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Aims Anterior lumbar interbody fusion procedures (ALIF) and total disc replacement (TDR) with anterior exposure of the lumbar spine entail a risk of a vascular injury and dysfunction of the sympathetic and parasympathetic nerves due to disturbance of the inferior and superior hypogastric plexus. While retrograde ejaculation is a known complication of the anterior spinal approach in males, post-operative sexual as well as urinary function in females has not yet been thoroughly investigated and was hence the aim of this study. Methods Fifteen female patients documented their sexual and urinary function preoperatively, 3 months and 6 months postoperatively, using the validated questionnaires FSFI (Female Sexual Function Index) and ICIQ (International Consultation of Incontinence Questionnaire). Randomization tests were used to statistically analyze expectation values over time (two-sided, P < 0.05). Results While no statistically significant change in the total FSFI score occurred over time, a significant increase in FSFI desire score was noted between preoperative (2.95 +/- 0.8) and 6 months follow-up (3.51 +/- 0.6, P = 0.02). Urinary continence remained unchanged over time. Conclusion In summary, ALIF and lumbar TDR do not seem to negatively influence sexual and urinary function in females. In contrast, increased sexual desire was noted, likely secondary to post-surgical pain relief.
Symptoms of anxiety and depression in young athletes using the hospital anxiety and depression scale
(2018)
Elite young athletes have to cope with multiple psychological demands such as training volume, mental and physical fatigue, spatial separation of family and friends or time management problems may lead to reduced mental and physical recovery. While normative data regarding symptoms of anxiety and depression for the general population is available (Hinz and Brahler, 2011), hardly any information exists for adolescents in general and young athletes in particular. Therefore, the aim of this study was to assess overall symptoms of anxiety and depression in young athletes as well as possible sex differences. The survey was carried out within the scope of the study "Resistance Training in Young Athletes" (KINGS-Study). Between August 2015 and September 2016, 326 young athletes aged (mean +/- SD) 14.3 +/- 1.6 years completed the Hospital Anxiety and Depression Scale (HAD Scale). Regarding the analysis of age on the anxiety and depression subscales, age groups were classified as follows: late childhood (12-14 years) and late adolescence (15-18 years). The participating young athletes were recruited from Olympic weight lifting, handball, judo, track and field athletics, boxing, soccer, gymnastics, ice speed skating, volleyball, and rowing. Anxiety and depression scores were (mean +/- SD) 4.3 +/- 3.0 and 2.8 +/- 2.9, respectively. In the subscale anxiety, 22 cases (6.7%) showed subclinical scores and 11 cases (3.4%) showed clinical relevant score values. When analyzing the depression subscale, 31 cases (9.5%) showed subclinical score values and 12 cases (3.7%) showed clinically important values. No significant differences were found between male and female athletes (p >= 0.05). No statistically significant differences in the HADS scores were found between male athletes of late childhood and late adolescents (p >= 0.05). To the best of our knowledge, this is the first report describing questionnaire based indicators of symptoms of anxiety and depression in young athletes. Our data implies the need for sports medical as well as sports psychiatric support for young athletes. In addition, our results demonstrated that the chronological classification concerning age did not influence HAD Scale outcomes. Future research should focus on sports medical and sports psychiatric interventional approaches with the goal to prevent anxiety and depression as well as teaching coping strategies to young athletes.
Research question: This study aimed to establish reference values in 1-14 year old healthy children and to implement FPA-percentile curves for daily clinical use. Methods: 5910 healthy children performed at least 3 repetitions of barefoot walking over an instrumented walkway using a pressure measurement platform. The FPA [degrees] was extracted and analyzed by age and gender (mean +/- standard deviation; median with percentiles, MANOVA (age, gender) and Wilcoxon-Signed-Rank test for intra-individual side differences (alpha = 0.05). Results: FPA maximum was observed in 2-year-old children and diminished significant until the age of 4 to moderate out-toeing. For ages 5-14, no statistically significant differences in FPA values were present (p > 0.05). MANOVA confirmed age (p < 0.001) and gender (p < 0.001) as significant FPA influencing factors, without combined effect (p > 0.05). In every age group, right feet showed significantly greater out-toeing (p < 0.05). Significance: Percentile values indicate a wide FPA range in children. FPA development in young children shows a spontaneous shift towards moderate external rotation (age 2-4), whereby in-toeing <= 1-5 degrees can be present, but can return to normal. Bilateral in-toeing after the age of four and unilateral in-toeing after the age of seven should be monitored.
Vitamin D, either in its D-2 or D-3 form, is essential for normal human development during intrauterine life, kidney function and bone health. Vitamin D deficiency has also been linked to cancer development and some auto immune diseases. Given this huge impact of vitamin Don human health, it is important for daily clinical practice and clinical research to have reliable tools to judge on the vitamin D status. The major circulating form of vitamin D is 25-hydroxyvitamin D (25(OH)D), although it is not the most active metabolite, the concentrations of total 25-hydroxyvitamin D in the serum are currently routinely used in clinical practice to assess vitamin D status. In the circulation, vitamin D - like other steroid hormones - is bound tightly to a special carrier - vitamin D-binding protein (DBP). Smaller amounts are bound to blood proteins - albumin and lipoproteins. Only very tiny amounts of the total vitamin D are free and potentially biologically active. Currently used vitamin D assays do not distinguish between the three forms of vitamin D - DBP-bound vitamin D, albumin-bound vitamin D and free, biologically active vitamin D. Diseases or conditions that affect the synthesis of DBP or albumin thus have a huge impact on the amount of circulating total vitamin D. DBP and albumin are synthesized in the liver, hence all patients with an impairment of liver function have alterations in their total vitamin D blood concentrations, while free vitamin D levels remain mostly constant. Sex steroids, in particular estrogens, stimulate the synthesis of DBP. This explains why total vitamin D concentrations are higher during pregnancy as compared to nonpregnant women, while the concentrations of free vitamin D remain similar in both groups of women. The vitamin D-DBP as well as vitamin D-albumin complexes are filtered through the glomeruli and re-uptaken by megalin in the proximal tubule. Therefore, all acute and chronic kidney diseases that are characterized by a tubular damage, are associated with a loss of vitamin D-DBP complexes in the urine. Finally, the gene encoding DBP protein is highly polymorphic in different human racial groups. In the current review, we will discuss how liver function, estrogens, kidney function and the genetic background might influence total circulating vitamin D levels and will discuss what vitamin D metabolite is more appropriate to measure under these conditions: free vitamin D or total vitamin D.
Background Previous studies found evidence that dispositional optimism is related to lower pain sensitivity. Recent findings suggest that temporarily increasing optimism by means of imagining a positive future may also have pain-alleviating effects. Objectives The present experiment was designed to investigate conditioned pain modulation (CPM) as a potential underlying mechanism of this pain-alleviating effect of induced optimism. Methods For this purpose, 45 healthy participants were randomized into an optimistic or neutral imagery condition. Additionally, participants completed questionnaires on dispositional optimism, pain catastrophizing and pain expectations. CPM was assessed by delivering a series of five heat pain stimuli on the nondominant hand before and during immersion of the dominant hand in water of 5 degrees C for 70 s. Results A clear CPM effect was found, that is heat pain reports were lower during simultaneous cold water stimulation. Although the optimism manipulation successfully increased optimism, it did not affect pain ratings or CPM. Post hoc analyses indicated that dispositional optimism was not associated with the magnitude of CPM, but pain catastrophizing and pain expectations did significantly correlate with the CPM effect. Conclusion Pain-specific but not general cognitions appear to influence endogenous pain modulation. Significance Conditioned pain modulation is not the underlying mechanism of the pain-alleviating effects of induced optimism. However, pain-specific cognitions including pain catastrophizing and pain expectations affect endogenous pain modulation which should be taken into account in treatment and CPM research.
Objective: The aim of the present study was to examine the effect of Cold Water Immersion (CWI) on the recovery of physical performance, hematological stress markers and perceived wellness (i.e., Hooper scores) following a simulated Mixed Martial Arts (MMA) competition. Methods: Participants completed two experimental sessions in a counter-balanced order (CWI or passive recovery for control condition: CON), after a simulated MMAs competition (3 x 5-min MMA rounds separated by 1-min of passive rest). During CWI, athletes were required to submerge their bodies, except the trunk, neck and head, in the seated position in a temperature-controlled bath (similar to 10 degrees C) for 15-min. During CON, athletes were required to be in a seated position for 15-min in same room ambient temperature. Venous blood samples (creatine kinase, cortisol, and testosterone concentrations) were collected at rest (PRE-EX, i.e., before MMAs), immediately following MMAs (POST-EX), immediately following recovery (POST-R) and 24 h post MMAs (POST-24), whilst physical fitness (squat jump, countermovement-jump and 5- and 10-m sprints) and perceptual measures (well-being Hooper index: fatigue, stress, delayed onset muscle soreness (DOMS), and sleep) were collected at PRE-EX, POST-R and POST-24, and at PRE-EX and POST-24, respectively. Conclusion: The use of CWI resulted in an enhanced recovery of 10-m sprint performance, as well as improved perceived wellness 24-h following simulated MMA competition.
The influence of Pavlovian conditioned stimuli on ongoing behavior may contribute to explaining how alcohol cues stimulate drug seeking and intake. Using a Pavlovian-instrumental transfer task, we investigated the effects of alcohol-related cues on approach behavior (i.e., instrumental response behavior) and its neural correlates, and related both to the relapse after detoxification in alcohol-dependent patients. Thirty-one recently detoxified alcohol-dependent patients and 24 healthy controls underwent instrumental training, where approach or non-approach towards initially neutral stimuli was reinforced by monetary incentives. Approach behavior was tested during extinction with either alcohol-related or neutral stimuli (as Pavlovian cues) presented in the background during functional magnetic resonance imaging (fMRI). Patients were subsequently followed up for 6 months. We observed that alcohol-related background stimuli inhibited the approach behavior in detoxified alcohol-dependent patients (t = -3.86, p < .001), but not in healthy controls (t = -0.92, p = .36). This behavioral inhibition was associated with neural activation in the nucleus accumbens (NAcc) (t((30)) = 2.06, p < .05). Interestingly, both the effects were only present in subsequent abstainers, but not relapsers and in those with mild but not severe dependence. Our data show that alcohol-related cues can acquire inhibitory behavioral features typical of aversive stimuli despite being accompanied by a stronger NAcc activation, suggesting salience attribution. The fact that these findings are restricted to abstinence and milder illness suggests that they may be potential resilience factors.
The purpose of this study was to estimate the optimal body size, limb-segment length, girth or breadth ratios for 100-m backstroke mean speed performance in young swimmers. Sixty-three young swimmers (boys [n = 30; age: 13.98 ± 0.58 years]; girls [n = 33; age: 13.02 ± 1.20 years]) participated in this study. To identify the optimal body size and body composition components associated with 100-m backstroke speed performance, we adopted a multiplicative allometric log-linear regression model, which was refined using backward elimination. The multiplicative allometric model exploring the association between 100-m backstroke mean speed performance and the different somatic measurements estimated that biological age, sitting height, leg length for the lower-limbs, and two girths (forearm and arm relaxed girth) are the key predictors. Stature and body mass did not contribute to the model, suggesting that the advantage of longer levers was limb-specific rather than a general whole-body advantage. In fact, it is only by adopting multiplicative allometric models that the abovementioned ratios could have been derived. These findings highlighted the importance of considering somatic characteristics of young backstroke swimmers and can help swimming coaches to classify their swimmers and enable them to suggest what might be the swimmers’ most appropriate stroke (talent identification).
Intervertebral disc (IVD) cells are naturally exposed to high osmolarity and complex mechanical loading, which drive microenvironmental osmotic changes. Age- and degeneration-induced degradation of the IVD’s extracellular matrix causes osmotic imbalance, which, together with an altered function of cellular receptors and signalling pathways, instigates local osmotic stress. Cellular responses to osmotic stress include osmoadaptation and activation of pro-inflammatory pathways. This review summarises the current knowledge on how IVD cells sense local osmotic changes and translate these signals into physiological or pathophysiological responses, with a focus on inflammation. Furthermore, it discusses the expression and function of putative membrane osmosensors (e.g. solute carrier transporters, transient receptor potential channels, aquaporins and acid-sensing ion channels) and osmosignalling mediators [e.g. tonicity response-element-binding protein/nuclear factor of activated T-cells 5 (TonEBP/NFAT5), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)] in healthy and degenerated IVDs. Finally, an overview of the potential therapeutic targets for modifying osmosensing and osmosignalling in degenerated IVDs is provided.
Ramirez-Campillo, R, Alvarez, C, García-Pinillos, F, Sanchez-Sanchez, J, Yanci, J, Castillo, D, Loturco, I, Chaabene, H, Moran, J, and Izquierdo, M. Optimal reactive strength index: is it an accurate variable to optimize plyometric training effects on measures of physical fitness in young soccer players? J Strength Cond Res 32(4): 885–893, 2018—This study aimed to compare the effects of drop-jump training using a fixed drop-box height (i.e., 30-cm [FIXED]) vs. an optimal (OPT) drop-box height (i.e., 10-cm to 40-cm: generating an OPT reactive strength index [RSI]) in youth soccer players' physical fitness. Athletes were randomly allocated to a control group (n = 24; age = 13.7 years), a fixed drop-box height group (FIXED, n = 25; age = 13.9 years), or an OPT drop-box height group (OPT, n = 24; age = 13.1 years). Before and after 7 weeks of training, tests for the assessment of jumping (countermovement jump [CMJ], 5 multiple bounds), speed (20-m sprint time), change of direction ability (CODA [Illinois test]), strength {RSI and 5 maximal squat repetition test (5 repetition maximum [RM])}, endurance (2.4-km time trial), and kicking ability (maximal kicking distance) were undertaken. Analyses revealed main effects of time for all dependent variables (p < 0.001, d = 0.24–0.72), except for 20-m sprint time. Analyses also revealed group × time interactions for CMJ (p < 0.001, d = 0.51), depth jump (DJ) (p < 0.001, d = 0.30), 20-m sprint time (p < 0.001, d = 0.25), CODA (p < 0.001, d = 0.22), and 5RM (p < 0.01, d = 0.16). Post hoc analyses revealed increases for the FIXED group (CMJ: 7.4%, d = 0.36; DJ: 19.2%, d = 0.49; CODA: −3.1%, d = −0.21; 5RM: 10.5%, d = 0.32) and the OPT group (CMJ: 16.7%, d = 0.76; DJ: 36.1%, d = 0.79; CODA: −4.4%, d = −0.34; 5RM: 18.1%, d = 0.47). Post hoc analyses also revealed increases for the OPT group in 20-m sprint time (−3.7%, d = 0.27). Therefore, to maximize the effects of plyometric training, an OPT approach is recommended. However, using adequate fixed drop-box heights may provide a rational and practical alternative.
From a health and performance-related perspective, it is crucial to evaluate subjective symptoms and objective signs of acute training-induced immunological responses in young athletes. The limited number of available studies focused on immunological adaptations following aerobic training. Hardly any studies have been conducted on resistance-training induced stress responses. Therefore, the aim of this observational study was to investigate subjective symptoms and objective signs of immunological stress responses following resistance training in young athletes. Fourteen (7 females and 7 males) track and field athletes with a mean age of 16.4 years and without any symptoms of upper or lower respiratory tract infections participated in this study. Over a period of 7 days, subjective symptoms using the Acute Recovery and Stress Scale (ARSS) and objective signs of immunological responses using capillary blood markers were taken each morning and after the last training session. Differences between morning and evening sessions and associations between subjective and objective parameters were analyzed using generalized estimating equations (GEE). In post hoc analyses, daily change-scores of the ARSS dimensions were compared between participants and revealed specific changes in objective capillary blood samples. In the GEE models, recovery (ARSS) was characterized by a significant decrease while stress (ARSS) showed a significant increase between morning and evening-training sessions. A concomitant increase in white blood cell count (WBC), granulocytes (GRAN) and percentage shares of granulocytes (GRAN%) was found between morning and evening sessions. Of note, percentage shares of lymphocytes (LYM%) showed a significant decrease. Furthermore, using multivariate regression analyses, we identified that recovery was significantly associated with LYM%, while stress was significantly associated with WBC and GRAN%. Post hoc analyses revealed significantly larger increases in participants' stress dimensions who showed increases in GRAN%. For recovery, significantly larger decreases were found in participants with decreases in LYM% during recovery. More specifically, daily change-scores of the recovery and stress dimensions of the ARSS were associated with specific changes in objective immunological markers (GRAN%, LYM%) between morning and evening-training sessions. Our results indicate that changes of subjective symptoms of recovery and stress dimensions using the ARSS were associated with specific changes in objectively measured immunological markers.
Introduction
To date, several meta-analyses clearly demonstrated that resistance and plyometric training are effective to improve physical fitness in children and adolescents. However, a methodological limitation of meta-analyses is that they synthesize results from different studies and hence ignore important differences across studies (i.e., mixing apples and oranges). Therefore, we aimed at examining comparative intervention studies that assessed the effects of age, sex, maturation, and resistance or plyometric training descriptors (e.g., training intensity, volume etc.) on measures of physical fitness while holding other variables constant.
Methods
To identify relevant studies, we systematically searched multiple electronic databases (e.g., PubMed) from inception to March 2018. We included resistance and plyometric training studies in healthy young athletes and non-athletes aged 6 to 18 years that investigated the effects of moderator variables (e.g., age, maturity, sex, etc.) on components of physical fitness (i.e., muscle strength and power).
Results
Our systematic literature search revealed a total of 75 eligible resistance and plyometric training studies, including 5,138 participants. Mean duration of resistance and plyometric training programs amounted to 8.9 ± 3.6 weeks and 7.1±1.4 weeks, respectively. Our findings showed that maturation affects plyometric and resistance training outcomes differently, with the former eliciting greater adaptations pre-peak height velocity (PHV) and the latter around- and post-PHV. Sex has no major impact on resistance training related outcomes (e.g., maximal strength, 10 repetition maximum). In terms of plyometric training, around-PHV boys appear to respond with larger performance improvements (e.g., jump height, jump distance) compared with girls. Different types of resistance training (e.g., body weight, free weights) are effective in improving measures of muscle strength (e.g., maximum voluntary contraction) in untrained children and adolescents. Effects of plyometric training in untrained youth primarily follow the principle of training specificity. Despite the fact that only 6 out of 75 comparative studies investigated resistance or plyometric training in trained individuals, positive effects were reported in all 6 studies (e.g., maximum strength and vertical jump height, respectively).
Conclusions
The present review article identified research gaps (e.g., training descriptors, modern alternative training modalities) that should be addressed in future comparative studies.
Background: Core-specific sensorimotor exercises are proven to enhance neuromuscular activity of the trunk, improve athletic performance and prevent back pain. However, the dose-response relationship and, therefore, the dose required to improve trunk function is still under debate. The purpose of the present trial will be to compare four different intervention strategies of sensorimotor exercises that will result in improved trunk function. Discussion: The results of the study will be clinically relevant, not only for researchers but also for (sports) therapists, physicians, coaches, athletes and the general population who have the aim of improving trunk function.
Accuracy of training recommendations based on a treadmill multistage incremental exercise test
(2018)
Competitive runners will occasionally undergo exercise in a laboratory setting to obtain predictive and prescriptive information regarding their performance. The present research aimed to assess whether the physiological demands of lab-based treadmill running (TM) can simulate that of over-ground (OG) running using a commonly used protocol. Fifteen healthy volunteers with a weekly mileage of ≥ 20 km over the past 6 months and treadmill experience participated in this cross-sectional study. Two stepwise incremental tests until volitional exhaustion was performed in a fixed order within one week in an Outpatient Clinic research laboratory and outdoor athletic track. Running velocity (IATspeed), heart rate (IATHR) and lactate concentration at the individual anaerobic threshold (IATbLa) were primary endpoints. Additionally, distance covered (DIST), maximal heart rate (HRmax), maximal blood lactate concentration (bLamax) and rate of perceived exertion (RPE) at IATspeed were analyzed. IATspeed, DIST and HRmax were not statistically significantly different between conditions, whereas bLamax and RPE at IATspeed showed statistical significance (p < 0.05). Apart from RPE at IATspeed, IATspeed, DIST, HRmax and bLamax strongly correlate between conditions (r = 0.815–0.988). High reliability between conditions provides strong evidence to suggest that running on a treadmill are physiologically comparable to that of OG and that training recommendations and be made with assurance.
The aim of this study was to investigate the effect of a 6-week sensorimotor or resistance training on maximum trunk strength and response to sudden, high-intensity loading in athletes. Interventions showed no significant difference for maximum strength in concentric and eccentric testing (p>0.05). For perturbation compensation, higher peak torque response following SMT (Extension: +24Nm 95%CI +/- 19Nm; Rotation: + 19Nm 95%CI +/- 13Nm) and RT (Extension: +35Nm 95%CI +/- 16Nm; Rotation: +5Nm 95%CI +/- 4Nm) compared to CG (Extension: -4Nm 95%CI +/- 16Nm; Rotation: -2Nm 95%CI +/- 4Nm) was present (p<0.05).
Differences in neuromuscular activity of ankle stabilizing muscles during postural disturbances
(2018)
The purpose was to examine gender differences in ankle stabilizing muscle activation during postural disturbances. Seventeen participants (9 females: 27 +/- 2yrs., 1.69 +/- 0.1 m, 63 +/- 7 kg; 8 males: 29 +/- 2yrs., 1.81 +/- 0.1 m; 83 +/- 7 kg) were included in the study. After familiarization on a split-belt-treadmill, participants walked (1 m/s) while 15 right-sided perturbations were randomly applied 200 ms after initial heel contact. Muscle activity of M. tibialis anterior (TA), peroneus longus (PL) and gastrocnemius medialis (GM) was recorded during unperturbed and perturbed walking. The root mean square (RMS; [%]) was analyzed within 200 ms after perturbation. Co-activation was quantified as ratio of antagonist (GM)/agonist (TA) EMG-RMS during unperturbed and perturbed walking. Time to onset was calculated (ms). Data were analyzed descriptively (mean +/- SD) followed by three-way-ANOVA (gender/condition/muscle; alpha= 0.05). Perturbed walking elicited higher EMG activity compared to normal walking for TA and PL in both genders (p < 0.000). RMS amplitude gender comparisons revealed an interaction between gender and condition (F = 4.6, p = 0.049) and, a triple interaction among gender, condition and muscle (F = 4.7, p = 0.02). Women presented significantly higher EMG-RMS [%] PL amplitude than men during perturbed walking (mean difference = 209.6%, 95% confidence interval = -367.0 to -52.2%, p < 0.000). Co-activation showed significant lower values for perturbed compared to normal walking (p < 0.000), without significant gender differences for both walking conditions. GM activated significantly earlier than TA and PL (p < 0.01) without significant differences between the muscle activation onsets of men and women (p = 0.7). The results reflect that activation strategies of the ankle encompassing muscles differ between genders. In provoked stumbling, higher PL EMG activity in women compared to men is present. Future studies should aim to elucidate if this specific behavior has any relationship with ankle injury occurrence between genders.
Background: Optimal antibiotic exposure is a vital but challenging prerequisite for achieving clinical success in ICU patients. Objectives: To develop and externally validate a population pharmacokinetic model for continuous-infusion meropenem in critically ill patients and to establish a nomogram based on a routinely available marker of renal function. Methods: A population pharmacokinetic model was developed in NONMEM (R) 7.3 based on steady-state meropenem concentrations (C-ss) collected during therapeutic drug monitoring. Different serum creatinine-based markers of renal function were compared for their influence on meropenem clearance (the Cockcroft-Gault creatinine clearance CLCRcG, the CLCR bedside estimate according to Jelliffe, the Chronic Kidney Disease Epidemiology Collaboration equation and the four-variable Modification of Diet in Renal Disease equation). After validation of the pharmacokinetic model with independent data, a dosing nomogram was developed, relating renal function to the daily doses required to achieve selected target concentrations (4/8/16 mg/L) in 90% of the patients. Probability of target attainment was determined for efficacy (C-ss >= 8 mg/L) and potentially increased likelihood of adverse drug reactions (C-ss >32 mg/L). Results: In total, 433 plasma concentrations (3.20-48.0 mg/L) from 195 patients (median/P-0.05 - P-0.95 at baseline: weight 77.0/55.0-114 kg, CLCRCG 63.0/19.6-168 mL/min) were used for model building. We found that CLCRCG best described meropenem clearance (CL = 7.71 L/h, CLCRCG = 80 mL/min). The developed model was successfully validated with external data (n = 171, 73 patients). According to the nomogram, daily doses of 910/1480/2050/2800/ 3940 mg were required to reach a target C-ss = 8 mg/L in 90% of patients with CLCRCG = 20/50/80/120/180 mL/min, respectively. A low probability of adverse drug reactions (<0.5%) was associated with these doses. Conclusions: A dosing nomogram was developed for continuous-infusion meropenem based on renal function in a critically ill population.
Background and objective Optimisation of hydrocortisone replacement therapy in children is challenging as there is currently no licensed formulation and dose in Europe for children under 6 years of age. In addition, hydrocortisone has non-linear pharmacokinetics caused by saturable plasma protein binding. A paediatric hydrocortisone formulation, Infacort (R) oral hydrocortisone granules with taste masking, has therefore been developed. The objective of this study was to establish a population pharmacokinetic model based on studies in healthy adult volunteers to predict hydrocortisone exposure in paediatric patients with adrenal insufficiency. Methods Cortisol and binding protein concentrations were evaluated in the absence and presence of dexamethasone in healthy volunteers (n = 30). Dexamethasone was used to suppress endogenous cortisol concentrations prior to and after single doses of 0.5, 2, 5 and 10 mg of Infacort (R) or 20 mg of Infacort (R)/hydrocortisone tablet/hydrocortisone intravenously. A plasma protein binding model was established using unbound and total cortisol concentrations, and sequentially integrated into the pharmacokinetic model. Results Both specific (non-linear) and non-specific (linear) protein binding were included in the cortisol binding model. A two-compartment disposition model with saturable absorption and constant endogenous cortisol baseline (Baseline (cort),15.5 nmol/L) described the data accurately. The predicted cortisol exposure for a given dose varied considerably within a small body weight range in individuals weighing < 20 kg. Conclusions Our semi-mechanistic population pharmacokinetic model for hydrocortisone captures the complex pharmacokinetics of hydrocortisone in a simplified but comprehensive framework. The predicted cortisol exposure indicated the importance of defining an accurate hydrocortisone dose to mimic physiological concentrations for neonates and infants weighing < 20 kg.
Surface electromyographic (EMG) signal amplitude is typically used to compare the neural drive to muscles. We experimentally investigated this association by studying the motor unit (MU) behavior and action potentials in the vastus medialis (VM) and vastus lateralis (VL) muscles. Eighteen participants performed isometric knee extensions at four target torques [10. 30. 50, and 70% of the maximum torque (MVC)] while high-density EMG signals were recorded from the VM and VL. The absolute EMG amplitude was greater for VM than VL (P < 0.001), whereas the EMG amplitude normalized with respect to MVC was greater for VL than VM (P < 0.04). Because differences in EMG amplitude can be due to both differences in the neural drive and in the size of the MU action potentials, we indirectly inferred the neural drives received by the two muscles by estimating the synaptic inputs received by the corresponding motor neuron pools. For this purpose. we analyzed the increase in discharge rate from recruitment to target torque for motor units matched by recruitment threshold in the two muscles. This analysis indicated that the two muscles received similar levels of neural drive. Nonetheless, the size of the MU action potentials was greater for VM than VL (P < 0.001), and this difference explained most of the differences in EMG amplitude between the two muscles (similar to 63% of explained variance). These results indicate that EMG amplitude, even following normalization, does not reflect the neural drive to synergistic muscles. Moreover, absolute EMG amplitude is mainly explained by the size of MU action potentials. NEW & NOTEWORTHY Electromyographic (EMG) amplitude is widely used to compare indirectly the strength of neural drive received by synergistic muscles. However, there are no studies validating this approach with motor unit data. Here, we compared between-muscles differences in surface EMG amplitude and motor unit behavior. The results clarify the limitations of surface EMG to interpret differences in neural drive between muscles.
Purpose Moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) are associated with different adjustments in motor output. Changes in motor unit (MU) peripheral properties may contribute to these adjustments, but this is yet to be elucidated. This study evaluated early changes in MU conduction velocity (MUCV) and MU action potential amplitude after 2 wk of either HIIT or MICT. Methods Sixteen men were assigned to either an MICT group or HIIT group (n = 8 each), and participated in six training sessions over 14 d. HIIT: 8 to 12 x 60-s intervals at 100% peak power output. Moderate-intensity continuous training: 90 to 120 min continuous cycling at similar to 65% VO2peak. Preintervention and postintervention, participants performed maximal voluntary contractions (MVC) and submaximal (10%, 30%, 50%, and 70% of MVC) isometric knee extensions while high-density EMG was recorded from the vastus medialis (VM) and vastus lateralis (VL) muscles. The high-density EMG was decomposed into individual MU by convolutive blind-source separation and tracked preintervention and postintervention. Results Both training interventions induced changes in MUCV, but these changes depended on the type of training (P < 0.001). The HIIT group showed higher values of MUCV after training at all torque levels (P < 0.05), MICT only displayed changes in MUCV at low torque levels (10%-30% MVC, P < 0.002). There were no changes in MU action potential amplitude for either group (P = 0.2). Conclusions Two weeks of HIIT or MICT elicit differential changes in MUCV, likely due to the contrasting load and volume used in such training regimes. This new knowledge on the neuromuscular adaptations to training has implications for exercise prescription.