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Compared to the determination of exercise thresholds based on systemic changes in blood lactate concentrations or gas exchange data, the determination of breakpoints based on muscle oxygen saturation offers a valid alternative to provide specific information on muscle-derived thresholds. Our study explored the profiles and timing of the second muscle oxygenation threshold (MOT2) in different muscles. Twenty-six cyclists and triathletes (15 male: age = 23 ± 7 years, height = 178 ± 5 cm, body mass = 70.2 ± 5.3 kg; 11 female: age = 22 ± 4 years, height = 164 ± 4 cm, body mass = 58.3 ± 8.1 kg) performed a graded exercise test (GXT), on a cycle ergometer. Power output, blood lactate concentration, heart rate, rating of perceived exertion, skinfolds and muscle oxygen saturation were registered in five muscles (vastus lateralis, biceps femoris, gastrocnemius medialis, tibialis anterior and triceps brachii) and percentage at which MOT2 occurred for each muscle was determinated using the Exponential Dmax. The results of Statistical Parametric Mapping and ANOVA showed that, although muscle oxygenation displayed different profiles in each muscle during a GXT, MOT2 occurred at a similar percentage of the GXT in each muscle (77% biceps femoris, 75% tibalis anterior, 76% gastrocnemius medialis and 72% vastus lateralis) and it was similar that systemic threshold (73% of the GXT). In conclusion, this study showed different profiles of muscle oxygen saturation in different muscles, but without notable differences in the timing for MOT2 and concordance with systemic threshold. Finally, we suggest the analysis of the whole signal and not to simplify it to a breakpoint. [ABSTRACT FROM AUTHOR]

At a point during the latter third of an incremental exercise protocol, ventilation begins to exceed the rate of clearance of carbon dioxide (CO2) at the lungs ( V ˙ CO2). The onset of this hyperventilation, which is confirmed by a fall from a period of stability in end-tidal and arterial CO2 tensions (PCO2), is referred to as the respiratory compensation point (RCP). The mechanisms that contribute to the RCP remain debated as does its surrogacy for the maximal metabolic steady state of constant-power exercise (i.e., the highest work rate associated with maintenance of physiological steady state). The objective of this current opinion is to summarize the original research contributions that support and refute the hypotheses that: (i) the RCP represents a rapid, peripheral chemoreceptor-mediated reflex response engaged when the metabolic rate at which the buffering systems can no longer constrain the rise in hydrogen ions ([H+]) associated with rising lactate concentration and metabolic CO2 production is surpassed; and (ii) the metabolic rate at which this occurs is equivalent to the maximal metabolic steady state of constant power exercise. In doing so, we will shed light on potential mechanisms contributing to the RCP, attempt to reconcile disparate findings, make a case for its adoption for exercise intensity stratification and propose strategies for the use of RCP in aerobic exercise prescription. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated whether a running-adapted version of the cycling-based "step–ramp–step" (SRS) protocol would improve prediction of V ˙ O2 in treadmill exercise compared to the traditional prescriptive approach. Methods: Fourteen healthy individuals (6 females; 25 ± 6 years; 66.1 ± 12.7 kg) performed a treadmill-based SRS protocol including a ramp-incremental test to task failure followed by two constant-speed bouts within the moderate-(MODstep—below estimated lactate threshold; θLT), and heavy-intensity domains (HVYstep—between θLT and respiratory compensation point; RCP). Using the uncorrected V ˙ O2-to-speed relationship from the ramp exercise, three constant-speed bouts were performed at 40–50% between: baseline and θLT (CSEMOD); θLT and RCP (CSEHVY); and RCP and peak (CSESEV). For CSEMOD, CSEHVY, and CSESEV measured end-exercise V ˙ O2 was compared to predicted V ˙ O2 based on the: (i) "SRS-corrected" V ˙ O2-to-speed relationship (where MODstep and HVYstep were used to adjust the V ˙ O2 relative to speed); and (ii) linear "uncorrected" data. Results: Average treadmill speeds for CSEMOD and CSEHVY were 7.8 ± 0.8 and 11.0 ± 1.4 km·h−1, respectively, eliciting end-exercise V ˙ O2 of 1979 ± 390 and 2574 ± 540 mL·min−1. End-exercise V ˙ O2 values were not different compared to SRS-predicted V ˙ O2 at CSEMOD (mean difference: 5 ± 166 mL·min−1; p = 0.912) and CSEHVY (20 ± 128 mL·min−1; p = 0.568). The linear "uncorrected" estimates were not different for CSEMOD (− 91 ± 172 mL·min−1; p = 0.068) but lower for CSEHVY (− 195 ± 146 mL·min−1; p < 0.001). For CSESEV (running speed: 13.8 ± 1.7 km·h−1), the end-exercise V ˙ O2 was not different from peak V ˙ O2 achieved during the ramp (3027 ± 682 vs. 2979 ± 655 mL·min−1; p = 0.231). Conclusion: In healthy individuals, the SRS protocol more accurately predicts speeds for a target V ˙ O2 compared to traditional approaches. [ABSTRACT FROM AUTHOR]

Aims: Uric acid has been associated with several metabolic conditions, including bone diseases. Our objective here was to consider the relationship between serum uric acid levels and various bone parameters (bone mineral density, ultrasonographic parameters, vitamin D, PTH and serum calcium), as well as the prevalence and risk of fragility fracture. Methods: An observational and cross-sectional study carried out on 679 postmenopausal women, classified into 3 groups according to their serum uric acid levels, in whom bone densitometry, calcaneus ultrasounds, PTH, vitamin D and serum calcium analysis were done. Bone fractures were collected through the clinical history and lateral spinal X-ray. Results: Higher uric acid levels were found in women with older age, high BMI, diabetes, and high blood pressure. Higher levels of PTH and serum calcium were also observed, but did not effect on vitamin D. Serum uric acid was positively related to densitometric and ultrasonic parameters and negatively associated with vertebral fractures. Conclusions: In the population of postmenopausal women studied, sUA levels were correlated with BMD, BUA, and QUI-Stiffness, and this correlation was independent of age and BMI. In addition, sUA was associated with a decrease in vertebral fractures. These results imply a beneficial influence of sUA on bone metabolism, with both a quantitative and qualitative positive effect, reflected in the lower prevalence of vertebral fractures. [ABSTRACT FROM AUTHOR]

Purpose: Different strategies for near-infrared spectroscopy (NIRS)-derived muscle oxidative capacity assessment have been reported. This study compared and evaluated (I) approaches for averaging trials; (II) NIRS signals and blood volume correction equations; (III) the assessment of vastus lateralis (VL) and tibialis anterior (TA) muscles in two fitness levels groups. Methods: Thirty-six participants [18 chronically trained (CT: 14 males, 4 females) and 18 untrained (UT: 10 males, 8 females)] participated in this study. Two trials of twenty transient arterial occlusions were performed for NIRS-derived muscle oxidative capacity assessment. Muscle oxygen consumption ( V ˙ O2m) was estimated from deoxygenated hemoglobin (HHb), corrected for blood volume changes following Ryan (HHbR) and Beever (HHbB) equations, and from oxygen saturation (StO2) in VL and TA. Results: Superimposing or averaging V ˙ O2m or averaging the rate constants (k) from the two trials resulted in equivalent k values [two one-sided tests (TOST) procedure with 5% equivalence margin—P < 0.001]. Whereas HHbR (2.35 ± 0.61 min−1) and HHbB (2.34 ± 0.58 min−1) derived k were equivalent (P < 0.001), StO2 derived k (2.81 ± 0.92 min−1) was greater (P < 0.001) than both. k values were greater in CT vs UT in both muscles (VL: + 0.68 min−1, P = 0.002; TA: + 0.43 min−1, P = 0.01). Conclusion: Different approaches for averaging trials lead to similar k. HHb and StO2 signals provided different k, although different blood volume corrections did not impact k. Group differences in k were detected in both muscles. [ABSTRACT FROM AUTHOR]

Cancers present a significant medical problem despite the development of medical and pharmaceutical sciences leading to a search for further therapeutic approaches. One such approach could involve the use of curcumin or its derivatives. Curcumin reveals interesting antineoplastic effects that could help in the treatment of cancer diseases. However, this natural product possesses some limitations which prevent its application in medicine. Among its limitations, it is characterized by poor water solubility, low stability, and unsatisfactory bioavailability. Aiming to improve the pharmacokinetic properties and enhance the biological effects of curcumin, a series of 30 chemical compounds inspired by its structure was synthesized and characterized. New compounds were subjected to a preliminary MTT viability assessment of 5637 and SCaBER bladder cancer cell lines. Some derivatives revealed the cytotoxic activities already at the concentration of 1 µM. The most active compounds showed no significant acute toxicity in the Microtox test. Intracellular uptake on the basis of the fluorescent properties of the new compounds was analyzed. It was also found that the presence of the morpholine group in the structure improved the biological activity of studied curcumin derivatives. As selected compounds could be considered potential drug candidates, further studies are necessary towards recognition of the exact mechanism of cellular action, the in vivo stability, and toxicity. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the effects of sodium bicarbonate (NaHCO3) intake with divergent verbal and visual information on constant load cycling time-to-task failure, conducted within the severe intensity domain. Fifteen recreational cyclists participated in a randomized double-blind, crossover study, ingesting NaHCO3 or placebo (i.e., dextrose), but with divergent information about its likely influence (i.e., likely to induce ergogenic, inert, or harmful effects). Performance was evaluated using constant load cycling time to task failure trial at 115% of peak power output estimated during a ramp incremental exercise test. Data on blood lactate, blood acid–base balance, muscle electrical activity (EMG) through electromyography signal, and the twitch interpolation technique to assess neuromuscular indices were collected. Despite reduced peak force in the isometric maximal voluntary contraction and post-effort peripheral fatigue in all conditions (P < 0.001), neither time to task failure, EMG nor, blood acid–base balance differed between conditions (P > 0.05). Evaluation of effect sizes of all conditions suggested that informing participants that the supplement would be likely to have a positive effect (NaHCO3/Ergogenic: 0.46; 0.15–0.74; Dextrose/Ergogenic: 0.45; 0.04–0.88) resulted in improved performance compared to control. Thus, NaHCO3 ingestion consistently induced alkalosis, indicating that the physiological conditions to improve performance were present. Despite this, NaHCO3 ingestion did not influence performance or indicators of neuromuscular fatigue. In contrast, effect size estimates indicate that participants performed better when informed that they were ingesting an ergogenic supplement. These findings suggest that the apparently ergogenic effect of NaHCO3 may be due, at least in part, to a placebo effect. [ABSTRACT FROM AUTHOR]

The reversibility of a moderate thermal treatment (TT) at 120 °C on modern and historical oak wood samples was investigated by 1H nuclear magnetic resonance (NMR) relaxometry, equilibrium moisture content (EMC) determination, and measurements of volumetric deformations. The EMC values showed full reversibility after conditioning the samples at 65% relative humidity (RH) for one week, in agreement with previous research that utilized moderate TTs. However, 1H NMR relaxometry evidenced an irreversible effect on water mobility (i.e., molecular tumbling) for both wood samples. This result is compared to volumetric deformations that are determined by considering two reference states. When using, as a reference, the dry volume at each state, volumetric deformations are consistent with EMC values. However, when using the dry volume of the sample before TT, the volumetric deformations are found to be higher than the ones before TT for modern wood but remain lower for historical wood. The irreversible changes in water dynamics suggest that some modifications of the wood structure have not been completely recovered but are not linked to the changes in volumetric deformations. In addition, 13C solid-state NMR spectroscopy allowed the comparison of the composition between both wood samples, suggesting that their different behavior concerning volumetric deformations could be explained by a lower proportion of acetyl groups from hemicelluloses for historical wood due to its natural aging. We showed that combining macroscopic observations with molecular-level information gained from 1H and 13C NMR leads to a deeper understanding of the effects of thermal treatments and reversibility tests. [ABSTRACT FROM AUTHOR]

Background: Recovery is a key factor to promote adaptations and enhance performance. Sprint Interval Training (SIT) is known to be an effective approach to improve overall physical function and health. Although a 2-day rest period is given between SIT sessions, the time-course of recovery after SIT is unknown. Purpose: The aim of this study was to determine whether the neuromuscular and autonomic nervous systems would be impaired 24 and 48 h after an SIT session. Methods: Twenty-five healthy subjects performed an 8 × 15 s all-out session on a braked cycle ergometer with 2 min of rest between repetitions. Isometric maximal voluntary contraction (iMVC) and evoked forces to electrical nerve stimulation during iMVC and at rest were used to assess muscle contractile properties and voluntary activation before (Pre), 1 (Post24h), and 2 (Post48h) days after the session. Two maximal 7 s sprints with two different loads were performed at those same time-points to evaluate the maximal theoretical force (F0), velocity (V0) and maximal power (Pmax) production during a dynamic exercise. Additionally, nocturnal heart rate variability (HRV) was assessed the previous and the three subsequent nights to the exercise bout. Results: No significant impairments were observed for the iMVC or for the force evoked by electrical stimulation 1 day after the session. Similarly, F0, V0, and Pmax were unchanged at Post24h and Post48h. Furthermore, HRV did not reveal any temporal or frequential significant difference the nights following SIT compared to Pre. Conclusion: The results of this study show a full recovery of neuromuscular and autonomic functions a day after an all-out SIT session. [ABSTRACT FROM AUTHOR]

Introduction: Combined stent-retriever/large-bore distal aspiration catheter (LB-DAC) thrombectomy was recently introduced to treat large-vessel occlusion; however, it is unclear whether larger inner diameters improve outcomes. We compared angiographic and clinical outcomes in patients with occlusions of the M1 segment of the middle cerebral artery treated with mechanical thrombectomy using extra-LB-DAC versus LB-DAC in combination with stent-retrievers. Methods: We analyzed consecutive patients with M1 occlusion included in the ROSSETTI registry treated with non-balloon guide catheter combined LB-DAC/stent-retriever thrombectomy between June 2019 and April 2022. We compared demographics, baseline clinical variables, procedural variables, angiographic outcomes, and clinical outcomes [National Institute of Health Stroke Scale score at 24 h (24h-NIHSS) and modified Rankin scale score at 3 months] between patients treated with extra-LB-DAC (Sofia Plus, MIVI Q6, Catalyst7; inner diameter, 0.068″–0.070″) versus LB-DAC (Sofia 5F, MIVI Q5, Catalyst 6; inner diameter, 0.055″–0.064″). Primary outcome was the first-pass effect (FPE) rate, defined as near-complete/complete reperfusion (mTICI 2c–3) after a single pass of the device. Results: We included 324 patients (extra-LB-DAC, 185, 57.1% patients). Demographics, clinical data, and clinical outcomes were similar between the two groups; however, there was a trend towards improvement in National Institute of Health Stroke Scale score at 24 h (24h-NIHSS) in the cohort treated with extra-LB-DAC 9 points (IQR 4;16 points) vs. 12 points (IQR 4;18 points, P = 0.083). Patients treated with extra-LB-DAC had higher FPE rate (47% vs. 30.9%; P = 0.003) and higher modified FPE (mTICI ≥ 2b after a single pass) rate (65.9% vs 46.8%; P = 0.001). The use of extra-LB-DAC was an independent factor in predicting FPE (odds ratio 1.982, 95% confidence interval 1.250–3.143, P = 0.004). Conclusion: Our results suggest that in combined LB-DAC/stent-retriever thrombectomy, a larger aspiration catheter inner diameter is associated with higher rates of FPE and mFPE. [ABSTRACT FROM AUTHOR]

Visual exploration paradigms involving object arrays have been used to examine salience of social stimuli such as faces in ASD. Recent work suggests performance on these paradigms may associate with clinical features of ASD. We evaluate metrics from a visual exploration paradigm in 4-to-11-year-old children with ASD (n = 23; 18 males) and typical development (TD; n = 23; 13 males). Presented with arrays containing faces and nonsocial stimuli, children with ASD looked less at (p = 0.002) and showed fewer fixations to (p = 0.022) faces than TD children, and spent less time looking at each object on average (p = 0.004). Attention to the screen and faces correlated positively with social and cognitive skills in the ASD group (ps <.05). This work furthers our understanding of objective measures of visual exploration in ASD and its potential for quantifying features of ASD. [ABSTRACT FROM AUTHOR]

Bisphenol F (BPF) is replacing Bisphenol A (BPA) in the manufacture of products due to endocrine-disrupting effects. BPF monomers can also be released into the environment and enter the food chain, resulting in human exposure to low doses. Since bisphenols are primarily metabolized by the liver, this organ is more vulnerable to lower doses of bisphenols than others. Exposure during prenatal development may increase the risk of diseases in adulthood. The aim was to evaluate whether BPF administration could generate oxidative stress in liver of lactating rats, and whether these effects may be also observed in female and male postnatal day 6 (PND6) offspring. Long Evans rats received oral treatment: Control, BPF-low-dose (LBPF) 0.0365 mg/kg b.w./day, and BPF-high-dose (HBPF) 3.65 mg/kg b.w./day. The levels of antioxidant enzymes (CAT, SOD, GR, GPx and GST), glutathione system (GSH, GSSG) and lipid damage markers (MDA, LPO) were measured using colorimetric methods in liver of both lactating dams and in PND6 offspring. Mean values were analyzed using Prism-7. LBPF affected liver defense mechanisms (antioxidant enzymes and glutathione system), increasing ROS levels and producing lipid peroxidation in lactating dams. Similar effects were found in female and male PND6 offspring as a consequence of perinatal exposure. [ABSTRACT FROM AUTHOR]

We assessed different aspects of tactile perception in young children (3–6 years) with autism. Autistic and neurotypical children completed vibrotactile tasks assessing reaction time, amplitude discrimination (sequential and simultaneous) and temporal discrimination (temporal order judgment and duration discrimination). Autistic children had elevated and more variable reaction times, suggesting slower perceptual-motor processing speed and/or greater distractibility. Children with autism also showed higher amplitude discrimination and temporal order judgement thresholds compared to neurotypical children. Tactile perceptual metrics did not associate with social or tactile sensitivities measured by parent-reports. Altered tactile behavioral responses appear in early childhood, can be quantified but appear dissociated from sensitivity. This implies these measures are complementary, but not necessarily related, phenomena of atypical tactile perception in autism. [ABSTRACT FROM AUTHOR]

MUSCAT is a new large-format 1.1 mm continuum camera for local and extra-galactic astronomy currently being installed at the 50 m Large Millimetre Telescope Alfonso Serrano, LMT. The focal plane is populated with 1458 feedhorn coupled Aluminium LEKIDs, cooled to 130 mk, and read out with 6 frequency division multiplexed RF readout chains, each with a 500 MHz bandwidth. The nominal mux ratio is ∼ 250 resonators per chain with an average spacing of 2 MHz between resonators. In each RF chain, the multiplexed waveform generation/decomposition is performed with the BLAST-TNG firmware on a ROACH2 FPGA board with a MUSIC DAC/ADC. The quadrature modulated IF signals are mixed to and from the LEKID readout band on a custom card that houses IQ mixers, a programmable synthesizer, and additional programmable input and output gain control and filtering. Within the cryostat, the RF signals are attenuated prior to reaching the focal plane array and then amplified at 4K. A novel software system controls all the programmable hardware and handles instructions from the LMT instrument control system to record and store observation data, as well as performing automated resonator retuning and providing results of quick look analysis to the telescope operators. In this paper, we present the detailed design and in-lab performance of the cryogenic and room temperature electronics, and the software control system. [ABSTRACT FROM AUTHOR]

Purpose: Data concerning reperfusion strategies of intracranial atherosclerosis-related occlusion (ICARO) and clinico-angiographic outcomes remain scarce, particularly in Caucasians. We aim to compare the reperfusion rate and functional outcome between reperfusion strategies in the setting of the ICARO. Methods: Retrospective analysis of prospectively maintained endovascular thrombectomy (EVT) registries at three high-volume stroke centers were retrospectively analyzed for consecutive ICARO patients from January 2015 to December 2019. We defined ICARO as any fixed high-degree (> 70%) focal narrowing or stenosis of any degree with a perpetual tendency for reocclusion. We categorized reperfusion strategies into four groups: EVT [group 1], balloon angioplasty [(BAp), group 2], placement of self-expandable stents [(SES), group 3], and BAp combined with implantation of SES; or direct placement of balloon mounted stents (BMS) [(BAp-SES/BMS), group 4]. We evaluated the association with the successful reperfusion [mTICI 2b − 3] and favorable outcome [mRS 0–2] with logistic regression analysis. Results: Out of 2550 EVT, 124 patients (median age, 70 (61–80) years; 76 men) with ICARO and 130 reperfusion attempts [36 EVT, 38 BAp, 17 SES, and 39 BAp + SES/BMS] were analyzed. SES implantation showed the highest frequency of post-procedural symptomatic intracranial hemorrhage [(18%, 3/17), p =.03]; however, we observed no significant differences in the mortality rate. Overall, we achieved successful reperfusion in 71% (92/130) and favorable outcomes in 42% (52/124) of the patients. BAp + SES/BMS was the only independent predictor of the final successful reperfusion [aOR, 4.488 (95% CI, 1.364–14.773); p =.01], which was significantly associated with the 90-day favorable outcome [aOR, 10.837 (95% CI, 3.609–32.541); p = <.001] after adjustment for confounding variables between the reperfusion strategies. Conclusion: Among patients with ICARO, the rescue angioplasty stenting effectively contributed to higher odds of successful reperfusion with no increased risk for intracranial hemorrhage. [ABSTRACT FROM AUTHOR]

Background: Mechanical thrombectomy is the standard of care for acute ischemic stroke due to large-vessel occlusion; however, mechanical thrombectomy fails to achieve adequate recanalization in nearly one third of these cases. Rescue therapy using two stentrievers simultaneously yields good results in clots refractory to single stentriever treatment. We aimed to determine the safety and efficacy of first-line double stentriever thrombectomy for acute occlusion of the M1 segment of the middle cerebral artery and/or terminal internal carotid artery (TICA). Methods: This single-center study prospectively enrolled consecutive patients with a single M1/TICA occlusion to undergo double stentriever thrombectomy between May and October 2020. Outcomes included successful recanalization (modified thrombolysis in cerebral infarction, TICI 2b/3), first-pass effect, procedure times, number of device passes, symptomatic intracerebral hemorrhage, National Institutes of Health Stroke Scale Score (NIHSS) at discharge, 90-day functional independence (modified Rankin scale 0–2), and 90-day mortality. Results: We analyzed 39 patients median age 79 years (range 42–96 years); 23 (58.9%) female; 19 (48.7%) with TICA occlusions; 5 (12.8%) with mRS 3–5 at admission; mean NIHSS at admission, 17 ± 4.39). Mean time from symptom onset to final angiogram was 238.0 ± 94.6 min; mean intervention duration was 36.0 ± 24.2 min. The mean number of device passes was 1.5 ± 1.07. All patients had final TICI 2b/3, and 27 (69%) had TICI 2c/3 after the first pass. We observed 3 (7.9%) cases of intracerebral symptomatic hemorrhages. At 90 days, 16 (41%) patients were functionally independent and 9 (23%) had died. The percentage of patients with good clinical outcome at 90 days was 55.5% in the first-pass subgroup. Conclusion: Our findings suggest that first-line double stentriever thrombectomy is safe and effective for M1/TICA occlusions. [ABSTRACT FROM AUTHOR]

The aim of liveable, sustainable cities has become one of the major challenges for urban planning. However, achieving both goals at the same time is no easy task, particularly when liveability and sustainability may be defined by certain elements that tend to be in conflict. The main goal of this work is to analyse the relationship between liveability and environmental sustainability within the context of Spanish urban spaces. To this end, we propose two synthetic indicators: one for liveability and the other for urban environmental sustainability. Each of these indicators is constructed using a technique based on goal programming. A bivariate analysis is carried out using these indicators, which allows us to compare the extent to which Spanish cities are liveable and sustainable. This analysis should be useful for urban planners when taking and implementing policy decisions. By comparing cities with similar profiles using a benchmarking system, it becomes possible to judge the margin for improvement in one attribute without detriment to the other. This benchmarking system also allows us to reveal the specific dimensions of liveability or sustainability for which there is the greatest opportunity for improvement. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infections in children are frequently asymptomatic or mild and can go unnoticed. This study aimed to describe the seroprevalence and clinical course of SARS-CoV-2 in a cohort of children with rheumatic diseases in a real-life setting and assess possible risk factors. A cross-sectional study was performed in a paediatric rheumatology unit (September 2020 to February 2021). At inclusion, a specific questionnaire was completed and SARS-CoV-2 serology was performed. Demographics, treatment and disease activity of patients with and without laboratory-confirmed SARS-CoV-2 infection were compared. A total of 105 children were included. SARS-CoV-2 infection was demonstrated in 27 patients (25.7%). The mean age was 11.8 years, and most patients were females (72.4%). The most frequent underlying condition was juvenile idiopathic arthritis (70.3%; 19/27). Patients received immunosuppressive treatment in 78% of cases (21/27). Overall, 44.4% (12/27) of infected patients were asymptomatic. A total of 66.7% (18/27) of patients did not require medical assistance. Three patients required hospital admission because of COVID-19. Children with confirmed SARS-CoV-2 infection were less frequently in remission (52% vs 72%; p 0.014). Moderate disease activity and treatment with oral corticosteroids were associated with higher risk for SARS-CoV-2 (OR 5.05; CI 95%: 1.56–16.3 and OR 4.2; CI 95%: 1.26–13.9, respectively). In a cohort of Spanish paediatric patients with rheumatic diseases, clinical course of COVID-19 was mild, with more than one third of asymptomatic cases. Higher disease activity and oral corticosteroids appear to be risk factors for SARS-CoV-2 infection. Key Points • We aimed to investigate the seroprevalence of SARS-CoV-2 infection in a cohort of Spanish paediatric patients with RD, testing both symptomatic and asymptomatic patients. We also compared treatment and disease activity of patients with and without laboratory-confirmed SARS-CoV-2 infection. • In our cohort of 105 paediatric patients with rheumatic diseases, the clinical course of COVID-19 was mild and 44% of cases were asymptomatic. Three cases required hospital admission with no complications. Seroprevalence was 20%. • No association was found between disease activity or treatment with corticosteroids and symptomatic or asymptomatic infection. Higher disease activity and treatment with oral corticosteroids appeared to be risk factors for laboratory-confirmed SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

During incremental exercise, two thresholds may be identified from standard gas exchange and ventilatory measurements. The first signifies the onset of blood lactate accumulation (the lactate threshold, LT) and the second the onset of metabolic acidosis (the respiratory compensation point, RCP). The ability to explain why these thresholds occur and how they are identified, non-invasively, from pulmonary gas exchange and ventilatory variables is fundamental to the field of exercise physiology and requisite to the understanding of core concepts including exercise intensity, assessment, prescription, and performance. This review is intended as a unique and comprehensive theoretical and practical resource for instructors, clinicians, researchers, lab technicians, and students at both undergraduate and graduate levels to facilitate the teaching, comprehension, and proper non-invasive identification of exercise thresholds. Specific objectives are to: (1) explain the underlying physiology that produces the LT and RCP; (2) introduce the classic non-invasive measurements by which these thresholds are identified by connecting variable profiles to underlying physiological behaviour; (3) discuss common issues that can obscure threshold detection and strategies to identify and mitigate these challenges; and (4) introduce an online resource to facilitate learning and standard practices. Specific examples of exercise gas exchange and ventilatory data are provided throughout to illustrate these concepts and a novel online application tool designed specifically to identify the estimated LT (θLT) and RCP is introduced. This application is a unique platform for learners to practice skills on real exercise data and for anyone to analyze incremental exercise data for the purpose of identifying θLT and RCP. [ABSTRACT FROM AUTHOR]

Introduction: Hypofractionated whole breast irradiation (hWBI) and intraoperative radiotherapy (IORT) could be associated in breast cancer patients showing high-risk factors of local recurrence after breast conserving therapy (BSC). The aim of this trial was to evaluate, for the first time, the toxicity and cosmesis of hWBI after photon-IORT in high-risk patients treated by adjuvant chemotherapy. Materials and methods: Thirty-one high-risk localized breast cancer patients treated by BCS, IORT (20 Gy), and adjuvant chemotherapy were included from February 2019 to August 2020 in this prospective trial, of hWBI (40.5 Gy/2.67 Gy/15 fractions). Acute and late toxicity (CTCAEv5.0) and cosmesis (Harvard scale), were assessed after treatment. Results: All patients completed their treatment and were evaluable after treatment. No patients showed severe (G3) acute/late toxicity. Excellent/good cosmesis at least 6 months after completing the treatment, was present in 93.6% of the patients. Conclusion: hWBI in high-risk localized breast cancer patients treated by chemotherapy seems to have similar toxicity and cosmetic results than conventionally fractionated WBI in combination to photon-IORT after BCS. [ABSTRACT FROM AUTHOR]

Background: Appropriate quantification of exertional intensity remains elusive. Objective: To compare, in a large and heterogeneous cohort of healthy females and males, the commonly used intensity classification system (i.e., light, moderate, vigorous, near-maximal) based on fixed ranges of metabolic equivalents (METs) to an individualized schema based on the exercise intensity domains (i.e., moderate, heavy, severe). Methods: A heterogenous sample of 565 individuals (females 165; males 400; age range 18–83 years old) were included in the study. Individuals performed a ramp-incremental exercise test from which gas exchange threshold (GET), respiratory compensation point (RCP) and maximum oxygen uptake (VO2max) were determined to build the exercise intensity domain schema (moderate = METs ≤ GET; heavy = METs > GET but ≤ RCP; severe = METs > RCP) for each individual. Pearson's chi-square tests over contingency tables were used to evaluate frequency distribution within intensity domains at each MET value. A multi-level regression model was performed to identify predictors of the amplitude of the exercise intensity domains. Results: A critical discrepancy existed between the confines of the exercise intensity domains and the commonly used fixed MET classification system. Overall, the upper limit of the moderate-intensity domain ranged between 2 and 13 METs and of the heavy-intensity domain between 3 and 18 METs, whereas the severe-intensity domain included METs from 4 onward. Conclusions: Findings show that the common practice of assigning fixed values of METs to relative categories of intensity risks misclassifications of the physiological stress imposed by exercise and physical activity. These misclassifications can lead to erroneous interpretations of the dose–response relationship of exercise and physical activity. [ABSTRACT FROM AUTHOR]

Eye-tracking is often used to study attention in children with autism spectrum disorder (ASD). Previous research has identified multiple atypical patterns of attention in children with ASD based on areas-of-interest analysis. Fewer studies have investigated gaze path, a measure which is dependent on the dynamic content of the stimulus presented. Here, rather than looking at proportions of looking time to areas of interest, we calculated mean fixations frame-by-frame in a group of typically developing children (36 to 72 months) and determined the distance from those typical fixations for 155 children with ASD (27–95 months). Findings revealed that distance from the typical scan path among the children with ASD was associated with lower communication abilities and greater ASD symptomatology. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the cardiovascular individual response to 6 weeks (3×/week) of work-matched within the severe-intensity domain (high-intensity interval training, HIIT) or moderate-intensity domain (moderate-intensity continuous training, MICT). In addition, we analyzed the cardiovascular factors at baseline underlying the response variability.Methods: 42 healthy sedentary participants were randomly assigned to HIIT or MICT. We applied the region of practical equivalence-method for identifying the levels of responders to the maximal oxygen uptake (V̇O2max) response. For investigating the influence of cardiovascular markers, we trained a Bayesian machine learning model on cardiovascular markers.Results: Despite that HIIT and MICT induced significant increases in V̇O2max, HIIT had greater improvements than MICT (p < 0.001). Greater variability was observed in MICT, with approximately 50% classified as "non-responder" and "undecided". 20 "responders", one "undecided" and no "non-responders" were observed in HIIT. The variability in the ∆V̇O2max was associated with initial cardiorespiratory fitness, arterial stiffness, and left-ventricular (LV) mass and LV end-diastolic diameter in HIIT; whereas, microvascular responsiveness and right-ventricular (RV) excursion velocity showed a significant association in MICT.Conclusion: Our findings highlight the critical influence of exercise-intensity domains and biological variability on the individual V̇O2max response. The incidence of "non-responders" in MICT was one third of the group; whereas, no "non-responders" were observed in HIIT. The incidence of "responders" was 11 out of 21 participants in MICT, and 20 out of 21 participants in HIIT. The response in HIIT showed associations with baseline fitness, arterial stiffness, and LV-morphology; whereas, it was associated with RV systolic function in MICT. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated (i) the relationship between oxygen uptake ([Formula: see text]O2) kinetics and maximal [Formula: see text]O2 ([Formula: see text]O2max) within groups differing in fitness status, and (ii) the adjustment of [Formula: see text]O2 kinetics compared to that of central [cardiac output (Q̇), heart rate (HR)] and peripheral (deoxyhemoglobin over [Formula: see text]O2 ratio ([HHb]/[Formula: see text]O2)] O2 delivery, during step-transitions to moderate-intensity exercise.Methods: Thirty-six young healthy male participants (18 untrained; 18 trained) performed a ramp-incremental test to exhaustion and 3 step-transitions to moderate-intensity exercise. Q̇ and HR kinetics were measured in 18 participants (9 untrained; 9 trained).Results: No significant correlation between τ̇[Formula: see text]O2 and [Formula: see text]O2max was found in trained participants (r = 0.29; p > 0.05) whereas a significant negative correlation was found in untrained (r = - 0.58; p < 0.05) and all participants (r = - 0.82; p < 0.05). τQ̇ (18.8 ± 5.5 s) and τHR (20.1 ± 6.2 s) were significantly greater than τ[Formula: see text]O2 (13.9 ± 2.7 s) for trained (p < 0.05). No differences were found between τQ̇ (22.8 ± 8.45 s), τHR (21.2 ± 8.3 s) and τ[Formula: see text]O2 (28.9 ± 5.7 s) for untrained (p > 0.05). τQ̇ demonstrated a significant strong positive correlation with τHR in trained (r = 0.76; p < 0.05) but not untrained (r = 0.61; p > 0.05). A significant overshoot in the [HHb]/[Formula: see text]O2 ratio was found in the untrained groups (p < 0.05) but not in the trained groups (p > 0.05) CONCLUSION: The results indicated that when comparing participants of different fitness status (i) there is a point at which greater V̇O2max values are not accompanied by faster [Formula: see text]O2 kinetics; (ii) central delivery of O2 does not seem to limit the kinetics of [Formula: see text]O2; and (iii) O2 delivery within the active tissues might contribute to the slower [Formula: see text]O2 kinetics response in untrained participants. [ABSTRACT FROM AUTHOR]

Amblyopia is the leading cause of vision impairment in children, and its early detection can avoid irreversible consequences for a child's visual ability. In this prospective study, to detect amblyopia risk factors, we examined patients aged 18 to 30 months in primary care settings. Patients were referred to an ophthalmologist for confirmation. The main aims were to detect amblyogenic risk factors and to assess the usefulness of a photoscreener in such settings. Out of 453 patients, 42 (9.3%) presented visual alterations according to the photoscreener, with astigmatism being the most common. The instrument had good sensitivity (89%) and specificity (91%), with a positive predictive value of 76% and a negative predictive value of 96%. Overall, 38% of the patients required follow-up, and 47% needed glasses. The automated screening device allowed these children to be diagnosed at an early stage. Conclusions: The use of a photoscreener to screen 2-year-old children in primary care settings was helpful and accurate. What is Known: • Early detection of amblyopic risk factors is important to avoid vision defects. However, it is very difficult to measure visual acuity using visual charts in children younger than 4 years old. What is New: • Instrument-based screening in children aged 18 to 30 months allows excellent detection of early amblyopia risk factors in primary care settings. [ABSTRACT FROM AUTHOR]

10-Alkylthiocolchicines have been obtained and characterized by spectroscopic methods and their biological activities as: cytotoxic, anti-inflammatory and analgesic activities have been tested. Cytotoxic activity against SKOV-3 ovarian cell line for 10-alkylthiocolchicine analogues was reported and tested compounds showed to be more active than commonly used doxorubicin. Some of tested C-10 alkylthiolated colchicines have been found to exhibit cytotoxicity at levels comparable to that of the natural product—colchicine. 10-Methylthiocolchicine has IC50 = 8 nM and 10-ethylthiocolchicine has IC50 = 47 nM in comparison to colchicine IC50 = 37 nM. Moreover for 10-alkylthioderivatives apoptosis test, cyclin B1 and cell cycle tests were performed. 10-n-Butylthiocolchicine was tested for anti-inflammatory and analgesic activities it showed to produce analgesic rather than anti-inflammatory effect. [ABSTRACT FROM AUTHOR]

SCA36 is an autosomal dominant spinocerebellar ataxia (SCA) affecting many families from Costa da Morte, a northwestern region of Spain. It is caused by an intronic GGCCTG repeat expansion in NOP56. In order to characterize the cognitive and affective manifestations of this cerebellar disease, a group of 30 SCA36 mutation carriers (11 preataxic and 19 ataxic patients) were assessed with a comprehensive battery of standardized tests. Phonological verbal fluency – but not semantic fluency – was already mildly impaired in preataxic subjects. In ataxic patients, both phonological and semantic fluencies were significantly below normal. Depression, while more frequent and prominent in ataxic patients, was also often present in the preataxic stage. This is the first systematic study supporting the presence of a mild cerebellar cognitive and affective syndrome in SCA36. Routine evaluation of cognitive and emotional spheres in SCA36 patients as well as asymptomatic mutation carriers should allow early detection and timely therapeutic intervention. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) demonstrated improved overall survival (OS) in heavily pretreated unselected patients with metastatic gastro-esophageal junction (mGOJ)/gastric cancer (GC). Attempts to select patients based on programmed death-ligand 1 (PD-L1) expression appear to be suboptimal. A strong rationale suggests a prognostic role for inflammatory biomarkers for ICI-treated patients with mGOJ/GC.Objective: Our objective was to assess whether inflammatory markers are associated with survival in ICI-treated patients with mGOJ/GC.Methods: Ten inflammatory markers were retrospectively analyzed at baseline in 57 patients with mGOJ/GC with unknown PD-L1 status treated with second-line ICIs and correlated with OS. Selected variables were then analyzed in a multivariate Cox-regression model and used to build a GIPI nomogram.Results: Neutrophil/lymphocyte ratio (NLR) and C-reactive protein (CRP) as continuous variables and albumin categorized as less than versus greater than 30 g/dL were the most significant predictors of OS and were used to build the GIPI nomogram. Nomogram-based lowest, mid-low, mid-high, and highest risk quartiles were associated with median OS (mOS) of 14.9, 7.1, 5.6, and 2.1 months, respectively (hazard ratio [HR] of highest vs. lowest risk 4.94; p = 0.0002). By optimally dichotomizing CRP and NLR, patients with one or more of the risk factors NLR > 6, CRP > 15 mg/L, and albumin < 30 g/dL (n = 29) had an mOS of 3.9 versus 14.2 months for patients with no risk factor (n = 28) (HR 2.48; p = 0.0015).Conclusions: GIPI, combining NLR, CRP, and albumin, is the first inflammatory index with a significant prognostic value in patients with mOGJ/GC receiving ICIs. GIPI merits validation in independent cohorts and prospective clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: In theory, a slow oxygen uptake ([Formula: see text]) kinetics leads to a greater accumulation of anaerobic by-products, which can, in turn, induce more neuromuscular fatigue. However, the existence of this relationship has never been tested.Methods: After two sessions to measure peak [Formula: see text], peak power output (POpeak), and [Formula: see text] kinetics responses in the unfatigued state (τ [Formula: see text] MOD), 10 healthy young adults performed a 6-min cycling bout at 80% POpeak (INT6-min). [Formula: see text] kinetics responses were also measured during INT6-min. Neuromuscular fatigue was measured isometrically pre- and post-INT6-min (immediately post- and 15-s post-INT6-min) with an innovative cycle ergometer.Results: Maximal voluntary contraction (MVC) force, high-frequency doublet amplitude, and the ratio of low- to high-frequency doublet amplitudes decreased by 34 ± 7, 43 ± 11, and 31 ± 13%, respectively (all P < 0.01). A significant Spearman's rank correlation was observed between the change in low-frequency doublet force (ΔDb10) immediately after INT6-min and both τ [Formula: see text] MOD and τ [Formula: see text] INT6-min (ρ = -0.68 and ρ = -0.67, both P < 0.05). When considering the largest responses from the two neuromuscular evaluations post-INT6-min, significant correlations were also found between τ [Formula: see text] MOD and ΔDb10 (ρ = -0.74; P < 0.05) and between τ[Formula: see text] INT6-min and both ΔDb10 and low-frequency fatigue (ρ = -0.70 and ρ = -0.66; both P < 0.05).Conclusion: The present results suggest that subjects with slow [Formula: see text] kinetics experience more peripheral fatigue, in particular more excitation-contraction coupling failure, likely due to a greater accumulation of protons and/or inorganic phosphates. [ABSTRACT FROM AUTHOR]

Autism Spectrum Disorder (ASD) is characterized by early attentional differences that often precede the hallmark symptoms of social communication impairments. Development of novel measures of attentional behaviors may lead to earlier identification of children at risk for ASD. In this work, we first introduce a behavioral measure, Relative Average Look Duration (RALD), indicating attentional preference to different stimuli, such as social versus nonsocial stimuli; and then study its association with neurophysiological activity. We show that (1) ASD and typically developing (TD) children differ in both (absolute) Average Look Duration (ALD) and RALD to stimuli during an EEG experiment, with the most pronounced differences in looking at social stimuli; and (2) associations between looking behaviors and neurophysiological activity, as measured by EEG, are different for children with ASD versus TD. Even when ASD children show attentional engagement to social content, our results suggest that their underlying brain activity is different than TD children. This study therefore introduces a new measure of social/nonsocial attentional preference in ASD and demonstrates the value of incorporating attentional variables measured simultaneously with EEG into the analysis pipeline. [ABSTRACT FROM AUTHOR]

The ability to orient and navigate in spatial surroundings is a cognitive process that undergoes a prolonged maturation with progression of skills, strategies and proficiency over much of childhood. In the present study, we used functional Magnetic Resonance Imaging (fMRI) to investigate the neurological mechanisms underlying the ability to orient in a virtual interior environment in children aged 10 to 12 years of age, a developmental stage in which children start using effective spatial orientation strategies in large-scale surroundings. We found that, in comparison to young adults, children were not as proficient at the spatial orientation task, and revealed increased neural activity in areas of the brain associated with visuospatial processing and navigation (left cuneus and mid occipital area, left inferior parietal region and precuneus, right inferior parietal cortex, right precentral gyrus, cerebellar vermis and bilateral medial cerebellar lobes). When functional connectivity analyses of resting state fMRI data were performed, using seed areas that were associated with performance, increased connectivity was seen in the adults from the right hippocampal/parahippocampal gyrus to the contralateral caudate, the insular cortex, and the posterior supramarginal gyrus; children had increased connectivity from the right paracentral lobule to the right superior frontal gyrus as compared to adults. These findings support the hypothesis that, as children are maturing in their navigation abilities, they are refining and increasing the proficiency of visuospatial skills with a complimentary increase in connectivity of longer-range distributed networks allowing for flexible use of efficient and effective spatial orientation strategies. [ABSTRACT FROM AUTHOR]

Summary: It has been shown previously that molecules built on benzanilide and thiobenzanilide scaffolds possess differential biological properties including selective anticancer activity. In our previous study, we examined the cytotoxic activity and mechanism of action of the thiobenzanilide derivative N,N′-(1,2-phenylene)bis3,4,5–trifluorobenzothioamide (63 T) as a potential chemotherapeutic compound in an experimental model employing A549 lung adenocarcinoma cells and CCD39Lu non-tumorigenic lung fibroblasts. Since the results suggested oxidative stress as a co-existing mechanism of the cytotoxic effect exerted by 63 T on tested cells, studies involving the analysis of reactive oxygen species (ROS) generation and markers of oxidative stress in cells incubated with 63 T were carried out. It may be concluded that the selective activity of 63 T against cancer cells shown in our experiments is caused, at least in part, by the response of the tested cells to 63 T mediated oxidative stress in both tested cell lines. [ABSTRACT FROM AUTHOR]

Background: Mechanical ventilation is common in critically ill patients. This life-saving treatment can cause complications and is also associated with long-term sequelae. Patient-ventilator asynchronies are frequent but underdiagnosed, and they have been associated with worse outcomes. Main body: Asynchronies occur when ventilator assistance does not match the patient's demand. Ventilatory overassistance or underassistance translates to different types of asynchronies with different effects on patients. Underassistance can result in an excessive load on respiratory muscles, air hunger, or lung injury due to excessive tidal volumes. Overassistance can result in lower patient inspiratory drive and can lead to reverse triggering, which can also worsen lung injury. Identifying the type of asynchrony and its causes is crucial for effective treatment. Mechanical ventilation and asynchronies can affect hemodynamics. An increase in intrathoracic pressure during ventilation modifies ventricular preload and afterload of ventricles, thereby affecting cardiac output and hemodynamic status. Ineffective efforts can decrease intrathoracic pressure, but double cycling can increase it. Thus, asynchronies can lower the predictive accuracy of some hemodynamic parameters of fluid responsiveness. New research is also exploring the psychological effects of asynchronies. Anxiety and depression are common in survivors of critical illness long after discharge. Patients on mechanical ventilation feel anxiety, fear, agony, and insecurity, which can worsen in the presence of asynchronies. Asynchronies have been associated with worse overall prognosis, but the direct causal relation between poor patient-ventilator interaction and worse outcomes has yet to be clearly demonstrated. Critical care patients generate huge volumes of data that are vastly underexploited. New monitoring systems can analyze waveforms together with other inputs, helping us to detect, analyze, and even predict asynchronies. Big data approaches promise to help us understand asynchronies better and improve their diagnosis and management. Conclusions: Although our understanding of asynchronies has increased in recent years, many questions remain to be answered. Evolving concepts in asynchronies, lung crosstalk with other organs, and the difficulties of data management make more efforts necessary in this field. [ABSTRACT FROM AUTHOR]

This paper proposes a composite indicator intended to assess the degree of liveability provided by urban areas. This synthetic index makes two essential contributions to previous research. Firstly, it starts from a series of specifically urban partial indicators and dimensions. Secondly, the technique used to estimate the goal-programming-based index (Blancas et al. in Ecol Econ 69:2158–2172, 2010) enables urban managers to actively participate in constructing the indicator. The instrument was tested by estimating the index for a number of Spanish cities. The results reveal significant differences in the degree of liveability based on geographical location, population and functional hierarchy. Its application to Spain further highlights the tool's potential for liveability analysis by varying urban manager profiles. [ABSTRACT FROM AUTHOR]

The article focuses on the ventilated patient, patients with artificial respiration. Topics mentioned include the respiratory control system (RCS), the importance of patients care management, and the breathing measurement. Also mentioned are the irregular patterns of heart beat, the pressure-control ventilation, and the activation of inspiratory muscles.

Purpose: The aim of this study was to examine whether differences in vascular responsiveness associated with training status would be more prominent in the trained limb (leg) than in the untrained limb (arm) microvasculature.Methods: Thirteen untrained (26 ± 5 year) and twelve trained (29 ± 4 year) healthy men were submitted to a vascular occlusion test (VOT) (2 min baseline, 5 min occlusion, and 8 min re-oxygenation). The oxygen saturation signal (StO2) was assessed using near-infrared spectroscopy (NIRS) throughout the VOT. Vascular responsiveness within the microvasculature was evaluated by the re-oxygenation Slope 2 (Slope 2 StO2) and the area under the curve (StO2AUC) of (StO2) signal during re-oxygenation in the leg and arm.Results: There was a significant interaction between training status and limb for the slope 2 StO2 (P < 0.01). The leg of the trained group showed a steeper slope 2 StO2 (1.35 ± 0.12% s-1) when compared to the slope 2 StO2 of the leg in their untrained counterparts (0.86 ± 0.09% s-1) (P < 0.05). There was a medium effect size of 0.58 for slope 2 StO2 on the arm and a large effect size of 1.21 for slope 2 StO2 on the leg. In addition, there was a small effect size of 0.24 for StO2AUC on the arm and a medium effect size of 0.64 for StO2AUC on the leg.Conclusion: The present study suggests that the vascular adaptations induced by lower limb endurance exercise training are more prominent in the trained limb than in the untrained limb microvasculature. [ABSTRACT FROM AUTHOR]

Imbibition in poplar wood is studied from macroscopic measurements (mass and deformation) along with magnetic resonance imaging experiments allowing to observe bound and free water dynamics. Additional experiments with silicone oil allow to compare the characteristics of water imbibition with those of a liquid not hygroscopically adsorbed in wood. It was shown that, in contrast to porous media with an impermeable solid structure, the water imbibition in the hydraulic conduits of hardwood is not simply driven by the standard capillary effects associated with a good wetting of the solid surface, but it is in fact strongly affected by the adsorption of bound water in cell walls. More precisely bound water appears to progress far beyond the front of free water, and the free water penetration along the sample axis apparently coincides with the development of a region saturated with bound water. This likely explains that water imbibition is about three orders of magnitude slower than expected from standard Washburn imbibition process. [ABSTRACT FROM AUTHOR]

Oxygenation is one of the most important physiological parameters of biological systems. Low oxygen concentration (hypoxia) is associated with various pathophysiological processes in different organs. Hypoxia is of special importance in tumor therapy, causing poor response to treatment. Triaryl methyl (TAM) derivative radicals are commonly used in electron paramagnetic resonance (EPR) as sensors for quantitative spatial tissue oxygen mapping. They are also known as magnetic resonance imaging (MRI) contrast agents and fluorescence imaging compounds. We report the properties of the TAM radical tris(2,3,5,6-tetrachloro-4-carboxy-phenyl)methyl, (PTMTC), a potential multimodal (EPR/fluorescence) marker. PTMTC was spectrally analyzed using EPR and characterized by estimation of its sensitivity to the oxygen in liquid environment suitable for intravenous injection (1 mM PBS, pH = 7.4). Further, fluorescent emission of the radical was measured using the same solvent and its quantum yield was estimated. An in vitro cytotoxicity examination was conducted in two cancer cell lines, HT-29 (colorectal adenocarcinoma) and FaDu (squamous cell carcinoma) and followed by uptake studies. The stability of the radical in different solutions (PBS pH = 7.4, cell media used for HT-29 and FaDu cells culturing and cytotoxicity procedure, full rat blood and blood plasma) was determined. Finally, a primary toxicity test of PTMTC was carried out in mice. Results of spectral studies confirmed the multimodal properties of PTMTC. PTMTC was demonstrated to be not absorbed by cancer cells and did not interfere with luciferin-luciferase based assays. Also in vitro and in vivo tests showed that it was non-toxic and can be freely administrated till doses of 250 mg/kg BW via both i.v. and i.p. injections. This work illustrated that PTMTC is a perfect candidate for multimodal (EPR/fluorescence) contrast agent in preclinical studies. [ABSTRACT FROM AUTHOR]

We use magnetic resonance imaging to follow the adsorption of colloids during their transport through a porous medium (grain packing). We injected successive pulses of a suspension of nanoparticles able to adsorb onto the grains. To get quantitative information we carry out 2D imaging and 1D measurements of the evolution in time of the distribution profile of all particles (suspended or adsorbed) in cross-sectional layers along the sample axis during the flow. For the first injections we observe the 1D profile amplitude progressively damping as particles advance through the sample, due to their adsorption. 2D imaging shows that successive injections finally result in a coverage of grains by adsorbed particles regularly progressing along the sample. The analysis of the results makes it possible to get a clear description of the adsorption process. In our specific case (particle charged oppositely to the adsorption sites) it appears that the particles rapidly explore the pores and adsorb as soon as they encounter available sites on grains, and the surplus of particles goes on advancing in the sample. A further analysis of the profiles makes it possible to distinguish the respective concentration distribution of suspended and adsorbed particles over time at each step of the process. [ABSTRACT FROM AUTHOR]

Altered patterns of sensory responsiveness are a frequently reported feature of Autism Spectrum Disorder (ASD). Younger siblings of individuals with ASD are at a greatly elevated risk of a future diagnosis of ASD, but little is known about the neural basis of sensory responsiveness patterns in this population. Younger siblings (n = 20) of children diagnosed with ASD participated in resting electroencephalography (EEG) at an age of 18 months. Data on toddlers' sensory responsiveness were obtained using the Sensory Experiences Questionnaire. Correlations were present between hyporesponsiveness and patterns of oscillatory power, functional connectivity, and signal complexity. Our findings suggest that neural signal features hold promise for facilitating early identification and targeted remediation in young children at risk for ASD. [ABSTRACT FROM AUTHOR]

Background: The identification of anaerobic metabolism in critically ill patients is a challenging task. Observational studies have suggested that the ratio of venoarterial PCO (PCO) to arteriovenous oxygen content difference (CO) might be a good surrogate for respiratory quotient (RQ). Yet PCO/CO might be increased by other factors, regardless of anaerobic metabolism. At present, comparisons between PCO/CO and RQ have not been performed. We sought to compare these variables during stepwise hemorrhage and hemodilution. Since anemia predictably produces augmented PCO and decreased CO, our hypothesis was that PCO/CO might be an inadequate surrogate for RQ. Methods: This is a subanalysis of a previously published study. In anesthetized and mechanically ventilated sheep ( n = 16), we compared the effects of progressive hemodilution and hemorrhage by means of expired gases analysis. Results: There were comparable reductions in oxygen consumption and increases in RQ in the last step of hemodilution and hemorrhage. The increase in PCO/CO was higher in hemodilution than in hemorrhage (1.9 ± 0.2 to 10.0 ± 0.9 vs. 1.7 ± 0.2 to 2.5 ± 0.1, P < 0.0001). The increase in PCO was lower in hemodilution (6 ± 0 to 10 ± 1 vs. 6 ± 0 to 17 ± 1 mmHg, P < 0.0001). Venoarterial CO content difference and CO decreased in hemodilution and increased in hemorrhage (2.6 ± 0.3 to 1.2 ± 0.1 vs. 2.8 ± 0.2 to 6.9 ± 0.5, and 3.4 ± 0.3 to 1.0 ± 0.3 vs. 3.6 ± 0.3 to 6.8 ± 0.3 mL/dL, P < 0.0001 for both). In hemodilution, PCO/CO increased before the fall in oxygen consumption and the increase in RQ. PCO/CO was strongly correlated with Hb ( R = 0.79, P < 0.00001) and moderately with RQ ( R = 0.41, P < 0.0001). A multiple linear regression model found Hb, RQ, base excess, and mixed venous oxygen saturation and PCO as PCO/CO determinants (adjusted R = 0.86, P < 0.000001). Conclusions: In hemodilution, PCO/CO was considerably increased, irrespective of the presence of anaerobic metabolism. PCO/CO is a complex variable, which depends on several factors. As such, it was a misleading indicator of anaerobic metabolism in hemodilution. [ABSTRACT FROM AUTHOR]

Introduction: Variant detection protocols for clinical next-generation sequencing (NGS) need application-specific optimization. Our aim was to analyze the performance of single nucleotide variant (SNV) and copy number (CNV) detection programs on an NGS panel for a rare disease. Methods: Thirty genes were sequenced in 83 patients with hereditary spastic paraplegia. The variant calls obtained with LifeScope, GATK UnifiedGenotyper and GATK HaplotypeCaller were compared with Sanger sequencing. The calling efficiency was evaluated for 187 (56 unique) SNVs and indels. Five multiexon deletions detected by multiple ligation probe assay were assessed from the NGS panel data with ExomeDepth, panelcn.MOPS and CNVPanelizer software. Results: There were 48/51 (94%) SNVs and 1/5 (20%) indels consistently detected by all the calling algorithms. Two SNVs were not detected by any of the callers because of a rare reference allele, and one SNV in a low coverage region was only detected by two algorithms. Regarding CNVs, ExomeDepth detected 5/5 multi-exon deletions, panelcn.MOPs 4/5 and only 3/5 deletions were accurately detected by CNVPanelizer. Conclusions: The calling efficiency of NGS algorithms for SNVs is influenced by variant type and coverage. NGS protocols need to account for the presence of rare variants in the reference sequence as well as for ambiguities in indel calling. CNV detection algorithms can be used to identify large deletions from NGS panel data for diagnostic applications; however, sensitivity depends on coverage, selection of the reference set and deletion size. We recommend the incorporation of several variant callers in the NGS pipeline to maximize variant detection efficiency. [ABSTRACT FROM AUTHOR]

Background: The microvascular reperfusion injury after retransfusion has not been completely characterized. Specifically, the question of heterogeneity among different microvascular beds needs to be addressed. In addition, the identification of anaerobic metabolism is elusive. The venoarterial PCO to arteriovenous oxygen content difference ratio (PCO/CO) might be a surrogate for respiratory quotient, but this has not been validated. Therefore, our goal was to characterize sublingual and intestinal (mucosal and serosal) microvascular injury after blood resuscitation in hemorrhagic shock and its relation with O and CO metabolism. Methods: Anesthetized and mechanically ventilated sheep were assigned to stepwise bleeding and blood retransfusion ( n = 10) and sham ( n = 7) groups. We performed analysis of expired gases, arterial and mixed venous blood gases, and intestinal and sublingual videomicroscopy. Results: In the bleeding group during the last step of hemorrhage, and compared to the sham group, there were decreases in oxygen consumption (3.7 [2.8-4.6] vs. 6.8 [5.8-8.0] mL min kg, P < 0.001) and increases in respiratory quotient (0.96 [0.91-1.06] vs. 0.72 [0.69-0.77], P < 0.001). Retransfusion normalized these variables. The PCO/CO increased in the last step of bleeding (2.4 [2.0-2.8] vs. 1.1 [1.0-1.3], P < 0.001) and remained elevated after retransfusion, compared to the sham group (1.8 [1.5-2.0] vs. 1.1 [0.9-1.3], P < 0.001). PCO/CO had a weak correlation with respiratory quotient (Spearman R = 0.42, P < 0.001). All the intestinal and sublingual microcirculatory variables were affected during hemorrhage and improved after retransfusion. The recovery was only complete for intestinal red blood cell velocity and sublingual total and perfused vascular densities. Conclusions: Although there were some minor differences, intestinal and sublingual microcirculation behaved similarly. Therefore, sublingual mucosa might be an adequate window to track intestinal microvascular reperfusion injury. Additionally, PCO/CO was poorly correlated with respiratory quotient, and its physiologic behavior was different. Thus, it might be a misleading surrogate for anaerobic metabolism. [ABSTRACT FROM AUTHOR]

This study systematically examined the role of work rate (WR) increment on the kinetics of pulmonary oxygen uptake (VO(2p)) and near-infrared spectroscopy (NIRS)-derived muscle deoxygenation (Δ[HHb]) during moderate-intensity (Mod) cycling. Fourteen males (24 ± 5 years) each completed four to eight repetitions of Mod transitions from 20 to 50, 70, 90, 110 and 130 W. VO(2p) and Δ[HHb] responses were modelled as a mono-exponential; responses were then scaled to a relative % of the respective response (0-100 %). The Δ[HHb]/VO(2) ratio was calculated as the average Δ[HHb]/VO(2) during the 20-120 s period of the on-transient. When considered as a single group, neither the phase II VO(2p) time constant (τVO(2p); 27 ± 9, 26 ± 11, 25 ± 10, 27 ± 14, 29 ± 13 s for 50-130 W transitions, respectively) nor the Δ[HHb]/VO(2) ratio (1.04 ± 0.13, 1.10 ± 0.13, 1.08 ± 0.07, 1.09 ± 0.11, 1.09 ± 0.09, respectively) was affected by WR (p > 0.05); yet, the VO(2) functional gain (G; ΔVO(2)/ΔWR) increased with increasing WR transitions (8.6 ± 1.3, 9.1 ± 1.2, 9.5 ± 1.0, 9.5 ± 1.0, 9.9 ± 1.0 mL min(-1) W(-1); p < 0.05). When subjects were stratified into two groups [Fast (n = 6), τVO(2p130W) < 25 s < τVO(2p130W), Slower (n = 8)], a group by WR interaction was observed for τVO(2p). The increasing functional G persisted (p < 0.05) and did not differ between groups (p > 0.05). The Δ[HHb]/VO(2) ratio was smaller (p < 0.05) in the Fast than Slower group, but was unaffected by WR. In conclusion, the present study demonstrated (1) a non-uniform effect of Mod WR increment on τVO(2p); (2) that τVO(2p) in the Slower group is likely determined by an O(2) delivery limitation; and (3) that increasing Mod WR increments elicits an increased functional G, regardless of the τVO(2p) response. [ABSTRACT FROM AUTHOR]

This study compared the oxygen uptake (VO(2)) and muscle deoxygenation (∆HHb) of two intermittent protocols to responses during continuous constant load cycle exercise in males (24 year ± 2, n = 7). Subjects performed three protocols: (1) 10 s work/5 s active recovery (R), R at 20 W (INT1): (2) 10 s work/5 s R, R at moderate intensity (INT2); and (3) continuous exercise (CONT), all for 10 min, on separate days. The work rate of CONT and the 10 s work of INT1 and INT2 were set within the heavy intensity domain. VO(2) and ∆HHb data were filtered and averaged to 5 s bins. Average VO(2) (80-420 s) was highest during CONT (3.77 L/min), lower in INT2 (3.04 L/min), and lowest during INT1 (2.81 L/min), all (p < 0.05). Average ∆HHb (80-420 s) was higher during CONT (p < 0.05) than both INT exercise protocols (CONT; 25.7 ± 0.9 a.u. INT1; 16.4 ± 0.8 a.u., and INT2; 15.8 ± 0.8 a.u.). The repeated changes in metabolic rate elicited oscillations in ΔHHb in both intermittent protocols, whereas oscillations in VO(2) were only observed during INT1. The greater ΔHHb during CONT suggests a reduction in oxygen delivery compared to oxygen consumption relative to INT. The higher VO(2) for INT 2 versus INT 1 and similar ΔHHb during INT suggests an increase in oxygen delivery during INT 2. Thus the different demands of INT1, INT2, and CONT protocols elicited differing physiological responses to a similar heavy intensity power output. These intermittent exercise models seem to elicit an elevated O(2) delivery condition compared to CONT. [ABSTRACT FROM AUTHOR]

The relationship between the adjustment of muscle deoxygenation (∆[HHb]) and phase II VO(2p) was examined in subjects presenting with a range of slow to fast VO(2p) kinetics. Moderate intensity VO(2p) and ∆[HHb] kinetics were examined in 37 young males (24 ± 4 years). VO(2p) was measured breath-by-breath. Changes in ∆[HHb] of the vastus lateralis muscle were measured by near-infrared spectroscopy. VO(2p) and ∆[HHb] response profiles were fit using a mono-exponential model, and scaled to a relative % of the response (0-100%). The ∆[HHb]/∆VO(2p) ratio for each individual (reflecting the matching of O(2) distribution to O(2) utilization) was calculated as the average ∆[HHb]/∆VO(2p) response from 20 to 120 s during the exercise on-transient. Subjects were grouped based on individual phase II VO(2p) time-constant (τVO(2p)): <21 s [very fast (VF)]; 21-30 s [fast (F)]; 31-40 s [moderate (M)]; >41 s [slow (S)]. The corresponding ∆[HHb]/∆VO(2p) were 0.98 (VF), 1.05 (F), 1.09 (M), and 1.22 (S). The larger ∆[HHb]/∆VO(2p) in the groups with slower VO(2p) kinetics resulted in the ∆[HHb]/∆VO(2p) displaying a transient "overshoot" relative to the subsequent steady state level, which was progressively reduced as τVO(2) became smaller (r = 0.91). When τVO(2p) > ~20 s, the rate of adjustment of phase II VO(2p) appears to be mainly constrained by the matching of local O(2) distribution to muscle VO(2). These data suggest that in subjects with "slower" VO(2) kinetics, the rate of adjustment of VO(2) may be constrained by O(2) availability within the active tissues related to the matching of microvascular O(2) distribution to muscle O(2) utilization. [ABSTRACT FROM AUTHOR]

This study sought to determine the effect of the pre-transition work rate (WR) and WR transition magnitude on the adjustment of pulmonary oxygen uptake (VO(2p) kinetics) in older men. Seven men (69 ± 5 years; mean ± SD) each performed 4-6 cycling transitions from 20 W to either a WR corresponding to 90% estimated lactate threshold (full step, FS) or 2 equal-step transitions (lower step, LS; upper step, US) to the same end-exercise WR as in FS. Gas exchange was analysed breath-by-breath and muscle deoxygenation (∆[HHb]) was measured with NIRS. The time constant (τ) for VO(2p) was greater in US (53 ± 17 s) and FS (44 ± 11 s) compared to LS (37 ± 9 s); τVO(2p) for US also trended (p = 0.05) towards being greater than FS. The VO(2p) gain in US (9.97 ± 0.41 mL/min/W) was greater than LS (9.06 ± 1.17; p = 0.06) and FS (9.13 ± 0.54; p < 0.05). The O(2) deficit was greater in US (0.25 ± 0.08 L) than LS (0.19 ± 0.06 L); yet the 'accumulated O(2) deficit' (0.44 ± 0.13 L; O(2) deficit from LS + US) was similar to that of FS (0.42 ± 0.13 L; p = 0.38). The effective Δ[HHb] response time (τ'∆[HHb]) for US (36 ± 12 s) was greater than LS (27 ± 6 s; p = 0.07) and FS (26 ± 4 s; p < 0.05), suggesting that the slowed adjustment of muscle O(2) extraction was associated with the slowed VO(2) kinetics of the US. Despite already slowed VO(2p) kinetics, older men exhibit further slowing when small WR transitions are initiated from an elevated pre-transition WR, yet this results in no cumulative impact on O(2) deficit. This slowing in US compared to LS does not appear to be related to local O(2) availability. [ABSTRACT FROM AUTHOR]

This study compared the parameter estimates of pulmonary oxygen uptake (VO(2p)), heart rate (HR) and muscle deoxygenation (Δ[HHb]) kinetics when several moderate-intensity exercise transitions (MODs) were performed during a single visit versus several MODs performed during separate visits. Nine subjects (24 ± 5 years, mean ± SD) each completed two successive cycling MODs on six occasions (1-6A and 1-6B) from 20 W to a work rate corresponding to 80% estimated lactate threshold with 6 min recovery at 20 W. During one visit, subjects completed two series of three MODs (6A-F), separated by 20 min rest. VO(2p) time constants (τVO(2p); 27 ± 10 s, 25 ± 12 s, 25 ± 11 s) were similar (p > 0.05) for MODs 1-6A, 1-6B and 6A-F, respectively. τVO(2p) had reproducibility 95% confidence intervals (CI(95)) of 8.3, 8.2, 4.7, 4.9 and 4.7 s when comparing single (1A vs. 2A), the average of two (1-2A vs. 3-4A), three (1-3A vs. 4-6A), four (1-2AB vs. 3-4AB) and six (1-3AB vs. 4-6AB) MODs, respectively. The effective Δ[HHb] response time (τ'Δ[HHb]) was unaffected across conditions (1-6A: 19 ± 2 s, 1-6B: 19 ± 3 s, 6A-F: 17 ± 4 s) with reproducibility CI(95) of 5.3, 4.5, 3.1, 2.9 and 3.3 s when a single, two, three, four and six MODs were compared, respectively. τHR was reduced in MODs 6A-F compared to 1-6A and 1-6B (23 ± 5 s, 25 ± 5 s, 27 ± 6 s, respectively). This study showed that parameter estimates of VO(2p), HR and Δ[HHb] kinetics are largely unaffected by data collection sequence, and the day-to-day reproducibility of τVO(2p) and τ'Δ[HHb] estimates, as determined by the CI(95), was appreciably improved by averaging of at least three MODs. [ABSTRACT FROM AUTHOR]

To test the hypothesis that levosimendan increases systemic and intestinal oxygen delivery (DO2) and prevents intramucosal acidosis in septic shock. Prospective, controlled experimental study. University-based research laboratory. Nineteen anesthetized, mechanically ventilated sheep. Endotoxin-treated sheep were randomly assigned to three groups: control ( n = 7), dobutamine (10 μg/kg/min, n = 6) and levosimendan (100 μg/kg over 10 min followed by 100 μg/kg/h, n = 6) and treated for 120 min. After endotoxin administration, systemic and intestinal DO2 decreased (24.6 ± 5.2 vs 15.3 ± 3.4 ml/kg/min and 105.0 ± 28.1 vs 55.8 ± 25.9 ml/kg/min, respectively; p < 0.05 for both). Arterial lactate and the intramucosal–arterial PCO2 difference (ΔPCO2) increased (1.4 ± 0.3 vs 3.1 ± 1.5 mmHg and 9 ± 6 vs 23 ± 6 mmHg mmol/l, respectively; p < 0.05). Systemic DO2 was preserved in the dobutamine-treated group (22.3 ± 4.7 vs 26.8 ± 7.0 ml/min/kg, p = NS) but intestinal DO2 decreased (98.9 ± 0.2 vs 68.0 ± 22.9 ml/min/kg, p < 0.05) and ΔPCO2 increased (12 ± 5 vs 25 ± 11 mmHg, p < 0.05). The administration of levosimendan prevented declines in systemic and intestinal DO2 (25.1 ± 3.0 vs 24.0 ± 6.3 ml/min/kg and 111.1 ± 18.0 vs 98.2 ± 23.1 ml/min/kg, p = NS for both) or increases in ΔPCO2 (7 ± 7 vs 10 ± 8, p = NS). Arterial lactate increased in both the dobutamine and levosimendan groups (1.6 ± 0.3 vs 2.5 ± 0.7 and 1.4 ± 0.4 vs. 2.9 ± 1.1 mmol/l, p = NS between groups). Compared with dobutamine, levosimendan increased intestinal blood flow and diminished intramucosal acidosis in this experimental model of sepsis. [ABSTRACT FROM AUTHOR]

Background: The sorption of anthropogenic compounds on clay minerals is a complex molecular process with important implications for the fate of agrochemicals and organic pollutants in the environment. Results: The present study illustrates the use of a water-mediated NOE approach to study clay binding interactions. This method exploits the interfacial water layer on clay surfaces as a hydrogen reservoir for magnetization transfer. The interactions of four different xenobiotics with clay suspension were investigated through this method to demonstrate its capability to screen for the clay-xenobiotic molecular affinity. Further, based on the NOE build-up rates, epitope map of clay-xenobiotic interactions can be generated, explaining the orientation and mechanism of the interactions. Conclusions: The water-mediated NOE approach has the potential to reveal key insights into the role that interfacial water plays in the binding process, providing a better understanding of the partitioning of anthropogenic compounds from bulk water into aqueous clay suspensions. [ABSTRACT FROM AUTHOR]