surface electromyography measured neuromuscular activation of the quadriceps, biceps brachii (BB), and brachioradialis.

Results

MVIC torque of knee extensors and BB decreased by 6% (p = 0.001) and 2% (p = 0.014), respectively, by WI 3. Maximal IK torque of knee extensors increased by 11 and 5% post-WI on WIs 3 and 5 (p < 0.001) with greater neuromuscular activation post-WI than pre-WI (p < 0.001). Maximum IK elbow flexion torque did not change throughout the DW with BB neuromuscular activation greater post-WI than pre-WI (p < 0.001). MHG force output was 4% greater post-WI than pre-WI (p < 0.001) with increased brachioradialis activation through 72-h post-WI (p < 0.001). All muscle performance metrics returned baseline levels by 72-h post-WI.

Conclusion

Our findings indicate that repeated WIs caused noticeable decrements in neuromuscular activation and performance of load bearing muscles on WI 3 while full recovery was observed by 72-h post-WI.



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Blunted satellite cell response is associated with dysregulated IGF-1 expression after exercise with age

Abstract

Purpose

Insulin-like growth factor-1 (IGF-1) regulates protein synthesis and cell cycle kinetics. Given that aging is associated with anabolic resistance, we sought to determine if the attenuated exercise-induced satellite cell (SC) expression in older muscle is associated with a blunted IGF-1 response.

Methods

SC expression (Pax7+ cells) and protein (Western blot) and mRNA (RT-PCR) expression of IGF-1 splice variants and ubiquitous (IGFBP4) and muscle-specific (IGFBP3 and -5) IGF-1 binding proteins were measured in skeletal muscle of young (Y: 22 ± 2, n = 7) and older (O: 70 ± 2, n = 7) adults up to 48 h after an acute bout of resistance exercise.

Results

SC expression was greater in Y compared to O (age; P < 0.01) and increased (interaction; P < 0.05) by 24 h after exercise in Y only. IGF-1Ea and IGF-1Eb mRNA tended to be greater in O (age; P < 0.06–0.09). IGF-1Eb mRNA increased at 48 h (time; P < 0.05), whereas IGF-1Ec mRNA increased (interaction; P < 0.05) at 24 and 48 h in O only. IGF binding protein (IGFBP)4 mRNA was greater (age; P < 0.01) in O with the increase at 24 h and 48 h (time; P < 0.01) primarily driven by changes in O (interaction; P < 0.01). Despite IGFBP3 mRNA being greater in O (age; P < 0.01) and increasing at 48 h (time; P < 0.01), there was no effect of age or exercise on IGFBP3 protein expression. In contrast, IGFBP5 mRNA was greater (age; P < 0.01) despite IGFBP5 protein expression being lower (age; P < 0.01) in O compared to Y.

Conclusions

The greater muscle-specific expression of IGF-1 family members with a blunted post-exercise SC expression may be a compensatory attempt to rescue age-related anabolic resistance.



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The acute effects of walking exercise intensity on systemic cytokines and oxidative stress

Abstract

Purpose

Oxidative stress is associated with tissue cytokine secretion although the precise mechanism(s) underpinning this relationship during high intensity intermittent exercise remains unclear. This study investigates the acute response to a bout of high intensity intermittent walking (HIIW), compared to continuous moderate intensity walking (CMW), on various cytokines and biomarkers of oxidative stress.

Methods

Seventeen (n = 17) apparently healthy male participants (aged 22.6 ± 4.6 years; \(\dot{V}{\text{O}}_{2} \max\) : 53.7 ± 7.1 ml kg−1 min−1) undertook a randomised crossover study consisting of two exercise trials: (1) HIIW requiring 3 × 5 min bursts at 80% \(\dot{V}{\text{O}}_{2} \max\) (each separated by 5 min of walking at 30% \(\dot{V}{\text{O}}_{2} \max\) ) and (2) CMW (60% \(\dot{V}{\text{O}}_{2} \max\) for 30 min). Each trial was separated by 7 days. Venous blood samples were obtained pre-exercise, post-exercise and at 2, 4, 24 and 48 h post-exercise for determination of systemic inflammation (IL-6 and TNF-α), lipid soluble antioxidants and oxidative stress (LOOH, H2O2 and the ascorbyl free radical).

Results

Both IL-6 and TNF-α increased immediately post exercise, regardless of intensity and remained elevated until at least 4 h (main effect for time; p < 0.05). While there was no change in either lipid peroxidation or free radical metabolism (Asc· and H2O2), α-tocopherol increased (pooled HIIW and CMW, p < 0.05), whereas lycopene decreased at 2 h post HIIW (p < 0.05).

Conclusion

Bouts of both HIIW and CMW promote cytokine secretion post exercise, and this seems to be independent of oxidative stress. Further investigation is required to assess how such changes may underpin some of the transient health benefits of exercise.



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Exercise-induced trunk fatigue decreases double poling performance in well-trained cross-country skiers

Abstract

Purpose

To examine the effects of exercise-induced trunk fatigue on double poling performance, physiological responses and trunk strength in cross-country skiers.

Methods

Sixteen well-trained male cross-country skiers completed two identical pre- and post-performance tests, separated by either a 25-min trunk fatiguing exercise sequence or rest period in a randomized, controlled cross-over design. Performance tests consisted of a maximal trunk flexion and extension test, followed by a 3-min double poling (DP) test on a ski ergometer.

Results

Peak torque during isometric trunk flexion (− 66%, p < .001) and extension (− 7.4%, p = .03) decreased in the fatigue relative to the control condition. Mean external power output during DP decreased by 14% (p < .001) and could be attributed both to reduced work per cycle (− 9%, p = .019) and a reduced cycle rate (− 6%, p = .06). Coinciding physiological changes in peak oxygen uptake (− 6%, p < .001) and peak ventilation (− 7%, p < .001) could be observed. Skiers chose a more even-pacing strategy when fatigued, with the performance difference between fatigue and control condition being most prominent during the first 2 min of the post-test.

Conclusions

In well-trained cross-country skiers, exercise-induced trunk fatigue led to a substantial decrease in DP performance, caused by both decreased work per cycle and cycle rate and accompanied by reduced aerobic power. Hence, improved fatigue resistance of the trunk may therefore be of importance for high-intensity DP in cross-country skiing.



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Compression socks and the effects on coagulation and fibrinolytic activation during marathon running

Abstract

Purpose

Compression socks are frequently used in the treatment and prevention of lower-limb pathologies; however, when combined with endurance-based exercise, the impact of compression socks on haemostatic activation remains unclear.

Objectives

To investigate the effect of wearing compression socks on coagulation and fibrinolysis following a marathon.

Methods

Sixty-seven participants [43 males (mean ± SD: age: 46.7 ± 10.3 year) and 24 females (age: 40.0 ± 11.0 year)] were allocated into a compression (SOCK, n = 34) or control (CONTROL, n = 33) group. Venous blood samples were obtained 24 h prior to and immediately POST-marathon, and were analyzed for thrombin–anti-thrombin complex (TAT), tissue factor (TF), tissue factor pathway inhibitor (TFPI), and D-Dimer.

Results

Compression significantly attenuated the post-exercise increase in D-Dimer compared to the control group [median (range) SOCK: + 9.02 (− 0.34 to 60.7) ng/mL, CONTROL: + 25.48 (0.95–73.24) ng/mL]. TF increased following the marathon run [median (range), SOCK: + 1.19 (− 7.47 to 9.11) pg/mL, CONTROL: + 3.47 (− 5.01 to 38.56) pg/mL] in all runners. No significant post-exercise changes were observed for TAT and TFPI.

Conclusions

While activation of coagulation and fibrinolysis was apparent in all runners POST-marathon, wearing compression socks was shown to reduce fibrinolytic activity, as demonstrated by lower D-Dimer concentrations. Compression may reduce exercise-associated haemostatic activation when completing prolonged exercise.



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Aortic stiffness, central pulse pressure and cognitive function following acute resistance exercise

Abstract

Introduction

While resistance exercise (RE) is known to be beneficial for overall health, one bout of RE acutely increases aortic stiffness and pulse pressure (PP). Increases in aortic stiffness and PP in a setting of aging has been shown to detrimentally impact cognitive function. This study examined whether increased aortic stiffness and PP from an acute bout of RE is associated with cognitive function.

Methods

Thirty-five participants (21 ± 2 years) underwent cognitive testing before and after either an acute bout of RE or a non-exercise time-control condition. Cognitive function was assessed as reaction time and accuracy during memory recognition, attention (Flanker) and working memory (N-back) tasks. Aortic stiffness and PP were measured via pulse wave velocity (PWV) and pulse wave analysis, respectively, using a brachial oscillometric device.

Results

There were significant increases in aortic PWV and aortic PP following RE (p < 0.05) with no change in PWV or PP following the non-exercise control condition (p > 0.05). There was no change in accuracy metrics (% hits) across conditions for any cognitive task (p > 0.05). There was a condition-by-time interaction for reaction time for the memory task (p < 0.05) driven by a significant decrease in reaction times following RE (p < 0.05) with no change in reaction time following the non-exercise control (p > 0.05).

Conclusion

Functional increases in aortic stiffness and pulse pressure following acute RE occur in the absence of detrimental changes in cognitive function in young, healthy adults.



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Step time asymmetry increases metabolic energy expenditure during running

Abstract

To improve locomotor performance, coaches and clinicians encourage individuals with unilateral physical impairments to minimize biomechanical asymmetries. Yet, it is unknown if biomechanical asymmetries per se, affect metabolic energy expenditure in individuals with or without unilateral impairments during running. Thus, inter-leg biomechanical asymmetries may or may not influence distance-running performance. Purpose: We sought to determine whether running with asymmetric step times affects metabolic rate in unimpaired individuals. Methods: Ten unimpaired individuals were instructed to run on a force-measuring treadmill at 2.8 m/s and contact the ground simultaneously to the beat of an audible metronome. The metronome either played at time intervals equal to the respective participant's preferred step times (0% asymmetry), or at time intervals that elicited asymmetric step times between legs (7, 14, and 21% step time asymmetry); stride time remained constant across all trials. We measured ground reaction forces and metabolic rates during each trial. Results: Every 10% increase in step time and stance average vertical ground reaction force asymmetry increased net metabolic power by 3.5%. Every 10% increase in ground contact time asymmetry increased net metabolic power by 7.8%. More asymmetric peak braking and peak propulsive ground reaction forces, leg stiffness, as well as positive and negative external mechanical work, but not peak vertical ground reaction force, increased net metabolic power during running. Step time asymmetry increases the net metabolic power of unimpaired individuals during running. Therefore, unimpaired individuals likely optimize distance-running performance by using symmetric step times and overall symmetric biomechanics.



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The effects of multi-stage exercise with and without concurrent cognitive performance on cardiorespiratory and cerebral haemodynamic responses

Abstract

Introduction

Studies of cerebral haemodynamics have shown changes with increased exercise intensity, but the patterns have been highly variable and reliable associations with cognitive performance have not been identified. The aim of this study was to examine whether exercise-induced changes in oxygenated haemoglobin (O2Hb) led to changes in concomitant cognitive performance.

Methods

This study examined cardiorespiratory and cerebral haemodynamics during multi-stage exercise from rest to exhaustion, with (Ex + C) and without (Ex) concurrent cognitive performance (Go/No-go task).

Results

The presence of the cognitive task affected both cardiorespiratory and cerebral haemodynamics. The patterns in the cerebral haemodynamics during Ex and Ex + C diverged above the respiratory compensation threshold (RCT), but differences were significant only at 100% \(\dot {V}_}}\) , displaying increased deoxygenated haemoglobin (HHb), decreased difference between oxygenated and deoxygenated haemoglobin (HbDiff), and decreased cerebral oxygenation (COx) during Ex + C. More complex haemodynamic trends against intensity during Ex + C suggested that the presence of a cognitive task increases cerebral metabolic demand at high exercise intensities. The levels of O2Hb, HHb, HbDiff and total haemoglobin increased most steeply at intensities around the RCT during both Ex and Ex + C, but these changes were not accompanied by improved cognitive performance.

Conclusion

The primary hypothesis, that cognitive performance would match changes in O2Hb, was not supported. Small variations in reaction time and response accuracy across exercise intensities were not significant, suggesting that cognitive performance is unaffected by intense short-duration exercise. Our results add further evidence that exercise-induced changes in cerebral haemodynamics do not affect cognitive performance.



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Spatial and temporal migration of sweat: from skin to clothing

Abstract

Purpose

Moisture accumulation in clothing affects human performance and productivity through its impact on thermal balance and various aspects of discomfort. Building on our laboratory's work on mapping sweat production across the body, this study aimed to obtain detailed spatial and temporal maps showing how this sweat migrates into a single clothing layer (T-shirt) during physical exercise.

Method

Eight male participants performed running exercise in a warm environment. Garment sweat absorption was mapped over a total running time of 50 min, in 10 separated running trials of different durations (5 min increments). After running, the garment was dissected into 22 different parts and local sweat absorption (ABSlocal) was quantified by weighing each garment part before and after drying. From ABSlocal, garment total sweat absorption (ABStotal) was estimated.

Results

After 50 min, Tcore rose from 37 ± 0.2 to 38.6 ± 0.3 °C, HR increased from 69 ± 15 to 163 ± 12 bpm (p < 0.001), GSL was 586 ± 86 g m−2. Clear patterns of sweat absorption reduction from superior-to-inferior and from medial-to-lateral T-shirt zones were observed, with the mid back medial and the low front hem showing the highest, respectively.

Conclusions

Quantitative data on garment total and regional sweat absorption were obtained and considerable variation between different garment zones was identified. These data can support the development of sport and personal protective clothing with the end goal to prevent workers' heat-related injuries as well as maximise human performance and productivity.



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Analysis of oxygen uptake efficiency parameters in young people with cystic fibrosis

Abstract

Purpose

This study characterised oxygen uptake efficiency (OUE) in children with mild-to-moderate cystic fibrosis (CF). Specifically, it investigated (1) the utility of OUE parameters as potential submaximal surrogates of peak oxygen uptake ( \(\dot {V}_{2{\text{peak}}}}\) ), and (2) the relationship between OUE and disease severity.

Methods

Cardiopulmonary exercise test (CPET) data were collated from 72 children [36 CF, 36 age- and sex-matched controls (CON)], with OUE assessed as its highest 90-s average (plateau; OUEP), the gas exchange threshold (OUEGET) and respiratory compensation point (OUERCP). Pearson's correlation coefficients, independent t tests and factorial ANOVAs assessed differences between groups and the use of OUE measures as surrogates for \(\dot {V}_{2{\text{peak}}}}\) .

Results

A significant (p < 0.05) reduction in allometrically scaled \(\dot {V}_{2{\text{peak}}}}\) and all OUE parameters was found in CF. Significant (p < 0.05) correlations between measurements of OUE and allometrically scaled \(\dot {V}_{2{\text{peak}}}}\) , were observed in CF (r = 0.49–0.52) and CON (r = 0.46–0.52). Furthermore, measures of OUE were significantly (p < 0.05) correlated with pulmonary function (FEV1%predicted) in CF (r = 0.38–0.46), but not CON (r = −0.20–0.14). OUEP was able to differentiate between different aerobic fitness tertiles in CON but not CF.

Conclusions

OUE parameters were reduced in CF, but were not a suitable surrogate for \(\dot {V}_{2{\text{peak}}}}\) . Clinical teams should, where possible, continue to utilise maximal CPET parameters to measure aerobic fitness in children and adolescents with CF. Future research should assess the prognostic utility of OUEP as it does appear sensitive to disease status and severity.



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Comparison of two methods of determining lung de-recruitment, using the forced oscillation technique

Abstract

Airway closure has proved to be important in a number of respiratory diseases and may be the primary functional defect in asthma. A surrogate measure of closing volume can be identified using the forced oscillation technique (FOT), by performing a deflation maneuver and examining the resultant reactance (Xrs) lung volume relationship. This study aims to determine if a slow vital capacity maneuver can be used instead of this deflation maneuver and compare it to existing more complex techniques. Three subject groups were included in the study; healthy (n = 29), asthmatic (n = 18), and COPD (n = 10) for a total of 57 subjects. Reactance lung volume curves were generated via FOT recordings during two different breathing manoeuvres (both pre and post bronchodilator). The correlation and agreement between surrogate closing volume (Volcrit) and reactance (Xrscrit) at this volume was analysed. The changes in Volcrit and Xrscrit pre and post bronchodilator were also analysed. Across all three subject groups, the two different measures of Volcrit were shown to be statistically equivalent (p > 0.05) and demonstrated a strong fit to the data (R2 = 0.49, 0.78, 0.59, for asthmatic, COPD and healthy subject groups, respectively). A bias was evident between the two measurements of Xrscrit with statistically different means (p < 0.05). However, the two measurements of Xrscrit displayed the same trends. In conclusion, we have developed an alternative technique for measuring airway closure from FOT recordings. The technique delivers equivalent and possibly more sensitive results to previous methods while being simple and easily performed by the patient.



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Muscle fatigue in response to low-load blood flow-restricted elbow-flexion exercise: are there any sex differences?

Abstract

Purpose

This study aimed to determine whether men and women display a different magnitude of muscle fatigue in response to high-load (HL) and low-load blood flow-restricted (LLBFR) elbow-flexion exercise. We also explored to which extent both exercise protocols induce similar levels of muscle fatigue (i.e., torque decrement).

Methods

Sixty-two young participants (31 men and 31 women) performed dynamic elbow flexions at 20 and 75% of one-repetition maximum for LLBFR and HL exercise, respectively. Maximum voluntary isometric contractions were performed before and after exercise to quantify muscle fatigue.

Results

Men and women exhibited similar magnitude of relative torque decrement after both exercise protocols (p > 0.05). HL was more fatiguing (∆ torque output: 11.9 and 23 N.m in women and men, respectively) than LLBFR resistance exercise (∆ torque output: 8.3 and 15.4 N.m in women and men, respectively) in both sexes, but this was largely attenuated after controlling for the differences in volume load between protocols (p > 0.05).

Conclusions

These data show that torque decrement in response to LLBFR and HL dynamic elbow-flexion exercise does not follow a sexually dimorphic pattern. Our data also indicate that, if performed in a multiple-set fashion and prescribed for a given volume load, elbow-flexion LLBFR exercise induces similar levels of fatigue as HL acute training. Importantly, this occurs similarly in both sexes.



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Muscle health and performance in monozygotic twins with 30 years of discordant exercise habits

Abstract

Introduction

Physical health and function depend upon both genetic inheritance and environmental factors (e.g., exercise training).

Purpose

To enhance the understanding of heritability/adaptability, we explored the skeletal muscle health and physiological performance of monozygotic (MZ) twins with > 30 years of chronic endurance training vs. no specific/consistent exercise.

Methods

One pair of male MZ twins (age = 52 years; Trained Twin, TT; Untrained Twin, UT) underwent analyses of: (1) anthropometric characteristics and blood profiles, (2) markers of cardiovascular and pulmonary health, and (3) skeletal muscle size, strength, and power and molecular markers of muscle health.

Results

This case study represents the most comprehensive physiological comparison of MZ twins with this length and magnitude of differing exercise history. TT exhibited: (1) lower body mass, body fat%, resting heart rate, blood pressure, cholesterol, triglycerides, and plasma glucose, (2) greater relative cycling power, anaerobic endurance, and aerobic capacity (VO2max), but lower muscle size/strength and poorer muscle quality, (3) more MHC I (slow-twitch) and fewer MHC IIa (fast-twitch) fibers, (4) greater AMPK protein expression, and (5) greater PAX7, IGF1Ec, IGF1Ea, and FN14 mRNA expression than UT.

Conclusions

Several measured differences are the largest reported between MZ twins (TT expressed 55% more MHC I fibers, 12.4 ml/kg/min greater VO2max, and 8.6% lower body fat% vs. UT). These data collectively (a) support utilizing chronic endurance training to improve body composition and cardiovascular health and (b) suggest the cardiovascular and skeletal muscle systems exhibit greater plasticity than previously thought, further highlighting the importance of studying MZ twins with large (long-term) differences in exposomes.



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Validity of a triaxial accelerometer and simplified physical activity record in older adults aged 64–96 years: a doubly labeled water study

Abstract

Background

The aim was to examine the validity of a triaxial accelerometer (ACCTRI) and a simplified physical activity record (sPAR) in estimating total energy expenditure (TEE) and physical activity level (PAL) in older adults with the doubly labeled water (DLW) method.

Methods

A total of 44 Japanese elderly individuals (64–96 years), of which 28 were community-dwelling healthy adults with or without sporting habits (S or NS group) and 16 were care home residents with frailty (F group), were included in the study. Basal metabolic rate (BMR) was measured by indirect calorimetry, TEE was obtained by the DLW method, and PAL was calculated as TEE/BMR. Daily step count was monitored by a pedometer (Lifecorder). The 24-h average metabolic equivalent was assessed by ACCTRI and sPAR.

Results

The TEEDLW in men was 2704 ± 353, 2308 ± 442, and 1795 ± 338 kcal d−1, and that in women was 2260 ± 208, 1922 ± 285, and 1421 ± 274 kcal d−1 for the S, NS, and F groups, respectively. ACCTRI and sPAR systematically underestimated actual TEE (− 14.2 ± 11.6 and − 15.3 ± 12.3% for ACCTRI and sPAR, respectively). After diet-induced thermogenesis was taken into account for ACCTRI and sPAR, TEEDLW was significantly correlated with TEEACCTRI (R2 = 0.714) and TEEsPAR (R2 = 0.668). PALDLW was also significantly correlated with PALACCTRI (R2 = 0.438) and PALsPAR (R2 = 0.402).

Conclusions

Age, living conditions, frailty, and sporting habits contribute to TEE and PAL in the elderly population. ACCTRI and sPAR underestimated TEE and PAL, and adequate corrections are required. The corrected ACCTRI and sPAR are both useful tools to estimate TEE and PAL.



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Changes in pulmonary oxygen uptake and muscle deoxygenation kinetics during cycling exercise in older women performing walking training for 12 weeks

Abstract

Purpose

This study examined the hypothesis that walking training (WT) could accelerate the slowed time constant (τ) of phase II in pulmonary oxygen uptake ( \(\dot {V}\) O2) on-kinetics in older women. Also, we aimed to demonstrate that O2 delivery and O2 utilization were better matched at the site of gas exchange in exercising muscles when τ \(\dot {V}\) O2 was shortened.

Methods

20 recreationally active older women underwent WT sessions of approximately 60 min, 3–4 times a week for 12 weeks. We assessed \(\dot {V}\) O2, heart rate (HR) and deoxygenated-hemoglobin concentration ([HHb]) kinetics during a constant-load exercise test before training (0 week—Pre), and at 6 and 12 weeks (6 weeks—Mid, 12 weeks—Post) throughout the training period.

Results

Maximal oxygen uptake ( \(\dot {V}\) O2max) was unchanged throughout the training program. τHR tended to decline at Mid (58.6 ± 22.0 s), and was significantly shorter at Post (51.7 ± 21.7 s, p = 0.01) compared to Pre (67.1 ± 23.8 s). τ \(\dot {V}\) O2 significantly decreased from 38.9 ± 8.6 s for Pre, to 31.5 ± 7.9 s for Mid (p = 0.02), and 32.3 ± 10.5 s for Post (p = 0.03). The normalized [HHb] to \(\dot {V}\) O2 ratio (Δ[HHb]/Δ \(\dot {V}\) O2) at Pre (1.32 ± 0.93) gradually approached the perfectly matched value (= 1.0) at Mid (1.15 ± 0.61) and Post (1.07 ± 0.52).

Conclusions

The restoration to baseline (≒ 30 s) of the slower τ \(\dot {V}\) O2 due to WT, which may reflect better matching of O2 delivery and O2 utilization at the site of gas exchange, suggests that a longer period of WT could be a useful tool for improving exercise tolerance in older individuals.



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Boon or Burden: The Effect of Implementing Evidence-Based Practices on Teachers’ Emotional Exhaustion

Abstract

This study examined the association between (1) beginning-of-the-year emotional exhaustion and use of three evidence-based practices (EBP) for children with autism spectrum disorder; and (2) use of these EBP and end-of-year emotional exhaustion among 46 kindergarden to 2nd grade autism support teachers participating in a randomized trial. Emotional exhaustion was measured at the end and beginning of the school year using a subscale of the Maslach Burnout Inventory. Fidelity was measured using monthly observations, coded by research assistants trained to reliability. Correlations were used to examine unadjusted associations and ordinary least squares regression was used to examine associations adjusted for beginning-of-year burnout, years teaching, and average change in student cognitive functioning. Emotional exhaustion at the beginning of the year was not associated with EBP use. Greater fidelity to each EBP was associated with lower end-of-year emotional exhaustion (coefficients ranging from − .34 to − 1.13, all p's < .05). Results indicate that helping teachers implement EBP with greater fidelity may help reduce burnout, a substantial challenge in the field.



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Editorial Board

Publication date: October 2018

Source: Journal of Environmental Radioactivity, Volumes 193–194

Author(s):



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Required cefazolin concentration to maximize diagnostic accuracy of the basophil activation test for cefazolin-induced anaphylaxis

Abstract

Purpose

Identifying the causative agent of perioperative anaphylaxis is key to preventing its recurrence. Besides skin testing, the basophil activation test (BAT) is increasingly being accepted as an additional and reliable method. Cefazolin seems to be a major cause of perioperative anaphylaxis. However, few studies have described use of the BAT for cefazolin-induced anaphylaxis. In this study, we aimed to determine the optimum cefazolin concentration required in the BAT for an accurate diagnosis.

Methods

Seven patients who presented with immediate hypersensitivity to cefazolin and 21 control subjects were studied. We conducted skin tests and performed BATs using both CD203c and CD63 as markers of activated basophils. We measured the ratio of activated basophils after stimulation with serial dilutions of cefazolin and investigated the cefazolin concentration that resulted in better sensitivity and specificity.

Results

All patients demonstrated positive reactions to cefazolin, while all control subjects showed negative reactions on skin tests. The net percentage of both CD203c- and CD63-labeled activated basophils was greater when higher concentrations of cefazolin than previously reported were used. In control subjects, however, the number of activated basophils by cefazolin stimulation was negligible regardless of its concentration. In the case of CD203c, the sensitivity was 86% with a cefazolin concentration of 3 mg/ml, while in the case of CD63, the sensitivity was 100% with a cefazolin concentration of 10 mg/ml.

Conclusion

Using a higher concentration of cefazolin than previously reported for the BAT might increase the accuracy of diagnosis of cefazolin-induced anaphylaxis.



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Long-term outcomes of sport-related brain injuries: A psychophysiological perspective

Publication date: October 2018

Source: International Journal of Psychophysiology, Volume 132, Part A

Author(s): R. Davis Moore, Dave Ellemberg



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Editorial Board

Publication date: October 2018

Source: International Journal of Psychophysiology, Volume 132, Part A

Author(s):



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International Organization of Psychophysiology

Publication date: October 2018

Source: International Journal of Psychophysiology, Volume 132, Part A

Author(s):



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Evolutionarily conserved coding properties favour the neuronal representation of heterospecific signals of a sympatric katydid species

Abstract

To function as a mechanism in premating isolation, the divergent and species-specific calling songs of acoustic insects must be reliably processed by the afferent auditory pathway of receivers. Here, we analysed the responses of interneurons in a katydid species that uses long-lasting acoustic trills and compared these with previously reported data for homologous interneurons of a sympatric species that uses short chirps as acoustic signals. Some interneurons of the trilling species respond exclusively to the heterospecific chirp due to selective, low-frequency tuning and "novelty detection". These properties have been considered as evolutionary adaptations in the sensory system of the chirper, which allow it to detect signals effectively during the simultaneous calling of the sympatric sibling species. We propose that these two mechanisms, shared by the interneurons of both species, did not evolve in the chirper to guarantee its ability to detect the chirp under masking conditions. Instead we suggest that chirpers evolved an additional, 2-kHz component in their song and exploited pre-existing neuronal properties for detecting their song under masking noise. The failure of some interneurons to respond to the conspecific song in trillers does not prevent intraspecific communication, as other interneurons respond to the trill.



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Genomic screening in rare disorders: New mutations and phenotypes, highlighting ALG14 as a novel cause of severe intellectual disability

Clinical Genetics, Volume 0, Issue ja, -Not available-.


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Genomic duplication in the 19q13.42 imprinted region identified as a new genetic cause of intrauterine growth restriction

Clinical Genetics, Volume 0, Issue ja, -Not available-.


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PharmGKB summary: oxycodone pathway, pharmacokinetics

No abstract available

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Functional expression of human arylamine N-acetyltransferase NAT1*10 and NAT1*11 alleles: a mini review

The arylamine N-acetyltransferase (NAT) nomenclature committee assigns functional phenotypes for human arylamine N-acetyltransferase 1 (NAT1) alleles in those instances in which the committee determined a consensus has been achieved in the scientific literature. In the most recent nomenclature update, the committee announced that functional phenotypes for NAT1*10 and NAT1*11 alleles were not provided owing to a lack of consensus. Phenotypic inconsistencies observed among various studies for NAT1*10 and NAT1*11 may be owing to variable allelic expression among different tissues, the limitations of the genotyping assays (which mostly relied on techniques not involving direct DNA sequencing), the differences in recombinant protein expression systems used (bacteria, yeast, and mammalian cell lines) and/or the known inherent instability of human NAT1 protein, which requires very careful handling of native and recombinant cell lysates. Three recent studies provide consistent evidence of the mechanistic basis underlying the functional phenotype of NAT1*10 and NAT1*11 as 'increased-activity' alleles. Some NAT1 variants (e.g. NAT1*14, NAT1*17, and NAT1*22) may be designated as 'decreased-activity' alleles and other NAT1 variants (e.g. NAT1*15 and NAT1*19) may be designated as 'no-activity' alleles compared with the NAT1*4 reference allele. We propose that phenotypic designations as 'rapid' and 'slow' acetylator should be discontinued for NAT1 alleles, although these designations remain very appropriate for NAT2 alleles. Correspondence to David W. Hein, PhD, Kosair Charities Clinical and Translational Research Building, Room 303, 505 South Hancock Street, Louisville, KY 40202-1617, USA Tel: +1 502 852 6252; fax: +1 502 852 7868; e-mail: d.hein@louisville.edu Received May 17, 2018 Accepted August 28, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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The role of genetic polymorphisms in the thymidylate synthase (TYMS) gene in methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia

Objective Methotrexate (MTX) is an important drug in the treatment of pediatric acute lymphoblastic leukemia (ALL). MTX is cytotoxic as it impairs DNA and RNA synthesis by inhibiting the enzymes dihydrofolate reductase (DHFR) and thymidylate synthase (TYMS). The association between genetic variants within the TYMS gene and MTX-induced toxicity has been studied, but results are inconsistent. We determined the role of three previously described variants within the TYMS gene and MTX-induced oral mucositis in a prospective cohort of Dutch children with ALL and performed a meta-analysis of the previous results. Materials and methods We analyzed the presence of a 28-base pair tandem repeat (rs34743033; 2R3R), a single nucleotide polymorphism present within the 28-base pair repeat on the 3R allele (rs2853542; 3RG>C) and a 6-base pair deletion (rs15126436; TTAAAG) within the TYMS gene in germline DNA of 117 pediatric patients with ALL. Oral mucositis was defined as grade≥3 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v.3.0. Data were analyzed for the individual rs34743033 (2R3R) and rs151264360 (6 bp deletion) polymorphisms, whereas rs2853542 (3RG>C) was combined with rs34743033 (2R3R) and analyzed according to predicted expression levels of TYMS: low expression (2R/2R, 2R/3RC and 3RC/3RC), median expression (2R/3RG and 3RC/3RG) and high expression (3RG/3RG). We performed a meta-analysis of the current literature on these polymorphisms in relation to oral mucositis using a fixed effects model. Results The 2R2R genotype (rs34743033) was not significantly associated with developing MTX-induced oral mucositis compared with the 2R3R/3R3R genotypes, which was confirmed in a meta-analysis [odds ratio (OR): 1.17 (0.62–2.19)]. Patients carrying the low-expression TYMS genotype (2R2R, 2R3RC, 3RC3RC) had an increased odds of developing MTX-induced oral mucositis [OR: 2.42 (0.86–6.80)], which did not reach statistical significance. The 6-bp deletion [rs151264360, OR: 0.79 (0.20–3.19)] was not associated with the development of MTX-induced oral mucositis. Conclusion The TYMS 6-bp deletion and 2R3R polymorphism were not associated with MTX-induced oral mucositis. Validation studies in prospective cohorts are necessary to assess the possible role of the low-expression TYMS genotypes in relation to MTX-induced oral mucositis. Correspondence to Sandra G. Heil, PhD, Department of Clinical Chemistry, Erasmus University Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands Tel: +31 10 703 2433; fax: +31 10 704 4895; e-mail: s.heil@erasmusmc.nl Received February 5, 2018 Accepted July 25, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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