Decision making influences movement variability and performance of high-level female football players in an elastic resistance task.

Introduction: The inclusion of sport-specific constraints in resistance training promotes the development of player abilities in an integrated way, which maximises the effectiveness of player adaptations induced by training. Considering that perceptual-cognitive abilities play a fundamental role in football, decision making could be introduced to enhance the cognitive similarity of resistance tasks to sport actions. However, it is unknown how decision making as a constraint could affect the player during an elastic resistance task. Therefore, the aim of this study was to investigate the effects of decision making of high-level female football players on movement variability and performance during an elastic band resistance task. Methods: Twenty-three high-level female football players performed the elastic resistance task with a ball, both as attackers and as defenders without decision making (NDM) and with decision making (DM). The movement variability was quantified using the sample entropy derived from the acceleration recorded with an accelerometer placed at the lower back of each player. The passing accuracy of the attacker was quantified using a scoring scale. Results: Results revealed that adding decision making to an elastic resistance task increased the movement variability of the defender but did not affect the movement variability of the attacker. In contrast, the passing accuracy of the attacker was reduced. Overall, the attacker had a higher movement variability compared to the defender. Discussion: These findings suggest that decision making, as a football-specific constraint, can enhance the potential of an elastic resistance task in training. This is due to the fact that it reduces control and regularity of movement for the defensive role player and increases technical difficulty for the attacking role player. Furthermore, these effects are beneficial, as they can promote the adaptive processes necessary to optimise the performance of the players.

Validity of a low-cost friction encoder for measuring velocity, force and power in flywheel exercise devices.

The purpose of this study was to investigate the validity of a low-cost friction encoder against a criterion measure (strain gauge combined with a linear encoder) for assessing velocity, force and power in flywheel exercise devices. Ten young and physically active volunteers performed two sets of 14 maximal squats on a flywheel inertial device (YoYo Technology, Stockholm, Sweden) with five minutes rest between each set. Two different resistances were used (0.075 kg · m2 for the first set; 0.025 kg · m2 for the second). Mean velocity (Vrep), force (Frep) and power (Prep) for each repetition were assessed simultaneously via a friction encoder (Chronojump, Barcelona, Spain), and with a strain gauge combined with a linear encoder (MuscleLab 6000, Ergotest Technology, Porsgrunn, Norway). Results are displayed as (Mean [CI 90%]). Compared to criterion measures, mean bias for the practical measures of Vrep, Frep and Prep were moderate (-0.95 [-0.99 to -0.92]), small (0.53 [0.50 to 0.56]) and moderate (-0.68 [-0.71 to -0.65]) respectively. The typical error of estimate (TEE) was small for all three parameters; Vrep (0.23 [0.20 to 0.25]), Frep (0.20 [0.18 to 0.22]) and Prep (0.18 [0.16 to 0.20]). Correlations with MuscleLab were nearly perfect for all measures in all load configurations. Based on these findings, the friction encoder provides valid measures of velocity, force and power in flywheel exercise devices. However, as error did exist between measures, the same testing protocol should be used when assessing changes in these parameters over time, or when aiming to perform inter-individual comparisons.

A novel application of entropy analysis for assessing changes in movement variability during cumulative tackles in young elite rugby league players.

The aim of this study was to identify between-position (forwards vs. backs) differences in movement variability in cumulative tackle events training during both attacking and defensive roles. Eleven elite adolescent male rugby league players volunteered to participate in this study (mean ± SD, age; 18.5 ± 0.5 years, height; 179.5 ± 5.0 cm, body mass; 88.3 ± 13.0 kg). Participants performed a drill encompassing four blocks of six tackling (i.e. tackling an opponent) and six tackled (i.e. being tackled by an opponent while carrying a ball) events (i.e. 48 total tackles) while wearing a micro-technological inertial measurement unit (WIMU, Realtrack Systems, Spain). The acceleration data were used to calculate sample entropy (SampEn) to analyse the movement variability during tackles performance. In tackling actions SampEn showed significant between-position differences in block 1 (p = 0.0001) and block 2 (p = 0.0003). Significant between-block differences were observed in backs (block 1 vs 3, p = 0,0021; and block 1 vs 4, p = 0,0001) but not in forwards. When being tackled, SampEn showed significant between-position differences in block 1 (p = 0.0007) and block 3 (p = 0.0118). Significant between-block differences were only observed for backs in block 1 vs 4 (p = 0,0025). Movement variability shows a progressive reduction with cumulative tackle events, especially in backs and when in the defensive role (tackling). Forwards present lower movement variability values in all blocks, particularly in the first block, both in the attacking and defensive role. Entropy measures can be used by practitioners as an alternative tool to analyse the temporal structure of variability of tackle actions and quantify the load of these actions according to playing position.

The Influence of Functional Flywheel Resistance Training on Movement Variability and Movement Velocity in Elite Rugby Players.

The aim of this study was to identify the changes in movement variability and movement velocity during a six-week training period using a resistance horizontal forward-backward task without (NOBALL) or with (BALL) the constraint of catching and throwing a rugby ball in the forward phase. Eleven elite male rugby union players (mean ± SD: age 25.5 ± 2.0 years, height 1.83 ± 0.06 m, body mass 95 ± 18 kg, rugby practice 14 ± 3 years) performed eight repetitions of NOBALL and BALL conditions once a week in a rotational flywheel device. Velocity was recorded by an attached rotary encoder while acceleration data were used to calculate sample entropy (SampEn), multiscale entropy, and the complexity index. SampEn showed no significant decrease for NOBALL (ES = -0.64 ± 1.02) and significant decrease for BALL (ES = -1.71 ± 1.16; p < 0.007) conditions. Additionally, movement velocity showed a significant increase for NOBALL (ES = 1.02 ± 1.05; p < 0.047) and significant increase for BALL (ES = 1.25 ± 1.08; p < 0.025) between weeks 1 and 6. The complexity index showed higher levels of complexity in the BALL condition, specifically in the first three weeks. Movement velocity and complex dynamics were adapted to the constraints of the task after a four-week training period. Entropy measures seem a promising processing signal technique to identify when these exercise tasks should be changed.

Identification of 2-Imidazopyridine and 2-Aminopyridone Purinones as Potent Pan-Janus Kinase (JAK) Inhibitors for the Inhaled Treatment of Respiratory Diseases.

Janus kinases (JAKs) have a key role in regulating the expression and function of relevant inflammatory cytokines involved in asthma and chronic obstructive pulmonary disease. Herein are described the design, synthesis, and pharmacological evaluation of a series of novel purinone JAK inhibitors with profiles suitable for inhaled administration. Replacement of the imidazopyridine hinge binding motif present in the initial compounds of this series with a pyridone ring resulted in the mitigation of cell cytotoxicity. Further systematic structure-activity relationship (SAR) efforts driven by structural biology studies led to the discovery of pyridone 34, a potent pan-JAK inhibitor with good selectivity, long lung retention time, low oral bioavailability, and proven efficacy in the lipopolysaccharide-induced rat model of airway inflammation by the inhaled route.

Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of sulphone-based CRTh2 antagonists.

Monocyclic and bicyclic ring systems were investigated as the "core" section of a series of diphenylsulphone-containing acetic acid CRTh2 receptor antagonists. A range of potencies were observed and single-digit nanomolar potencies were obtained in both the monocyclic and bicyclic cores. Residence times for the monocyclic compounds were very short. Some of the bicyclic cores displayed better residence times. A methyl group in the northern part of the core, between the head and tail was a necessary requirement for the beginnings of long residence times. Variations of the tail substitution maximised potencies and residence times.

Cardiorespiratory Coordination after Training and Detraining. A Principal Component Analysis Approach.

Our purpose was to study the effects of different training modalities and detraining on cardiorespiratory coordination (CRC). Thirty-two young males were randomly assigned to four training groups: aerobic (AT), resistance (RT), aerobic plus resistance (AT + RT), and control (C). They were assessed before training, after training (6 weeks) and after detraining (3 weeks) by means of a graded maximal test. A principal component (PC) analysis of selected cardiovascular and cardiorespiratory variables was performed to evaluate CRC. The first PC (PC1) coefficient of congruence in the three conditions (before training, after training and after detraining) was compared between groups. Two PCs were identified in 81% of participants before the training period. After this period the number of PCs and the projection of the selected variables onto them changed only in the groups subject to a training programme. The PC1 coefficient of congruence was significantly lower in the training groups compared with the C group [H (3, N=32) = 11.28; p = 0.01]. In conclusion, training produced changes in CRC, reflected by the change in the number of PCs and the congruence values of PC1. These changes may be more sensitive than the usually explored cardiorespiratory reserve, and they probably precede it.

Piwi Is a Key Regulator of Both Somatic and Germline Stem Cells in the Drosophila Testis.

The Piwi-piRNA pathway is well known for its germline function, yet its somatic role remains elusive. We show here that Piwi is required autonomously not only for germline stem cell (GSC) but also for somatic cyst stem cell (CySC) maintenance in the Drosophila testis. Reducing Piwi activity in the testis caused defects in CySC differentiation. Accompanying this, GSC daughters expanded beyond the vicinity of the hub but failed to differentiate further. Moreover, Piwi deficient in nuclear localization caused similar defects in somatic and germ cell differentiation, which was rescued by somatic Piwi expression. To explore the underlying molecular mechanism, we identified Piwi-bound piRNAs that uniquely map to a gene key for gonadal development, Fasciclin 3, and demonstrate that Piwi regulates its expression in somatic cyst cells. Our work reveals the cell-autonomous function of Piwi in both somatic and germline stem cell types, with somatic function possibly via its epigenetic mechanism.

Discovery of 7-azaindole derivatives as potent Orai inhibitors showing efficacy in a preclinical model of asthma.

Synthesis and SAR of a series of 7-azaindoles as Orai channel inhibitors showing good potency inhibiting IL-2 production in Jurkat cells is described. Compound 14d displaying best pharmacokinetic properties was further characterized in a model of allergen induced asthma showing inhibition in the number of eosinophils in BALF. High lipophilicity remains as one of the main challenges for this class of compounds.

Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of bicyclic heteroaromatic acetic acids as potent CRTh2 antagonists I.

A knowledge-based design strategy led to the discovery of several new series of potent and orally bioavailable CRTh2 antagonists where a bicyclic heteroaromatic ring serves as the central core. Structure-kinetic relationships (SKR) opened up the possibility of long receptor residence times.

Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of bicyclic heteroaromatic acetic acids as potent CRTh2 antagonists II: lead optimization.

Extensive structure-activity relationship (SAR) and structure-kinetic relationship (SKR) studies in the bicyclic heteroaromatic series of CRTh2 antagonists led to the identification of several molecules that possessed both excellent binding and cellular potencies along with long receptor residence times. A small substituent in the bicyclic core provided an order of magnitude jump in dissociation half-lives. Selected optimized compounds demonstrated suitable pharmacokinetic profiles.

Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of bicyclic heteroaromatic acetic acids as potent CRTh2 antagonists III: the role of a hydrogen-bond acceptor in long receptor residence times.

The correct positioning and orientation of an hydrogen bond acceptor (HBA) in the tail portion of the biaryl series of CRTh2 antagonists is a requirement for long receptor residence time. The HBA in combination with a small steric substituent in the core section (R(core) ≠ H) gives access to compounds with dissociation half-lives of ⩾ 24h.

Novel triazolopyridylbenzamides as potent and selective p38α inhibitors.

A new class of p38α inhibitors based on a biaryl-triazolopyridine scaffold was investigated. X-ray crystallographic data of the initial lead compound cocrystallised with p38α was crucial in order to uncover a unique binding mode of the inhibitor to the hinge region via a pair of water molecules. Synthesis and SAR was directed towards the improvement of binding affinity, as well as ADME properties for this new class of p38α inhibitors and ultimately afforded compounds showing good in vivo efficacy.

Indolin-2-one p38α inhibitors III: bioisosteric amide replacement.

Crystallographic structural information was used in the design and synthesis of a number of bioisosteric derivatives to replace the amide moiety in a lead series of p38α inhibitors which showed general hydrolytic instability in human liver preparations. Triazole derivative 13 was found to have moderate bioavailability in the rat and demonstrated potent in-vivo activity in an acute model of inflammation.

Indolin-2-one p38α inhibitors II: Lead optimisation.

Optimisation of a series of indolin-2-one p38α inhibitors was achieved via both blocking of a potential metabolic 'hot spot' and by increasing overall polarity of the lead series leading to non-cytotoxic compounds which showed improved oral bioavailabilities in the rat.

Indolin-2-one p38α inhibitors I: design, profiling and crystallographic binding mode.

The use of structure-based design and molecular modeling led to the discovery of indolin-2-one derivatives as potent and selective p38α inhibitors. The predicted binding mode was confirmed by X-ray crystallography.

Discovery of LAS101057: A Potent, Selective, and Orally Efficacious A2B Adenosine Receptor Antagonist.

The structure-activity relationships for a series of pyrazine-based A2B adenosine receptor antagonists are described. From this work, LAS101057 (17), a potent, selective, and orally efficacious A2B receptor antagonist, was identified as a clinical development candidate. LAS101057 inhibits agonist-induced IL-6 production in human fibroblasts and is active in an ovalbumin (OVA)-sensitized mouse model after oral administration, reducing airway hyperresponsiveness to methacholine, Th2 cytokine production, and OVA-specific IgE levels.

Discovery of potent and selective bicyclic A(2B) adenosine receptor antagonists via bioisosteric amide replacement.

Several new potent and selective A(2B) adenosine receptor antagonists have been prepared in which the aryl-amide moiety of the lead series, exemplified by 1a, has been replaced by bioisosteric bicyclic moieties. Although the majority of compounds had generally improved microsomal stability as compared to 1a, this was not translated into overall improvements in the pharmacokinetic profiles of a representative set of compounds.

Discovery of N-(5,6-diarylpyridin-2-yl)amide derivatives as potent and selective A(2B) adenosine receptor antagonists.

The synthesis and SAR of a series of N-(5,6-diarylpyridin-2-yl)amide derivatives as potent A(2B) adenosine receptor antagonists is described. Several compounds showed good selectivity versus other adenosine receptors. The potent and selective analogue 9 was shown to have good oral bioavailability in the rat.