2,651 research outputs found

    Metabolomics reveals mouse plasma metabolite responses to acute exercise and effects of disrupting AMPK-glycogen interactions

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    Introduction: The AMP-activated protein kinase (AMPK) is a master regulator of energy homeostasis that becomes activated by exercise and binds glycogen, an important energy store required to meet exercise-induced energy demands. Disruption of AMPK-glycogen interactions in mice reduces exercise capacity and impairs whole-body metabolism. However, the mechanisms underlying these phenotypic effects at rest and following exercise are unknown. Furthermore, the plasma metabolite responses to an acute exercise challenge in mice remain largely uncharacterized. Methods : Plasma samples were collected from wild type (WT) and AMPK double knock-in (DKI) mice with disrupted AMPK-glycogen binding at rest and following 30-min submaximal treadmill running. An untargeted metabolomics approach was utilized to determine the breadth of plasma metabolite changes occurring in response to acute exercise and the effects of disrupting AMPK-glycogen binding. Results: Relative to WT mice, DKI mice had reduced maximal running speed (p \u3c 0.0001) concomitant with increased body mass (p \u3c 0.01) and adiposity (p \u3c 0.001). A total of 83 plasma metabolites were identified/annotated, with 17 metabolites significantly different (p \u3c 0.05; FDR \u3c 0.1) in exercised (↑ 6; ↓ 11) versus rested mice, including amino acids, acylcarnitines and steroid hormones. Pantothenic acid was reduced in DKI mice versus WT. Distinct plasma metabolite profiles were observed between the rest and exercise conditions and between WT and DKI mice at rest, while metabolite profiles of both genotypes converged following exercise. These differences in metabolite profiles were primarily explained by exercise-associated increases in acylcarnitines and steroid hormones as well as decreases in amino acids and derivatives following exercise. DKI plasma showed greater decreases in amino acids following exercise versus WT. Conclusion : This is the first study to map mouse plasma metabolomic changes following a bout of acute exercise in WT mice and the effects of disrupting AMPK-glycogen interactions in DKI mice. Untargeted metabolomics revealed alterations in metabolite profiles between rested and exercised mice in both genotypes, and between genotypes at rest. This study has uncovered known and previously unreported plasma metabolite responses to acute exercise in WT mice, as well as greater decreases in amino acids following exercise in DKI plasma. Reduced pantothenic acid levels may contribute to differences in fuel utilization in DKI mice

    Synthesis of the elements in stars: forty years of progress

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    Forty years ago Burbidge, Burbidge, Fowler, and Hoyle combined what we would now call fragmentary evidence from nuclear physics, stellar evolution and the abundances of elements and isotopes in the solar system as well as a few stars into a synthesis of remarkable ingenuity. Their review provided a foundation for forty years of research in all of the aspects of low energy nuclear experiments and theory, stellar modeling over a wide range of mass and composition, and abundance studies of many hundreds of stars, many of which have shown distinct evidence of the processes suggested by B2FH. In this review we summarize progress in each of these fields with emphasis on the most recent developments

    Prescription and Other Medication Use in Pregnancy

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    OBJECTIVE: To characterize prescription and other medication use in a geographically and ethnically diverse cohort of women in their first pregnancy. METHODS: In a prospective, longitudinal cohort study of nulliparous women followed through pregnancy from the first trimester, medication use was chronicled longitudinally throughout pregnancy. Structured questions and aids were used to capture all medications taken as well as reasons they were taken. Total counts of all medications taken including number in each category and class were captured. Additionally, reasons the medications were taken were recorded. Trends in medications taken across pregnancy and in the first trimester were determined. RESULTS: Of the 9,546 study participants, 9,272 (97.1%) women took at least one medication during pregnancy with 9,139 (95.7%) taking a medication in the first trimester. Polypharmacy, defined as taking at least five medications, occurred in 2,915 (30.5%) women. Excluding vitamins, supplements, and vaccines, 73.4% of women took a medication during pregnancy with 55.1% taking one in the first trimester. The categories of drugs taken in pregnancy and in the first trimester include the following: gastrointestinal or antiemetic agents (34.3%, 19.5%), antibiotics (25.5%, 12.6%), and analgesics (23.7%, 15.6%, which includes 3.6%; 1.4% taking an opioid pain medication). CONCLUSION: In this geographically and ethnically diverse cohort of nulliparous pregnant women, medication use was nearly universal and polypharmacy was common

    Characteristics of severe anemia and its association with malaria in young children of the Kassena-Nankana District of northern Ghana.

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    Severe anemia is thought to be the principal underlying cause of malaria death in areas of intense seasonal malaria transmission such as the Kassena-Nankana District of northern Ghana. Factors associated with severe anemia in young children, 6-24 months old, were elucidated by analyzing results of 2 malaria-associated anemia surveys (1996, 2000), separated by 4 years, but conducted in the same community and at the same seasonal time point. Age-adjusted comparison confirmed that the proportion of severely anemic children and overall mean hemoglobin (Hb) levels in the November 2000 sample were significantly improved over those of the 1996 sample (17.5 versus 26.4%, P = 0.03; Hb 7.5 versus 6.9 g/dL, P = 0.002). Weight-for-age Z-scores also indicated a significant improvement in the 2000 sample (-1.93 versus -2.20, P or = 6.0 g/dL, those with severe anemia (Hb < 6.0 g/dL) were older, more frequently parasitemic (odds ratio [OR], 1.60; 95% confidence interval [CI], 1.08-2.35), more often febrile (OR, 2.44; 95% CI, 1.71-3.48), and predominantly male (OR, 1.50; 95% CI, 1.05-2.13). An association was identified in both surveys between severe anemia and residence in the northern part of the district, but no clear link was observed in relation to irrigation. Blood transfusions, a likely surrogate index of severe anemia in young children, followed a distinct seasonal pattern. Evidence suggests that dramatic peaks and troughs of severe anemia are regular and possibly predictable events that may be used to gauge the health and survival of young children in this area

    Organizational preparedness for the use of large language models in pathology informatics

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    In this paper, we consider the current and potential role of the latest generation of Large Language Models (LLMs) in medical informatics, particularly within the realms of clinical and anatomic pathology. We aim to provide a thorough understanding of the considerations that arise when employing LLMs in healthcare settings, such as determining appropriate use cases and evaluating the advantages and limitations of these models. Furthermore, this paper will consider the infrastructural and organizational requirements necessary for the successful implementation and utilization of LLMs in healthcare environments. We will discuss the importance of addressing education, security, bias, and privacy concerns associated with LLMs in clinical informatics, as well as the need for a robust framework to overcome regulatory, compliance, and legal challenges

    Differences in muscle oxygenation between young and middle-aged recreationally active men during high-volume resistance exercise

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    The aim of this study was to compare muscle oxygenation of the vastus lateralis during a high-volume isokinetic resistance exercise protocol (HVP) between young adult (YA) and middle-aged adult (MA) men. Twenty recreationally trained men were assigned to either the YA (age 21.8±2.0 years, body mass 90.7±11.6 kg, body height 179±4.7 cm) or MA (age 47.0±4.4 years, body mass 96.1±21.6 kg, body height 177±7.7 cm) group. The HVP consisted of eight sets of 10 repetitions of unilateral isokinetic concentric knee extension and eccentric knee flexion at 60°·s-1. Changes in tissue hemoglobin saturation index (TSI), tissue oxygenated hemoglobin concentration (O2Hb), deoxygenated hemoglobin (HHb), and muscle oxidation index (O2Hb-HHb) were measured during the exercise session using the near-infrared spectroscopy (NIRS). Data were analyzed using two-way mix factorial analyses of variance. Prior to exercise, TSI was significantly greater (p=.024) for YA compared to MA. Significant decreases in O2Hb and O2Hb-HHb and increases in HHb were observed during each of the eight sets relative to the rest periods (p<.05) for both groups. The average change during the eight sets of the HVP revealed a significantly higher (p=.036) level of HHb and a lower (p=.029) level of O2Hb-HHb for MA compared to YA. A significant negative correlation was also noted at baseline between O2Hb-HHb index and the cross-sectional area of the vastus lateralis muscle (r=-.45, p=.045). During a high- volume resistance exercise, MA experienced reduced muscle oxygen saturation levels compared to YA. These results may be attributed to reductions in local tissue oxidative capacity and reduced blood delivery occurring during middle-age, and possibly due to group differences in muscle morphology

    The role of the g9/2 orbital in the development of collectivity in the A = 60 region: The case of 61Co

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    An extensive study of the level structure of 61Co has been performed following the complex 26Mg(48Ca, 2a4npg)61Co reaction at beam energies of 275, 290 and 320 MeV using Gammasphere and the Fragment Mass Analyzer (FMA). The low-spin structure is discussed within the framework of shell-model calculations using the GXPF1A effective interaction. Two quasi-rotational bands consisting of stretched-E2 transitions have been established up to spins I = 41/2 and (43/2), and excitation energies of 17 and 20 MeV, respectively. These are interpreted as signature partners built on a neutron {\nu}(g9/2)2 configuration coupled to a proton {\pi}p3/2 state, based on Cranked Shell Model (CSM) calculations and comparisons with observations in neighboring nuclei. In addition, four I = 1 bands were populated to high spin, with the yrast dipole band interpreted as a possible candidate for the shears mechanism, a process seldom observed thus far in this mass region
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