Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. Albrecht von Graefe's archive for clinical and experimental ophthalmology最新文献

{"title":"Exploring <i>Bifidobacterium</i> species community and functional variations with human gut microbiome structure and health beyond infancy.","authors":"Ruben Ladeira, Julien Tap, Muriel Derrien","doi":"10.20517/mrr.2023.01","DOIUrl":"10.20517/mrr.2023.01","url":null,"abstract":"<p><p><b>Aim:</b> The human gut <i>Bifidobacterium</i> community has been studied in detail in infants and following dietary interventions in adults. However, the variability of the distribution of <i>Bifidobacterium</i> species and intra-species functions have been little studied, particularly beyond infancy. Here, we explore the ecology of <i>Bifidobacterium</i> communities in a large public dataset of human gut metagenomes, mostly corresponding to adults. <b>Methods:</b> We selected 9.515 unique gut metagenomes from curatedMetagenomicData. Samples were partitioned by applying Dirichlet's multinomial mixture to <i>Bifidobacterium</i> species. A functional analysis was performed on > 2.000 human-associated <i>Bifidobacterium</i> metagenome-assembled genomes (MAGs) paired with participant gut microbiome and health features. <b>Results:</b> We identified several <i>Bifidobacterium</i>-based partitions in the human gut microbiome differing in terms of the presence and abundance of <i>Bifidobacterium</i> species. The partitions enriched in both <i>B. longum</i> and <i>B. adolescentis</i> were associated with gut microbiome diversity and a higher abundance of butyrate producers and were more prevalent in healthy individuals. <i>B. bifidum</i> MAGs harboring a set of genes potentially related to phages were more prevalent in partitions associated with a lower gut microbiome diversity and were genetically more closely related. <b>Conclusion:</b> This study expands our knowledge of the ecology and variability of the <i>Bifidobacterium</i> community, particularly in adults, and its specific association with the gut microbiota and health. Its findings may guide the rational selection of <i>Bifidobacterium</i> strains for gut microbiome complementation according to the individual's endogenous <i>Bifidobacterium</i> community. Our results also suggest that gut microbiome stratification for particular genera may be relevant for studies of variations of species and associations with the gut microbiome and health.</p>","PeriodicalId":75465,"journal":{"name":"Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. Albrecht von Graefe's archive for clinical and experimental ophthalmology","volume":"258 1","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2023-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10688807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89709234","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":"Two-year outcomes of episcleral brachytherapy adjunct to anti-VEGF therapy for treatment-resistant nAMD.","authors":"Jay Chhablani, Rama Jager, Joshua Ong, Ryan Lohrenz, Russell J Hamilton, Baldassare Stea, Mary Drew, Gregg Kokame","doi":"10.1007/s00417-022-05736-0","DOIUrl":"10.1007/s00417-022-05736-0","url":null,"abstract":"<p><strong>Purpose: </strong>This study was designed to demonstrate the safety and feasibility of episcleral brachytherapy (ESB) for the treatment of anti-vascular endothelial growth factor (anti-VEGF) resistant neovascular age-related macular degeneration (nAMD) in a 6-subject cohort adjunct to anti-VEGF therapy.</p><p><strong>Methods: </strong>Six eyes of six subjects with anti-VEGF resistant nAMD (persistent fluid or hemorrhage despite frequent anti-VEGF treatment) were treated with ESB between May 2018 and July 2018 as part of a larger early feasibility trial. Baseline and follow-up exams with multi-modal imaging were conducted.</p><p><strong>Results: </strong>In this analysis, six eyes were included. The mean age was 74.7 years; 33% were female; 67% had polypoidal choroidal vasculopathy. The mean number of lifetime anti-VEGF injections received prior to the study enrollment was 33.9 injections and 10 injections in the year prior to the study enrollment. In the first and second years following ESB, the mean number of injections was 8.5 and 8, respectively. No evidence of radiation-induced toxicity through 2 years following ESB was observed. The mean baseline VA was 55.3 letters. At 1 year, the mean VA increased by 3.2 letters and 1.7 letters at year 2. At 2 years, the mean change in vascular complex on ICGA was - 18%, - 43% on OCTA, and - 5% on FA. The subjects also experienced a mean decrease in CRT on OCT of 21% after 2 years.</p><p><strong>Conclusions: </strong>The results from this six-subject cohort with 2-year data support additional investigations of ESB for nAMD, specifically those with persistent disease activity and treatment resistant nAMD.</p>","PeriodicalId":75465,"journal":{"name":"Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. Albrecht von Graefe's archive for clinical and experimental ophthalmology","volume":"260 1","pages":"3791-3798"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44586033","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":"Transcription factor FOXP1 mediates vascular endothelial dysfunction in diabetic retinopathy.","authors":"Yekai Zhou, Yaling Xuan, Yi Liu, Jiaxuan Zheng, Xiaoyun Jiang, Yun Zhang, Jian Zhao, Yanli Liu, Meixia An","doi":"10.1007/s00417-022-05698-3","DOIUrl":"10.1007/s00417-022-05698-3","url":null,"abstract":"<p><strong>Background: </strong>Diabetic retinopathy (DR) is still the fastest growing cause of blindness in working aged adults, and its typical characteristics are endothelial cell dysfunction and pericytes loss. Transcription factor fork head box P1 (FOXP1) is a member of FOX family involved in diabetes progression and is expressed in endothelial cells. The purpose of this study was to investigate the role and mechanism of FOXP1 in DR.</p><p><strong>Methods: </strong>The vitreous of DR patients and non-DR patients were collected, and the expression of FOXP1 was detected by real-time polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs) cultured in high glucose simulated DR environment, and the expressions of FOXP1, vascular endothelial growth factor (VEGF), and pigment epithelium derived factor (PEDF) were detected by RT-qPCR and western blot (WB) after transfection of small interfering RNA (siRNA) to knock out FOXP1. At the same time, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay (MTT), 5-ethynyl-2'-deoxyuridine assay (EDU), flow cytometry, Transwell assay, and tube-forming experiment were performed to determine cell proliferation, migration, and tube-forming ability.</p><p><strong>Results: </strong>We found that FOXP1 was highly expressed in the vitreous of DR patients and HUVECs under high glucose condition. After FOXP1 was decreased, the activation of VEGF expression and inhibition of PEDF expression in HUVECs induced by high glucose were reversed; meanwhile, cell proliferation, migration, and tube formation decreased, and apoptosis was promoted.</p><p><strong>Conclusion: </strong>Generally, FOXP1 is highly expressed in the vitreous of DR patients, and its silence prevented VEGF/PEDF signaling pathway stimulated by high glucose and also reduced the proliferation, migration, and tube formation of endothelial cell, thus improving vascular endothelial dysfunction caused by DR. The results indicate that FOXP1 may be a therapeutic target of DR.</p>","PeriodicalId":75465,"journal":{"name":"Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. Albrecht von Graefe's archive for clinical and experimental ophthalmology","volume":"260 1","pages":"3857-3867"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51916747","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":"Evaluation of macular blood flow after intermittent intravenous infusion of high-dose corticosteroids (pulse therapy) in patients with thyroid-associated orbitopathy (TAO) using angio-OCT.","authors":"Nilay Yuksel","doi":"10.1007/s00417-022-05714-6","DOIUrl":"10.1007/s00417-022-05714-6","url":null,"abstract":"","PeriodicalId":75465,"journal":{"name":"Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. Albrecht von Graefe's archive for clinical and experimental ophthalmology","volume":"260 1","pages":"4025"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43678156","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":"Spectrum and resistance in bacterial infections of the ocular surface in a German tertiary referral center 2009-2019.","authors":"Mathias Roth, Paul Goerke, Christoph Holtmann, Andreas Frings, Colin R MacKenzie, Gerd Geerling","doi":"10.1007/s00417-022-05721-7","DOIUrl":"10.1007/s00417-022-05721-7","url":null,"abstract":"<p><strong>Purpose: </strong>Aim of this study was to evaluate the frequencies, trends, and antibiotic resistance of bacteria collected from ocular surface or contact lens material in a German tertiary referral center from 2009 to 2019.</p><p><strong>Methods: </strong>Microbiological data from 2009 to 2019 was analyzed. Culture-dependent microbial identification and analysis of antibiotic sensitivity was completed by the Institute of Microbiology. Statistical analysis of age- and sex-specific differences as well as changes in the microbial spectrum and resistance over the study period was performed with GraphPad Prism 9.0 applying nonparametric tests (level of significance: p ≦ 0.05).</p><p><strong>Results: </strong>A total of 6361 specimens were analyzed. Positivity rate was 18.6%. Sixty-three percent (n = 680) of the bacterial isolates were derived from ocular surface and 37% (n = 399) from contact lens material. The ratio of gram-negative bacteria was significantly higher in contact lens material. Multiresistant bacteria showed a significant increase with patient age (p < 0.0001). An overall increase in resistance to levofloxacin (p = 0.0239) was detected. Only 2.4% and 3.1% isolates were resistant to a combination of moxifloxacin and gentamicin, respectively, levofloxacin and gentamicin.</p><p><strong>Conclusions: </strong>The reported bacterial spectrum is similar to comparable centers. Our data show that it should not be assumed that the newest classes of antibiotics have the best efficacy or lowest resistance levels. In suspected bacterial conjunctivitis, we propose using gentamicin as first-line therapy. In therapy refractive cases and in involvement of the cornea, we recommend a combination of gentamicin and ofloxacin or moxifloxacin. Overall, the evaluated organisms showed good sensitivity to the regularly used antibiotics.</p>","PeriodicalId":75465,"journal":{"name":"Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. Albrecht von Graefe's archive for clinical and experimental ophthalmology","volume":"260 1","pages":"3909-3917"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9666293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47095830","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":"Reply to Letter: Evaluation of macular blood flow after intermittent intravenous infusion of high-dose corticosteroids (pulse therapy) in patients with thyroid-associated orbitopathy (TAO) using angio-OCT.","authors":"Chiara Del Noce, Lorenzo Ferro Desideri, Matilde Roda, Aldo Vagge","doi":"10.1007/s00417-022-05715-5","DOIUrl":"10.1007/s00417-022-05715-5","url":null,"abstract":"","PeriodicalId":75465,"journal":{"name":"Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. Albrecht von Graefe's archive for clinical and experimental ophthalmology","volume":"260 1","pages":"4027"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42572501","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":"SriniVas Sadda, Andrew Schachat, Charles Wilkinson, David Hinton, Peter Wiedemann, K. Bailey Freund, David Sarraf (eds): Ryanʼs Retina, 3 Volume Set 7th Edition, Elsevier, 2022 (eBook ISBN: 9780323722148; Hardcover ISBN: 9780323722131)","authors":"B. Kirchhof","doi":"10.1007/s00417-022-05874-5","DOIUrl":"https://doi.org/10.1007/s00417-022-05874-5","url":null,"abstract":"","PeriodicalId":75465,"journal":{"name":"Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. Albrecht von Graefe's archive for clinical and experimental ophthalmology","volume":"261 1","pages":"599 - 599"},"PeriodicalIF":0.0,"publicationDate":"2022-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45663841","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":"Comparison of subjective cyclofusion ranges and objective ocular torsion in normal participants according to age.","authors":"Manami Kawai, Toshiaki Goseki, Takashi Okano, Hitoshi Ishikawa","doi":"10.1007/s00417-022-05734-2","DOIUrl":"10.1007/s00417-022-05734-2","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the relationship between subjective cyclofusion ranges and objective ocular torsion in normal participants according to age.</p><p><strong>Methods: </strong>This cross-sectional study included 120 participants aged ≥ 20 years with no ocular diseases. The subjective cyclofusion ranges were measured centrifugally and centripetally in the direction of excyclotorsion and incyclotorsion, respectively, concurrently with rotational diplopia production by rotation using synoptophore. Disc fovea angle (DFA) was defined as the angle formed by two lines: a line passing through the center of the optic nerve papilla and fovea and a horizontal line passing through the center of gravity of the optic papilla using fundus photographs.</p><p><strong>Results: </strong>The participants were aged 49.1 ± 17.7 years. The total cyclofusion centrifugal (sum of extorsion and intorsion) and centripetal ranges were 10.9 ± 2.2° and 7.2 ± 1.8°, respectively, both of which decreased in participants in their 60 s and 70 s (p < 0.01). The DFA was - 7.0 ± 3.4° in the right eye (- : excyclo, + : incyclo) and - 8.0 ± 3.2° in the left, which was associated with age (p < 0.001). The correlation between the DFA and centrifugal (r =  - 0.13, p = 0.16) and centripetal (r =  - 0.002, p = 0.99) cyclofusion ranges of extorsion was not significantly different. The centrifugal (r = 0.37, p < 0.001) and centripetal (r = 0.40, p < 0.001) cyclofusion ranges of intorsion were positively correlated.</p><p><strong>Conclusion: </strong>Subjective cyclofusion ranges decreased in both extorsion and intorsion in the elderly. Objective ocular torsion showed excyclotorsion with age. When strabismus surgery is performed in elderly patients with torsional strabismus, the decrease in subjective cyclofusion ranges should be considered.</p>","PeriodicalId":75465,"journal":{"name":"Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. Albrecht von Graefe's archive for clinical and experimental ophthalmology","volume":"260 1","pages":"3675-3681"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43385664","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":"Cataract surgery astigmatism incisional management. Manual relaxing incision versus femtosecond laser-assisted arcuate keratotomy. A systematic review.","authors":"Timoteo González-Cruces, Antonio Cano-Ortiz, María Carmen Sánchez-González, José-María Sánchez-González","doi":"10.1007/s00417-022-05728-0","DOIUrl":"10.1007/s00417-022-05728-0","url":null,"abstract":"<p><strong>Purpose: </strong>This systematic review aims to compare corneal astigmatism correction in cataract surgery through corneal relaxing incision, manually and femtosecond laser assisted.</p><p><strong>Methods: </strong>The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We used PubMed, Scopus, and Web of Science (WOS) as databases from January 2010 to March 30, 2021. Patients with keratoconus, corneal ectasia, and a previous history of eye surgery were excluded because our aim was to analyze only healthy eyes.</p><p><strong>Results: </strong>A total of 1025 eyes were evaluated from 946 patients (mean age was 68.90 ± 5.12) in manual incision group articles, while 1905 eyes of 1483 patients (mean age was 65.05 ± 4.57) were evaluated in femtosecond laser arcuate keratotomy (FLAK) articles. The mean uncorrected distance visual acuity (UDVA) was 0.19 ± 0.12 and 0.15 ± 0.05 logMAR for manual incision and FLAK articles, respectively (p = 0.39). The mean correction index (CI) was similar in both groups: 0.77 ± 0.18 in manual incision and 0.79 ± 0.17 in femtosecond laser assisted incision (p = 0.70). Refractive stability was found after 3 months and no serious complications were reported during the follow-up in any group.</p><p><strong>Conclusion: </strong>Both techniques are safe and moderately effective in corneal astigmatism correction in cataract surgery. FLAK represents a more precise and predictable approach. However, since visual and refractive outcomes appear to be similar in both cases, the cost-benefit analysis is controversial.</p>","PeriodicalId":75465,"journal":{"name":"Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. Albrecht von Graefe's archive for clinical and experimental ophthalmology","volume":"260 1","pages":"3437-3452"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48791784","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":"Use of selective laser trabeculoplasty as an alternative in patients who developed ocular hypertension after intravitreal dexamethasone implants: a series of 35 eyes.","authors":"Jérémy Billant, Emilie Agard, Ikrame Douma, Antoine Levron, Olivier Brunet, Charles-Henry Remignon, Lucas Sejournet, Corinne Dot","doi":"10.1007/s00417-022-05725-3","DOIUrl":"10.1007/s00417-022-05725-3","url":null,"abstract":"<p><strong>Purpose: </strong>Steroid-induced ocular hypertension (OHT) occurs in about a third of cases after dexamethasone implant (DEXi) intravitreal injection (IVI), for which treatment discontinuation may be required. The aim of this study was to assess the benefit of selective laser trabeculoplasty (SLT) in patients who developed transient OHT after DEXi injection to prevent subsequent steroid-induced OHT peaks during reinjections.</p><p><strong>Methods: </strong>A real-life, retrospective, and observational study was conducted to assess the intraocular pressure (IOP) after SLT in steroid responders after DEXi injection (IOP > 21 mmHg). Were analyzed: IOP 1 and 2 months after SLT, maximum IOP (IOP_max) after each new DEXi IVI, and the number of prophylactic hypotensive treatments needed at the time of DEXi reinjections.</p><p><strong>Results: </strong>Thirty-five eyes of 29 patients were included. The mean macular edema follow-up duration was 38.4 ± 28.4 months. SLT was performed after a mean number of 6.3 ± 4.7 DEXi IVIs. After SLT, the IOP_max measured after the first reinjection was lowered by 36.6 ± 14.7% (p < 0.0001). The mean number of hypotensive treatments was 2.1 ± 0.9 before versus 1.5 ± 0.8 after SLT. The post-reinjection lowering in OHT peak was maintained during the subsequent 3 DEXi IVIs: - 29.1 ± 25.5% (p = 0.0009), - 35.8 ± 13.1% (p = 0.0078), and - 45.4 ± 8.6% (p = 0.0312) after the second, third, and fourth DEXi reinjections. SLT allowed continuing injections in 88.6% of patients.</p><p><strong>Conclusion: </strong>The use of 180° SLT in this indication could be an effective therapeutic alternative to control steroid-induced OHT and safely continue DEXi injections.</p>","PeriodicalId":75465,"journal":{"name":"Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. Albrecht von Graefe's archive for clinical and experimental ophthalmology","volume":"260 1","pages":"3665-3673"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45446232","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}