Search

Chronic low-grade systemic inflammation plays a role in the development of cardiovascular (CV) disease. Habitual endurance exercise training reduces the risk of CV disease in part through anti-inflammatory mechanisms. The purpose of this study was to investigate the effects of age, endurance training status, and their interaction on pro-inflammatory plasma cytokines involved in the pathogenesis of CV disease. Subjects were BMI-matched young (25 ± 3 years, endurance trained: n = 9,sedentary: n = 11) and older (62 ± 5 years, endurance-trained: n = 12,sedentary: n = 11) men. Plasma cytokine concentrations were determined by multiplex cytometric bead assay. Soluble intercellular adhesion molecule-1 (sICAM-1) levels were 40 % higher in sedentary older men compared to young sedentary subjects ( P = 0.048),but they were not different between the young and older trained men. Furthermore,sICAM-1 levels were negatively correlated with maximal oxygen uptake (V' O 2 max,r = - 0.38,P = 0.01) across all subjects. There were no significant differences among the groups in plasma concentrations of monocyte chemoattractant protein-1 (MCP-1),soluble tumor necrosis-α receptor (sTNFR),soluble CD40 ligand (sCD40L),orresistin. We conclude that habitual endurance training is associated with an attenuated agerelated increase in plasma sICAM-1. [ABSTRACT FROM AUTHOR]

Lakes emit substantial amounts of carbon dioxide (CO 2 ) into the atmosphere, but why they do remains debated. The long-standing vision of lakes as solely respirators of the organic matter leaking from the soils has been challenged by evidence that inorganic carbon produced by weathering of the catchment bedrock could also support lake CO 2 emissions. How inorganic carbon inputs ultimately generate lake CO 2 outgassing remains a blind spot. We develop and introduce a calcite module in a coupled one-dimensional physical-biogeochemical model that we use to simulate the carbon cycle of the large Lake Geneva over the past 40 years. We mechanistically demonstrate how the so-far neglected process of calcite precipitation boosts net CO 2 emissions at the annual scale. Far from being anecdotal, we show that calcite precipitation could explain CO 2 outgassing across various lakes globally, including some of the largest lakes in the world.

Extracellular vesicles (EVs) carry diverse biomolecules derived from their parental cells, making their components excellent biomarker candidates. However, purifying EVs is a major hurdle in biomarker discovery since current methods require large amounts of samples, are time-consuming and typically have poor reproducibility. Here we describe a simple, fast, and sensitive EV fractionation method using size exclusion chromatography (SEC) on a fast protein liquid chromatography (FPLC) system. Our method uses a Superose 6 Increase 5/150, which has a bed volume of 2.9 mL. The FPLC system and small column size enable reproducible separation of only 50 µL of human plasma in 15 min. To demonstrate the utility of our method, we used longitudinal samples from a group of individuals who underwent intense exercise. A total of 838 proteins were identified, of which, 261 were previously characterized as EV proteins, including classical markers, such as cluster of differentiation (CD)9 and CD81. Quantitative analysis showed low technical variability with correlation coefficients greater than 0.9 between replicates. The analysis captured differences in relevant EV proteins involved in response to physical activity. Our method enables fast and sensitive fractionation of plasma EVs with low variability, which will facilitate biomarker studies in large clinical cohorts., (© 2024 Battelle Memorial Institute. PROTEOMICS published by Wiley‐VCH GmbH.)

The year of 2023 displayed the highest average global temperatures since it has been recorded-the duration and severity of extreme heat are projected to increase. Rising global temperatures represent a major public health threat, especially to occupations exposed to hot environments, such as construction and agricultural workers, and first responders. Despite efforts of the scientific community, there is still a need to characterize the pathophysiological processes leading to heat related illness and develop biomarkers that can predict its onset. Here, we performed a plasma lipidomic analysis on male and female subjects who underwent heat tolerance testing (HTT), consisting of a 2-h treadmill walk at 5 km/h with 2% inclination at a controlled temperature of 40°C. We identified 995 lipids from 27 classes, with nearly half of all detected lipids being responsive to HTT. Lipid classes related to substrate utilization were predominantly affected by HTT, with a downregulation of triacylglycerols and upregulation of free fatty acids and acyl-carnitines (CARs). We additionally examined correlations between changes in plasma lipids by using the physiological strain index (PSI). Here, even chain CAR 4:0, 14:0 and 16:1, suggested by-products of incomplete beta oxidation, and diacylglycerols displayed the highest correlation to PSI. PSI did not correlate with plasma lactate levels, suggesting that correlations between even chain CARs and PSI is related to metabolic efficiency versus physical exertion. Overall, our results show that HTT has a strong impact on the plasma lipidome and that metabolic inefficiencies may underlie heat intolerance., Competing Interests: Competing interests The authors declare that they have no competing interests.

In hardwater lakes, calcite precipitation is an important yet poorly understood process in the lacustrine carbon cycle, in which catchment-derived alkalinity (Alk) is both transformed and translocated. While the physico-chemical conditions supporting the supersaturation of water with respect to calcite are theoretically well described, the magnitude and conditions underlying calcite precipitation at fine temporal and spatial scales are poorly constrained. In this study, we used high frequency, depth-resolved (0-30 m) data collected over 18 months (June 2019 - November 2020) in the deeper basin of Lake Geneva to describe the dynamics of calcite precipitation fluxes at a fine temporal resolution (day to season) and to scale them to carbon fixation by primary production. Calcite precipitation occurred during the warm stratified periods when surface water CO 2 concentrations were below atmospheric equilibrium. Seasonally, the extent of Alk loss due to calcite precipitation (i.e., [30-42] g C m -2 ) depended upon the level of Alk in surface waters. Moreover, interannual variability in seasonal calcite precipitation depended on the duration of stratification, which determined the volume of the water layer susceptible to calcite precipitation. At finer timescales, calcite precipitation was characterized by marked daily variability with dynamics strongly related to that of planktonic autotrophic metabolism. Increasing daily calcite precipitation rates (i.e., maximum values 9 mmol C m -3 d -1 ) coincided with increasing net ecosystem production (NEP) during periods of enhanced water column stability. In these conditions, calcite precipitation could remove as much inorganic carbon from the productive layers as NEP. This study provides mechanistic insights into the conditions driving pelagic calcite precipitation, and quantifies its essential contribution to the coupling of organic and inorganic carbon cycling in lakes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Medically underserved (US) populations have an increased level of atherosclerotic cardiovascular disease (ASCVD) risk, however, few studies investigated ASCVD risk reduction in US., Methods: Of 217 subjects with ApoB ≥120 mg/dL and carotid atherosclerosis (≥15% stenosis by ultrasound) enrolled in the Carotid Plaque Composition by MRI (CPC) study between 2005 and 2011, US (n=33) was defined as those without adequate healthcare insurance, while AS (n=184) included those with adequate healthcare coverage. All subjects received atorvastatin-based lipid therapies and lifestyle intervention for 2 years. Metabolic and inflammatory risk factors were compared between AS and US., Results: At baseline, compared to AS, US displayed higher levels of metabolic and inflammatory risk including systolic blood pressure (140±27 vs. 131±18 mmHg, p=0.04), fasting glucose (125±59 vs. 102±22 mg/dL, p=0.03) and fasting insulin (39±33 vs. 28±20 µU/dL, p=0.03) which resulted in higher insulin resistance (HOMA-IR 2.2±0.4 vs. 1.3±0.1, p=0.03), and hsCRP (5.6±1.5 vs. 2.8±0.2 mg/L, p=0.03). Over 2 years of intervention, US and AS showed similar reductions in LDL-C (-10.7% vs. -16% per year, p=0.2), triglycerides (-16.7% vs. -15.9% per year, p=0.4), and hsCRP (-0.11% vs. -0.04% per year, p=0.1). However, US continued to show significantly higher levels of fasting blood glucose (115±6.0 vs. 101±2.0 mg/dL, p=0.03) and HOMA-IR (1.9±0.2 vs. 1.5±0.1, p=0.047), and hsCRP (3.9±0.7 vs. 1.9±0.2 mg/L, p<0.001) than AS following 2 years of interventions., Conclusions: US displayed higher ASCVD risk than AS at baseline and over 2 years despite similar reductions following the intervention. These findings highlight the unmet needs for improved intervention strategies and implementation methods for ASCVD risk reduction in US., Clinical Trial Registration: NCT00715273 at ClinicalTrials.gov., Competing Interests: Michael P. Chu: None Gina Many: None Daniel A Isquith: None Susan McKeeth: None Jayne Williamson: None Moni B Neradilek: None Patrick Colletti: None Xue-Qiao Zhao: Research grants from Amgen, AstraZeneca, and Novartis., (© 2021 The Authors.)

Background: The incidence of mucinous appendiceal adenocarcinomas (MAA) has increased over the past three decades. Advanced stage tumor diagnosis is likely attributable to non-specific findings. Here we describe advanced stage appendiceal MAA presenting as inguinal ulcers, scrotal abscesses, and other nonspecific symptoms. To our knowledge, this is the first report of MAA presenting as inguinal pain with inflamed phlegmonous tissue and scrotal abscess., Case Presentation: A 67-year-old male presented to a rural facility complaining of weight-loss, fatigue, hematuria, dysuria, painful right inguinal ulceration, and right scrotal abscess drainage. Computed tomography of the abdomen and pelvis revealed a distended appendix (> 1.3 cm) and a fistula between the appendix, urinary bladder, right scrotum, and right groin. Laparoscopic appendectomy was performed and diagnosed as MAA. After a right hemicolectomy, the MAA was staged as pT3b pN0 M0 G2., Conclusion: This case highlights a unique presentation of late stage appendiceal MAA. Due to the increased incidence of appendiceal MAAs, reports of unique clinical features are needed to facilitate early diagnosis and intervention, especially in rural settings with limited access to specialists.

Epigenomic regulation of the transcriptome by DNA methylation and posttranscriptional gene silencing by miRNAs are potential environmental modulators of skeletal muscle plasticity to chronic exercise in healthy and diseased populations. We utilized transcriptome networks to connect exercise-induced differential methylation and miRNA with functional skeletal muscle plasticity. Biopsies of the vastus lateralis were collected from middle-aged Polynesian men and women with morbid obesity (44 kg/m(2) ± 10) and Type 2 diabetes before and following 16 wk of resistance (n = 9) or endurance training (n = 8). Longitudinal transcriptome, methylome, and microRNA (miRNA) responses were obtained via microarray, filtered by novel effect-size based false discovery rate probe selection preceding bioinformatic interrogation. Metabolic and microvascular transcriptome topology dominated the network landscape following endurance exercise. Lipid and glucose metabolism modules were connected to: microRNA (miR)-29a; promoter region hypomethylation of nuclear receptor factor (NRF1) and fatty acid transporter (SLC27A4), and hypermethylation of fatty acid synthase, and to exon hypomethylation of 6-phosphofructo-2-kinase and Ser/Thr protein kinase. Directional change in the endurance networks was validated by lower intramyocellular lipid, increased capillarity, GLUT4, hexokinase, and mitochondrial enzyme activity and proteome. Resistance training also lowered lipid and increased enzyme activity and caused GLUT4 promoter hypomethylation; however, training was inconsequential to GLUT4, capillarity, and metabolic transcriptome. miR-195 connected to negative regulation of vascular development. To conclude, integrated molecular network modelling revealed differential DNA methylation and miRNA expression changes occur in skeletal muscle in response to chronic exercise training that are most pronounced with endurance training and topographically associated with functional metabolic and microvascular plasticity relevant to diabetes rehabilitation., (Copyright © 2014 the American Physiological Society.)

Unlabelled: We initiated a pilot study to investigate the effects of 8 wks of aerobic exercise training (ET) on insulin sensitivity and inflammatory markers in obese and insulin-resistant minority adolescents. Eleven morbidly obese (BMI 41.4 ± 1.8 kg/m2) minority adolescents were entered into a supervised ET intervention (~180 min/wk at 40-55%VO2PeakR [(VO2Peak-VO2Rest)/VO2Rest]). The effects of training on insulin sensitivity (SI), inflammation and other metabolic syndrome features were examined., Results: Insulin action improved in response to training, as indicated by a ~37% increase in SI (p = .018). Plasma levels of several proinflammatory cytokines were reduced in response to ET, as indicated by significant decrements in sTNF-R, CCL2, MPO, IL-6, resistin, and leptin, with no significant changes in hsCRP. ET induced reductions in BMI and percent total body fat., Conclusions: The present study supports the efficacy of ET interventions on metabolic syndrome features in morbidly obese minority youth.

The SORT1 locus was originally identified by genome-wide association studies of low-density lipoprotein cholesterol (LDL-C) in adults. Although the effect sizes of this locus are relatively small, we hypothesized that a younger population would show a greater genetic effect because of fewer confounding variables. As such, we investigated the association between the SORT1 locus and LDL-C in a group of healthy young adults. Subjects (n = 122, mean age = 23.2 years) were recruited from the University of Calgary. Lipid measures and genomic DNA were collected from peripheral blood after an overnight fast. Blood pressure, percent body fat (%BF), and maximal oxygen consumption were also measured. Associations between genotype and LDL-C were investigated using linear regression. Nearly one half (42.9%) of the female and 21.7% of the male subjects had a %BF that was above a healthy range. More than one quarter of the subjects had LDL-C values that were considered nonoptimal. Although the association was not significant when both sexes were combined, a significant association was observed between the SORT1 locus (GG: 2.46 ± 0.11 mmol·L(-1) vs. GT-TT: 2.06 ± 0.12 mmol·L(-1), p = 0.016) and LDL-C in male subjects, with genotype explaining 3.0% of the variability in LDL-C. A high prevalence of nonoptimal LDL-C exists in this young population even though it is otherwise fit and healthy. A significant association was found between LDL-C and the minor SORT1 allele in male subjects, with an effect size larger than previously reported in older populations. SORT1 is a valuable target for identifying individuals who would most benefit from early interventions to prevent cardiovascular disease.