Journal of Vascular Research最新文献

{"title":"Perfusion Staining Methods for Visualization of Intact Microvascular Networks in Whole Mount Skeletal Muscle Preparations.","authors":"Barbara M Hyde-Lay, Mackenzie E Charter, Coral L Murrant","doi":"10.1159/000542663","DOIUrl":"10.1159/000542663","url":null,"abstract":"<p><strong>Introduction: </strong>Visualization of the intact microvascular network in skeletal muscle requires labeling the entire network in whole mount preparations where muscle fibre length can be set to near optimal but the tools to do this are not clear.</p><p><strong>Methods: </strong>We intravascularly injected CD-1 mice with different fluorescently labelled lectins (fluorescent isolectin GS-IB4 [ISO], wheat germ agglutinin [WGA], lycopersicon esculentum [LYCO]) or FITC-labelled gel. Soleus, extensor digitorum longus, diaphragm, gluteus maximus and cremaster muscles were excised, pinned at optimal sarcomere length and viewed using fluorescence microscopy.</p><p><strong>Results: </strong>WGA and LYCO were effective at labeling the entire vascular network with WGA labeling capillaries more brightly. ISO labelled the arteriolar vasculature and early segments of the capillaries but not the full length of the capillaries or the venular network. FITC-labelled gel was effective at labelling the microvascular network but not all small vessels were consistently labelled. The pattern of staining for each labelling method was similar across all muscle fibre-types tested.</p><p><strong>Conclusions: </strong>WGA was optimal for perfusion labeling and visualization of the intact microvascular network in whole mount skeletal muscle preparations and can be used in combination with ISO to distinguish the arteriolar and venous sides of the network.</p><p><strong>Introduction: </strong>Visualization of the intact microvascular network in skeletal muscle requires labeling the entire network in whole mount preparations where muscle fibre length can be set to near optimal but the tools to do this are not clear.</p><p><strong>Methods: </strong>We intravascularly injected CD-1 mice with different fluorescently labelled lectins (fluorescent isolectin GS-IB4 [ISO], wheat germ agglutinin [WGA], lycopersicon esculentum [LYCO]) or FITC-labelled gel. Soleus, extensor digitorum longus, diaphragm, gluteus maximus and cremaster muscles were excised, pinned at optimal sarcomere length and viewed using fluorescence microscopy.</p><p><strong>Results: </strong>WGA and LYCO were effective at labeling the entire vascular network with WGA labeling capillaries more brightly. ISO labelled the arteriolar vasculature and early segments of the capillaries but not the full length of the capillaries or the venular network. FITC-labelled gel was effective at labelling the microvascular network but not all small vessels were consistently labelled. The pattern of staining for each labelling method was similar across all muscle fibre-types tested.</p><p><strong>Conclusions: </strong>WGA was optimal for perfusion labeling and visualization of the intact microvascular network in whole mount skeletal muscle preparations and can be used in combination with ISO to distinguish the arteriolar and venous sides of the network.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"37-50"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Adaptations in Coronary Reactivity following Healthy Pregnancy in Swine.","authors":"Selina M Tucker, Salman I Essajee, Cooper M Warne, Gregory M Dick, Styliani Goulopoulou, Johnathan D Tune","doi":"10.1159/000543116","DOIUrl":"10.1159/000543116","url":null,"abstract":"<p><strong>Introduction: </strong>This study was designed to test the hypothesis that coronary artery adaptations during the postpartum period are related to underlying reductions in endothelium-dependent relaxation and/or augmented smooth muscle vasoconstrictor responsiveness.</p><p><strong>Methods: </strong>In vivo experiments were performed in control (nonpregnant) and postpartum swine 35-45 days of postdelivery, with isometric tension experiments performed in isolated coronary arteries from those animals.</p><p><strong>Results: </strong>Coronary artery rings demonstrated increases in active tension generation following incremental increases in passive stretch with no differences between groups. Endothelium-dependent relaxation to bradykinin was attenuated in arteries from postpartum swine versus control (p < 0.005). Concentration-dependent contractions to the thromboxane A2 mimetic U46619 (0.1 n<sc>m</sc>-1 µ<sc>m</sc>) were shifted rightward (EC50 27 ± 10 n<sc>m</sc> vs. 238 ± 66 n<sc>m</sc>; p < 0.01) in arteries from postpartum swine, with no changes in maximum contractile responses (p = 0.68). Intracoronary administration of U46619 (1 n<sc>m</sc>-1 µ<sc>m</sc>) in open-chest swine decreased coronary blood flow ∼45 ± 3% in nonpregnant controls but had no effect on coronary blood flow in postpartum swine. Concentration-dependent contractions to KCl (5-90 m<sc>m</sc>) showed a rightward shift in arteries from postpartum swine (15.6 ± 1.4 m<sc>m</sc> vs. 21.8 ± 1.9 m<sc>m</sc>; p = 0.03), with no change in maximum response. Taken together, the postpartum period is associated with reduced endothelium-dependent relaxation and responsiveness to receptor-dependent and -independent vasoconstrictor stimuli.</p><p><strong>Conclusion: </strong>These findings indicate that chronic exposure of the coronary circulation to the pregnancy/postpartum milieu results in functional adaptations in sensitivity to paracrine/hormonal compounds that should be further explored.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"78-87"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Preclinical Model of Peripheral Artery Disease in Swine for Investigating Flow-Induced Angiogenesis.","authors":"Grzegorz Jodlowski, May Dvir, Colin Price, Amy Benike, Joanna Jaroch, Jonathan J Morrison","doi":"10.1159/000547455","DOIUrl":"10.1159/000547455","url":null,"abstract":"<p><strong>Introduction: </strong>Peripheral artery disease (PAD) affects over 200 million people globally and remains a therapeutic challenge, particularly in patients who are not candidates for standard revascularization. While shear stress-induced angiogenesis holds promise as a novel therapeutic strategy, translational platforms to evaluate its efficacy are lacking.</p><p><strong>Methods: </strong>We developed a large-animal model of PAD using familial hypercholesterolemic miniature swine fed an atherogenic diet to induce metabolic syndrome. Hindlimb ischemia was surgically induced by excising the right external iliac artery with collateral ligation. After a 3-4 week ischemic phase, targeted retrograde perfusion was delivered via a miniaturized extracorporeal centrifugal pump to generate sustained flow-mediated shear stress. Functional, imaging, and molecular endpoints were assessed throughout the protocol.</p><p><strong>Conclusion: </strong>This reproducible swine model offers a metabolically relevant platform for investigating perfusion-driven angiogenesis and evaluating novel flow-based revascularization therapies for PAD. It addresses a critical translational gap in preclinical vascular research.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"249-253"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Biennial Meeting of the European Society for Microcirculation (ESM 2025) Szeged, Hungary, May 19-22, 2025.","authors":"","doi":"10.1159/000545972","DOIUrl":"10.1159/000545972","url":null,"abstract":"<p><p>This is the collection of abstracts for the Biennial Meeting of the European Society for Microcirculation (ESM 2025), to be held in Szeged, Hungary between May 19-22, 2025.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":"62 Suppl 1","pages":"1-73"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Functional Unit of the Lymphatic System: Towards Understanding the Importance of a Well-Rehearsed Interaction of Lymphatic Capillaries, Collecting Vessels, and Lymph Nodes.","authors":"Katrin Sabine Roth, Reinhard Pabst","doi":"10.1159/000545084","DOIUrl":"10.1159/000545084","url":null,"abstract":"<p><strong>Introduction: </strong>Lymphatic vessels and lymph nodes (LNs) are part of the lymphatic system taking care of interstitial tissue homoeostasis, lipid transport, and immune response. The interposition of LNs in between the lymphatic vasculature allows the filtration of lymph fluid, cell-cell interactions, and also the transfer of lymph fluid into the venous system. An important role of lymphatic flow, which is often underestimated, is the active involvement of lymph flow and the lymphatic vasculature in immunologic function.</p><p><strong>Summary: </strong>The present review summarizes the current knowledge of the different functional units of the lymphatic transport system trying to create a model of their interplay and options to react to inflammatory conditions. Remodelling of the lymphatic system during inflammation includes lymphangiogenesis, changed fluid transport rates, and modification of LN morphology. Alterations of these processes can aggravate inflammatory processes, leading to an incomplete resolution of the inflammation and often ending in chronic inflammatory condition. Despite the development of histological markers to visualize lymphatic vessels, new imaging methods and increased knowledge about the different parts of the lymphatic system the general overview about the interplay of the different components is missing.</p><p><strong>Key messages: </strong>We show the importance of lymphatic flow in the initiation of the immune response and the solution of an inflammation. We speculate that the increase in density and vessel diameter of lymph vessels is necessary to increase the fluid influx, efflux and the migration of cells into the LN. A failure of antigen-tissue clearance leads to chronic inflammation. Remodelling of LN morphology and vasculature is also necessary in this reaction. An overrun of the defending capacity of the LN is prevented by the immune system via control of the lymph vessel transport capacity and LN remodelling.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"183-192"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heat Therapy as a Viable Treatment for Peripheral Artery Disease: A Mini Review.","authors":"Min-Hyeok Jang, Song-Young Park, Sun Dong Kim, Sang Ho Lee","doi":"10.1159/000546163","DOIUrl":"10.1159/000546163","url":null,"abstract":"<p><strong>Background: </strong>Peripheral artery disease (PAD) is a prevalent and debilitating condition characterized by reduced blood flow to the lower limb extremities due to arterial plaque buildup. Traditional exercise/walking therapies have been used to improve vascular function and walking performance but suffer from low adherence rates due to pain and discomfort. Heat therapy has emerged as a promising alternative, showing similar improvements in vascular and cardiovascular function, often with higher adherence rates.</p><p><strong>Summary: </strong>This review explores various forms of heat therapy, including passive and active modalities, and their effects on patients with PAD. Heat therapies have demonstrated similar or even superior outcomes compared to traditional exercise/walking therapies, with higher adherence rates.</p><p><strong>Key messages: </strong>Despite promising results, further research is needed to standardize heat therapy protocol and understand the underlying mechanisms. Optimizing heat therapy could offer a viable, patient-friendly alternative to improve vascular function, reduce pain, and enhance quality of life in patients with PAD.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"219-231"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria-Targeted SS31-Conjugated Liposome Attenuates Oxidative Stress in Endothelial and Skeletal Muscle Cells.","authors":"Eun-Mi Kim, Yeon-Hee Han, Phil-Sun Oh, Wang Qi, Seok-Tae Lim, Hwan-Jeong Jeong","doi":"10.1159/000547281","DOIUrl":"10.1159/000547281","url":null,"abstract":"<p><strong>Introduction: </strong>Mitochondria play a pivotal role as therapeutic targets in a range of disorders, including metabolic and neurodegenerative diseases. SS31, a peptide engineered to target mitochondria, offers potent antioxidant activity, positioning it as a promising therapeutic option. Nevertheless, the hydrophilic profile of SS31 poses challenges such as reduced stability, suboptimal delivery, and poor mitochondrial localization in clinical applications. This study was designed to develop a mitochondria-targeted liposomal carrier by conjugating SS31KRKC to the liposome surface (SS31-LP) and to investigate its biological effects in vitro.</p><p><strong>Methods: </strong>A lysine-arginine-lysine-cysteine (KRKC) linker was incorporated with SS31 to facilitate surface conjugation to liposomes via thiol-based coupling. The hydrodynamic diameter and zeta potential of the resulting formulations were quantified to determine the optimal lipid-to-peptide ratio for mitochondrial targeting. The in vitro mitochondrial localization, cytotoxicity, antioxidant potential, and anti-apoptotic efficacy of SS31-LP were evaluated in HUVECs and C2C12 cells.</p><p><strong>Results: </strong>SS31-LP demonstrated pronounced mitochondrial localization and showed variable cellular internalization based on zeta potential. Pretreatment with SS31-LP enhanced cellular viability, mitigated oxidative damage, and reduced apoptosis in response to oxidative stress caused by H₂O₂ or blue LEDs.</p><p><strong>Conclusion: </strong>Overall, SS31-LP presents a valuable therapeutic strategy for cellular protection against oxidative injury and may be an advantageous platform for targeted drug-delivery applications.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"274-288"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Metabolism-Associated Proteins in Abdominal Aortic Aneurysm.","authors":"Amanda Balboa Ramilo, Nikiforos Chandrinos, Elefantia Tsichlia, Josefin Jönsson, Kevin Mani, Anders Wanhainen, Dick Wågsäter","doi":"10.1159/000543768","DOIUrl":"10.1159/000543768","url":null,"abstract":"<p><strong>Introduction: </strong>Abdominal aortic aneurysm (AAA) development is inversely associated with diabetes mellitus. Targeting glucose metabolism seems to be a beneficial strategy for preventing AAA growth. Several metabolism-related factors are associated with AAA development. This study aimed to analyse the expression of the so far unstudied proteins irisin, follistatin, activin A, and ghrelin (ligand and receptor) in human and murine aneurysmal tissue, to assess the involvement of these pathways in AAA.</p><p><strong>Methods: </strong>Gene and protein expression was evaluated in aneurysmal and control tissue samples, by qPCR and immunohistochemistry. Vascular smooth muscle cells (VSMCs) were studied in vitro for expression. Circulating levels of the proteins of interest in human plasma samples were evaluated by ELISA.</p><p><strong>Results: </strong>In human aneurysmal tissue, the proteins of interest were predominantly expressed by VSMCs in neovessels. Expression by human VSMCs was confirmed in vitro. In human plasma, the concentration of irisin was higher in AAA (+/- diabetes) compared to controls. Patients with AAA and type 2 diabetes treated with metformin had lower levels of follistatin and ghrelin.</p><p><strong>Conclusion: </strong>This study demonstrates irisin, follistatin, and ghrelin as interesting proteins to be studied in the context of the observed negative association between AAA development and type 2 diabetes.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"145-156"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcapillary PO₂ Gradients in Contracting Muscle of Rat Model of Sepsis.","authors":"Narumi Fukuzaki, Kazuki Hotta, Kota Izawa, Naoki Hitosugi, Miki Sakamoto, Rin Kataoka, Shuri Arai, Kentaro Kamiya, Atsuhiko Matsunaga","doi":"10.1159/000547568","DOIUrl":"10.1159/000547568","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to evaluate the effect of cecal ligation and puncture (CLP)-induced sepsis on transcapillary PO₂ gradients (ΔPO₂) in contracting skeletal muscles.</p><p><strong>Methods: </strong>Male Wistar rats (n = 16, 10 weeks old) were randomly assigned to sham or CLP groups. Seven days after surgery, microvascular (PO₂mv) and interstitial (PO₂is) PO₂ levels in the tibialis anterior muscle were measured using the phosphorescence quenching method during the transition from rest to electrically induced muscle contractions. ΔPO₂ was calculated as PO₂mv minus PO₂is.</p><p><strong>Results: </strong>At rest, there were no differences in PO₂mv, PO₂is, and ΔPO₂ between the sham and CLP groups. The PO₂mv and PO₂is decreased during the transition from rest to contractions in both groups. During muscle contractions, the PO₂mv and ΔPO₂ were significantly lower in the CLP group than in the sham group (PO₂mv, 7.79 ± 5.03 vs. 4.43 ± 2.23; ΔPO₂, 5.50 ± 4.46 vs. 1.82 ± 2.66 mm Hg; sham vs. CLP; p < 0.05). The ΔPO₂ of the rats in the sham group remained unchanged; however, it markedly decreased during muscle contractions in the CLP group.</p><p><strong>Conclusion: </strong>Sepsis reduced ΔPO₂ in contracting skeletal muscles.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"266-273"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Noninvasive Bedside Approaches for Assessing Microvascular Dysfunction.","authors":"Jacob Widaeus, Ingemar Fredriksson, Sara Tehrani","doi":"10.1159/000547636","DOIUrl":"10.1159/000547636","url":null,"abstract":"<p><strong>Background: </strong>Microvascular dysfunction is implicated in a range of acute and chronic conditions, ranging from cardiovascular disease to sepsis, often preceding organ damage and clinical symptoms. Within conditions such as diabetes or septic shock, microvascular compromise frequently correlates with disease severity and outcomes, emphasizing the importance of timely, targeted assessment. Noninvasive bedside methods for evaluating microvascular function have rapidly evolved, driven by advances in computational power, artificial intelligence, and novel imaging hardware.</p><p><strong>Summary: </strong>This review provides an overview of clinically feasible noninvasive techniques - including optical coherence tomography angiography, handheld videomicroscopy, laser speckle contrast imaging, reflectance spectroscopy, and related techniques. These methods allow observation under resting conditions and can be combined with functional tests such as post-occlusive reactive hyperemia, heating provocation, or iontophoresis to evaluate microvascular function.</p><p><strong>Key messages: </strong>Collectively, these methods provide valuable insights into the structural and functional aspects of the microcirculation, but their clinical application is constrained by need for standardized protocols, validation, and evidence linking microvascular metrics to meaningful patient outcomes. Collaborations among academia, industry, and healthcare remain pivotal to transitioning these methods into regulated, accessible devices. As standardization progresses and evidence grows, this integrative approach of evaluating microvascular function may emerge as a mainstay in clinical practice and translational research.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"233-248"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}