Twelve Weeks of Nitrate, Beta-Alanine, or Combined Treatment in NCAA Division III Male Soccer Players

In a sport of long duration, such as soccer, with many high-intensity bouts interspersed within the match, enhancing performance to last the duration of the match and maintain high levels of intensity is paramount. Thus, with proper nutrition and physical preparation, supplements such as beta-alanine (due to its intracellular buffering capacity) and nitrate (due to its vasodilatory and ergogenic effects in endurance exercise) may have value in this population. PURPOSE: The purpose of this investigation was to examine the effects of chronic supplementation with nitrate, beta-alanine, or combined treatment in NCAA Division III male soccer players. METHODS: Twenty-two NCAA Division III male soccer players (age: 19.1 ± 1.1yrs; mass: 74.8 ± 8.0kg; body fat: 13.6 ± 4.0%) were randomly assigned into one of four groups: nitrate plus placebo (NIT), beta-alanine plus placebo (BA), placebo (PLA), or active treatments (ACT) and participated in this 12-week double-blind, placebo-controlled study. At pre-intervention testing, participants completed body composition measures, VO2 max, 30-second Wingate test on day one, and 40-yard dash and Yo-Yo Intermittent Recovery: Level 2 (YOYOIR2) on day two and testing sessions were repeated at 6- and 12-weeks post training and supplementation. A 4x3 repeated measures ANOVA was used to analyze the data with a-priori p value set at ≤0.05. RESULTS: There was a significant time effect for the following variables indicating that the training protocol induced performance adaptations: VO2 max (p = 0.0), Wingate peak power and mean power (p = 0.04; p = 0.006), 40-yard dash (p = 0.003), and YOYOIR2 (p = 0.0). Change in performance over time (% change) for VO2 max was NIT: 9%, BA: 7%, ACT: 12% vs PLA: 8%. Wingate mean power % change was NIT: 17%, BA: 6%, ACT: 4% vs PLA: 5%. Wingate peak power % change was NIT: 10%, BA: 11%, ACT: 10% vs PLA: 9%. YOYOIR2 % change was NIT: 48%, BA: 54%, ACT: 74% vs PLA: 10%. Despite this, there were no significant group by time effects for any variables. CONCLUSION: Although further research is warranted, addition of these supplements may be beneficial to soccer players

Resurfacing Patella Using Pedicled Soleus Perforator Flap

Soft-tissue reconstruction in the knee area requires thin, pliable, and tough skin. To resurface the wound, many flaps are used, including free flaps, musculocutaneous flaps, axillary flaps, local flaps, and sometimes distant flaps. However, each flap has disadvantages. In this report, we present 2 cases of soft-tissue defects on the surface of the patella reconstructed with a pedicled soleus perforator flap, resulting in a successful outcome. Pedicled soleus perforator flaps enable the reconstruction of local soft-tissue defects of the patella without microvascular anastomoses and with minimal donor-site morbidity. We conclude that the pedicled soleus perforator flap is a favorable option for defect coverage around the knee, because of its fast and easy harvesting and very good esthetic results

The pestivirus N terminal protease N(pro) redistributes to mitochondria and peroxisomes suggesting new sites for regulation of IRF3 by N(pro.)

The N-terminal protease of pestiviruses, N(pro) is a unique viral protein, both because it is a distinct autoprotease that cleaves itself from the following polyprotein chain, and also because it binds and inactivates IRF3, a central regulator of interferon production. An important question remains the role of N(pro) in the inhibition of apoptosis. In this study, apoptotic signals induced by staurosporine, interferon, double stranded RNA, sodium arsenate and hydrogen peroxide were inhibited by expression of wild type N(pro), but not by mutant protein N(pro) C112R, which we show is less efficient at promoting degradation of IRF3, and led to the conclusion that N(pro) inhibits the stress-induced intrinsic mitochondrial pathway through inhibition of IRF3-dependent Bax activation. Both expression of N(pro) and infection with Bovine Viral Diarrhea Virus (BVDV) prevented Bax redistribution and mitochondrial fragmentation. Given the role played by signaling platforms during IRF3 activation, we have studied the subcellular distribution of N(pro) and we show that, in common with many other viral proteins, N(pro) targets mitochondria to inhibit apoptosis in response to cell stress. N(pro) itself not only relocated to mitochondria but in addition, both N(pro) and IRF3 associated with peroxisomes, with over 85% of N(pro) puncta co-distributing with PMP70, a marker for peroxisomes. In addition, peroxisomes containing N(pro) and IRF3 associated with ubiquitin. IRF3 was degraded, whereas N(pro) accumulated in response to cell stress. These results implicate mitochondria and peroxisomes as new sites for IRF3 regulation by N(pro), and highlight the role of these organelles in the anti-viral pathway

An Investigation into the Cognition Behind Spontaneous String Pulling in New Caledonian Crows

The ability of some bird species to pull up meat hung on a string is a famous example of spontaneous animal problem solving. The “insight” hypothesis claims that this complex behaviour is based on cognitive abilities such as mental scenario building and imagination. An operant conditioning account, in contrast, would claim that this spontaneity is due to each action in string pulling being reinforced by the meat moving closer and remaining closer to the bird on the perch. We presented experienced and naïve New Caledonian crows with a novel, visually restricted string-pulling problem that reduced the quality of visual feedback during string pulling. Experienced crows solved this problem with reduced efficiency and increased errors compared to their performance in standard string pulling. Naïve crows either failed or solved the problem by trial and error learning. However, when visual feedback was available via a mirror mounted next to the apparatus, two naïve crows were able to perform at the same level as the experienced group. Our results raise the possibility that spontaneous string pulling in New Caledonian crows may not be based on insight but on operant conditioning mediated by a perceptual-motor feedback cycle

Clinical Features, Inpatient Trajectories and Frailty in Older Inpatients with COVID-19: A Retrospective Observational Study

Introduction: We describe the clinical features and inpatient trajectories of older adults hospitalized with COVID-19 and explore relationships with frailty. Methods: This retrospective observational study included older adults admitted as an emergency to a University Hospital who were diagnosed with COVID-19. Patient characteristics and hospital outcomes, primarily inpatient death or death within 14 days of discharge, were described for the whole cohort and by frailty status. Associations with mortality were further evaluated using Cox Proportional Hazards Regression (Hazard Ratio (HR), 95% Confidence Interval). Results: 214 patients (94 women) were included of whom 142 (66.4%) were frail with a median Clinical Frailty Scale (CFS) score of 6. Frail compared to nonfrail patients were more likely to present with atypical symptoms including new or worsening confusion (45.1% vs. 20.8%, p 0.001) and were more likely to die (66% vs. 16%, p = 0.001). Older age, being male, presenting with high illness acuity and high frailty were independent predictors of death and a dose–response association between frailty and mortality was observed (CFS 1–4: reference; CFS 5–6: HR 1.78, 95% CI 0.90, 3.53; CFS 7–8: HR 2.57, 95% CI 1.26, 5.24). Conclusions: Clinicians should have a low threshold for testing for COVID-19 in older and frail patients during periods of community viral transmission, and diagnosis should prompt early advanced care planning

The role of phosphodiesterase 12 (PDE12) as a negative regulator of the innate immune response and the discovery of antiviral inhibitors

2',5'-Oligoadenylate synthetase (OAS) enzymes and RNase-L constitute a major effector arm of interferon (IFN)-mediated antiviral defense. OAS produces a unique oligonucleotide second messenger, 2',5'-oligoadenylate (2-5A), that binds and activates RNase-L. This pathway is down-regulated by virus- and host-encoded enzymes that degrade 2-5A. Phosphodiesterase 12 (PDE12) was the first cellular 2-5A- degrading enzyme to be purified and described at a molecular level. Inhibition of PDE12 may up-regulate the OAS/RNase-L pathway in response to viral infection resulting in increased resistance to a variety of viral pathogens. We generated a PDE12-null cell line, HeLaΔPDE12, using transcription activator-like effector nuclease-mediated gene inactivation. This cell line has increased 2-5A levels in response to IFN and poly(I-C), a double-stranded RNA mimic compared with the parental cell line. Moreover, HeLaΔPDE12 cells were resistant to viral pathogens, including encephalomyocarditis virus, human rhinovirus, and respiratory syncytial virus. Based on these results, we used DNA-encoded chemical library screening to identify starting points for inhibitor lead optimization. Compounds derived from this effort raise 2-5A levels and exhibit antiviral activity comparable with the effects observed with PDE12 gene inactivation. The crystal structure of PDE12 complexed with an inhibitor was solved providing insights into the structure-activity relationships of inhibitor potency and selectivity

The impact of submaximal exercise during heat and/or hypoxia on the cardiovascular and monocyte HSP72 responses to subsequent (post 24 h) exercise in hypoxia

BACKGROUND: The aims of this study were to describe the cellular stress response to prolonged endurance exercise in acute heat, hypoxia and the combination of heat and hypoxia and to determine whether prior acute exposure to these stressors improved cellular tolerance to a subsequent exercise bout in hypoxia 24 h later. METHODS: Twelve males (age 22 ± 4 years, height 1.77 ± 0.05 m, mass 79 ± 12.9 kg, VO(2) max 3.57 ± 0.7 L · min(-1)) completed four trials (30-min rest, 90-min cycling at 50% normoxic VO(2) max) in normothermic normoxia (NORM; 18°C, F(I)O(2) = 0.21), heat (HEAT; 40°C, 20% RH), hypoxia (HYP; F(I)O(2) = 0.14) or a combination of heat and hypoxia (COM; 40°C, 20% RH, F(I)O(2) = 0.14) separated by at least 7 days. Twenty-four hours after each trial, participants completed a hypoxic stress test (HST; 15-min rest, 60-min cycling at 50% normoxic VO(2) max, F(I)O(2) = 0.14). Monocyte heat shock protein 72 (mHSP72) was assessed immediately before and after each exercise bout. RESULTS: mHSP72 increased post exercise in NORM (107% ± 5.5%, p > 0.05), HYP (126% ± 16%, p < 0.01), HEAT (153% ± 14%, p < 0.01) and COM (161% ± 32%, p < 0.01). mHSP72 had returned to near-resting values 24 h after NORM (97% ± 8.6%) but was elevated after HEAT (130% ± 19%), HYP (118% ± 17%) and COM (131% ± 19%) (p < 0.05). mHSP72 increased from baseline after HST(NORM) (118% ± 12%, p < 0.05), but did not increase further in HST(HEAT), HST(HYP) and HST(COM). CONCLUSIONS: The prior induction of mHSP72 as a result of COM, HEAT and HYP attenuated further mHSP72 induction after HST and was indicative of conferred cellular tolerance

Clinical Features, Inpatient Trajectories and Frailty in Older Inpatients with COVID-19: A Retrospective Observational Study

Introduction: We describe the clinical features and inpatient trajectories of older adults hospitalized with COVID-19 and explore relationships with frailty. Methods: This retrospective observational study included older adults admitted as an emergency to a University Hospital who were diagnosed with COVID-19. Patient characteristics and hospital outcomes, primarily inpatient death or death within 14 days of discharge, were described for the whole cohort and by frailty status. Associations with mortality were further evaluated using Cox Proportional Hazards Regression (Hazard Ratio (HR), 95% Confidence Interval). Results: 214 patients (94 women) were included of whom 142 (66.4%) were frail with a median Clinical Frailty Scale (CFS) score of 6. Frail compared to nonfrail patients were more likely to present with atypical symptoms including new or worsening confusion (45.1% vs. 20.8%, p 0.001) and were more likely to die (66% vs. 16%, p = 0.001). Older age, being male, presenting with high illness acuity and high frailty were independent predictors of death and a dose–response association between frailty and mortality was observed (CFS 1–4: reference; CFS 5–6: HR 1.78, 95% CI 0.90, 3.53; CFS 7–8: HR 2.57, 95% CI 1.26, 5.24). Conclusions: Clinicians should have a low threshold for testing for COVID-19 in older and frail patients during periods of community viral transmission, and diagnosis should prompt early advanced care planning

Galaxy ecology: groups and low-density environments in the SDSS and 2dFGRS

We analyse the observed correlation between galaxy environment and Hα emission-line strength, using volume-limited samples and group catalogues of 24 968 galaxies at 0.05 < z < 0.095, drawn from the 2dF Galaxy Redshift Survey ( < −19.5) and the Sloan Digital Sky Survey (Mr < −20.6). We characterize the environment by: (1) Σ5, the surface number density of galaxies determined by the projected distance to the fifth nearest neighbour; and (2) ρ1.1 and ρ5.5, three-dimensional density estimates obtained by convolving the galaxy distribution with Gaussian kernels of dispersion 1.1 and 5.5 Mpc, respectively. We find that star-forming and quiescent galaxies form two distinct populations, as characterized by their Hα equivalent width, W0(Hα). The relative numbers of star-forming and quiescent galaxies vary strongly and continuously with local density. However, the distribution of W0(Hα) amongst the star-forming population is independent of environment. The fraction of star-forming galaxies shows strong sensitivity to the density on large scales, ρ5.5, which is likely independent of the trend with local density, ρ1.1. We use two differently selected group catalogues to demonstrate that the correlation with galaxy density is approximately independent of group velocity dispersion, for σ= 200-1000 km s-1. Even in the lowest-density environments, no more than ∼70 per cent of galaxies show significant Hα emission. Based on these results, we conclude that the present-day correlation between star formation rate and environment is a result of short-time-scale mechanisms that take place preferentially at high redshift, such as starbursts induced by galaxy-galaxy interaction

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death