Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation

Inflammasome activation, with subsequent release of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18, has recently been implicated in atherosclerosis-associated inflammation. This study aims to assess in acute coronary syndrome (ACS) patients (1) inflammasome activation in circulating monocytes and (2) whether short-term oral colchicine, a recognized anti-inflammatory agent that has been shown to be cardio-protective in clinical studies, might acutely suppress inflammasome-dependent inflammation. ACS patients (n=21) were randomized to oral colchicine (1 mg followed by 0.5 mg 1 h later) or no treatment, and compared with untreated healthy controls (n=9). Peripheral venous blood was sampled pre- (day 1) and 24 h post- (day 2) treatment. Monocytes were cultured and stimulated with ATP. Analysis of key inflammasome markers was performed by ELISA. IL-1β secretion increased by 580.4% (P<0.01) in ACS patients compared with controls but only with ATP stimulation. Untreated ACS patients secreted significantly higher levels of IL-18 compared with healthy controls independent of ATP stimulation (P<0.05). Colchicine treatment in ACS patients markedly reduced intracellular and secreted levels of IL-1β compared with pre-treatment levels (P<0.05 for both), as well as significantly reducing pro-caspase-1 mRNA levels by 57.7% and secreted caspase-1 protein levels by 30.2% compared with untreated patients (P<0.05 for both). Monocytes from ACS patients are ‘primed’ to secrete inflammasome-related cytokines and short-term colchicine acutely and markedly suppresses monocyte caspase-1 activity, thereby reducing monocyte secretion of IL-1β

New insights into the cardiorespiratory physiology of weaned southern elephant seals (Mirounga leonina)

Southern elephant seal (Mirounga leonina) pups must strike a balance between conserving energy during their post-weaning fast and simultaneously developing diving abilities to attain nutritional independence. Little is known about environmental influences on cardiorespiratory patterns, hence energy use, throughout the 6 week fast. Continuous heart rates were recorded for free-ranging, newly weaned southern elephant seals using heart rate time-depth recorders for 5-9 days at Sub-Antarctic Macquarie Island, during October 1994 (n = 1), 1995 (n = 4) and 1996 (n = 1). Daytime observations of respiration and behaviour were made throughout. We present the first instance of synchronous heart rate traces recorded simultaneously for individual weaners. Generalized additive models revealed that a sinusoidal pattern of diurnal heart rate elevation and nocturnal depression was evident in all seals and, on at least one occasion, a conspicuous break in this pattern coincided with an extreme cold weather event. Seals in this study were capable of considerable cardiorespiratory control and regularly demonstrated bradycardia during periods of resting apnoea. Apnoeic duration ranged from 33 to 291 s (mean 134 s). Apnoeic heart rates (mean 67 ± 15 beats min(-1), range 40-114 beats min(-1)) were on average 19.7% lower than those exhibited during periods of eupnoea (mean 83 ± 15 beats min(-1), range 44-124 beats min(-1)). The early development of the cardiorespiratory response is characterized by arrhythmic heart and respiration rates. The strong temporal patterns observed are being driven by the opposing requirements of maximizing time spent fasting in order to develop diving capabilities and of maximizing departure mass. This pilot study has highlighted a potentially large effect of ambient weather conditions on newly weaned southern elephant seal cardiorespiratory activity. Given the increasing westerlies and more erratic and increasing storminess associated with the Southern Annular Mode predicted in the Southern Ocean, the patterns observed here warrant further investigation

Importance, reliability and usefulness of acceleration measures in team sports

Abstract: Delaney, JA, Cummins, CJ, Thornton, HR, and Duthie, GM. Importance, reliability and usefulness of acceleration measures in team sports. J Strength Cond Res 32(12): 3494-3502, 2018-The ability to accelerate, decelerate, and change direction efficiently is imperative to successful team sports performance. Traditional intensity-based thresholds for acceleration and deceleration may be inappropriate for time-series data and have been shown to exhibit poor reliability, suggesting other techniques may be preferable. This study assessed movement data from one professional rugby league team throughout 2 full seasons and 1 preseason period. Using both 5 and 10 Hz global positioning systems (GPS) units, a range of acceleration-based variables were evaluated for their interunit reliability, ability to discriminate between positions, and associations with perceived muscle soreness. The reliability of 5 Hz global positioning systems for measuring acceleration and deceleration ranged from good to poor (CV = 3.7-27.1%), with the exception of high-intensity deceleration efforts (CV = 11.1-11.8%), the 10 Hz units exhibited moderate-to-good interunit reliability (CV = 1.2-6.9%). Reliability of average metrics (average acceleration/deceleration, average acceleration, and average deceleration) ranged from good to moderate (CV = 1.2-6.5%). Substantial differences were detected between positions using time spent accelerating and decelerating for all magnitudes, but these differences were less clear when considering the count or distance above acceleration/deceleration thresholds. All average metrics detected substantial differences between positions. All measures were similarly related to perceived muscle soreness, with the exception of high-intensity acceleration and deceleration counts. This study has proposed that averaging the acceleration/deceleration demands over an activity may be a more appropriate method compared with threshold-based methods, because a greater reliability between units, while not sacrificing sensitivity to within-subject and between-subject changes

Sports-related injuries in New Zealand: National Insurance (Accident Compensation Corporation) claims for five sporting codes from 2012 to 2016

**Objectives** To provide epidemiological data and related costs for sport-related injuries of five sporting codes (cricket, netball, rugby league, rugby union and football) in New Zealand for moderate-to-serious and serious injury claims. **Methods** A retrospective analytical review using detailed descriptive epidemiological data obtained from the Accident Compensation Corporation (ACC) for 2012–2016. **Results** Over the 5 years of study data, rugby union recorded the most moderate-to-serious injury entitlement claims (25 226) and costs (New Zealand dollars (NZD$)267 359 440 (£139 084 749)) resulting in the highest mean cost (NZD$10 484 (£5454)) per moderate-to-serious injury entitlement claim. Rugby union recorded more serious injury entitlement claims (n=454) than cricket (t(4)=−66.6; P<0.0001); netball (t(4)=−45.1; P<0.0001); rugby league (t(4)=−61.4; P<0.0001) and football (t(4)=66.6; P<0.0001) for 2012–2016. There was a twofold increase in the number of female moderate-to-serious injury entitlement claims for football (RR 2.6 (95%CI 2.2 to 2.9); P<0.0001) compared with cricket, and a threefold increase when compared with rugby union (risk ratio (RR) 3.1 (95%CI 2.9 to 3.3); P<0.0001). Moderate-to-serious concussion claims increased between 2012 and 2016 for netball (RR 3.7 (95%CI 1.9 to 7.1); P<0.0001), rugby union (RR 2.0 (95% CI 1.6 to 2.4); P<0.0001) and football (RR 2.3 (95%CI 1.6 to 3.2); P<0.0001). Nearly a quarter of moderate-to-serious entitlement claims (23%) and costs (24%) were to participants aged 35 years or older. **Conclusions** Rugby union and rugby league have the highest total number and costs associated with injury. Accurate sport exposure data are needed to enable injury risk calculations

Genome streamlining via complete loss of introns has occurred multiple times in lichenized fungal mitochondria.

Reductions in genome size and complexity are a hallmark of obligate symbioses. The mitochondrial genome displays clear examples of these reductions, with the ancestral alpha-proteobacterial genome size and gene number having been reduced by orders of magnitude in most descendent modern mitochondrial genomes. Here, we examine patterns of mitochondrial evolution specifically looking at intron size, number, and position across 58 species from 21 genera of lichenized Ascomycete fungi, representing a broad range of fungal diversity and niches. Our results show that th

Nonpathological Extracellular Amyloid Is Present during Normal Epididymal Sperm Maturation

Amyloids are aggregated proteins characterized by a specific cross-β-sheet structure and are typically associated with neurodegenerative diseases including Alzheimer's disease. Recently, however, several nonpathological amyloids have been found in intracellular organelles of normal mammalian tissues suggesting that amyloid may also carry out biological functions. We previously have shown that the epididymal cystatin CRES (cystatin-related epididymal spermatogenic), cst8, a reproductive-specific member of the cystatin superfamily of cysteine protease inhibitors, forms amyloid in vitro suggesting that CRES amyloid may also form in vivo within the epididymal lumen. Here we show that amyloid structures containing CRES are a component of the normal mouse epididymal lumen without any apparent cytotoxic effects on spermatozoa and that these structures change along the length of the tubule. These studies suggest the presence of a functional amyloid structure that may carry out roles in sperm maturation or maintenance of the luminal milieu and which itself may undergo maturational changes along the epididymis. In contrast to previous examples of functional amyloid which were intracellular, our studies now show that nonpathological/functional amyloid can also be extracellular. The presence of an extracellular and nonpathological amyloid in the epididymis suggests that similar amyloid structures may be present in other organ systems and may carry out distinctive tissue-specific functions

A Simultaneous Dual-site Technosignature Search Using International LOFAR Stations

The Search for Extraterrestrial Intelligence aims to find evidence of technosignatures, which can point toward the possible existence of technologically advanced extraterrestrial life. Radio signals similar to those engineered on Earth may be transmitted by other civilizations, motivating technosignature searches across the entire radio spectrum. In this endeavor, the low-frequency radio band has remained largely unexplored; with prior radio searches primarily above 1 GHz. In this survey at 110-190 MHz, observations of 1,631,198 targets from TESS and Gaia are reported. Observations took place simultaneously with two international stations (noninterferometric) of the Low Frequency Array in Ireland and Sweden. We can reject the presence of any Doppler drifting narrowband transmissions in the barycentric frame of reference, with equivalent isotropic radiated power of 10 17 W, for 0.4 million (or 1.3 million) stellar systems at 110 (or 190) MHz. This work demonstrates the effectiveness of using multisite simultaneous observations for rejecting anthropogenic signals in the search for technosignatures.Comment: 15 Pages, 16 Figures, 2 Machine Readable Table