To assess current pregame (PIVFH) and halftime intravenous fluid hyperhydration (HIVFH) practices, protocols, indications, complications, and perceived efficacy in National Collegiate Athletic Association Football Bowl Subdivision (NCAA-FBS) football players. Cross-sectional survey. NCAA-FBS. Head team physicians and athletic trainers from 71 unique NCAA-FBS Division 1 schools. Voluntary anonymous 28-question validated survey. Number of teams using PIVFH and HIVFH. 73 (30.7%) institutions completed surveys, representing 71 of 238 (29.8%) unique NCAA-FBS institutions. Twenty eight of 71 (39.4%) of institutions reported using PIVFH, while 29 of 71 (40.8%) reported using HIVFH. For PIVFH (20/28, 71.4%) and HIVFH (18/21, 85.7%), most institutions reported 1 L of IV fluid was administered, typically normal saline. Most teams (20/29, 68.9%) reported that 1 to 3 players received HIVFH when the temperature was above 80°F, while 12 of 29 (41.4%) teams used HIVFH regardless of temperature. Complications related to IVFH were reported by 28 of 71 (39.4%) institutions. The most commonly cited complications were provider needlestick, pulmonary edema, and infection. The use of PIVFH at NCAA-FBS institutions has remained relatively stable compared with prior studies. HIVFH, which was not previously reported, was used slightly more frequently than PIVFH and with greater variability based on ambient temperature. Many institutions reported complications related to IVFH, emphasizing the importance of carefully considering potential risks and benefits when implementing IVFH protocols.
Patients with heart failure and preserved ejection fraction (HFpEF) experience significant exercise intolerance, yet its underlying mechanisms remain poorly defined and are multifactorial. Iron deficiency (ID) occurs frequently in HFpEF and may contribute to exercise impairment. This study evaluated mitochondrial oxidative muscle metabolism in HFpEF using in vivo  31phosphorus magnetic resonance spectroscopy (31P-MRS) employing two exercise protocols, and assessed whether ID influences exercise energetics. In this parallel analysis of prospective studies at two sites, patients with HFpEF and control individuals performed either isometric exercise (isolated leg protocol) or dynamic exercise (cardiopulmonary protocol) with concomitant phosphocreatine recovery assessment using in vivo  31P-MRS. Associations between clinical factors and oxidative metabolism were evaluated. ID was defined as ferritin <100 µg/L, or ferritin 100-299 µg/L with transferrin saturation <20%. Fifty-eight patients with HFpEF and 16 controls performed isometric exercise (n = 46 HFpEF; n = 16 control) or cardiopulmonary exercise (n = 12 HFpEF). Phosphocreatine recovery halftime after isometric exercise was prolonged in patients versus controls [27 (23-32) vs 24 (19-28) seconds, respectively; P = .03]. Phosphocreatine recovery halftime after dynamic exercise in patients was 39 (27-57) seconds. Both cohorts consisted of patients with and without ID (n = 19 and 27, and n = 6 and 6, respectively), who had comparable exercise and oxidative muscle capacity (all P > .42). High-sensitive C-reactive protein was associated with prolonged phosphocreatine recovery halftime (P =. 01). Patients with HFpEF exhibit impaired whole-muscle oxidative capacity of skeletal muscle, as shown by two different 31P-MRS protocols with upper leg measurements, independent of ID status. NTR6605, NTR7297 (https://onderzoekmetmensen.nl/nl/trial/55673); NCT05750940 (https://clinicaltrials.gov/study/NCT05750940).
This exploratory study investigated the effects of a 3-minute re-warm-up protocol implemented during halftime on sprint and jump performance in female soccer players. Twenty-two professional female soccer players from 2 Portuguese clubs from First and Second Divisions were randomly assigned to either a control group (G1: passive rest) or an experimental group (G2: re-warm-up). The Integrated Re-warm-up soccer protocol, performed by G2, consisted of 6 FIFA 11+ power exercises and a small-sided game. Performance was measured using a 20-m sprint and countermovement jump at baseline (post-warm-up) and after the half-time intervention. A 2-way analysis of variance (group × time) was conducted for analysis, with effect sizes reported as partial eta squared (ηp2). A time × group interaction was found for sprint performance (F = 6.66, P = .019, ηp2=.27), favoring the experimental group (G1: -0.25 s vs G2: -0.40 s). For countermovement jump performance, no time × group interaction was observed (F = 2.66, P = .483, ηp2=.02), although a main effect of time effect was detected (F = 10.34, P = .005, ηp2=.36); both groups showed a decrease in jump height, but to a lesser extent in the re-warm-up group (G1: -2.85 cm vs G2: -1.82 cm). A brief 3-minute re-warm-up protocol implemented at halftime improved sprint performance compared to passive rest. These findings suggest that time-efficient re-warm-up protocols, combining FIFA 11+ power exercises and small-sided games may be useful during the half-time interval in female soccer players.
The Modified Maddocks Questions Tool (MMQT) is part of the Concussion Recognition Protocol used for sideline assessment of suspected concussion. Although widely used in English-speaking populations, it has not been validated in Spanish-speaking children. This study aimed to evaluate comprehension and response accuracy of a Spanish-adapted MMQT in soccer players aged 4-8 years. We conducted a cross-sectional observational study in Montevideo, Uruguay, between July and October 2024. Eighty-eight male soccer players aged 4-8 years were assessed at halftime using a Spanish-adapted version of the MMQT. Comprehension was evaluated by asking participants to reformulate each question. Associations between age, comprehension, and response accuracy were analyzed using chi-square or Fisher's exact tests and logistic regression models. No statistically significant association was found between age and either comprehension or accuracy. Overall comprehension exceeded 96%. However, Question 4 ("Which team won the last match?") consistently showed a lower correct response rate across all ages. Our findings reinforce previous observations showing that questions assessing recall of past events can be challenging for younger children and suggest caution when evaluating MMQT responses in this age group. The Spanish-adapted MMQT demonstrates high comprehension and may be suitable for sideline concussion screening in children aged 5-8 years. However, Question 4 appears less reliable and should be reconsidered in future versions. A conservative approach is recommended, whereby any incorrect response warrants removal from play for further evaluation.
Body temperatures of salmon do not always match the temperatures of their immediate environment. We investigated the relationship between varying ambient water temperatures and body temperatures of adult sockeye salmon Oncorhynchus nerka using Newton's law of cooling and non-linear mixed models. The median estimated coefficient of heat exchange k $$ k $$ for O. nerka in this study was 0.09 min-1 with corresponding temperature change halftime and thermal time constant values of 7.7 and 11.1 min, respectively. There was little support for salmon condition factor and mass impacting k $$ k $$ , or differences in k $$ k $$ when the body was cooling or warming. Metabolically produced heat had a very small effect on body temperature. The bodies of the salmon did not instantaneously equilibrate with ambient temperatures. Model-averaged predictions showed that it would take approximately 60 min for the core body temperature of an adult O. nerka to equilibrate with ambient temperature (i.e., rate of body temperature change <0.01°C min-1) after moving into water temperatures 10°C cooler or warmer than their initial body temperature. Greater differences in body and ambient temperatures were predicted when the salmon experienced rapid and larger changes in ambient temperature. The differences in body and ambient temperatures experienced by Babine Lake O. nerka in this study highlight a need to exhibit caution when equating water temperature to the body temperature of fish in thermally heterogeneous environments across short timescales. The estimated values of k $$ k $$ and T m $$ {T}_m $$ from this study could be applied to other research requiring body temperature predictions for free-ranging adult O. nerka or possibly other similarly sized and shaped salmonids without using internal temperature loggers.
Carbocyclic nicotinamide cofactors are attractive NAD(P)+ analogues that retain native redox activity while offering substantially enhanced chemical and thermal stability. Their broader use, however, has been limited by demanding multistep chemical syntheses involving complex protection strategies and limited exploration of enzymatic alternatives. In this study, we studied both chemical and enzymatic approaches for the synthesis of carba-analogues. For the enzymatic route, we identify and characterize the key enzymes involved in cofactor assembly, evaluating their tolerance toward non-native, carbocyclic substrates and extending the assembly to further generate the phosphorylated analogue, cNADP+. In addition, extending the analysis to cofactor thermostability, carba-NAD+ displayed a remarkable halftime (t 1/2 > 1386 h at 50 °C), far exceeding that of NAD+ (t 1/2 = 76 h) and is accepted by a broad panel of oxidoreductases. Collectively, this work outlines a modular workflow and details the synthesis landscape for accessing thermostable, synthetic nicotinamide cofactor analogues, cNAD+ and cNADP+, unveiling new opportunities for their application in cofactor engineering and synthetic biocatalysis.
This observational longitudinal study examined the impact of six contextual on the match demands of professional soccer players using Principal Component Analysis (PCA). Data were collected from 17 male players across 37 official matches (September 2023-May 2024) of a Tier 3 Spanish team, utilizing 10 Hz GPS units. PCA, combined with hierarchical cluster analysis, effectively reduced the 17 initial external load metrics to eight representative variables, optimizing relevant information and minimizing redundancy inherent in performance monitoring systems. Six contextual factors (match outcome, location, player position, goal difference, halftime score evolution, and competitive block) were analyzed for their influence using ANOVA. Results indicated that player position was the most influential variable (p ≤ 0.001, large effect sizes), significantly affecting all external load metrics, with distinct profiles for forwards, midfielders, and defenders. Specifically, forwards excelled in high-intensity actions; midfielders recorded higher values in medium-intensity distances and decelerations, while defenders consistently exhibited the lowest overall physical demands. Match location significantly influenced high-intensity distance and decelerations (higher at home, small effect sizes). The competitive block showed a significant effect only on low-intensity distance, peaking during intermediate periods, suggesting that effective load management strategies mitigated fluctuations in high-intensity activity. Conversely, match outcome, goal difference, and score difference evolution had no significant effects on most physical demands. This study confirms player position as the predominant contextual factor and highlights the utility of PCA in refining load monitoring. Practical applications include individualized training regimens tailored to positional demands and optimized monitoring strategies for efficient performance analysis.
This study aimed to investigate the acute effects of the Band-French Contrast Method (Band-FCM) and Band-Post-Activation Performance Enhancement (Band-PAPE) protocols on throwing velocity, countermovement jump (CMJ) height, and internal training load (RPE) in elite youth male handball players. A total of 23 athletes from the U18 national team voluntarily participated in the study. The experimental design included four sessions: an initial familiarization and band-1RM testing day, followed by three intervention sessions arranged in a Latin square design. The Band-PAPE protocol consisted of two sets of shoulder press actions performed at 90% band-1RM, incorporating 3-second isometric holds followed immediately by explosive concentric movements, followed by 4 min of passive recovery before performance testing. The Band-FCM protocol comprised three sets of upper-body isometric, dynamic, and plyometric exercises applied in a sequential structure. Throwing velocity (measured via radar), CMJ height (assessed using Optojump), and RPE (CR-10 scale) were recorded before and 2–4 min after the intervention. The significance level was set at α = 0.05. Results showed that the Band-PAPE protocol significantly increased throwing velocity (+ 5.6 km·h⁻¹) without elevating RPE. Both protocols induced moderate improvements in CMJ height; however, only Band-FCM significantly increased RPE. In conclusion, Band-PAPE may be suitable for pre-competition and in-game use (e.g., pre-match warm-up, halftime, and preparing substitute players) due to its performance benefits with minimal increase in internal load, whereas Band-FCM appears more appropriate as a training-oriented strategy for longer-term power development rather than acute performance enhancement.
Recreational use of nitrous oxide is rapidly increasing in France and across Europe, accompanied by a rise in neurological, cardiovascular and psychiatric complications. In this context, portable devices, particularly those based on infrared spectroscopy (IR), are being proposed to detect N2O several hours after inhalation. However, physiological data show that N2O has very low blood solubility, diffuses rapidly, and is almost completely eliminated within approximately 30 minutes, with a half-time of about 5 minutes. The prolonged detection reported in profile and is based on controlled conditions that are difficult to extrapolate to real-world settings. Exhaled concentrations are strongly influenced by ventilation, cardiac output and breathing technique, resulting in significant interindividual variability. From an analytical perspective, headspace gas chromatography-mass spectrometry (HS/GC-MS) remains the laboratory reference method but is not suitable for rapid field screening. Infrared spectroscopy offers a promising portable alternative, yet it still faces methodological limitations, variability issues and a lack of robust validation. Based on current knowledge, a breath test could serve as a qualitative screening tool for recent exposure, but it does not yet allow reliable quantification or robust medico-legal interpretation without further scientific evidence and an appropriate regulatory framework.
Near-infrared spectroscopy (NIRS) has been widely used in rock-climbing research to assess muscle oxygenation (StO2) in the flexor digitorum profundus (FDP). However, the deep anatomical location of the FDP, combined with the maximum penetration depth of ∼20 mm for most NIRS devices, raises uncertainty regarding whether the currently used optode placement is adequate for studying the FDP. This study aimed to characterize forearm morphology in climbers and examine the effect of NIRS optode placement on haemodynamic outcomes. This study comprised two parts. In Part 1 (n = 28), adipose tissue thickness (ATT), flexor digitorum superficialis (FDS) thickness, and FDP thickness were measured at three forearm sites (proximal, reference, and distal; 20 mm spacing) in supination and pronation using ultrasound. The reference site was defined as 33% of the distance between the medial epicondyle and lunate. Part 2 (n = 22) consisted of a vascular occlusion and incremental finger flexor endurance test with NIRS optodes positioned either perpendicular or parallel to the FDP fibres. The outcomes included half-time recovery of reoxygenation (StO₂ HTR) from the vascular occlusion test, reoxygenation between contractions during the first (ΔStO2 relief-first) and final stages (ΔStO2 relief-last), and mean oxygenation (StO2 mean) during the incremental test. The FDS-FDP border was located 17.6 ± 4.0 mm deep, indicating that the FDS dominated the near-infrared signal. During the incremental test, ΔStO2 relief-last was 2.7 ± 2.9% lower (p < 0.001, g = 0.87) and StO2 mean was 5.5 ± 3.4% higher (p < 0.001, g = 1.56) with perpendicular optode orientation than with parallel optode orientation. StO2 HTR and ΔStO2 relief-first were not different between optode orientations (p = .145, g = 0.33; p = 0.799, rrb  = 0.06). In conclusion, only a small portion of the FDP lies within the NIRS penetration depth. StO2 reoxygenation between contractions was more pronounced when the optodes were aligned parallel to the muscle fibres, although this was observed only at moderate intensities. Based on these findings, we recommend positioning the NIRS optodes over the reference site, aligning them parallel to the muscle fibres, and using the term "flexores digitorum" when referring to the muscles under investigation.
Peak oxygen consumption (V̇o2peak) is reduced in patients with chronic kidney disease (CKD). Although cardiovascular and skeletal muscle factors are implicated in the declines of V̇o2peak, few studies have evaluated muscle oxygenation responses during exercise. We hypothesized that lower V̇o2peak in CKD would be associated with attenuated responses in muscle oxygenation compared with those without CKD. Forty-six male Veterans [CKD stages 3 and 4, n = 23; referent controls (REF), n = 23] completed the study. Cardiopulmonary exercise testing was performed on a treadmill using the modified Bruce protocol. Peak change in dominant medial gastrocnemius deoxygenated hemoglobin/myoglobin {Δ[deoxy(Hb-Mb)]peak}, total hemoglobin/myoglobin {Δ[total(Hb-Mb)]peak}, tissue saturation index (ΔTSI), and ΔTSI reoxygenation half-time recovery (ΔTSIreoxy1/2time) were assessed via near-infrared spectroscopy (NIRS). V̇o2peak, exercise time, HRpeak, V̇o2 at gas-exchange threshold (GET), and exercise time after GET were lower in the CKD group versus the REF group (P = 0.002, P < 0.001, P = 0.020, P = 0.044, and P = 0.005, respectively). For NIRS outcomes, Δ[total(Hb-Mb)]peak was lower, and ΔTSIreoxy1/2time prolonged, in the CKD group compared with the REF group (P = 0.032 and P = 0.031, respectively). V̇o2peak was positively associated with HRpeak (CKD, r = 0.57, P = 0.005; REF, r = 0.63, P = 0.001) and Δ[total(Hb-Mb)]peak (CKD, r = 0.63, P = 0.001; REF, r = 0.52, P = 0.012) in both groups. Conversely, V̇o2peak was positively associated with Δ[deoxy(Hb-Mb)]peak in the CKD group only (r = 0.64, P < 0.001). These findings suggest that skeletal muscle impairments, in addition to cardiovascular impairments, contribute to reduced V̇o2peak in patients with CKD.NEW & NOTEWORTHY Peak oxygen consumption is associated with peak heart rate, oxygen extraction, and microvascular blood volume in patients with chronic kidney disease (CKD), highlighting the importance of cardiovascular and skeletal muscle health in this patient population. Future studies are necessary to determine which exercise approaches are most efficacious at enhancing cardiorespiratory fitness and whether, and to what extent, improvements in cardiorespiratory fitness result from changes in cardiovascular factors, skeletal muscle factors, or a combination of both.
Coexistent mild aortic valve disease is frequently observed in patients undergoing mitral valve surgery, yet the clinical significance and progression of these lesions remain uncertain. This study aimed to evaluate the progression and clinical outcomes of mild aortic valve disease following mitral valve surgery. This single-centre observational study included 80 patients who underwent primary mitral valve surgery with documented mild aortic valve disease. Patients were evaluated through a hybrid design, consisting of a retrospective cohort (n=43) from 2010 to 2017 and a prospective cohort (n=37) from 2016 to 2019, using echocardiographic and clinical assessments. At baseline, out of the 80 patients, 82.5% (n=66) presented with aortic regurgitation (AR) lesions, which comprised isolated mild AR (n=53; 66.2%), trivial AR (n=4; 5%), moderate AR (n=4; 5%), and mixed mild AR with mild aortic stenosis (AS) (n=5; 6.2%). The remaining 17.5% (n=14) presented with isolated mild AS. Follow-up clinical and echocardiographic assessment was completed in 74 patients, while six patients were lost to follow-up. During follow-up (mean duration: 3.54±1.48 years), most assessed patients remained clinically and echocardiographically stable. Among patients with isolated mild AR at baseline, eight patients progressed to moderate AR, while the remaining patients did not demonstrate clinically meaningful progression. Pressure half-time decreased from 643.53±103.90 ms preoperatively to 592.30±120.55 ms postoperatively (t=5.122; p<0.001), and vena contracta increased from 0.26±0.05 cm to 0.31±0.10 cm (t=4.472; p<0.001), without clinically significant deterioration. In patients with aortic stenosis, the aortic valve area decreased from 1.66±0.04 cm² to 1.59±0.02 cm² (t=2.047; p=0.044), and the mean gradient increased from 16±1.73 mmHg to 19±1.00 mmHg (t=2.145; p=0.035). Kaplan-Meier analysis demonstrated an event-free survival rate of 94.6% at the final follow-up. Multivariate analysis identified preoperative aortic valve lesion as the only significant predictor of disease progression (OR: 0.038; 95% CI: 0.002-0.948; p=0.046). Mild aortic valve disease in patients undergoing mitral valve surgery generally remains stable and does not demonstrate significant clinical progression. Routine echocardiographic surveillance remains important to identify the minority of patients who may develop progressive valve dysfunction.
To establish normal ranges for [99mTc] Tc-Mebrofenin hepatobiliary scintigraphy (HBS) indices of liver function and the associated uncertainty in clinical measures due to region placement. 47 patients referred for gallbladder assessment with no history of liver disease were included in the study. Patients underwent dynamic HBS following injection of 200 MBq of [99mTc] Tc-Mebrofenin at 10 seconds/frame for 36 frames. Analysis was performed by 5 experienced technologists using in-house software (MIM Software, Cleveland, Ohio) to establish blood pool (BP) clearance rate (%/min), blood clearance half-time (min), mebrofenin liver uptake rate (MUR) (%/min) and MUR normalised to body-surface-area (MURBSA) (%/min/m2). Limits of normal ranges (95%) were established and correlation of functional indices with age was investigated. Analysis was repeated after a minimum of 4 weeks to establish intra-user variability and uncertainty associated with measures. Data were collected for 27 women and 20 men, with an age range of 20 - 81 years. Twenty-seven patients were aged over 50 and 20 patients were aged below 50. The data were found to have a normal distribution. The mean values derived for the entire cohort for BP clearance rate, blood clearance half time, MUR, and MURBSA were 16.8±2.6 %/min, 4.3±0.7 min, 14.4±2.0 %/min and 8.0±1.5 %/min/m2, respectively. No significant difference in values was found between age groups and no correlation between liver function and age was found. The lower range of normal for MURBSA was established as 5.1%/min/m2, with clinical measures expected to have an uncertainty of ±0. 6 %/min/m2. The MURBSA value for a patient with normal liver function can be expected to be approximately 8.0±1.5 %/min/m2, with a lower limit of normal function at 5.1 %/min/m2. Patients receiving liver surgery or treatment that express MURBSA values below this may be at higher risk and should potentially be treated with caution.
Pseudohypoaldosteronism type II (PHAII), also known as Gordon syndrome, is an autosomal-dominant disorder caused by mutations in with-no-lysine kinase 4 (WNK4) and is characterized by increased renal sodium chloride (NaCl) reabsorption and impaired potassium (K+) secretion. We examined the relative contributions of renal outer medullary K+ (ROMK) channels and large-conductance Ca2+-activated K+ (BK; Maxi-K) channels to distal K+ secretion in wild-type (TgWnk4WT) and PHAII mutant (TgWnk4PHAII) mice. Renal clearance and stationery microperfusion techniques were used to assess urinary Na+ and K+ excretion and K+ secretion in the late distal tubule. Potassium secretion (JK) and the half-time to reach steady-state luminal K+ concentration (T1/2) were measured under control-K+ (CK) and high-K+ (HK) dietary conditions. Quantitative PCR revealed reduced ROMK expression in TgWnk4PHAII mice compared with wild-type mice. Micropuncture studies showed significantly reduced K+ secretion in the late distal tubule under CK conditions in TgWnk4PHAII mice. Iberiotoxin had no effect on JK or T1/2 in either genotype under CK conditions. In contrast, HK feeding increased distal K+ secretion in both genotypes, and this increase was completely abolished by iberiotoxin. These findings indicate that impaired K+ secretion in TgWnk4PHAII mice is due to reduced ROMK-mediated transport and is not compensated by Maxi-K channels under normal K+ intake. The TgWnk4PHAII mutation does not impair HK-stimulated Maxi-K channel-mediated K+ secretion in the distal nephron.NEW & NOTEWORTHY Our findings demonstrate that PHAII-associated WNK4 mutations impair ROMK-dependent distal K+ secretion while preserving high-K+-stimulated Maxi-K channel function, thereby revealing distinct contributions of these channels to renal K+ homeostasis.
We introduce a novel approach for predicting fixed-bed adsorption involving two competing contaminants. The method leads to simple analytical expressions for the concentrations and amount adsorbed throughout the column during an experiment. It primarily relies on equilibrium (isotherm) data, with just a single parameter fitted to breakthrough data. The advantage of employing the isotherm is that the coefficients are obtained using a range and combination of concentrations ensuring a wide range of validity. The isotherm analysis provides key information such as shifts in breakthrough time due to competition, the magnitude of the roll-up effect and relations between adsorption and displacement rates. From the breakthrough data we are able to determine the coefficient describing the rate at which the dominant species replaces the other species and from this all other coefficients may be calculated. Although the dynamic model neglects desorption it is accounted for through the isotherm analysis. The method is validated against novel and literature-based competitive column experiments, where the isotherm-based predictions reproduce full curves with R2>0.95 and a low relative error. Compared to a previous travelling wave approximation, on which this work is based, the present approach yields similar accuracy with the added advantage of providing physically interpretable parameters and allowing predictions of half-times and roll-up height over a wider range of validity. This may then be used to reduce experimental effort while maintaining strong predictive performance.
Wiskott-Aldrich Syndrome (WAS), a rare X-linked disorder, features microthrombocytopenia, eczema, immunodeficiency, and elevated malignancy risk due to genomic instability. While prior studies noted DNA repair deficits, the kinetics of ionizing radiation-induced DSB repair in WAS patients remain unclear. This study aimed to characterize DSB repair dynamics and radiation sensitivity in WAS lymphocytes using γH2AX and 53BP1 markers. Lymphocytes from four WAS patients, their carrier mothers, and healthy controls were analyzed. Baseline DSBs were quantified in non-irradiated cells, and repair kinetics assessed post 2 Gy gamma irradiation over 24 h. Immunofluorescence staining for γH2AX (early DSB marker) and 53BP1 (repair facilitator) was performed at multiple time points, with foci quantified via confocal microscopy. Repair half-lives were calculated using exponential decay models. WAS patients exhibited 16-24 fold higher baseline γH2AX and 53BP1 foci than control (mean), indicating spontaneous genomic instability. Post-irradiation, DSB repair in WAS lymphocytes was significantly delayed, with the mean foci repair half-life (T½) in WAS patients being approximately 1.6-fold longer than that of the control (mean). At 24 h post-irradiation, WAS patients retained nearly twice the number of residual foci compared to healthy controls, while carrier mothers mirrored control repair efficiency. This study provides the first evidence of prolonged DSB repair kinetics in WAS patients, emphasising heightened radiosensitivity and genomic instability. These findings suggest tailored radiation strategies in WAS management, particularly for bone marrow transplantation or genotoxic therapies, to mitigate risks and optimize outcomes.
This series of case studies provides the first clinical experience with the fibroblast activation protein-α (FAP)-targeting radiopharmaceutical [177Lu]Lu-RTX-2358 in patients with advanced solid tumors. Methods: Six patients with advanced FAP-expressing solid tumor malignancies and no standard treatment options remaining, underwent radiopharmaceutical therapy (RPT) with [177Lu]Lu-RTX-2358. Biodistribution was monitored using whole-body planar and SPECT/CT imaging, and dosimetric parameters were calculated for critical organs, red marrow, and tumors. Adverse events were graded according to the Common Terminology Criteria for Adverse Events version 5.0. Preliminary antitumor effects were evaluated after 2 RPT cycles. Results: RPT with [177Lu]Lu-RTX-2358 was tolerable with no dose-limiting toxicity. The mean red marrow absorbed dose was 0.131 ± 0.044 Gy/GBq (range, 0.057-0.227 Gy/GBq). The mean kidney absorbed dose was 0.509 ± 0.169 Gy/GBq (range, 0.272-0.893 Gy/GBq). The mean tumor absorbed dose varied across patients, ranging from 0.346 to 2.70 Gy/GBq. Tumor effective half-times ranged from 95.9 to 159.5 h. Disease stabilization was achieved in 4 patients; progressive disease occurred in 2 patients. Conclusion: [177Lu]Lu-RTX-2358 demonstrated a manageable safety profile in a series of patients who were heavily pretreated for their disease. Given a promising therapeutic index as a result of prolonged retention in tumors and clearance from normal organs, further clinical evaluation is warranted.
Soccer referees play a crucial role in maintaining the laws and spirit of the game. Since the early 2000s, research has focused on understanding and enhancing their performance. However, research on mental fatigue in soccer referees remains in its early stages. This Current Opinion article aims to critically summarize current knowledge of this phenomenon in soccer referees and highlight areas requiring future research. It explores how cognitive and physical demands during matches contribute to mental fatigue development, its potential impact on refereeing performance, and how pre-match, half-time, and post-match interventions might help alleviate or aid recovery from this phenomenon. Although only a small number of studies have investigated mental fatigue in soccer referees, evidence suggests that the combination of intense and prolonged cognitive and physical demands makes both field and assistant referees susceptible to mental fatigue during matches. This phenomenon may negatively impact multiple performance components, particularly decision-making accuracy. Although interventions such as brain endurance training, mindfulness practices, structured routines, recovery strategies, and sleep optimization could help mitigate mental fatigue, the application of these modalities in and around match play remains unexplored in refereeing populations, representing a critical research gap.
The persistence of chemicals in the marine environment can be assessed based on simulation biodegradation tests. However, there is a lack of studies that systematically investigate how the origin of the inoculum in these tests affects biodegradation kinetics and discuss the implications for persistence assessment. This study aims to (1) quantify the effect of inoculum pre-exposure on biodegradation kinetics, (2) quantify the variation in biodegradation kinetics between marine locations across a salinity gradient, and (3) explain differences in biodegradation kinetics based on bacterial abundance and composition. Seawater samples collected in three harbors and open waters (6-8 km from shore) were spiked with 0.5% produced water from an offshore oil platform and incubated for 1-60 days at 10 °C. Primary biodegradation kinetics of 27 petrochemicals were determined by solid phase microextraction GC-MS. Biodegradation half-times were on average 2.9-3.6 times shorter in harbor compared to open water samples, and varied on average by a factor of 1.2-1.9 between open water samples. Higher pre-exposure in harbors had the strongest impact on biodegradation kinetics, whereas geographic sampling location and salinity had the strongest impact on bacterial composition. Faster biodegradation in harbors could not be explained by differences in the overall inoculum composition or bacterial diversity.
Ethanolic fermentation by Saccharomyces cerevisiae is a key part of biochemical conversion of lignocellulosic feedstocks. Although abundant, lignocellulose typically requires pretreatment for efficient bioconversion. During pretreatment, inhibitory compounds are formed. p-Benzoquinone (p-BQ) is a lignin-derived inhibitor that is highly toxic to S. cerevisiae. White-rot fungi, efficient degraders of lignin, produce 1,4-benzoquinone reductases (QRDs), which have been suggested to play a role in defense against oxidative stress caused by quinones formed during lignin biodegradation. The hypothesis that QRDs from white-rot fungi can be used to engineer S. cerevisiae with improved resistance against quinone toxicity was explored in experiments with QRD-encoding genes, with and without an N-terminal putative leader sequence, the function of which has not yet been deciphered. Constitutive recombinant expression of QRDs from the white-rot fungi Trametes versicolor and Phanerochaete chrysosporium in S. cerevisiae resulted in increased tolerance against p-BQ toxicity compared to an empty vector control containing insert-less plasmid, with QRD-expressing constructs requiring 34 to 42% less time to reach half-time of maximum growth in p-BQ conditions adverse for the growth of the empty vector control (10 mg L- 1). All QRD constructs were able to overcome p-BQ toxicity in concentrations that would otherwise be strongly inhibitory (20 mg L- 1). Full-length constructs of both T. versicolor and P. chrysosporium QRD typically exhibited 1.5 times higher specific activity than leaderless counterparts and were better detoxifiers. An inverse correlation between QRD enzymatic activity and the time necessary to reach half-time of maximum growth (R2 = 0.954) was observed during strongly inhibitory conditions. Transformants expressing QRD exhibited maintained glycerol and ethanol yields with increasing p-BQ concentrations, up to 0.44 g g- 1 ethanol at 10 mg L- 1 p-BQ, whereas the empty vector control exhibited increased glycerol yield and decreased ethanol yield, amounting to 0.15 g g- 1 ethanol at 10 mg L- 1 p-BQ. Heterologous expression of QRDs from white-rot fungi in S. cerevisiae confers protection against p-BQ toxicity. This investigation supports a role of QRD in the protection against toxic quinones and proposes a biodetoxification strategy against lignin-derived inhibitory p-BQ which can occur simultaneously with fermentation of sugars into ethanol in S. cerevisiae.