Plasminogen and its active form, plasmin, have diverse functions related to the inflammatory response in mammals. Due to these roles in inflammation, plasminogen has been implicated in the ...progression of a wide range of diseases with an inflammatory component. In this review, we discuss the functions of plasminogen in inflammatory regulation and how this system plays a role in the pathogenesis of diseases spanning organ systems throughout the body.
We aimed to determine the effect of resistance exercise intensity (%1 repetition maximum-1RM) and volume on muscle protein synthesis, anabolic signaling, and myogenic gene expression.
Fifteen men ...(21+/-1 years; BMI=24.1+/-0.8 kg/m2) performed 4 sets of unilateral leg extension exercise at different exercise loads and/or volumes: 90% of repetition maximum (1RM) until volitional failure (90FAIL), 30% 1RM work-matched to 90%FAIL (30WM), or 30% 1RM performed until volitional failure (30FAIL). Infusion of ring-13C6 phenylalanine with biopsies was used to measure rates of mixed (MIX), myofibrillar (MYO), and sarcoplasmic (SARC) protein synthesis at rest, and 4 h and 24 h after exercise. Exercise at 30WM induced a significant increase above rest in MIX (121%) and MYO (87%) protein synthesis at 4 h post-exercise and but at 24 h in the MIX only. The increase in the rate of protein synthesis in MIX and MYO at 4 h post-exercise with 90FAIL and 30FAIL was greater than 30WM, with no difference between these conditions; however, MYO remained elevated (199%) above rest at 24 h only in 30FAIL. There was a significant increase in AktSer473 at 24h in all conditions (P=0.023) and mTORSer2448 phosphorylation at 4 h post-exercise (P=0.025). Phosporylation of Erk1/2Tyr202/204, p70S6KThr389, and 4E-BP1Thr37/46 increased significantly (P<0.05) only in the 30FAIL condition at 4 h post-exercise, whereas, 4E-BP1Thr37/46 phosphorylation was greater 24 h after exercise than at rest in both 90FAIL (237%) and 30FAIL (312%) conditions. Pax7 mRNA expression increased at 24 h post-exercise (P=0.02) regardless of condition. The mRNA expression of MyoD and myogenin were consistently elevated in the 30FAIL condition.
These results suggest that low-load high volume resistance exercise is more effective in inducing acute muscle anabolism than high-load low volume or work matched resistance exercise modes.
The origin of the apparent thermalization in high-energy collisions is investigated using the data of the ATLAS and CMS Collaborations at the LHC. For this purpose, we analyze the transverse momentum ...distributions in the following proton-proton collision processes, all at s=13 TeV: (i) inclusive inelastic pp collisions; (ii) single- and double-diffractive Drell-Yan production pp→μ+μ−X; and (iii) Higgs boson production. We confirm the relation between the effective temperature and the hard scattering scale observed at lower energies, and find that it extends even to the Higgs boson production process. In addition we find that the thermal component disappears in diffractive events (even though many charged hadrons are still produced). We discuss the implications of our study for the mechanism of multiparticle production-in particular, we test the hypothesis about the link between quantum entanglement and thermalization in high-energy collisions.
We assessed late mortality in 1479 individuals who had survived 2 or more years after allogeneic hematopoietic cell transplantation (HCT). Median age at HCT was 25.9 years and median length of ...follow-up was 9.5 years. The conditional survival probability at 15 years from HCT was 80.2% (SE = 1.9%) for those who were disease-free at entry into the cohort, and the relative mortality was 9.9 (95% confidence interval, 8.7-11.2). Relative mortality decreased with time from HCT, but remained significantly elevated at 15 years after HCT (standardized mortality ratio = 2.2). Relapse of primary disease (29%) and chronic graft-versus-host disease (cGVHD: 22%) were the leading causes of premature death. Nonrelapse-related mortality was increased among patients older than 18 years at HCT (18-45 years: relative risk RR = 1.7; 46+ years: RR = 3.7) and among those with cGVHD (RR = 2.7), and was lower among patients who received methotrexate for GVHD prophylaxis (RR = 0.5). HCT survivors were more likely to report difficulty in holding jobs (odds ratio OR = 13.9), and in obtaining health (OR = 7.1) or life (OR = 9.9) insurance compared with siblings. This study demonstrates that mortality rates remain twice as high as that of the general population among 15-year survivors of HCT, and that the survivors face challenges affecting their health and well-being.
To reach the pressures and densities required for ignition, it may be necessary to develop an approach to design that makes it easier for simulations to guide experiments. Here, we report on a new ...short-pulse inertial confinement fusion platform that is specifically designed to be more predictable. The platform has demonstrated 99%+0.5% laser coupling into the hohlraum, high implosion velocity (411 km/s), high hotspot pressure (220+60 Gbar), and high cold fuel areal density compression ratio (>400), while maintaining controlled implosion symmetry, providing a promising new physics platform to study ignition physics.
Digital drawing tests have been proposed for cognitive screening over the past decade. However, the diagnostic performance is still to clarify. The objective of this study was to evaluate the ...diagnostic performance among different types of digital and paper-and-pencil drawing tests in the screening of mild cognitive impairment (MCI) and dementia. Diagnostic studies evaluating digital or paper-and-pencil drawing tests for the screening of MCI or dementia were identified from OVID databases, included Embase, MEDLINE, CINAHL, and PsycINFO. Studies evaluated any type of drawing tests for the screening of MCI or dementia and compared with healthy controls. This study was performed according to PRISMA and the guidelines proposed by the Cochrane Diagnostic Test Accuracy Working Group. A bivariate random-effects model was used to compare the diagnostic performance of these drawing tests and presented with a summary receiver-operating characteristic curve. The primary outcome was the diagnostic performance of clock drawing test (CDT). Other types of drawing tests were the secondary outcomes. A total of 90 studies with 22,567 participants were included. In the screening of MCI, the pooled sensitivity and specificity of the digital CDT was 0.86 (95% CI = 0.75 to 0.92) and 0.92 (95% CI = 0.69 to 0.98), respectively. For the paper-and-pencil CDT, the pooled sensitivity and specificity of brief scoring method was 0.63 (95% CI = 0.49 to 0.75) and 0.77 (95% CI = 0.68 to 0.84), and detailed scoring method was 0.63 (95% CI = 0.56 to 0.71) and 0.72 (95% CI = 0.65 to 0.78). In the screening of dementia, the pooled sensitivity and specificity of the digital CDT was 0.83 (95% CI = 0.72 to 0.90) and 0.87 (95% CI = 0.79 to 0.92). The performances of the digital and paper-and-pencil pentagon drawing tests were comparable in the screening of dementia. The digital CDT demonstrated better diagnostic performance than paper-and-pencil CDT for MCI. Other types of digital drawing tests showed comparable performance with paper-and-pencil formats. Therefore, digital drawing tests can be used as an alternative tool for the screening of MCI and dementia.
Neural stem cells have been adopted to model a wide range of neuropsychiatric conditions in vitro. However, how well such models correspond to in vivo brain has not been evaluated in an unbiased, ...comprehensive manner. We used transcriptomic analyses to compare in vitro systems to developing human fetal brain and observed strong conservation of in vivo gene expression and network architecture in differentiating primary human neural progenitor cells (phNPCs). Conserved modules are enriched in genes associated with ASD, supporting the utility of phNPCs for studying neuropsychiatric disease. We also developed and validated a machine learning approach called CoNTExT that identifies the developmental maturity and regional identity of in vitro models. We observed strong differences between in vitro models, including hiPSC-derived neural progenitors from multiple laboratories. This work provides a systems biology framework for evaluating in vitro systems and supports their value in studying the molecular mechanisms of human neurodevelopmental disease.
•Quantitative framework permits comparisons of in vitro models to in vivo brain•phNPCs recapitulate cortical development up to late mid-fetal periods•In vivo cortical gene networks implicated in ASD are preserved in phNPCs•Highlights key differences between widely used stem cell models and in vivo brain
Human neural stem cells have been adopted to model a wide range of neuropsychiatric conditions in vitro. Here, Stein et al. develop a bioinformatic framework to quantitatively evaluate their ability to model in vivo cortical development and their translational potential.
To examine whether the menstrual or monophasic oral contraceptive cycle phases affect submaximal (oxygen uptake (V˙O2) kinetics, maximal lactate steady‐state (MLSS)) and maximal (V˙O2max, ...time‐to‐exhaustion (TTE)) responses to exercise in healthy, active women. During the mid‐follicular or inactive‐pill phase and the mid‐luteal or active‐pill phase of the respective menstrual or oral contraceptive cycle, 15 non‐oral contraceptive users (mean and standard deviation (SD) (±): 27 ± 6 years; 171 ± 5 cm; 65 ± 7 kg) and 15 monophasic oral contraceptive users (24 ± 4 years; 169 ± 10 cm; 68 ± 10 kg) performed: one V˙O2 kinetics test; one ramp‐incremental test; two to three 30‐minute constant‐load cycling trials to determine the power output corresponding to MLSS (MLSSp), followed by a TTE trial. The phase of the menstrual or oral contraceptive cycle did not affect the time constant of the V˙O2 kinetics response (τV˙O2) (mid‐follicular, 20 ± 5 seconds and mid‐luteal, 18 ± 3 seconds; inactive‐pill, 22 ± 8 seconds and active‐pill, 23 ± 6 seconds), V˙O2max (mid‐follicular, 3.06 ± 0.32 L min−1 and mid‐luteal, 3.00 ± 0.33 L min−1; inactive‐pill, 2.87 ± 0.39 L min−1 and active‐pill, 2.87 ± 0.45 L min−1), MLSSp (mid‐follicular, 181 ± 30 W and mid‐luteal, 182 ± 29 W; inactive‐pill, 155 ± 26 W and active‐pill, 155 ± 27 W), and TTE (mid‐follicular, 147 ± 42 seconds and mid‐luteal, 128 ± 54 seconds; inactive‐pill, 146 ± 70 seconds and active‐pill, 139 ± 77 seconds) (P > .05). The rate of perceived exertion (RPE) at minute 30 of the MLSSp trials was greater in the mid‐follicular phase (6.2 ± 1.5) compared with the mid‐luteal phase (5.3 ± 1.4) for non‐oral contraceptive users (P = .022). The hormonal fluctuations between the menstrual and oral contraceptive cycle phases had no detectable effects on submaximal and maximal exercise performance, even when RPE differed.
Abstract
Background
Survivors of childhood acute myeloid leukemia (AML) are vulnerable to medical late effects of treatment; however, less is known about their psychosocial outcomes. This study ...evaluated neurocognitive and psychosocial outcomes in long-term AML survivors treated with bone marrow transplantation (BMT) or intensive chemotherapy (IC) without BMT.
Methods
AML survivors (N = 482; median age at diagnosis = 8 range = 0-20 years; median age at evaluation = 30 range = 18-49 years) treated with BMT (n = 183) or IC (n = 299) and sibling controls (N = 3190; median age at evaluation = 32 range = 18-58 years) from the Childhood Cancer Survivor Study were compared on emotional distress (Brief Symptom Inventory-18), neurocognitive problems (Childhood Cancer Survivor Study Neurocognitive Questionnaire), health-related quality of life (SF-36), and social attainment. Outcomes were dichotomized (impaired vs nonimpaired) using established criteria, and relative risks (RRs) were estimated with multivariable Poisson regression, adjusted for age at evaluation and sex.
Results
AML survivors were more likely than siblings to report impairment in overall emotional (RR = 2.19, 95% confidence interval CI = 1.51 to 3.18), neurocognitive (RR = 2.03, 95% CI = 1.47 to 2.79), and physical quality of life (RR = 2.71, 95% CI = 1.61 to 4.56) outcomes. Survivors were at increased risk for lower education (RR = 1.15, 95% CI = 1.03 to 1.30), unemployment (RR = 1.41, 95% CI = 1.16 to 1.71), lower income (RR = 1.39, 95% CI = 1.17 to 1.65), and not being married or having a partner (RR = 1.33, 95% CI = 1.17 to 1.51). BMT-treated survivors did not differ statistically significantly from IC-treated on any outcome measure.
Conclusions
AML survivors are at increased risk for psychosocial impairment compared with siblings; however, BMT does not confer additional risk for psychosocial late effects compared with treatment without BMT.
We reported, using a unilateral resistance training (RT) model, that training with high or low loads (mass per repetition) resulted in similar muscle hypertrophy and strength improvements in RT-naïve ...subjects. Here we aimed to determine whether the same was true in men with previous RT experience using a whole-body RT program and whether postexercise systemic hormone concentrations were related to changes in hypertrophy and strength. Forty-nine resistance-trained men (23 ± 1 yr, mean ± SE) performed 12 wk of whole-body RT. Subjects were randomly allocated into a higher-repetition (HR) group who lifted loads of ∼30-50% of their maximal strength (1RM) for 20-25 repetitions/set (n = 24) or a lower-repetition (LR) group (∼75-90% 1RM, 8-12 repetitions/set, n = 25), with all sets being performed to volitional failure. Skeletal muscle biopsies, strength testing, dual-energy X-ray absorptiometry scans, and acute changes in systemic hormone concentrations were examined pretraining and posttraining. In response to RT, 1RM strength increased for all exercises in both groups (P < 0.01), with only the change in bench press being significantly different between groups (HR, 9 ± 1, vs. LR, 14 ± 1 kg, P = 0.012). Fat- and bone-free (lean) body mass and type I and type II muscle fiber cross-sectional area increased following training (P < 0.01) with no significant differences between groups. No significant correlations between the acute postexercise rise in any purported anabolic hormone and the change in strength or hypertrophy were found. In congruence with our previous work, acute postexercise systemic hormonal rises are not related to or in any way indicative of RT-mediated gains in muscle mass or strength. Our data show that in resistance-trained individuals, load, when exercises are performed to volitional failure, does not dictate hypertrophy or, for the most part, strength gains.
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