American journal of physiology. Heart and circulatory physiology最新文献

{"title":"Examining oxidative stress as a mechanistic link between sleep irregularity and cardiovascular risk in young adults with chronic anxiety.","authors":"Jacob W Richardson, Emily A Buck, Jennifer B Weggen, Brad T Bakken, Brandon J Fitzpatrick, Raven G Campbell, Ryan S Garten","doi":"10.1152/ajpheart.00006.2026","DOIUrl":"10.1152/ajpheart.00006.2026","url":null,"abstract":"<p><p>Chronic anxiety is a highly prevalent condition in young adults that is often associated with irregular sleep patterns, potentially augmenting cardiovascular disease (CVD) risk. Sleep irregularity is significantly associated with elevated oxidative stress and lower vascular function and blood pressure control in individuals with chronic anxiety. This study examined whether these impairments in vascular function and blood pressure control are driven by elevations in oxidative stress. Twenty-five young adults (24 ± 4 yr) with generalized anxiety disorder (GAD) or elevated GAD symptoms were assessed for total sleep time irregularity (TSTI) via wrist-worn accelerometry and separated into high TSTI and low TSTI groups via median split. Precursors to CVD development including oxidative stress (whole blood superoxide levels), vascular function (exercise-induced flow-mediated dilation), and blood pressure control (cardiovagal baroreflex sensitivity) were evaluated in both groups following both acute antioxidant (alpha-lipoic acid, vitamin C, and vitamin E) or placebo (microcrystalline cellulose) supplementation. The high TSTI group displayed significantly greater oxidative stress, significantly lower vascular function, and significantly lower blood pressure control. Following antioxidant supplementation, oxidative stress and blood pressure control were significantly improved in the high TSTI group, whereas vascular function was significantly improved independent of group. Antioxidant supplementation reduced oxidative stress and normalized blood pressure control differences between groups, implicating oxidative stress as a key mechanism linking sleep irregularity and CVD risk in young adults with chronic anxiety.<b>NEW & NOTEWORTHY</b> This study is the first to identify oxidative stress as a mediator of early cardiovascular disease (CVD) risk associated with total sleep time irregularity (TSTI) in young adults with chronic anxiety. Antioxidant supplementation reduced oxidative stress and improved blood pressure regulation in the high TSTI group. These findings suggest that oxidative stress plays a central role in linking chronic anxiety, sleep irregularity, and elevated CVD risk.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H919-H926"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147289143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ENAC blockade reduces blood pressure and arterial stiffness in adults with obesity and insulin resistance.","authors":"Jaume Padilla, Francisco I Ramirez-Perez, James A Smith, Rogerio N Soares, Mya Burken, Emma Uptergrove, Suhwon Lee, Luis A Martinez-Lemus, Camila Manrique-Acevedo","doi":"10.1152/ajpheart.00084.2026","DOIUrl":"10.1152/ajpheart.00084.2026","url":null,"abstract":"<p><p>Obesity and insulin resistance promote arterial stiffening and hypertension, increasing cardiovascular risk. Activation of the epithelial sodium channel (ENAC) contributes to vascular stiffening in preclinical models, but the vascular effects of ENAC inhibition in adults with obesity and insulin resistance are not well defined. In this phase II, 24-wk, randomized, double-blind, single-center, placebo-controlled trial, 137 adults aged 30-70 yr with overweight or obesity and at least one metabolic syndrome feature were randomized (2:1) to the ENAC inhibitor amiloride (5 mg daily) or placebo. Carotid-femoral pulse wave velocity (cfPWV), blood pressure, and vascular function were assessed at baseline, 12 wk, and 24 wk. Amiloride significantly reduced arterial stiffness, with decreases in cfPWV at 12 and 24 wk, whereas no changes were observed with placebo. Systolic blood pressure was also reduced, with a mean reduction of 5.6 mmHg at 24 wk. Older age was associated with greater reductions in cfPWV and systolic blood pressure. Amiloride increased serum potassium and lowered fasting glucose, but did not significantly affect brachial artery flow-mediated dilation. No severe adverse events were observed. In conclusion, low-dose amiloride improves blood pressure and arterial stiffness in adults with overweight or obesity and features of metabolic syndrome, without major safety concerns. These findings suggest that blood pressure lowering with amiloride is associated with favorable changes in vascular stiffness in this population.<b>NEW & NOTEWORTHY</b> Obesity and insulin resistance accelerate arterial stiffening and hypertension, increasing cardiovascular risk. Activation of the epithelial sodium channel (ENAC) contributes to vascular stiffening in preclinical models, yet the vascular effects of ENAC inhibition in adults with obesity and insulin resistance remain poorly characterized. Here, we demonstrate that low-dose amiloride reduces blood pressure and improves arterial stiffness in adults with overweight or obesity and features of metabolic syndrome, without major safety concerns.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1274-H1282"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13048834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic syndrome and a broken heart: trust your gut or risk your heart.","authors":"Jeffrey D Salomon, Amanda C Karl, Rizwan Ahmad, Dhundy Bastola, Amar B Singh, Paras K Mishra","doi":"10.1152/ajpheart.00482.2025","DOIUrl":"10.1152/ajpheart.00482.2025","url":null,"abstract":"<p><p>Gut dysbiosis is increasingly recognized as a contributor to heart failure; however, its specific role in the development of metabolic syndrome-induced heart failure (MetS-HF) remains poorly defined. A defining feature of MetS-HF is cardiac steatosis, which drives lipotoxicity, maladaptive remodeling, and progressive cardiac dysfunction. This review integrates mechanistic and translational evidence showing how gut microbiota dysbiosis initiates and exacerbates MetS-HF by disrupting lipid homeostasis, leading to myocardial steatosis, metabolic remodeling, cardiomyocyte death, adverse structural remodeling, and impaired cardiac performance. We also highlight how gut dysbiosis promotes systemic inflammation and hypertension, further aggravating cardiac dysfunction in MetS-HF. Finally, we discuss the potential of artificial intelligence, integrative multiomics, and network-based bioinformatics to elucidate the molecular pathways linking gut dysbiosis to MetS-HF and to identify novel therapeutic targets.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1144-H1161"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147363849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Digital thermal monitoring of reactive hyperemia: potential mechanisms and clinical relevance among patients with heart failure with reduced ejection fraction.","authors":"Molly K Courish, Myles W O'Brien","doi":"10.1152/ajpheart.00980.2025","DOIUrl":"10.1152/ajpheart.00980.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1235-H1238"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145861633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blazing through a workout: cannabis and postexercise cardiovascular risk.","authors":"Ian M Greenlund, Gianna C L Migliaccio, Joshua E Gonzalez, Kun Xie, Virend K Somers","doi":"10.1152/ajpheart.00129.2026","DOIUrl":"10.1152/ajpheart.00129.2026","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1141-H1143"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular disease, perceived stress, and physical activity: population-level associations relevant to cardiovascular physiology.","authors":"Rikke Elmose Mols, István Bakos, Morten Madsen, Erzsébet Horváth-Puhó, Henrik Toft Sørensen, Hans Erik Bøtker","doi":"10.1152/ajpheart.01007.2025","DOIUrl":"10.1152/ajpheart.01007.2025","url":null,"abstract":"<p><p>Medical advances have markedly improved survival among patients with cardiovascular disease (CVD). Psychosocial and behavioral factors, including stress and physical activity, are increasingly recognized as key determinants of outcomes in this population. We investigated the association between existing CVD and perceived stress and examined how this association was modulated by physical activity levels in a Danish cohort, accounting for physiological and psychosocial conditions. We analyzed data on 102,650 Danish residents aged 50-65 yr by linking self-reported questionnaire data from the Better Health in Late Life cohort with national health registry data. CVD was identified using hospital discharge diagnoses. Stress was measured with the 10-item Perceived Stress Scale. Physical activity was assessed with a pilot-tested questionnaire. Seven percent of participants had CVD. Compared with those without CVD, they had a higher prevalence of moderate-to-high perceived stress (42% vs. 33%) and a slightly lower prevalence of meeting guideline-recommended physical activity (42% vs. 45%). High stress was associated with physical activity not meeting the recommended level in both groups; however, this association was stronger among those with versus without CVD {prevalence ratio 2.01 [95% confidence interval (CI): 1.89-2.14] vs. 1.52 (95% CI: 1.48-1.56)}. We observed similar associations between stress and cardiovascular risk factors, comorbidity, psychosocial factors, and socioeconomic status. The association between stress and low physical activity persisted after stratification by these conditions. In conclusion, high stress was most strongly associated with low physical activity among adults with CVD. The underlying mechanisms seem to extend beyond physiological pathways and need further investigation.<b>NEW & NOTEWORTHY</b> In this population-based study of over 100,000 Danish adults, participants with cardiovascular disease reported higher perceived stress than those without. Elevated stress was associated with low physical activity across all participants, particularly among those with cardiovascular disease, but also with medical, psychosocial, and behavioral factors. These findings highlight the complex interplay between physiological and nonphysiological determinants of stress, underscoring the importance of integrating stress management and physical activity promotion into cardiovascular prevention and management strategies.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H1222-H1234"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuregulin-1β augments adaptive concentric remodeling and systolic function without exacerbating hypertrophy during pressure overload.","authors":"Lifen Xu, Parisa Aghagolzadeh, Christian Morandi, Jasmin Wagner, Lilia M Lépine, Vincent F M Segers, Gilles W de Keulenaer, Marijke Brink","doi":"10.1152/ajpheart.00371.2025","DOIUrl":"10.1152/ajpheart.00371.2025","url":null,"abstract":"<p><p>Neuregulin-1β (NRG1) improves cardiac output in heart failure patients, yet concerns remain that erythroblastic oncogene B (ErbB) activation may promote maladaptive hypertrophy, particularly during hemodynamic stress. We investigated how NRG1 influences structural, functional, and molecular remodeling during pressure overload. Male and female C57BL/6NRj mice underwent transverse aortic constriction (TAC) or sham surgery and received saline or recombinant NRG1 via osmotic minipumps or daily injection. In male mice, NRG1 increased ejection fraction at 1 and 4 wk after TAC. NRG1 accentuated TAC-induced concentric remodeling without increasing left ventricular weight or cardiomyocyte cross-sectional area. It markedly reduced fibrosis and macrophage infiltration and prevented progression toward early cardiac decompensation. NRG1 amplified TAC-induced <i>Myh7</i> and <i>Nppa</i> expression and also shifted <i>Glut1/Glut4</i> toward their fetal profile. Transcriptomic analysis identified two novel NRG1-regulated genes: NRG1 reversed TAC-induced upregulation of the skeletal muscle gene myosin binding protein C (<i>Mybpc2</i>) and induced the expression of Popeye domain-containing protein 2 (<i>Popdc2</i>). Furthermore, NRG1 increased expression of <i>Gja1</i> and localization of connexin 43 at the intercalated disc, consistent with enhanced electrical coupling. In female mice, NRG1 increased systolic function and regulated similar molecular targets yet did not reduce the modest increase in fibrosis that was observed. In conclusion, our findings show that NRG1 promotes adaptive molecular and structural remodeling under pressure overload and enhances contractile performance without exacerbating hypertrophy. The identification of NRG1-responsive genes linked to contraction and conduction highlights potential mechanisms and supports further exploration of NRG1-based strategies for cardiac disease.<b>NEW & NOTEWORTHY</b> Our study demonstrates that neuregulin-1β (NRG1) enhances systolic function during pressure overload while promoting adaptive remodeling without exacerbating hypertrophy. NRG1 regulates fetal gene programs in both sexes and reduces fibrosis in male mice. The identification of myosin binding protein C (<i>Mybpc2</i>) and Popeye domain-containing protein 2 (<i>Popdc2</i>) as novel NRG1-responsive genes reveals previously unrecognized mechanisms underlying its cardioprotective effects. These findings support further investigation of NRG1-based therapeutic strategies and highlight potential sex-specific responses.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H818-H837"},"PeriodicalIF":4.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A mirrored decision in the newborn heart: divergent cardiovascular paths after early-onset preeclampsia.","authors":"A'Kaychia T Lowery, Junie P Warrington","doi":"10.1152/ajpheart.00058.2026","DOIUrl":"10.1152/ajpheart.00058.2026","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H816-H817"},"PeriodicalIF":4.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Completion of Fontan circulation does not affect the low longitudinal contribution to stroke volume in patients with single ventricles.","authors":"Pia Sjöberg, Petter Frieberg, Zahraa Alsafi, Petru Liuba, Håkan Arheden","doi":"10.1152/ajpheart.00959.2025","DOIUrl":"10.1152/ajpheart.00959.2025","url":null,"abstract":"<p><p>Ventricular function is vital in patients with single ventricles but repeated surgeries and changes in ventricular volume load may change the relation between longitudinal and radial function. To expand the knowledge of cardiac mechanics in this population, the aim of this study was to assess longitudinal and radial contribution to stroke volume using cardiac magnetic resonance (CMR) imaging in patients before and after Fontan operation. We also aimed to assess whether the atrioventricular coupling was intact in these patients despite multiple pericardiotomies. Twelve children underwent CMR before and after completion of Fontan circulation. Endocardial borders of the atria and the ventricle as well as the epicardial border of the heart were delineated. The percentage of the stroke volume attributed to longitudinal and radial function was calculated and pulmonary venous blood flow during the cardiac cycle was assessed. Longitudinal function correlated strongly with atrial filling (<i>r</i>² = 0.90, ICC = 0.92) and its contribution to stroke volume was 40 [38-49] % before and 39 [33-45] % after completion of Fontan circulation (<i>P</i> = 0.092). All patients lacked the late systolic flow peak in the pulmonary veins corresponding to the lack of a normal right ventricle. In conclusion, patients with single ventricles exhibit preserved atrioventricular coupling but the ventricle has lower longitudinal and higher radial contribution to stroke volume as a consequence of the passive pulmonary blood flow relative to healthy hearts. Completion of Fontan circulation does not change this relationship.<b>NEW & NOTEWORTHY</b> This study shows that patients with single ventricles exhibit lower longitudinal systolic function than healthy subjects. The longitudinal contribution to stroke volume was about 40% compared with ∼80% in a normal right ventricle and 60% in a normal left ventricle. This difference is likely related to the passive blood flow through the lungs and did not change after Fontan completion. Furthermore, atrioventricular coupling seems to be preserved despite previous pericardiotomies.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H722-H728"},"PeriodicalIF":4.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146091717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attenuated peripheral vascular responsiveness contributes to baroreflex dysfunction in patients with wild-type transthyretin amyloidosis.","authors":"Jarred J Iacovelli, Jeremy K Alpenglow, Jill Stratford Waldron, Jonah M Simmons, Kanokwan Bunsawat, Spencer J Carter, D Walter Wray","doi":"10.1152/ajpheart.00827.2025","DOIUrl":"10.1152/ajpheart.00827.2025","url":null,"abstract":"<p><p>Autonomic dysfunction is a common clinical feature of wild-type transthyretin amyloidosis (wtATTR) that may include disease-related changes in baroreflex function. We tested the hypothesis that central and peripheral hemodynamic responses to progressive lower-body negative pressure (LBNP; -10, -20, -30, -40 mmHg; 5 min per stage)-induced hypovolemia would be attenuated in patients with wtATTR (<i>n</i> = 13, 74 ± 6 yr) compared with control subjects with HFpEF of nonamyloid etiology (<i>n</i> = 13, 72 ± 4 yr). Changes in heart rate (HR) and stroke volume (SV) during LBNP assessed central cardiac responsiveness, and changes in forearm blood flow (FBF) and vascular conductance (FVC) evaluated peripheral vascular responsiveness. Lower levels of LBNP (-10 and -20 mmHg) were used to evaluate the cardiopulmonary baroreflex, whereas higher levels of LBNP (-30 and -40 mmHg) assessed integrated (cardiopulmonary + arterial) baroreflex function. There were no group differences in LBNP-induced changes in HR or SV at any stage of LBNP (<i>P</i> > 0.05 for all comparisons). Vasoconstriction, as quantified by changes in FVC, was reduced in wtATTR at -30 mmHg (CON, -0.20 ± 0.20 mL/min/mmHg; wtATTR, -0.04 ± 0.17 mL/min/mmHg; <i>P</i> = 0.011) and -40 mmHg (CON, -0.26 ± 0.22 mL/min/mmHg; wtATTR, -0.02 ± 0.20 mL/min/mmHg; <i>P</i> < 0.01). MAP was unchanged across all levels of LBNP in controls, but decreased in the wtATTR group at the highest level of LBNP (<i>P</i> = 0.039). These findings provide new evidence for derangements in integrative baroreflex function beyond what is present in HFpEF from nonamyloid etiology that may contribute to blood pressure dysregulation during orthostasis in wtATTR.<b>NEW & NOTEWORTHY</b> Wild-type transthyretin amyloidosis (wtATTR) is a unique cause of heart failure typically associated with orthostatic hypotension, likely implicating baroreflex dysfunction; however, this is yet to be investigated. Using the lower-body negative pressure technique to simulate orthostatic stress, we have identified impaired peripheral vascular responsiveness, which occurred in tandem with an inability to arterial blood pressure, suggesting that diminished sympathetic vasomotor responsiveness likely contributes to baroreflex dysfunction and impaired blood pressure regulation in patients with wtATTR.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H788-H798"},"PeriodicalIF":4.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146091726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}