Current Hypertension Reviews最新文献

{"title":"Relationship between Augmentation Index and Wall Thickening Fraction during Hypotension in an Animal Model of Myocardial Ischemia-Reperfusion and Heart Failure.","authors":"Sandra Wray,&nbsp;Elena Lascano,&nbsp;Jorge Negroni,&nbsp;Edmundo C Fischer","doi":"10.2174/1573402117666210322161445","DOIUrl":"https://doi.org/10.2174/1573402117666210322161445","url":null,"abstract":"<p><strong>Aims: </strong>Non-invasive indices to evaluate left ventricular changes during ischemic heart failure are needed to quantify the myocardial impairment and the effectiveness of therapeutic manoeuvres. The aims of this work were to calculate the Wall Thickening Fraction (WTF) and the Augmentation Index (AIx) and to assess the relationship between WTF and AIx using data obtained from an animal model with heart failure followed by a myocardial ischemia stage and a reperfusion stage.</p><p><strong>Methods: </strong>Nine Corriedale sheep that had been monitored for 10 minutes during a basal stage underwent 5-minute myocardial ischemia, followed by 60-minute reperfusion. Seven of them were subjected to an induced heart failure through an overdose of halothane, two of which were treated with intra-aortic counterpulsation during the reperfusion stage. The remaining two animals were monitored during their ischemia-reperfusion stage.</p><p><strong>Results: </strong>Data obtained in the 5 animals suffering from heart failure followed by myocardial ischemia showed that: a) heart failure induction determined decrease in cardiac output, cardiac index and systolic and diastolic aortic pressure (AoP) with respect to their basal values (p<0.05), b) myocardial ischemia decreased the WTF compared with basal and induced heart failure values (p<0.05), c) during the reperfusion stage accompanied by induced heart failure, WTF increased with respect to values observed during the ischemia induction stage (p<0.05); nevertheless, basal values were not recovered after reperfusion (p<0.05). During this 60-minute stage, systolic and diastolic AoP values were lower (p<0.05) than those at the basal stage.</p><p><strong>Conclusion: </strong>AIx and WTF values calculated from synchronically recorded values of aortic pressure and left ventricular wall thickness during the reperfusion stage in all animals (n = 9) showed a negative correlation (p<0.05). Analysed data provided evidence of a negative relationship between a left ventricular index of myocardial function and an arterial index obtained from AoP waves.</p>","PeriodicalId":45941,"journal":{"name":"Current Hypertension Reviews","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39072738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Novel Benefits of Sodium Restriction in Chronic Kidney Disease.","authors":"Rodolfo Valtuille","doi":"10.2174/1573402116666200615152139","DOIUrl":"https://doi.org/10.2174/1573402116666200615152139","url":null,"abstract":"<p><p>Chronic kidney disease is a global public health issue, and it has been considered as the epidemic of the 21st century. Therefore, all initiatives addressed to slow down the evolution and complications of this condition should be well received. While the effects of salt reduction on cardiovascular disease have some controversial issues, in chronic kidney disease, such a policy is beneficial in multiple aspects. In chronic kidney disease patients, dietary sodium restriction is regularly recommended to control extracellular fluid expansion, hypertension and cardiovascular risk. Instead, the effects of sodium reduction on chronic kidney disease progression are still controversial. In the last years, potentially beneficial effects of a low sodium diet on chronic kidney disease evolution have emerged. Firstly, recent magnetic resonance-based findings of increased Na depots in skin and muscle associated with renal function, ageing and sodium intake open a vast body of investigation as a potential tool for monitoring effects of sodium restriction. In this narrative review, we also discussed novel aspects of sodium restriction in chronic kidney disease to manage metabolic acidosis as well as renal effects on fibroblast growth factor 23 or gut microbiota. Beyond current evidence, these approaches showed that common findings of kidney failure environment such as sodium -sensitivity, micro-inflammation, arterial stiffness metabolic acidosis and sarcopenia could be delayed controlling dietary sodium. Additional studies are now needed in populations with chronic kidney disease to confirm these new findings, addressed to slow down the evolution and complications of this condition.</p>","PeriodicalId":45941,"journal":{"name":"Current Hypertension Reviews","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38044391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology of Hypertension and Diabetes Mellitus in Latin America.","authors":"Patricio Lopez-Jaramillo,&nbsp;Jose Lopez-Lopez,&nbsp;Daniel Cohen,&nbsp;Natalia Alarcon-Ariza,&nbsp;Margarita Mogollon-Zehr","doi":"10.2174/1573402116999200917152952","DOIUrl":"https://doi.org/10.2174/1573402116999200917152952","url":null,"abstract":"<p><p>Hypertension and type 2 diabetes mellitus are two important risk factors that contribute to cardiovascular diseases worldwide. In Latin America, hypertension prevalence varies from 30 to 50%. Moreover, the proportion of awareness, treatment and control of hypertension is very low. The prevalence of type 2 diabetes mellitus varies from 8 to 13% and around 40% of patients are unaware of their condition. In addition, the prevalence of prediabetes varies from 6 to 14% and this condition has also been associated with increased risk of cardiovascular diseases. The principal factors linked to a higher risk of hypertension in Latin America are increased adiposity, low muscle strength, unhealthy diet, low physical activity and low education. Besides being chronic conditions, leading causes of cardiovascular mortality, both hypertension and type 2 diabetes mellitus, represent a substantial cost for the weak health systems of Latin American countries. Therefore, it is necessary to implement and reinforce public health programs to improve awareness, treatment and control of hypertension and type 2 diabetes mellitus, in order to reach the mandate of the United Nations to decrease the premature mortality for CVD.</p>","PeriodicalId":45941,"journal":{"name":"Current Hypertension Reviews","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38393455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Safety and Tolerability of Azilsartan Medoxomil Alone or in Combination With Chlorthalidone in the Management of Hypertension: A Systematic Review.","authors":"Vasiliki Katsi,&nbsp;Christos Michalakeas,&nbsp;Stergios Soulaidopoulos,&nbsp;Alexios S Antonopoulos,&nbsp;Charalambos Vlachopoulos,&nbsp;Dimitris Tousoulis,&nbsp;Konstantinos Tsioufis","doi":"10.2174/1573402117666210112144505","DOIUrl":"https://doi.org/10.2174/1573402117666210112144505","url":null,"abstract":"<p><strong>Background: </strong>Azilsartan medoxomil (AZM) is the newest representative in the class of angiotensin receptor blockers. Azilsartan medoxomil in combination with the older diuretic chlorthalidone (CLD) in fixed-doses of AZM/CLD 40/12.5 mg and 40/25 mg has been approved by the FDA for use in patients with essential hypertension. We sought to evaluate the safety and tolerability of AZL-M alone and in combination with CLD.</p><p><strong>Methods: </strong>We conducted a search in PubMed using the keywords 'azilsartan', 'azilsartan medoxomil', 'chlorthalidone, 'safety', 'tolerability' in order to find scientific studies evaluating the safety of these drugs. We included studies reporting side effects of these drugs, alone or in combination, in comparison to placebo or other antihypertensive medications. For our systematic review, we followed the PRISMA guidelines.</p><p><strong>Results: </strong>Azilsartan medoxomil is a potent antihypertensive medicine with an acceptable safety profile. The most commonly reported adverse events are dizziness, headache, fatigue, upper respiratory tract infection and urinary tract infection. Chlorthalidone is more potent and has a considerably longer duration of action than the most commonly prescribed diuretic hydrochlorothiazide. Safety and tolerability between these two drugs are similar except higher serum uric acid and lower potassium levels with chlorthalidone.</p><p><strong>Conclusion: </strong>The combination of azilsartan medoxomil with chlorthalidone has been shown to be effective in lowering blood pressure with an acceptable safety and tolerability profile. This fixeddose combination is an attractive treatment option for hypertension management.</p>","PeriodicalId":45941,"journal":{"name":"Current Hypertension Reviews","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38813394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vascular Inflammation in Hypertension: Targeting Lipid Mediators Unbalance and Nitrosative Stress.","authors":"Alexandre S Bruno,&nbsp;Patricia das Dores Lopes,&nbsp;Karla C M de Oliveira,&nbsp;Anizia K de Oliveira,&nbsp;Stefany B de Assis Cau","doi":"10.2174/1573402116666191220122332","DOIUrl":"https://doi.org/10.2174/1573402116666191220122332","url":null,"abstract":"<p><p>Arterial hypertension is a worldwide public health threat. High Blood Pressure (BP) is commonly associated with endothelial dysfunction, nitric oxide synthases (NOS) unbalance and high peripheral vascular resistance. In addition to those, inflammation has also been designated as one of the major components of BP increase and organ damage in hypertension. This minireview discusses vascular inflammatory triggers of high BP and aims to fill the existing gaps of antiinflammatory therapy of hypertension. Among the reasons discussed, enhanced prostaglandins rather than resolvins lipid mediators, immune cell infiltration and oxidative/nitrosative stress are pivotal players of BP increase within the inflammatory hypothesis. To address these inflammatory targets, this review also proposes new concepts in hypertension treatment with non-steroidal antiinflammatory drugs (NSAIDs), nitric oxide-releasing NSAIDs (NO-NSAIDs) and specialized proresolving mediators (SPM). In this context, the failure of NSAIDs in hypertension treatment seems to be associated with the reduction of endogenous NO bioavailability, which is not necessarily an effect of all drug members of this pharmacological class. For this reason, NO-releasing NSAIDs seem to be safer and more specific therapy to treat vascular inflammation in hypertension than regular NSAIDs.</p>","PeriodicalId":45941,"journal":{"name":"Current Hypertension Reviews","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37476099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiotensin-Converting Enzyme 2 Roles in the Pathogenesis of COVID-19.","authors":"Azra Kenarkoohi,&nbsp;Maryam Maleki,&nbsp;Tahereh Safari,&nbsp;Mohammad Reza Kaffashian,&nbsp;Fateme Saljoughi,&nbsp;Shahla Sohrabipour","doi":"10.2174/1573402116666200810134702","DOIUrl":"https://doi.org/10.2174/1573402116666200810134702","url":null,"abstract":"<p><p>The new pandemic Coronavirus Disease 2019 (COVID-19) causes a wide range of clinical consequences, from asymptomatic infection to acute respiratory failure, and it is very heterogeneous. The renin-angiotensin system (RAS) is well recognized as a key regulating system in circulatory homeostasis that plays prominent roles in pathophysiological processes in abnormal activation, for instance, renal and cardiovascular diseases, obesity, and stroke. Angiotensin-converting enzyme 2(ACE2) is a component of the RAS system. However, unlike the ACE, its activity is not inhibited by the ACE inhibitors. The major product of ACE2 is Ang1-7, known as a vasodilator peptide and part of the depressant arm of the RAS. There are two forms of ACE2; Transmembrane ACE2 and soluble ACE2. Coronavirus is covered with some proteins in order to help viral attachment to the cell membrane ACE2 as a receptor and then fuse and enter the cells. ACE2 was expressed in the oral cavity, salivary glands of the mouth, esophagus, myocardial cells, kidney, and enterocytes, along with all the respiratory tract, intestine, and blood vessels. In this article, the renin- angiotensin system and its components have been explained. Moreover, the organs involved in COVID-19 disease, and the possible causes of damage to these organs have also been discussed. The probable mechanism of using ACE2 in viral attachment and the probable treatment processes will also be reviewed based on the surface proteins of the virus and ACE2. In addition, we briefly discuss anti-angiotensin drugs and why patients with chronic diseases are more susceptible to COVID-19 infection and show worse progression.</p>","PeriodicalId":45941,"journal":{"name":"Current Hypertension Reviews","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38249448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vascular Dysfunction in the Brain; Implications for Heavy Metal Exposures.","authors":"Nzube F Olung,&nbsp;Oritoke M Aluko,&nbsp;Sikirullai O Jeje,&nbsp;Ayotunde S Adeagbo,&nbsp;Omamuyovwi M Ijomone","doi":"10.2174/1573402117666210225085528","DOIUrl":"https://doi.org/10.2174/1573402117666210225085528","url":null,"abstract":"<p><p>Normal or diseased conditions that alter the brain's requirement for oxygen and nutrients via alterations to neurovascular coupling have an impact on the level of the neurovascular unit; comprising neuronal, glial and vascular components. The communications between the components of the neurovascular unit are precise and accurate for its functions; hence a minute disturbance can result in neurovascular dysfunction. Heavy metals such as cadmium, mercury, and lead have been identified to increase the vulnerability of the neurovascular unit to damage. This review examines the role of heavy metals in neurovascular dysfunctions and the possible mechanisms by which these metals act. Risk factors ranging from lifestyle, environment, genetics, infections, and physiologic ageing involved in neurological dysfunctions were highlighted, while stroke was discussed as the prevalent consequence of neurovascular dysfunctions. Furthermore, the role of these heavy metals in the pathogenesis of stroke consequently pinpoints the importance of understanding the mechanisms of neurovascular damage in a bid to curb the occurrence of neurovascular dysfunctions.</p>","PeriodicalId":45941,"journal":{"name":"Current Hypertension Reviews","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25405518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heart Failure and Diabetes: Perspective of a Dangerous Association.","authors":"Liliana E Favaloro,&nbsp;Roxana D Ratto,&nbsp;Carla Musso","doi":"10.2174/1573402117666210406111927","DOIUrl":"https://doi.org/10.2174/1573402117666210406111927","url":null,"abstract":"<p><p>The relationship between diabetes and risk of heart failure has been described in previous trials, releasing the importance of the hyperglycemic state that, added to other risk factors, favors the development of coronary heart disease. The mechanism by which, in the absence of hypertension, obesity and/or dyslipidemia, diabetic patients develop cardiomyopathy has been less studied. Recently, the Sodium Glucose Co-transporter type 2 inhibitors (SGLT2 inhibitors) used for the treatment of heart failure patients with or without diabetes has been a breakthrough in the field of medicine. This review describes the established pathophysiology of diabetic cardiomyopathy and SGLT2 inhibitors, their mechanisms of action, and benefits in this group of patients.</p>","PeriodicalId":45941,"journal":{"name":"Current Hypertension Reviews","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25564755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renal Function, Albumin-Creatinine Ratio and Pulse Wave Velocity Predict Silent Coronary Artery Disease and Renal Outcome in Type 2 Diabetic and Prediabetic Subjects.","authors":"Ramiro A Sanchez,&nbsp;Maria J Sanchez,&nbsp;Agustin J Ramirez","doi":"10.2174/1573402116999201210194817","DOIUrl":"https://doi.org/10.2174/1573402116999201210194817","url":null,"abstract":"<p><strong>Introduction: </strong>Silent coronary heart disease is frequently undetected in type 2 diabetes mellitus (DM2) and pre-diabetes determined by glucose intolerance (GI). Pulse wave velocity (PWV) and albumin-creatinine ratio (ACR) have been considered markers of cardiovascular mortality, coronary heart disease and chronic renal failure.</p><p><strong>Aim: </strong>To evaluate the incidence of coronary artery disease (CAD) and the relationship between urinary albumin-creatinine ratio, glomerular filtration rate (GFR) and PWV in type 2 DM with silent CAD.</p><p><strong>Methods: </strong>We analyzed 92 individuals (44 male), 49 (60±7y) type 2 DM non-insulin dependents and 43 prediabetics (43±4y), with Grade I-II hypertension and no symptoms of CAD. All type 2 DM patients were under antidiabetic treatment with A1C hemoglobin between 5.5 and 6.5%. Every patient underwent a myocardial perfusion SPECT scan. In those subjects with ischemic patterns, coronary angiography was performed. In addition, PWV, glomerular filtration rate, and ACR were evaluated.</p><p><strong>Statistics: </strong>mean±SEM, and ANOVA among groups.</p><p><strong>Results: </strong>48.59% of DM2 and 25.58% of GI patients had silent coronary artery had silent coronary artery disease and higher ACR, PWV and reduced GFR. Higher ACR and PWV and reduced GFR. DM2 and GI showed a negative relationship between GFR and ACR. Moreover, this relation was also observed in different levels of GFR (>60 ml/min and <60ml.min (p<0.05) in patients with CAD, suggesting a cardio-renal interaction in DM2.</p><p><strong>Conclusion: </strong>Higher PWV, lower GFR and ACR predict the incidence of CAD in DM2. Dysglycemic individuals also represent a group of higher risk for coronary artery disease with similar predictors as in DM2. Diabetic and prediabetics still develop renal microalbuminuria. Thus, PWV seems to represent a reliable marker of renal impairment and coronary artery disease.</p>","PeriodicalId":45941,"journal":{"name":"Current Hypertension Reviews","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38702603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Low BMI with Aortic Stiffness in Young Healthy Individuals","authors":"Satish G Patil,&nbsp;Sneha Arakeri,&nbsp;Vitthal Khode","doi":"10.2174/1573402117666210121100936","DOIUrl":"https://doi.org/10.2174/1573402117666210121100936","url":null,"abstract":"<p><strong>Background: </strong>Increased arterial stiffness is an independent predictor of cardiovascular morbidity and mortality. It is unknown whether low BMI has any detrimental effect on the arterial wall during young age.</p><p><strong>Objectives: </strong>The present study was aimed to determine if low BMI can increase arterial stiffness in young, healthy individuals.</p><p><strong>Methods: </strong>A cross-sectional study was conducted on young, healthy subjects (n=100) with low BMI <18.5 (n=50) and normal BMI: 18.5-24.9 (n=50) with ages ranging between 15-23 years. BMI, heart rate, blood pressure, and arterial stiffness indices such as regional pulse wave velocity (PWV) between brachial-ankle (baPWV), carotid-femoral (cfPWV), heart-ankle (haPWV), heartbrachial (hbPWV) were measured.</p><p><strong>Results: </strong>A significantly increased pulse pressure (p=0.014), baPWV (1059.2 ± 140.26 cm/s vs 994.66 ± 129.23 cm/s; p=0.019) and cfPWV (641.03 ± 113.83 cm/s vs 583.96 ± 120.48 cm/s; p=0.017) was found in individuals with low BMI than normal BMI group. There was a significant negative correlation between BMI and central arterial PWV. Further multiple regression analysis showed that BMI was robustly associated with cf-PWV (p=0.004) and baPWV (p=0.016) even after multiple adjustments with potential confounders using several models.</p><p><strong>Conclusion: </strong>These findings show a significant increased aortic stiffness and pulse pressure in low BMI subjects compared to those with normal BMI. Low BMI was inversely and independently associated with central arterial or aortic stiffness. These findings suggest that low BMI may be a risk factor for aortic stiffness in young, healthy individuals.</p>","PeriodicalId":45941,"journal":{"name":"Current Hypertension Reviews","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38842823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}