The evolving genetic landscape of telomere biology disorder dyskeratosis congenita.

Dyskeratosis congenita (DC) is a rare inherited bone marrow failure syndrome, caused by genetic mutations that principally affect telomere biology. Approximately 35% of cases remain uncharacterised at the genetic level. To explore the genetic landscape, we conducted genetic studies on a large collection of clinically diagnosed cases of DC as well as cases exhibiting features resembling DC, referred to as 'DC-like' (DCL). This led us to identify several novel pathogenic variants within known genetic loci and in the novel X-linked gene, POLA1. In addition, we have also identified several novel variants in POT1 and ZCCHC8 in multiple cases from different families expanding the allelic series of DC and DCL phenotypes. Functional characterisation of novel POLA1 and POT1 variants, revealed pathogenic effects on protein-protein interactions with primase, CTC1-STN1-TEN1 (CST) and shelterin subunit complexes, that are critical for telomere maintenance. ZCCHC8 variants demonstrated ZCCHC8 deficiency and signs of pervasive transcription, triggering inflammation in patients' blood. In conclusion, our studies expand the current genetic architecture and broaden our understanding of disease mechanisms underlying DC and DCL disorders.

Music Timing Differentiates Fatigue Perception and Performance during Isometric Strength Exercises: A Crossover Randomised Trial.

Music is well-known to elicit ergogenic effects on exercise performance; however, the moderating role of application timing remains unclear. This study examined the effects of the timing of music on fatigue perception and performance during isometric strength exercises. Using a within-subject, randomised crossover design, twelve recreationally active young adults performed two isometric strength tasks (plank-hold and wall-sit) in three separate conditions (MEE: music played during the entire exercise task; MDF: music played during fatigue alone; CON: no music). The total time to volitional exhaustion (TTE), time to the onset of fatigue perception (TFP), heart rate, and blood lactate responses were assessed during each trial. MEE resulted in a significantly longer TTE than CON in both the plank-hold (p < 0.05, d = 0.76) and wall-sit exercises (p < 0.05, d = 0.72), whereas MDF led to a significantly longer TTE than CON in wall-sit exercises alone (p < 0.05, d = 0.60). TFP was significantly longer in MEE than in CON in both the plank-hold (p < 0.05, d = 0.54) and wall-sit exercises (p < 0.05, d = 0.64). The music condition did not influence the heart rate or blood lactate changes in any of the trials. Our results suggest that listening to music during the entire exercise can delay the onset of fatigue perception in isometric strength tasks, whereas listening to music during fatigue has only a modest effect. Athletes and exercisers should consider extending music exposure throughout the entire exercise task to maximise performance benefits.

Reactive-Agility in Touch Plays an Important Role in Elite Playing Level: Reliability and Validity of a Newly Developed Repeated Up-and-Down Agility Test.

Successful athletes are better at performing efficiently than the inferior in particular sports scenarios, while most existing performance tests in the field do not cover the sport-specific context fully. There were two purposes in this study: 1) to evaluate the reliability and validity of a novel Sector Reactive Agility Test (SRAT) which mimicked a reactive-agility defensive scenario in Touch, and 2) to determine the relationships between Touch players' agility and sprint performance. Twenty male Touch players from the elite division and another 20 from the amateur division were invited to participate in this study. They performed SRAT and a 20-m sprint test in two days. Excellent reliability and high precision were found in SRAT (intraclass correlation coefficient [ICC] = 0.97) and 20-m sprint test (ICC = 0.91). The time of completion in SRAT of the elite Touch players (23.93 s) was 2.95 s significantly shorter than that of the amateur players with a large effect size. Elite Touch players also demonstrated moderately faster (0.11 s) than the amateur Touch players in the 20-m sprint test. SRAT demonstrated high test-retest reliability and accuracy in measuring reactive-agility performance in Touch. The minimal detectable changes in SRAT and 20-m sprint test were 1.04 s and 0.13 s respectively. Furthermore, the speed of the 20-m sprint test and playing experience were associated with the time of completion of SRAT, explaining 56% of its variance (p < 0.001). Other factors, such as cognition and the ability to control own central gravity, are deemed possible to influence Touch players' agility. Therefore, SRAT should be adopted in Touch player selection and training monitoring.

Global Positioning System Activity Profile in Touch Rugby: Does Training Meet the Match-Play Intensity in a Two-Day International Test Match Series?

This study quantified the match-play activity profiles of international touch rugby and different positional physical outputs in comparison with training specificity. Between November 2019 and January 2020, 82 half-matches and 173 training global positioning system data from 16 national male touch rugby players (mean ± SD: age 23.71 ± 3.90 years, height 1.73 ± 0.05 m, weight 65.38 ± 9.08 kg, touch rugby training experience 6.09 ± 3.31 years) were recorded. The distance covered by wings in half-match (1676.66 ± 444.80 m) was more than that of link (1311.35 ± 223.59 m) and middle (1383.52 ± 246.55 m) by a large effect (partial η2 = 0.19), which was mainly attributed to walking and jogging (< 4.00 m·s-1). Meanwhile, the middles covered more running distance (4.00-5.50 m·s-1) than other positions. No significant positional group difference was observed for distance covered >5.50 m·s-1, maximum velocity, and the ratio of acceleration and deceleration in matches. Training intensity was close to the match-play outputs only for the high-speed running distance at ≥ 5.50 m·s-1. However, the training activity pattern consistently showed a disparity with the match-play outputs, in terms of shorter normalized training distance covered, less recovery distance covered at ≤ 5.50 m·s-1, higher maximum velocity, and heavier weighting to acceleration in training activities. The current study highlights for the first time that in-match deceleration capacity and active recovery pacing strategy may be essential to touch rugby players. The data provided practitioners a deeper understanding of the physical demands of national touch rugby and allowed them to align the training with the match-play intensity.