Pulse最新文献

{"title":"Effectiveness of Vitamin D Supplementation for Cardiovascular Health Outcomes.","authors":"Panagiota Veloudi,&nbsp;Graeme Jones,&nbsp;James E Sharman","doi":"10.1159/000452742","DOIUrl":"https://doi.org/10.1159/000452742","url":null,"abstract":"<p><p>There is a plausible physiological theory, supported by many observational studies, that vitamin D supplementation should be effective for improving cardiovascular end points, such as blood pressure (BP), large artery stiffness, atherosclerosis, endothelial function and clinical events. However, results from randomised controlled trials (RCTs) have been inconsistent. In this review, we evaluated the evidence regarding the effectiveness of vitamin D supplementation for cardiovascular surrogate and hard clinical end points. RCTs were assessed in terms of sample size, duration of supplementation, baseline vitamin D level inclusion criteria (i.e., absence of vitamin D deficiency), dosage of vitamin D and population under investigation. Forty-five RCTs were identified. Eight RCTs with BP and 6 RCTs with large artery stiffness as the end points were found to comply with guidelines for the optimal design of clinical trials evaluating nutrient effects. Only 2 of the RCTs with an optimal design were effective in decreasing BP with vitamin D supplementation, although these were of moderate sample size (<150) and very short duration (8 weeks for both), whilst no RCT was effective in reducing large artery stiffness. Similar results were observed for atherosclerotic and endothelial function markers as end points. Only 1 RCT reported cardiovascular events as an end point and found neither increased nor decreased incident cardiovascular events over 7 years of follow-up. In conclusion, results from published RCTs indicate that vitamin D supplementation is ineffective in improving cardiovascular health among various patient populations, including in the presence or absence of vitamin D deficiency.</p>","PeriodicalId":29774,"journal":{"name":"Pulse","volume":"4 4","pages":"193-207"},"PeriodicalIF":2.2,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000452742","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34756851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular Effects of Long-Term Vitamin D Supplementation: Summarised by Many but Studied by Few.","authors":"Mark Butlin,&nbsp;Alberto P Avolio","doi":"10.1159/000452939","DOIUrl":"https://doi.org/10.1159/000452939","url":null,"abstract":"Vitamin D supplementation has been primarily studied for its effect on mineral metabolism and, therefore, bone resorption. Vitamin D is also known to play a role in the reninangiotensin-aldosterone system [1] and in inflammation [2] and is produced by vascular endothelial cells [3] . It is, therefore, a strong hypothesis that plasma vitamin D levels influence cardiovascular factors in terms of blood pressure, vascular function and cardiovascular risk. In this issue of Pulse , Veloudi et al. [4] provide a qualitative review of a selection of randomised controlled trials (RCTs) concerning the effect of vitamin D supplementation on blood pressure and measures of arterial stiffness. They also include a descriptive review of some studies concerning cardiovascular outcomes of low serum levels of vitamin D. The article presents a graphical representation of sample size and study duration of 36 studies investigating peripheral blood pressure and 9 studies investigating arterial stiffness. In so doing, the article highlights that very few of these studies show a beneficial effect of vitamin D supplementation. The graphical presentation of the data also allows a visual representation of the previous finding, demonstrated statistically, that there is no relationship between an increased dose of vitamin D supplement and beneficial cardiovascular effect [5] . The effect of vitamin D supplementation on cardiovascular factors is of great clinical interest, demonstrated by the number of studies identified in meta-analyses in recent years. This year alone, quantitative meta-analyses of arterial stiffness outcomes have been published by Upala et al. [6] and Rodríguez et al. [7] summarising 7 and 18 RCTs, respectively. A recent quantitative meta-analysis on peripheral blood pressure outcomes identified 46 independent vitamin D supplementation trials [5] . These quantitative studies, although not included in the review by Veloudi et al. [4] , support the same conclusion which Veloudi et al. [4] make from a qualitative review of RCTs, namely that vitamin D supplementation has no effect on arterial stiffness or blood pressure. However, Rodríguez et al. [7] surmise that larger, well-designed Received: October 28, 2016 Accepted: October 28, 2016 Published online: December 8, 2016","PeriodicalId":29774,"journal":{"name":"Pulse","volume":"4 4","pages":"172-174"},"PeriodicalIF":2.2,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000452939","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34756918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comparative Study on Skin and Plasma Advanced Glycation End Products and Their Associations with Arterial Stiffness.","authors":"Chang-Yuan Liu,&nbsp;Qi-Fang Huang,&nbsp;Yi-Bang Cheng,&nbsp;Qian-Hui Guo,&nbsp;Qi Chen,&nbsp;Yan Li,&nbsp;Ji-Guang Wang","doi":"10.1159/000453581","DOIUrl":"https://doi.org/10.1159/000453581","url":null,"abstract":"<p><strong>Background: </strong>We compared skin and plasma measurements of advanced glycation end products (AGEs), with particular focus on their levels in the presence of hypertension or diabetes and prediabetes and their associations with arterial stiffness in outpatients with suspected or diagnosed hypertension.</p><p><strong>Methods: </strong>Skin AGE accumulation was measured as autofluorescence on the left forearm using the skin autofluorescence Reader and expressed in arbitrary units in the range from 0 to 25. Plasma AGE concentration was measured by the enzyme-linked immunosorbent assay method and logarithmically transformed for statistical analysis. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV) using the SphygmoCor system (Sydney, Australia).</p><p><strong>Results: </strong>The 218 participants (96 [44.0%] men, mean age 51.9 years) had a mean skin autofluorescence of 1.89 arbitrary units, plasma AGE concentration of 4.47 μg/ml, and cfPWV of 8.0 m/s. Skin autofluorescence was significantly correlated with plasma AGEs in diabetic or prediabetic patients (<i>n</i> = 31, <i>r</i> = 0.37, <i>p</i> = 0.04) but not in subjects with normoglycemia (<i>n</i> = 187, <i>r</i> = -0.05, <i>p</i> = 0.48). Nonetheless, both measurements were significantly (<i>p</i> ≤ 0.001) higher in men (2.00 arbitrary units and 6.73 μg/ml, respectively) than women (1.81 arbitrary units and 3.60 μg/ml, respectively) and in diabetic or prediabetic (2.03 arbitrary units and 6.61 μg/ml, respectively) than normoglycemia subjects (1.87 arbitrary units and 4.17 μg/ml, respectively), but similar in hypertensive (<i>n</i> = 105) and normotensive subjects (<i>n</i> = 113, <i>p</i> ≥ 0.35). In adjusted multiple regression analyses, plasma AGE concentration, but not skin autofluorescence (<i>p</i> ≥ 0.37), was significantly associated with cfPWV in all subjects (β 0.44 m/s for each 10-fold increase; <i>p</i> = 0.04) and in subgroups of men and diabetes and prediabetes (β 0.12-0.55 m/s for each 10-fold increase; <i>p</i> ≤ 0.02).</p><p><strong>Conclusions: </strong>Although skin and plasma AGEs were similarly associated with gender and diabetes or prediabetes, they might measure something different and have different clinical relevance, such as for arterial stiffness.</p>","PeriodicalId":29774,"journal":{"name":"Pulse","volume":"4 4","pages":"208-218"},"PeriodicalIF":2.2,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000453581","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34756852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Epoch for Arterial Stiffness Measurement in the Clinic.","authors":"Jeong Bae Park,&nbsp;Kazuomi Kario","doi":"10.1159/000448497","DOIUrl":"https://doi.org/10.1159/000448497","url":null,"abstract":"Age changes the vascular structure and function in the normal population, but it has a different effect on wave reflection and pulse wave transmission [1, 2] . Many longitudinal studies have found that arterial stiffness measurement among hypertensive patients, diabetic patients, healthy elderly, and people with high cardiovascular (CV) risk will better evaluate arterial health and predict CV events. European guidance for arterial stiffness measurements described in the European consensus document (2006) [3] , the publication of the international reference standards (2010) [4] and the American Heart Association (AHA) scientific statement on arterial stiffness measurements in the USA (2015) have standardized arterial measurement [5] , and thus arterial stiffness measurements have been more widely used in clinical settings. The question now is which measurement of arterial stiffness is more accurate to precisely predict future CV events. Most of the guidelines designated aortic pulse wave velocity (PWV; carotid-femoral PWV) as the golden standard (especially in the Western society) [6] , but in Japan, where arterial stiffness is the most widely used and where they achieved a great amount of data on brachial-ankle PWV and cardio-ankle vascular index (CAVI) [7] , studies found a relationship between organ damage and future CV events. Townsend’s [8] brief review on recommendations and standardization of PWV measurements also justified its clinical and scholarly use. The articles from Korea [9] and Thailand [10] describe CV risk factors and outcomes using the CAVI. The modified RAMA-EGAT score from Thailand combined the conventional risk prevention model with arterial function. It would be helpful to have ageand genderstratified values of the CAVI in healthy Koreans and in high-risk patients of a metabolically risky condition. The study from Thailand developed its own risk prediction model called the RAMA-EGAT score, which proved to be accurate in the prediction of CV risk in patients with intermediate atherosclerotic risk factors in the Thai population [11] , and a further modification of the RAMA-EGAT score with the CAVI enhanced its accuracy. Now they are conducting a long-term prognosis study in patients with diverse risk conditions. The Framingham-CAVI Published online: December 23, 2016 www.karger.com/pls DOI: 10.1159/000448497","PeriodicalId":29774,"journal":{"name":"Pulse","volume":"4 Suppl 1","pages":"1-2"},"PeriodicalIF":2.2,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000448497","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34796178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of Arterial Stiffness Using the Cardio-Ankle Vascular Index.","authors":"Toru Miyoshi,&nbsp;Hiroshi Ito","doi":"10.1159/000445214","DOIUrl":"https://doi.org/10.1159/000445214","url":null,"abstract":"<p><strong>Background: </strong>Arterial stiffness is an independent predictor of outcomes for patients with cardiovascular disease. Although measurement of pulse wave velocity is a widely accepted, noninvasive approach for the assessment of arterial stiffness, its accuracy is affected by changes in blood pressure.</p><p><strong>Summary: </strong>The cardio-ankle vascular index (CAVI) is an index of the overall stiffness of the artery from the origin of the aorta to the ankle and is theoretically independent of blood pressure at the time of measurement. CAVI increases linearly with age and is elevated even in mild arteriosclerotic disease. It can identify differences in the degree of arteriosclerosis among patients with severe arteriosclerotic disease and better reflects the severity of disease of the coronary artery than does brachial-ankle pulse wave velocity. Patients with higher CAVI values show a poor prognosis compared with those with lower CAVI values. Furthermore, CAVI can be lowered by controlling diabetes mellitus and hypertension.</p><p><strong>Key messages: </strong>The primary aims of assessing arterial stiffness using CAVI are to assist in the early detection of arteriosclerosis, allowing timely treatment and lifestyle modification, and to quantitatively evaluate the progression of disease and the effectiveness of treatment. Whether CAVI-guided therapy can improve prognosis in high-risk patients needs to be further examined to confirm the clinical usefulness of this measure.</p>","PeriodicalId":29774,"journal":{"name":"Pulse","volume":" ","pages":"11-23"},"PeriodicalIF":2.2,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000445214","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34624855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carotid Stiffness: A Novel Cerebrovascular Disease Risk Factor.","authors":"Thomas T van Sloten,&nbsp;Coen D A Stehouwer","doi":"10.1159/000445354","DOIUrl":"https://doi.org/10.1159/000445354","url":null,"abstract":"<p><p>Carotid stiffening is considered an important element in the pathogenesis of cerebrovascular diseases. These include stroke as well as vascular dementia and depression. However, results of individual studies evaluating the association between carotid stiffening and incident stroke have been inconsistent. Therefore, we have conducted a systematic review and meta-analysis, showing that carotid stiffening is associated with incident stroke independently of cardiovascular risk factors and aortic stiffness. In addition, carotid stiffening improved stroke risk prediction beyond the Framingham stroke risk factors and aortic stiffness. Other studies have shown that carotid stiffening is associated with a higher incidence of vascular dementia and depressive symptoms. This suggests that carotid stiffness is a potential separate target for prevention strategies of cerebrovascular disease. </p>","PeriodicalId":29774,"journal":{"name":"Pulse","volume":" ","pages":"24-7"},"PeriodicalIF":2.2,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000445354","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34624856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relation of Habitual Chocolate Consumption to Arterial Stiffness in a Community-Based Sample: Preliminary Findings.","authors":"Georgina E Crichton,&nbsp;Merrill F Elias,&nbsp;Ala'a Alkerwi,&nbsp;Saverio Stranges,&nbsp;Walter P Abhayaratna","doi":"10.1159/000445876","DOIUrl":"https://doi.org/10.1159/000445876","url":null,"abstract":"<p><strong>Background: </strong>The consumption of chocolate and cocoa has established cardiovascular benefits. Less is known about the effects of chocolate on arterial stiffness, a marker of subclinical cardiovascular disease. The aim of this study was to investigate whether chocolate intakes are independently associated with pulse wave velocity (PWV), after adjustment for cardiovascular, lifestyle and dietary factors.</p><p><strong>Methods: </strong>Prospective analyses were undertaken on 508 community-dwelling participants (mean age 61 years, 60% women) from the Maine-Syracuse Longitudinal Study (MSLS). Habitual chocolate intakes, measured using a food frequency questionnaire, were related to PWV, measured approximately 5 years later.</p><p><strong>Results: </strong>Chocolate intake was significantly associated with PWV in a non-linear fashion with the highest levels of PWV in those who never or rarely ate chocolate and lowest levels in those who consumed chocolate once a week. This pattern of results remained and was not attenuated after multivariate adjustment for diabetes, cardiovascular risk factors and dietary variables (p = 0.002).</p><p><strong>Conclusions: </strong>Weekly chocolate intake may be of benefit to arterial stiffness. Further studies are needed to explore the underlying mechanisms that may mediate the observed effects of habitual chocolate consumption on arterial stiffness.</p>","PeriodicalId":29774,"journal":{"name":"Pulse","volume":" ","pages":"28-37"},"PeriodicalIF":2.2,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000445876","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34624857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The J-Curve Phenomenon in Hypertension.","authors":"Yuan-Yuan Kang,&nbsp;Ji-Guang Wang","doi":"10.1159/000446922","DOIUrl":"https://doi.org/10.1159/000446922","url":null,"abstract":"<p><p>Almost immediately after antihypertensive therapy was proven effective in preventing cardiovascular events, the J-curve issue emerged as a hot topic. The Hypertension Optimal Treatment (HOT) trial attempted to address this question (diastolic blood pressure <80, <85, and <90 mm Hg) but ended up with a post hoc analysis indicating a nadir of 138.5 mm Hg systolic and 82.6 mm Hg diastolic blood pressure. Nevertheless, this observational finding was supported by the results of observational studies in the general population and by post hoc analyses of antihypertensive treatment trials. The currently ongoing Systolic Hypertension Optimal Treatment (SHOT) trial investigates whether the relationship between systolic blood pressure and stroke recurrence is linear or J-shaped by treating systolic blood pressure to <125, <135, and <145 mm Hg in patients with a history of recent stroke. This trial may provide additional but probably inconclusive evidence, because optimal blood pressure might differ between individuals and across outcomes. Nevertheless, a universal beneficial, instead of optimal, level of blood pressure for antihypertensive treatment may exist approximating 130/80 mm Hg and should be investigated by comparing 130/80 mm Hg with 140/90 mm Hg as a target blood pressure in hypertensive patients with the simultaneous use of modern blood pressure measuring techniques, such as home and ambulatory blood pressure monitoring. </p>","PeriodicalId":29774,"journal":{"name":"Pulse","volume":" ","pages":"49-60"},"PeriodicalIF":2.2,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000446922","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34624859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Within-Home Blood Pressure Variability on a Single Occasion Has Clinical Significance.","authors":"Seiichi Shibasaki,&nbsp;Satoshi Hoshide,&nbsp;Kazuomi Kario","doi":"10.1159/000445837","DOIUrl":"https://doi.org/10.1159/000445837","url":null,"abstract":"<p><p>There is growing evidence that diversely defined blood pressure variability (BPV) is an independent predictor of hypertensive target organ damage (TOD) and cardiovascular events. Several mechanisms have been speculated to underlie episodes of increased BPV, including the impairment of autonomic or hormonal regulation, renal dysfunction, and increased arterial stiffness. Within-home BPV, defined as differences in BP values obtained on a single occasion at home, could have prognostic significance for hypertensive TOD. It is typically thought that BP values are decreased with repeated measurements on a single occasion at home, but in the present subanalysis of 4,149 J-HOP (Japan Morning Surge-Home Blood Pressure) study patients, approximately 20% of the patients' home BP values were increased or unchanged by repeated measurements on a single occasion. In addition, those patients were likely to have hypertensive TOD. Thus, home BP measurement should be taken twice or more to detect the increase trend in home BP, which has been defined as within-home BPV. </p>","PeriodicalId":29774,"journal":{"name":"Pulse","volume":" ","pages":"38-42"},"PeriodicalIF":2.2,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000445837","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34624858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anatomical and Functional Estimations of Brachial Artery Diameter and Elasticity Using Oscillometric Measurements with a Quantitative Approach.","authors":"Keiichiro Yoshinaga,&nbsp;Satoshi Fujii,&nbsp;Yuuki Tomiyama,&nbsp;Keisuke Takeuchi,&nbsp;Nagara Tamaki","doi":"10.1159/000444368","DOIUrl":"https://doi.org/10.1159/000444368","url":null,"abstract":"<p><p>Noninvasive vascular function measurement plays an important role in detecting early stages of atherosclerosis and in evaluating therapeutic responses. In this regard, recently, new vascular function measurements have been developed. These new measurements have been used to evaluate vascular function in coronary arteries, large aortic arteries, or peripheral arteries. Increasing vascular diameter represents vascular remodeling related to atherosclerosis. Attenuated vascular elasticity may be a reliable marker for atherosclerotic risk assessment. However, previous measurements for vascular diameter and vascular elasticity have been complex, operator-dependent, or invasive. Therefore, simple and reliable approaches have been sought. We recently developed a new automated oscillometric method to measure the estimated area (eA) of a brachial artery and its volume elastic modulus (VE). In this review, we further report on this new measurement and other vascular measurements. We report on the reliability of the new automated oscillometric measurement of eA and VE. Based on our findings, this measurement technique should be a reliable approach, and this modality may have practical application to automatically assess muscular artery diameter and elasticity in clinical or epidemiological settings. In this review, we report the characteristics of our new oscillometric measurements and other related vascular function measurements. </p>","PeriodicalId":29774,"journal":{"name":"Pulse","volume":" ","pages":"1-10"},"PeriodicalIF":2.2,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000444368","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34624854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}