BMC DermatologyPub Date : 2017-06-10DOI: 10.1186/s12895-017-0060-y
Leslie Calapre, Elin S Gray, Sandrine Kurdykowski, Anthony David, Pascal Descargues, Mel Ziman
{"title":"SIRT1 activation mediates heat-induced survival of UVB damaged Keratinocytes.","authors":"Leslie Calapre, Elin S Gray, Sandrine Kurdykowski, Anthony David, Pascal Descargues, Mel Ziman","doi":"10.1186/s12895-017-0060-y","DOIUrl":"https://doi.org/10.1186/s12895-017-0060-y","url":null,"abstract":"<p><strong>Background: </strong>Exposure to heat stress after UVB irradiation induces a reduction of apoptosis, resulting in survival of DNA damaged human keratinocytes. This heat-mediated evasion of apoptosis appears to be mediated by activation of SIRT1 and inactivation of p53 signalling. In this study, we assessed the role of SIRT1 in the inactivation of p53 signalling and impairment of DNA damage response in UVB plus heat exposed keratinocytes.</p><p><strong>Results: </strong>Activation of SIRT1 after multiple UVB plus heat exposures resulted in increased p53 deacetylation at K382, which is known to affect its binding to specific target genes. Accordingly, we noted decreased apoptosis and down regulation of the p53 targeted pro-apoptotic gene BAX and the DNA repair genes ERCC1 and XPC after UVB plus heat treatments. In addition, UVB plus heat induced increased expression of the cell survival gene Survivin and the proliferation marker Ki67. Notably, keratinocytes exposed to UVB plus heat in the presence of the SIRT1 inhibitor, Ex-527, showed a similar phenotype to those exposed to UV alone; i.e. an increase in p53 acetylation, increased apoptosis and low levels of Survivin.</p><p><strong>Conclusion: </strong>This study demonstrate that heat-induced SIRT1 activation mediates survival of DNA damaged keratinocytes through deacetylation of p53 after exposure to UVB plus heat.</p>","PeriodicalId":9014,"journal":{"name":"BMC Dermatology","volume":"17 1","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2017-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12895-017-0060-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35076322","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}
BMC DermatologyPub Date : 2017-05-18DOI: 10.1186/s12895-017-0059-4
Erina Lie, Sarah Sung, Steven Hoseong Yang
{"title":"Adult autoimmune enteropathy presenting initially with acquired Acrodermatitis Enteropathica: a case report.","authors":"Erina Lie, Sarah Sung, Steven Hoseong Yang","doi":"10.1186/s12895-017-0059-4","DOIUrl":"https://doi.org/10.1186/s12895-017-0059-4","url":null,"abstract":"<p><strong>Background: </strong>Acrodermatitis enteropathica (AE) is a rare dermatitis secondary to zinc deficiency most commonly seen as an inherited disease in infants. In the last decade, increased number of reports have been published on the acquired form that presents in adulthood. Unlike its inherited counterpart, acquired AE (AAE) is often secondary to underlying pathologic or iatrogenic etiologies that interfere with nutritional absorption, such as inflammatory bowel disease or alcoholism. Various gastrointestinal pathologies have been associated with AAE, but there is currently no report on its association with adult autoimmune enteropathy (AIE), a rare gastrointestinal disorder commonly seen in infants, with limited cases reported in adults. Here we present a case in which AAE was the initial clinical manifestation in an adult patient subsequently diagnosed with AIE.</p><p><strong>Case presentation: </strong>A 41-year-old African American female presented to our emergency department at the Johns Hopkins Hospital with several months of progressively worsening dermatitis in the legs and acral regions, along with worsening symptoms of diarrhea, alopecia, poor oral intake, lethargy, hematochezia, peripheral edema, and weight loss. Our dermatology team was consulted given a presentation of exquisitely tender, erythematous, and diffusely desquamating skin lesions in the setting of two prior outside hospitalizations in the last 3 months with the same dermatitis that was refractory to topical and oral corticosteroids. Low serum zinc level and positive response to zinc supplementation confirmed the diagnosis of AAE. However, persistent hypovitaminosis and mineral deficiency despite aggressive nutritional supplementation prompted further investigation for an underlying malabsorption etiology. Jejunal biopsy and associated autoantibodies confirmed a diagnosis of adult AIE.</p><p><strong>Conclusion: </strong>This case highlights the fact that adult AIE can present initially with clinical findings of AE. While proper zinc supplementation can resolve the latter, recognizing this association can trigger earlier diagnosis, minimize unnecessary tests, and establish earlier intervention to improve quality of life and prevent recurrence of AAE. The case also highlights the importance of collaboration between general and subspecialist physicians in identifying a primary etiology to a secondary clinical presentation. This report can be beneficial to general internists and emergency physicians, as much as it can be to dermatologists, rheumatologists, and gastroenterologists.</p>","PeriodicalId":9014,"journal":{"name":"BMC Dermatology","volume":"17 1","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2017-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12895-017-0059-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35008648","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}
BMC DermatologyPub Date : 2017-05-08DOI: 10.1186/s12895-017-0057-6
Selma Atalay, Juul M P A van den Reek, Lieke J van Vugt, Marisol E Otero, Peter C M van de Kerkhof, Alfons A den Broeder, Wietske Kievit, Elke M G J de Jong
{"title":"Tight controlled dose reduction of biologics in psoriasis patients with low disease activity: a randomized pragmatic non-inferiority trial.","authors":"Selma Atalay, Juul M P A van den Reek, Lieke J van Vugt, Marisol E Otero, Peter C M van de Kerkhof, Alfons A den Broeder, Wietske Kievit, Elke M G J de Jong","doi":"10.1186/s12895-017-0057-6","DOIUrl":"10.1186/s12895-017-0057-6","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is an immune-mediated chronic inflammatory skin disorder for which several targeted biologic therapies became available in the last 10 years. Data from patients with rheumatoid arthritis revealed that dose tapering combined with tight control of disease activity is successful. For psoriasis patients the lowest effective dose of biologics needs to be determined. The objective was to assess whether dose tapering of biologics guided by Psoriasis Area and Severity Index (PASI) and Dermatology Quality of Life Index (DLQI) scores in psoriasis patients with controlled disease activity is non-inferior (NI) to usual care.</p><p><strong>Methods/design: </strong>This is a multicenter, pragmatic, randomized, non-inferiority trial with cost- effectiveness analysis. One hundred and twenty patients with stable low disease activity (PASI ≤ 5 and DLQI ≤ 5) for at least 6 months with a stable use of adalimumab, etanercept or ustekinumab will be randomized 1:1 to the dose reduction group or usual care. In the dose reduction group, the treatment intervals will be prolonged stepwise, resulting in a 33% and 50% dose reduction, respectively. Disease activity is monitored every three months with PASI and DLQI. In case of flare the treatment is adjusted to the previous effective dose. The primary outcome (PASI) at 12 months will be analyzed with ANCOVA in which the baseline PASI will be included as covariate to gain efficiency. The secondary outcomes include number of and time to disease flares, health-related quality of life, serious adverse events, and costs.</p><p><strong>Discussion: </strong>With this study we want to assess whether disease activity guided dose reduction of biologics can be achieved for psoriasis patients with low stable disease activity, without losing disease control. By using the lowest effective dose of biologics, we expect to minimize side effects and save costs.</p><p><strong>Trial registration: </strong>This trial was registered at ClinicalTrials.gov ( NCT 02602925 ). Trial registration date October 9 2015.</p>","PeriodicalId":9014,"journal":{"name":"BMC Dermatology","volume":"17 1","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2017-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12895-017-0057-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34976997","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":"Evaluation of therapeutic potential of VB-001, a leave-on formulation, for the treatment of moderate adherent dandruff.","authors":"Anamika Bhattacharyya, Nilu Jain, Sudhanand Prasad, Shilpi Jain, Vishal Yadav, Shamik Ghosh, Shiladitya Sengupta","doi":"10.1186/s12895-017-0058-5","DOIUrl":"https://doi.org/10.1186/s12895-017-0058-5","url":null,"abstract":"<p><strong>Background: </strong>Dandruff is a common scalp condition characterized by excessive scaling and itch. Aberrant colonization of the scalp by commensal Malassezia spp. is a major contributor in the multifactorial etiology of dandruff. Literature based understanding of Malassezia linked pathophysiology of dandruff allowed us to comprehend a strategy to potentiate the efficacy of a known antifungal agent used in dandruff therapy. The aim of this study was to determine the efficacy and skin safety of VB-001 antidandruff leave-on formulation in comparison with marketed antidandruff ZPTO shampoo in patients with moderate adherent dandruff of the scalp.</p><p><strong>Methods: </strong>Healthy males or females aged ≥ 15 years and ≤ 65 with a clinical diagnosis of moderate adherent dandruff of the scalp were recruited for the study to monitor the effects of topical VB-001 versus those of marketed antidandruff ZPTO shampoo.</p><p><strong>Results: </strong>168 subjects were randomized to the treatment (VB-001, n = 84) and control (ZPTO shampoo, n = 84) groups. The efficacy of each product was evaluated by comparing proportion of subjects who have shown reduction in flaking by ASFS (adherent scalp flaking score) and pruritus by IGA (investigator global assessment) score. VB-001 imparted consistently better reduction in ASFS and enabled early reduction of pruritus in comparison to marketed ZPTO shampoo.</p><p><strong>Conclusion: </strong>VB-001, a leave-on formulation with ingredients chosen to selectively disturb the Malassezia niche on dandruff scalp by denying extra nutritional benefits to the microbe, provides unique advantages over existing best in class ZPTO shampoo therapy. It has the potential to emerge as an attractive novel treatment for moderate adherent dandruff.</p><p><strong>Trial registration: </strong>CTRI Registration number: CTRI/2013/01/003283 . Registered on: 02/01/2013.</p>","PeriodicalId":9014,"journal":{"name":"BMC Dermatology","volume":"17 1","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2017-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12895-017-0058-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34963473","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}
BMC DermatologyPub Date : 2017-03-20DOI: 10.1186/s12895-017-0056-7
Benjamin Momo Kadia, Christian Akem Dimala, Desmond Aroke, Cyril Jabea Ekabe, Reine Suzanne Mengue Kadia, Alain Chichom Mefire
{"title":"A prospective analysis of pinch grafting of chronic leg ulcers in a series of elderly patients in rural Cameroon.","authors":"Benjamin Momo Kadia, Christian Akem Dimala, Desmond Aroke, Cyril Jabea Ekabe, Reine Suzanne Mengue Kadia, Alain Chichom Mefire","doi":"10.1186/s12895-017-0056-7","DOIUrl":"10.1186/s12895-017-0056-7","url":null,"abstract":"<p><strong>Background: </strong>Chronic leg ulcers (CLUs) pose serious public health concerns worldwide. They mainly affect the elderly population. Pinch grafting (PG) could be used to treat a variety of CLUs. However, in Cameroon, there is scarce data on the outcome of PG of CLUs in elderly patients in rural hospitals where most of these patients seek for medical attention and where clinicians rely on unconventional wound dressing methods to treat CLUs. Our objective was to describe the outcome of PG of CLUs in elderly patients in rural Cameroon.</p><p><strong>Methods: </strong>This was a prospective study conducted in a rural hospital of North West Cameroon. From February 2015 to January 2016, comprehensive historical and clinical data were collected per elderly patient who presented with a chronic leg ulcer necessitating PG. PG was done using a simple procedure and each patient followed up for 8 months. Outcome was described in terms of ulcer healing and pain and donor site complications.</p><p><strong>Results: </strong>Our series included 13 patients: 8 males (61.54%; 95% CI: 31.58-86.14) and 5 females (38.46%; 95% CI: 13.86-68.42) aged from 69 to 88 years (mean: 77.54 ± 5.70 years). Three patients (23.08%; 95% CI: 5.04-53.81) had associated co-morbidities. All the ulcers were unilateral with durations ranging from 7 to 41 months (mean: 19.46 ± 11.03 months). The ulcers ranged in size from 9.0 to 38.1 cm<sup>2</sup> (mean: 17.66 ± 8.35 cm <sup>2</sup>). We registered one (7.69%; 95% CI: 0.19-36.03) graft rejection. Concerning the other ulcers, ten (83.33%; 95% CI: 51.59-97.91) had healed after 12 postoperative weeks while 2 (16.67%; 95% CI: 2.09%-48.41) had healed after 14 postoperative weeks and the mean healing time was 12.33 ± 0.78 weeks. Patients with healed ulcers had reduced ulcer site pain from the immediate postoperative period but there was no significant difference in the mean pain scores before and after graft (6.77 against 4.23, p = 0.13). These ulcers remained healed after 8 postoperative months. Each donor site had healed 2 weeks after PG. Donor site problems were minimal and included hypopigmentation.</p><p><strong>Conclusion: </strong>The outcome of PG of CLUs in our series of older patients was satisfactory. This finding does not discount the role of conservative therapy, but we encourage clinicians in rural Cameroon to consider PG over long-term unconventional conservative therapy in the elderly.</p>","PeriodicalId":9014,"journal":{"name":"BMC Dermatology","volume":"17 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2017-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12895-017-0056-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34835776","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}
BMC DermatologyPub Date : 2017-02-22DOI: 10.1186/s12895-017-0054-9
Lara M Hochfeld, Thomas Anhalt, Céline S Reinbold, Marisol Herrera-Rivero, Nadine Fricker, Markus M Nöthen, Stefanie Heilmann-Heimbach
{"title":"Expression profiling and bioinformatic analyses suggest new target genes and pathways for human hair follicle related microRNAs.","authors":"Lara M Hochfeld, Thomas Anhalt, Céline S Reinbold, Marisol Herrera-Rivero, Nadine Fricker, Markus M Nöthen, Stefanie Heilmann-Heimbach","doi":"10.1186/s12895-017-0054-9","DOIUrl":"https://doi.org/10.1186/s12895-017-0054-9","url":null,"abstract":"<p><strong>Background: </strong>Human hair follicle (HF) cycling is characterised by the tight orchestration and regulation of signalling cascades. Research shows that micro(mi)RNAs are potent regulators of these pathways. However, knowledge of the expression of miRNAs and their target genes and pathways in the human HF is limited. The objective of this study was to improve understanding of the role of miRNAs and their regulatory interactions in the human HF.</p><p><strong>Methods: </strong>Expression levels of ten candidate miRNAs with reported functions in hair biology were assessed in HFs from 25 healthy male donors. MiRNA expression levels were correlated with mRNA-expression levels from the same samples. Identified target genes were tested for enrichment in biological pathways and accumulation in protein-protein interaction (PPI) networks.</p><p><strong>Results: </strong>Expression in the human HF was confirmed for seven of the ten candidate miRNAs, and numerous target genes for miR-24, miR-31, and miR-106a were identified. While the latter include several genes with known functions in hair biology (e.g., ITGB1, SOX9), the majority have not been previously implicated (e.g., PHF1). Target genes were enriched in pathways of interest to hair biology, such as integrin and GnRH signalling, and the respective gene products showed accumulation in PPIs.</p><p><strong>Conclusions: </strong>Further investigation of miRNA expression in the human HF, and the identification of novel miRNA target genes and pathways via the systematic integration of miRNA and mRNA expression data, may facilitate the delineation of tissue-specific regulatory interactions, and improve our understanding of both normal hair growth and the pathobiology of hair loss disorders.</p>","PeriodicalId":9014,"journal":{"name":"BMC Dermatology","volume":"17 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2017-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12895-017-0054-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34756464","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":"Skin cancer knowledge and attitudes in the region of Fez, Morocco: a cross-sectional study.","authors":"Awatef Kelati, Hanane Baybay, Mariam Atassi, Samira Elfakir, Salim Gallouj, Mariame Meziane, Fatima Zahra Mernissi","doi":"10.1186/s12895-017-0055-8","DOIUrl":"10.1186/s12895-017-0055-8","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of skin cancers is constantly increasing in Morocco, and they have gradually become more aggressive due to a significant delay in the diagnosis. Our aim was to assess the levels of awareness and the influencing factors related to skin cancer knowledge in Morocco.</p><p><strong>Methods: </strong>This cross-sectional study was carried out in Morocco through the medium of a validated questionnaire, which contained several items - demographics, skin cancer knowledge and attitudes towards skin cancer patients- during a period of 1 year (2014).</p><p><strong>Results: </strong>Out of the 700 participants enrolled in the study, 17.9% had never heard of skin cancer, 32.5% had a low score of skin cancer knowledge, 66.7% had a moderate score, and only 0.85% had a high score of skin cancer knowledge. Further, 15.1% of the participants were under the assumption that this cancer is contagious. The sun was the most incriminated risk factor in skin cancer occurrence by 74.3% of the participants, and 57.9% of them believed that prevention is important through using various means of photoprotection. After univariate and multivariate analysis, the influencing factors related to the skin cancer knowledge in Morocco were: the socioeconomic status (P = 0.003, OR = 7. 3) and the educational level (p < 0.001, OR = 20. 9).</p><p><strong>Conclusions: </strong>Due to the lack of knowledge or the underestimation of skin cancer in our study population, efforts are needed to promote skin cancer surveillance behaviors in Morocco.</p>","PeriodicalId":9014,"journal":{"name":"BMC Dermatology","volume":" ","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2017-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12895-017-0055-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42669992","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}
BMC DermatologyPub Date : 2017-02-16DOI: 10.1186/s12895-017-0053-x
E. Kouotou, J. R. Nansseu, Alexandra Dominique Ngangue Engome, S. Tatah, Anne-Cécile Zoung-Kanyi Bissek
{"title":"Knowledge, attitudes and practices of the medical personnel regarding atopic dermatitis in Yaoundé, Cameroon","authors":"E. Kouotou, J. R. Nansseu, Alexandra Dominique Ngangue Engome, S. Tatah, Anne-Cécile Zoung-Kanyi Bissek","doi":"10.1186/s12895-017-0053-x","DOIUrl":"https://doi.org/10.1186/s12895-017-0053-x","url":null,"abstract":"","PeriodicalId":9014,"journal":{"name":"BMC Dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12895-017-0053-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41854191","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}
BMC DermatologyPub Date : 2016-10-03DOI: 10.1186/s12895-016-0051-4
K. Papp, R. Bissonnette, M. Gooderham, S. Feldman, L. Iversen, J. Soung, Z. Draelos, C. Mamolo, V. Purohit, Cunshan Wang, W. Ports
{"title":"Treatment of plaque psoriasis with an ointment formulation of the Janus kinase inhibitor, tofacitinib: a Phase 2b randomized clinical trial","authors":"K. Papp, R. Bissonnette, M. Gooderham, S. Feldman, L. Iversen, J. Soung, Z. Draelos, C. Mamolo, V. Purohit, Cunshan Wang, W. Ports","doi":"10.1186/s12895-016-0051-4","DOIUrl":"https://doi.org/10.1186/s12895-016-0051-4","url":null,"abstract":"","PeriodicalId":9014,"journal":{"name":"BMC Dermatology","volume":"108 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12895-016-0051-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66136057","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}