Astaxanthin Reduces Heart Rate and Carbohydrate Oxidation Rates During Exercise in Overweight Individuals

International Journal of Exercise Science 16(2): 252-266, 2023. Astaxanthin (AX) is an antioxidant which may spare endogenous carbohydrates and improve fat oxidation rates, thus improving metabolic flexibility. To date, no studies have attempted to examine the impact of AX in an overweight cohort, whom often suffer from metabolic inflexibility. Nineteen subjects (mean ± SD: age: 27.5 ± 6.3 years; height: 169.7 ± 9.0 cm; body mass: 96.4 ± 17.9 kg; BF%: 37.9 ± 7.0%; BMI: 33.4 ± 5.6 kg/m2; VO2peak: 25.9 ± 6.7 ml·kg−1·min−1) were recruited and supplemented with either 12 mg of AX or placebo (PLA) for 4 weeks. Subjects completed a graded exercise test on a cycling ergometer to examine changes in substrate oxidation rates. A total of 5 stages, each lasting 5 min and resistance increased 15 W each stage, were completed to examine changes in levels of glucose and lactate, fat and carbohydrate (CHO) oxidation rates, heart rate, and rating of perceived exertion (RPE). Although there were no changes found in rates of fat oxidation, blood lactate or glucose, or RPE (all p \u3e 0.05), a significant decrease was observed in CHO oxidation from pre to post supplementation in the AX group only. Further, the AX group demonstrated a 7% decrease in heart rate across the graded exercise test. These findings suggest that 4 weeks of AX supplementation may offer some cardiometabolic benefits to overweight individuals, and be a favorable supplement for these individuals beginning an exercise program

FORENSIC PAIN MEDICINE SECTION Original Research Article Societal Costs of Prescription Opioid Abuse, Dependence, and Misuse in the United Statesp me_1075 657..667

Abstract Objectives. The objective of this study was to estimate the societal costs of prescription opioid abuse, dependence, and misuse in the United States. Methods. Costs were grouped into three categories: health care, workplace, and criminal justice. Costs were estimated by 1) quantity method, which multiplies the number of opioid abuse patients by cost per opioid abuse patient; and 2) apportionment method, which begins with overall costs of drug abuse per component and apportions the share associated with prescription opioid abuse based on relative prevalence of prescription opioid to overall drug abuse. Excess health care costs per patient were based on claims data analysis of privately insured and Medicaid beneficiaries. Other data/ information were derived from publicly available survey and other secondary sources. Conclusions. The costs of prescription opioid abuse represent a substantial and growing economic burden for the society. The increasing prevalence of abuse suggests an even greater societal burden in the future

Correction to: The Edinburgh Consensus: preparing for the advent of disease-modifying therapies for Alzheimer's disease.

Since the publication of this article [1], it has come to the attention of the authors that information for one of the authors was not included in the competing interests section. Craig Richie has declared potential competing interests with the following companies; Janssen, Eisai, Pfizer, Eli Lilly, Roche Diagnostics, Boeringher Ingleheim, Novartis, AC Immune, Ixico, Aridhia, Amgen, Berry Consultants, Lundbeck, Sanofi, Quintiles (IQVIA) and Takeda. The full competing interests section for this article can be found below

Creating a model of diseased artery damage and failure from healthy porcine aorta

Large quantities of diseased tissue are required in the research and development of new generations of medical devices, for example for use in physical testing. However, these are difficult to obtain. In contrast, porcine arteries are readily available as they are regarded as waste. Therefore, reliable means of creating from porcine tissue physical models of diseased human tissue that emulate well the associated mechanical changes would be valuable. To this end, we studied the effect on mechanical response of treating porcine thoracic aorta with collagenase, elastase and glutaraldehyde. The alterations in mechanical and failure properties were assessed via uniaxial tension testing. A constitutive model composed of the Gasser-Ogden-Holzapfel model, for elastic response, and a continuum damage model, for the failure, was also employed to provide a further basis for comparison (Calvo and Pena, 2006 and Gasser et al., 2006). For the concentrations used here it was found that: collagenase treated samples showed decreased fracture stress in the axial direction only; elastase treated samples showed increased fracture stress in the circumferential direction only; and glutaraldehyde samples showed no change in either direction. With respect to the proposed constitutive model, both collagenase and elastase had a strong effect on the fibre-related terms. The model more closely captured the tissue response in the circumferential direction, due to the smoother and sharper transition from damage initiation to complete failure in this direction. Finally, comparison of the results with those of tensile tests on diseased tissues suggests that these treatments indeed provide a basis for creation of physical models of diseased arteries

MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis

Myelin loss is associated with axonal damage in established multiple sclerosis. This relationship is challenging to study in vivo in early disease. Here, we ask whether myelin loss is associated with axonal damage at diagnosis, by combining non-invasive neuroimaging and blood biomarkers. We performed quantitative microstructural MRI and single molecule ELISA plasma neurofilament measurement in 73 patients with newly diagnosed, immunotherapy naïve relapsing-remitting multiple sclerosis. Myelin integrity was evaluated using aggregate g-ratios, derived from magnetization transfer saturation (MTsat) and neurite orientation dispersion and density imaging (NODDI) diffusion data. We found significantly higher g-ratios within cerebral white matter lesions (suggesting myelin loss) compared with normal-appearing white matter (0.61 vs 0.57, difference 0.036, 95% CI 0.029 to 0.043, p < 0.001). Lesion volume (Spearman’s rho rs= 0.38, p < 0.001) and g-ratio (rs= 0.24 p < 0.05) correlated independently with plasma neurofilament. In patients with substantial lesion load (n = 38), those with higher g-ratio (defined as greater than median) were more likely to have abnormally elevated plasma neurofilament than those with normal g-ratio (defined as less than median) (11/23 [48%] versus 2/15 [13%] p < 0.05). These data suggest that, even at multiple sclerosis diagnosis, reduced myelin integrity is associated with axonal damage. MRI-derived g-ratio may provide useful additional information regarding lesion severity, and help to identify individuals with a high degree of axonal damage at disease onset. York, Martin et al. simultaneously measured g-ratio and plasma neurofilament in 73 relapsing-remitting multiple sclerosis patients at diagnosis using advanced MRI and single molecule ELISA. They demonstrate that g-ratio of cerebral white matter lesions varies at diagnosis, and show that high g-ratio of lesions is associated with elevated plasma neurofilament

The James Webb Space Telescope Mission: Optical Telescope Element Design, Development, and Performance

The James Webb Space Telescope (JWST) is a large, infrared space telescope that has recently started its science program which will enable breakthroughs in astrophysics and planetary science. Notably, JWST will provide the very first observations of the earliest luminous objects in the Universe and start a new era of exoplanet atmospheric characterization. This transformative science is enabled by a 6.6 m telescope that is passively cooled with a 5-layer sunshield. The primary mirror is comprised of 18 controllable, low areal density hexagonal segments, that were aligned and phased relative to each other in orbit using innovative image-based wavefront sensing and control algorithms. This revolutionary telescope took more than two decades to develop with a widely distributed team across engineering disciplines. We present an overview of the telescope requirements, architecture, development, superb on-orbit performance, and lessons learned. JWST successfully demonstrates a segmented aperture space telescope and establishes a path to building even larger space telescopes.Comment: accepted by PASP for JWST Overview Special Issue; 34 pages, 25 figure

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

The Influence of Manga on the Graphic Novel

This material has been published in The Cambridge History of the Graphic Novel edited by Jan Baetens, Hugo Frey, Stephen E. Tabachnick. This version is free to view and download for personal use only. Not for re-distribution, re-sale or use in derivative works. © Cambridge University PressProviding a range of cogent examples, this chapter describes the influences of the Manga genre of comics strip on the Graphic Novel genre, over the last 35 years, considering the functions of domestication, foreignisation and transmedia on readers, markets and forms

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival