Test-Retest Reliability of Running Economy and Metabolic and Cardiorespiratory Parameters During a Multistage Incremental Treadmill Test in Male Middle- and Long-Distance Runners.

This study investigated the test-retest reliability of running economy (RE) and metabolic and cardiorespiratory parameters related to endurance running performance using a multistage incremental treadmill test. On two occasions separated by 21-28 days, 12 male middle- and long-distance runners ran at 10, 11, 12, 13, and 14 km/hr for 8 min each stage, immediately followed by a ramp test to volitional exhaustion. Carbohydrate (10% maltodextrin solution) was consumed before and during the test to provide ∼1 g/min of exercise. RE, minute ventilation (V˙E), oxygen consumption (V˙O2), carbon dioxide production (V˙CO2), respiratory exchange ratio (RER), heart rate (HR), ratings of perceived exertion (RPE), and blood glucose and lactate concentrations were recorded for each stage and at volitional exhaustion. Time-to-exhaustion (TTE) and peak oxygen consumption (V˙O2peak) during the ramp test were also recorded. Absolute reliability, calculated as the coefficient of variation (CV) between repeated measures, ranged from 2.3% to 3.1% for RE, whereas relative reliability, calculated as the intraclass correlation coefficient (ICC), ranged from .42 to .79. V˙E, V˙O2, V˙O2peak, V˙CO2, RER, and HR had a CV of 1.1%-4.3% across all stages. TTE and RPE had a CV of 7.2% and 2.3%-10.8%, respectively, while glucose and lactate had a CV of 4.0%-17.8%. All other parameters, except for blood glucose, were demonstrated to have good-to-excellent relative reliability assessed by ICC. Measures of RE, V˙O2peak, and TTE were reliable during this two-phase multistage incremental treadmill test in a cohort of trained and highly trained male middle- and long-distance runners.

Acute Ingestion of a Ketone Monoester without Co-ingestion of Carbohydrate Improves Running Economy in Male Endurance Runners.

PURPOSE: Acute ingestion of a ketone monoester, with and without co-ingestion of carbohydrate, was investigated for effects on running economy (RE), time to exhaustion (TTE), and other related indices of endurance running performance. METHODS: Using a three condition, placebo-controlled, randomized crossover design, 11 male middle- and long-distance runners ran at five submaximal speeds (10-14 km·h -1 ) on a motorized treadmill for 8 min each, immediately followed by a ramp test to volitional exhaustion. Participants consumed either a 10% carbohydrate solution (CHO), a 10% carbohydrate solution with 750 mg·kg -1 body mass of an ( R )-3-hydroxybutyl ( R )-3-hydroxybutyrate ketone monoester (CHO + KE), or 750 mg·kg -1 body mass of the ketone monoester in flavored water (KE) before (two-thirds of the dose) and during (one-third of the dose) exercise. RESULTS: ß-hydroxybutyrate concentration averaged 1.8 ± 0.3 and 2.1 ± 0.3 mM during exercise in CHO + KE and KE, respectively. RE was lower at each submaximal running speed (effect size = 0.48-0.98) by an average of 4.1% in KE compared with CHO, but not between CHO + KE and CHO. TTE did not differ between CHO (369 ± 116 s), CHO + KE (342 ± 99 s), or KE (333 ± 106 s) ( P = 0.093). CONCLUSIONS: Acute ingestion of a ketone monoester without carbohydrate, but not when coingested with carbohydrate, improved RE in middle- and long-distance runners at a range of submaximal running speeds and did not alter TTE in a short-duration ramp test to volitional exhaustion. Further investigation is required to examine if these differences translate into positive performance outcomes over longer durations of exercise.

Keloidal atypical fibroxanthoma of the scalp.

Atypical fibroxanthoma (AFX) is a rare low-grade sarcoma that occurs mainly in the elderly and may recur locally. There are multiple variants including keloidal AFX (KAF). KAF is characterised by a proliferation of atypical spindled and epithelioid cells admixed with bizarre pleomorphic cells. These cells intersect among broad bands of keloidal collagen. AFX is a diagnosis of exclusion so a broad panel of immunohistochemical staining should be applied to rule out other differentials (squamous cell carcinoma (SCC), melanoma, leiomyosarcoma, etc). There is added difficulty with the diagnosis of KAF as it may mimic multiple keloidal lesions, including exuberant scarring, as in this case. p53 immunohistochemistry staining can be useful in highlighting the presence of tumour cells. Additionally, next generation sequencing can detect genetic mutations identified in clonal proliferations consistent with tumour formation. KAF is easily overlooked and it should be included in the differential diagnosis for keloidal lesions showing even mild atypia.

Competitive level differences in the activity profile of elite Gaelic football referees.

The purpose of this study was to compare the activity profile of elite Gaelic football referees (GFR) between the National Football League (NFL) and the All-Ireland Championship (AIC), and across the four divisions of the NFL and three phases of the AIC. Match activity data was collected during 125 NFL and 201 AIC games using 10-Hz global positioning system technology from 41 elite GFR. Game duration, total distance, very low-speed movement (<0.70 m·s-1), walking (≥0.70-1.65 m·s-1), low-speed running (≥1.66-3.27 m·s-1), moderate-speed running (≥3.28-4.86 m·s-1), high-speed running (≥4.87-6.48 m·s-1), very high-speed running (≥6.49 m·s-1) distance, and peak running speed were compared between competitions. Games in the AIC were longer than in the NFL (ES = 0.59) but the total distance was similar between the NFL (119.6 ± 9.5 m·min-1) and AIC (122.6 ± 8.4 m·min-1, ES = 0.11). No other differences were found between the NFL and AIC or across the four divisions of the NFL and three phases of the AIC, except for a higher peak running speed during the All-Ireland Series (6.93 ± 0.52 m·s-1) than the All-Ireland Qualifiers (6.65 ± 0.46 m·s-1, ES = 0.35). This information can be used to design specific conditioning programmes to ensure optimal physical development of GFR at all competitive levels.

Physical Match Demands of International Women's Rugby Union: A Three-Year Longitudinal Analysis of a Team Competing in The Women's Six Nations Championship.

There is a paucity of studies describing the physical match demands of elite international women's rugby union, which limits coaches' ability to effectively prepare players for the physical demands required to compete at the elite level. Global positioning system technologies were used to measure the physical match demands of 53 international female rugby union players during three consecutive Women's Six Nations Championships (2020-2022), resulting in 260 individual match performances. Mixed-linear modelling was used to investigate differences in physical match demands between positions. Significant effects (p < 0.05) of the position were observed for all variables, with the exception of relative distances (m.min-1) at velocities of 1.01-3.00 m·s-1 (p = 0.094) and 3.01-5.00 m·s-1 (p = 0.216). This study provides valuable data on the physical match demands of elite international women's rugby union match play that may aid practitioners in the physical preparation of players to compete at this level. Training methodologies for elite-level female rugby union players should consider the unique demands across positional groups with specific considerations of high-velocity running and collision frequency.

Activity profile of elite Gaelic football referees during competitive match play.

The purpose of this study was to examine the activity profile of elite Gaelic football referees (GFR) and to examine temporal changes between the first and second half and across the four quarters. Global positioning systems technology (10-Hz) was used to collect activity data during 202 competitive games from 23 elite GFR. Relative distance, peak running speed and relative distance covered in six movement categories [very low-speed movement (VLSM) (<0.70 m·s-1), walking (≥0.70-1.65 m·s-1), low-speed running (LSR) (≥1.66-3.27 m·s-1), moderate-speed running (MSR) (≥3.28-4.86 m·s-1), high-speed running (HSR) (≥4.87-6.48 m·s-1), very high-speed running (VHSR) (≥6.49 m·s-1)] were examined during the full game, first and second half, and across the four quarters. The relative distance covered was 122.6 ± 8.4 m·min-1, with 13.1 ± 4.9 m·min-1 of HSR and VHSR. The peak running speed was 6.75 ± 0.49 m·s-1. The relative (ES=0.60), MSR (ES=0.50) and HSR (ES=0.14) distance was higher in the first half than the second half. A higher relative (ES=0.62-0.91) and HSR (ES=0.51-0.61) distance was found in the first quarter than any other period. No differences in HSR distance were found between the second, third and fourth quarters (ES=0.04-0.10). This study provides, for the first time, a detailed insight into the activity profile of elite GFR during competitive games and demonstrates the demanding, intermittent nature of elite refereeing in Gaelic football. This information may be used as a framework for coaches to design training programmes specific to GFR.

Effects of 8 wk of 16:8 Time-restricted Eating in Male Middle- and Long-Distance Runners.

PURPOSE: Eight weeks of time-restricted eating (TRE) in concert with habitual exercise training was investigated for effects on body composition, energy and macronutrient intakes, indices of endurance running performance, and markers of metabolic health in endurance athletes. METHODS: Male middle- and long-distance runners (n = 23) were randomly assigned to TRE (n = 12) or habitual dietary intake (CON; n = 11). TRE required participants to consume all of their dietary intake within an 8-h eating window (so-called 16:8 TRE), but dietary patterns, food choices, and energy intake were ad libitum during this window. Participants continued their habitual training during the intervention period. Participants completed an incremental exercise test before (PRE) and after (POST) the 8-wk intervention for the assessment of blood lactate concentrations, running economy, and maximal oxygen uptake. Fasted blood samples were analyzed for glucose, insulin, and triglyceride concentrations. Dietary intake was assessed at PRE, MID (week 4), and POST using a 4-d semiweighed food diary. RESULTS: Seventeen participants (TRE, n = 10; CON, n = 7) completed the intervention. Training load did not differ between groups for the duration of the intervention period. TRE resulted in a reduction in body mass (mean difference of -1.92 kg, 95% confidence interval = -3.52 to -0.32, P = 0.022). Self-reported daily energy intake was lower in TRE at MID and POST (group-time interaction, P = 0.049). No effect of TRE was observed for oxygen consumption, respiratory exchange ratio, running economy, blood lactate concentrations, or heart rate during exercise, nor were there any effects on glucose, insulin, or triglyceride concentrations observed. CONCLUSION: Eight weeks of 16:8 TRE in middle- and long-distance runners resulted in a decrease in body mass commensurate with a reduction in daily energy intake, but it did not alter indices of endurance running performance or metabolic health.

A wearable sensor for the detection of sodium and potassium in human sweat during exercise.

The SwEatch platform, a wearable sensor for sampling and measuring the concentration of electrolytes in human sweat in real time, has been improved in order to allow the sensing of two analytes. The solid contact ion-sensitive electrodes (ISEs) for the detection of Na+ and K+ have been developed in two alternative formulations, containing either poly(3,4-ethylenedioxythiophene) (PEDOT) or poly(3-octylthiophene-2,5-diyl) (POT) as a conductive polymer transducing component. The solution-processable POT formulation simplifies the fabrication process, and sensor to sensor reproducibility has been improved via partial automation using an Opentron® automated pipetting robot. The resulting electrodes showed good sensitivity (52.4 ± 6.3 mV/decade (PEDOT) and 56.4 ± 2.2 mV/decade (POT) for Na+ ISEs, and 45.7 ± 7.4 mV/decade (PEDOT) and 54.3 ± 1.5 mV/decade (POT) for K+) and excellent selectivity towards potential interferents present in human sweat (H+, Na+, K+, Mg2+, Ca2+). The 3D printed SwEatch platform has been redesigned to incorporate a double, mirrored fluidic unit which is capable of drawing sweat from the skin through passive capillary action and bring it in contact with two independent electrodes. The potentiometric signal generated by the electrodes is measured by an integrated electronics board, digitised and transmitted via Bluetooth to a laptop. The results obtained from on-body trials on athletes during cycling show a relatively small increase in sodium (1.89 mM-2.97 mM) and potassium (3.31 mM-7.25 mM) concentrations during the exercise period of up to 90 min.

Development of dynamic cell and organotypic skin models, for the investigation of a novel visco-elastic burns treatment using molecular and cellular approaches.

BACKGROUND: Burn injuries are a major cause of morbidity and mortality worldwide. Despite advances in therapeutic strategies for the management of patients with severe burns, the sequelae are pathophysiologically profound, up to the systemic and metabolic levels. Management of patients with a severe burn injury is a long-term, complex process, with treatment dependent on the degree and location of the burn and total body surface area (TBSA) affected. In adverse conditions with limited resources, efficient triage, stabilisation, and rapid transfer to a specialised intensive care burn centre is necessary to provide optimal outcomes. This initial lag time and the form of primary treatment initiated, from injury to specialist care, is crucial for the burn patient. This study aims to investigate the efficacy of a novel visco-elastic burn dressing with a proprietary bio-stimulatory marine mineral complex (MXC) as a primary care treatment to initiate a healthy healing process prior to specialist care. METHODS: A new versatile emergency burn dressing saturated in a >90% translucent water-based, sterile, oil-free gel and carrying a unique bio-stimulatory marine mineral complex (MXC) was developed. This dressing was tested using LabSkin as a burn model platform. LabSkin a novel cellular 3D-dermal organotypic full thickness human skin equivalent, incorporating fully-differentiated dermal and epidermal components that functionally models skin. Cell and molecular analysis was carried out by in vitro Real-Time Cellular Analysis (RTCA), thermal analysis, and focused transcriptomic array profiling for quantitative gene expression analysis, interrogating both wound healing and fibrosis/scarring molecular pathways. In vivo analysis was also performed to assess the bio-mechanical and physiological effects of this novel dressing on human skin. RESULTS: This hybrid emergency burn dressing (EBD) with MXC was hypoallergenic, and improved the barrier function of skin resulting in increased hydration up to 24 h. It was demonstrated to effectively initiate cooling upon application, limiting the continuous burn effect and preventing local tissue from damage and necrosis. xCELLigence RTCA® on primary human dermal cells (keratinocyte, fibroblast and micro-vascular endothelial) demonstrated improved cellular function with respect to tensegrity, migration, proliferation and cell-cell contact (barrier formation) [1]. Quantitative gene profiling supported the physiological and cellular function finding. A beneficial quid pro quo regulation of genes involved in wound healing and fibrosis formation was observed at 24 and 48 h time points. CONCLUSION: Utilisation of this EBD + MXC as a primary treatment is an effective and easily applicable treatment in cases of burn injury, proving both a cooling and hydrating environment for the wound. It regulates inflammation and promotes healing in preparation for specialised secondary burn wound management. Moreover, it promotes a healthy remodelling phenotype that may potentially mitigate scarring. Based on our findings, this EBD + MXC is ideal for use in all pre-hospital, pre-surgical and resource limited settings.

No Benefit of Ingestion of a Ketone Monoester Supplement on 10-km Running Performance.

PURPOSE: Preexercise ingestion of exogenous ketones alters the metabolic response to exercise, but effects on exercise performance have been equivocal. METHODS: On two occasions in a double-blind, randomized crossover design, eight endurance-trained runners performed 1 h of submaximal exercise at approximately 65% V˙O2max immediately followed by a 10-km self-paced time trial (TT) on a motorized treadmill. An 8% carbohydrate-electrolyte solution was consumed before and during exercise, either alone (CHO + PLA), or with 573 mg·kg of a ketone monoester supplement (CHO + KME). Expired air, HR, and RPE were monitored during submaximal exercise. Serial venous blood samples were assayed for plasma glucose, lactate, and ß-hydroxybutyrate concentrations. RESULTS: CHO + KME produced plasma ß-hydroxybutyrate concentrations of approximately 1.0 to 1.3 mM during exercise (P < 0.001), but plasma glucose and lactate concentrations were similar during exercise in both trials. V˙O2, running economy, respiratory exchange ratio, HR, and RPE were also similar between trials. Performance in the 10-km TT was not different (P = 0.483) between CHO + KME (mean, 2402 s; 95% confidence interval, 2204-2600 s) and CHO + PLA (mean, 2422 s; 95% confidence interval, 2217-2628 s). Cognitive performance, measured by reaction time and a multitasking test, did not differ between trials. CONCLUSIONS: Compared with carbohydrate alone, coingestion of KME by endurance-trained athletes elevated plasma ß-hydroxybutyrate concentrations, but did not improve 10-km running TT or cognitive performance.

Epidermal growth factor receptor (EGFR), HER2 and insulin-like growth factor-1 receptor (IGF-1R) status in ovarian adult granulosa cell tumours.

AIMS: Adult granulosa cell tumours (AGCTs) are uncommon ovarian sex cord-stromal tumours which recur following surgical removal in up to 50% of patients. Treatment options for recurrent and advanced stage AGCTs are limited, with poor response to chemotherapy and radiotherapy. We aimed to assess epidermal growth factor receptor (EGFR), HER2 and insulin-like growth factor-1 receptor (IGF-1R) status in AGCTs with a view to investigating whether or not these receptors might be potential therapeutic targets in these neoplasms. METHODS AND RESULTS: Immunohistochemical staining for EGFR, HER2 and IGF-1R was undertaken in 31 AGCTs. Tumour DNA was also analysed for mutations in the tyrosine kinase domain of EGFR (exons 18-21) by Cobas mutation RT-PCR. Twenty-three of 31 (74%) AGCTs showed some degree of EGFR expression, generally with cytoplasmic or mixed membranous and cytoplasmic staining of variable intensity. Eleven of 27 (41%) cases exhibited strong membranous and cytoplasmic expression of IGF-1R. HER2 expression was not seen. No mutations were found in exons 18-21 of the EGFR gene in hot-spots of therapeutic relevance. CONCLUSIONS: This study raises the possibility that anti-EGFR and/or anti-IGF-1R therapies may be of potential benefit in ovarian AGCTs, and this requires further study. Lack of known mutations within the tyrosine kinase domain of EGFR suggests that EGFR-related tyrosine kinase inhibitors may not be useful therapeutically.

Ectodermal structures within the uterine cervix and vagina: report of a series of cases.

Ectodermal structures, in the form of sebaceous glands and hair follicles, are extremely rare within the cervix and vagina. We describe the clinicopathologic findings in 11 cases (10 cervix, 1 vagina) with a view to exploring the histogenesis of this unusual phenomenon. The cases occurred in patients aged 33 to 71. In 10 of the cases, sebaceous glands were present that were associated with hair follicle-like structures in 3 cases forming pilosebaceous units. In the other case, hair follicle- and sweat gland-like structures were present; the latter have not been previously described in the cervix. The ectodermal structures were usually either attached to the basal layer of the surface squamous epithelium or lay "free" within the superficial stroma, although in 1 case sebaceous glands were located within the squamous epithelium. The squamous epithelium overlying the ectodermal structures typically exhibited hyperkeratosis. Although we were unable to definitively resolve the debate as to whether ectodermal structures within the cervix and vagina represent misplaced embryonal tissue and a true heterotopia or a "metaplastic" process, we favor the latter as a response to prolonged irritation or chronic injury.

A detailed immunohistochemical analysis of 2 cases of papillary cystadenoma of the broad ligament: an extremely rare neoplasm characteristic of patients with von hippel-lindau disease.

We report 2 cases of papillary cystadenoma, a rare neoplasm characteristic of patients with Von Hippel-Lindau (VHL) disease, involving the pelvic soft tissues of women and probably arising within the broad ligament. In only one of the women was there a history of VHL disease. The other woman was investigated for VHL disease after the diagnosis of papillary cystadenoma and all tests were negative. There has been debate as to whether papillary cystadenomas in women are of mesonephric (Wolffian) or of Mullerian origin and to investigate this we undertook a detailed immunohistochemical analysis. Both tumors were positive with AE1/3, Ber EP4, epithelial membrane antigen, CK7, CD10, CA125, CA19.9, calretinin, and vimentin. One exhibited focal nuclear staining with WT1 and PAX8. The tumors were negative with estrogen receptor, progesterone receptor, androgen receptor, CK20, CEA, TTF1, inhibin, RCC marker, and hepatocyte nuclear factor 1ß. Although favoring a mesonephric origin, the immunohistochemical findings are essentially inconclusive and not definitive for either a mesonephric or a Mullerian origin. We believe that patients found to have papillary cystadenoma should be investigated for VHL disease if there is no history of this. This is the second reported example of papillary cystadenoma in a woman not known to have VHL disease and the first in which investigations have excluded this disease.

Postirradiation primary vaginal angiosarcoma with widespread intra-abdominal metastasis.

We report a primary vaginal angiosarcoma with widespread intra-abdominal metastasis occurring in a 73-yr-old woman 13 yr after vaginal brachytherapy for an endometrial carcinoma. This is an extremely rare phenomenon with only 7 previously reported cases of vaginal angiosarcoma, 5 of which were associated with earlier irradiation. All of the earlier reported cases have been localized to the pelvis without metastatic disease.