Life-Basel最新文献

{"title":"Epigenetic Modulation Directs Recovery Post LASIK and SMILE Surgery: An Experimental Study.","authors":"Rohit Shetty, Pooja Khamar, Ramaraj Kannan, Puja Thacker, Nimisha Rajiv Kumar, Arkasubhra Ghosh, Vrushali Deshpande","doi":"10.3390/life15020246","DOIUrl":"10.3390/life15020246","url":null,"abstract":"<p><strong>Purpose: </strong>refractive surgery, such as LASIK and SMILE, induces a wound healing response that leads to significant corneal stromal remodeling. We have shown that the protein profile in the stroma changes dramatically immediately post-surgery. However, the methylation status of the DNA post-refractive surgery remains unknown.</p><p><strong>Design/participants: </strong>DNA methylation study. Refractive surgery (SMILE/LASIK) performed on donor eye globes.</p><p><strong>Method: </strong>we investigated the epigenetic changes post-surgery in relation to long term ECM remodeling in an experimental ex vivo study design. Donor globes (n = 19) were obtained from the eye bank. Three globes served as non-surgical controls while SMILE (-6DS) and LASIK surgery (-6DS) were performed on eight globes each and incubated for 3 days and 2 weeks (n = 4 per group per time point). Here, we compared the DNA methylation landscapes of LASIK and SMILE stroma using the Illumina Infinium Human Methylation 850 EPIC array (HM850).</p><p><strong>Results: </strong>significant changes in DNA methylation patterns were observed post-operatively in both LASIK and SMILE groups. Specific genes involved in the activation of actin cytoskeleton and inflammation (<i>smad3</i>, <i>prkca</i> and <i>ssh2</i>) showed hypomethylation in LASIK after 2 weeks and LASIK SMILE after 3 days, respectively, suggesting their active role in corneal repair. The genes (<i>gaa</i>, <i>gstm1</i>, <i>mgat1</i>, <i>galnt9</i> and <i>galnt5</i>) involved in sphingolipid metabolism and mucin biosynthesis showed hypomethylation in SMILE after 3 days.</p><p><strong>Conclusions: </strong>our results suggest that altered DNA methylation patterns may have relevance to the development of complications of haze post-refractive surgery. It also presents the opportunity to utilize drugs that regulate chromatin remodeling for optimal outcomes.</p>","PeriodicalId":56144,"journal":{"name":"Life-Basel","volume":"15 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11856829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Hand Function Using Relative Motion Extension Concept (with or Without Night Wrist Orthosis) or Dynamic Extension Orthosis for Extensor Tendon Injuries in Zones 4-6-A Randomized Controlled Trial.","authors":"Vida Bojnec, Jerneja Vidmar, Zvezdana Sužnik, Aleksandra Orož Koprivnik, Milena Špes Škrlec, Maša Frangež, Neža Majdič, Gaj Vidmar, Breda Jesenšek Papež","doi":"10.3390/life15020249","DOIUrl":"10.3390/life15020249","url":null,"abstract":"<p><p>This study aimed to compare outcomes of early active motion (EAM) using the relative motion extension (RME) approach to outcomes of early passive motion (EPM) with a dynamic extension orthosis (DEO) and to evaluate whether the RME-only approach is equivalent to the RME-plus approach. Fifty adults were randomized into one of the three intervention groups receiving the DEO, RME only, or RME plus orthosis. The score of the Jebsen-Taylor hand function test (JTHFT) without writing and QuickDASH at T1, all measures of mobility at T1 and T2, and grip strength were better in the RME-only and RME-plus group compared to the DEO group, whereas the values of Patient Evaluation Measure (PEM) at T1 and T2, as well as QuickDASH score at T2, orthosis adherence, and the patient's comfort while wearing the orthoses did not statistically significantly differ among the three groups. The RME concept after extensor tendon injuries in zones 4-6 is superior to the DEO protocol in terms of earlier regain of hand function. The DEO and RME protocols were equivalent regarding patients' adherence and satisfaction with the orthosis. We found no differences in the RME-plus and RME-only protocols, indicating the safe use of the RME-only protocol in single extensor tendon injuries in zones 4-6.</p>","PeriodicalId":56144,"journal":{"name":"Life-Basel","volume":"15 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11856411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cohort-Based Evaluation of the Risk of Low Back Pain After Total Hip Arthroplasty: A Long-Term Study.","authors":"Francisco José Gallego-Peñalver, Armando Chaure-Pardos, Silvia Beatriz Romero-de-la-Higuera, Eva María Gómez-Trullén","doi":"10.3390/life15020248","DOIUrl":"10.3390/life15020248","url":null,"abstract":"<p><p>Low back pain (LBP) is a potential complication after total hip arthroplasty (THA). However, some studies suggest that THA not only alleviates joint pain but also resolves LBP in up to 88.2% of patients. Most of these observations are limited to short-term follow-ups. This study investigates the long-term relationship between THA and LBP, challenging the notion that THA resolves LBP. A retrospective review was conducted on 236 patients who underwent THA (2010-2020). Multiple statistical models were applied, including unadjusted unmatched, adjusted unmatched, adjusted matched, and target trial emulation with 7887 subjects, to evaluate LBP incidence. Of the 236 patients, 119 developed postoperative LBP. The unadjusted unmatched analysis showed a relative risk (RR) of 2.23 (95%CI: 1.5-3.2). Adjusting for age, sex, body mass index (BMI), and recruitment period reduced the RR to 1.64 (95%CI: 1.0-2.6). The adjusted matched analysis showed an RR of 1.09 (95%CI: 0.4-3.0), while the target trial emulation simulated an RR of 1.03 (95%CI: 0.7-1.8), indicating no significant differences. Despite an apparent initial association, adjusted analyses do not support a significant long-term relationship between THA and LBP. No reduction in postoperative LBP incidence was observed, suggesting THA is safe regarding LBP risk but lacks a curative effect. Rigorous confounding adjustment is essential in retrospective studies.</p>","PeriodicalId":56144,"journal":{"name":"Life-Basel","volume":"15 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11856784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143504868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On the Origin of Information Dynamics in Early Life.","authors":"Robert A Gatenby, Jill Gallaher, Hemachander Subramanian, Emma U Hammarlund, Christopher J Whelan","doi":"10.3390/life15020234","DOIUrl":"10.3390/life15020234","url":null,"abstract":"<p><p>We hypothesize that predictable variations in environmental conditions caused by night/day cycles created opportunities and hazards that initiated information dynamics central to life's origin. Increased daytime temperatures accelerated key chemical reactions but also caused the separation of double-stranded polynucleotides, leading to hydrolysis, particularly of single-stranded RNA. Daytime solar UV radiation promoted the synthesis of organic molecules but caused broad damage to protocell macromolecules. We hypothesize that inter-related simultaneous adaptations to these hazards produced molecular dynamics necessary to store and use information. Self-replicating RNA heritably reduced the hydrolysis of single strands after separation during warmer daytime periods by promoting sequences that formed hairpin loops, generating precursors to transfer RNA (tRNA), and initiating tRNA-directed evolutionary dynamics. Protocell survival during daytime promoted sequences in self-replicating RNA within protocells that formed RNA-peptide hybrids capable of scavenging UV-induced free radicals or catalyzing melanin synthesis from tyrosine. The RNA-peptide hybrids are precursors to ribosomes and the triplet codes for RNA-directed protein synthesis. The protective effects of melanin production persist as melanosomes are found throughout the tree of life. Similarly, adaptations mitigating UV damage led to the replacement of Na⁺ by K⁺ as the dominant mobile cytoplasmic cation to promote diel vertical migration and selected for homochirality. We conclude that information dynamics emerged in early life through adaptations to predictably fluctuating opportunities and hazards during night/day cycles, and its legacy remains observable in extant life.</p>","PeriodicalId":56144,"journal":{"name":"Life-Basel","volume":"15 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11856217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obstetrics and Gynecology Medicine: Go from Bench to Bedside.","authors":"Stefano Canosa, Anna Maria Nuzzo","doi":"10.3390/life15020233","DOIUrl":"10.3390/life15020233","url":null,"abstract":"<p><p>As we reach the conclusion of this Special Issue, Obstetrics and Gynecology Medicine: Go From Bench to Bedside, it is evident that the dynamic intersection between basic science and clinical practice continues to drive the evolution of care in women's health [...].</p>","PeriodicalId":56144,"journal":{"name":"Life-Basel","volume":"15 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11856250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD56-Positive NK Cells and CD138-Positive Plasma Cells in Basal Decidua of Term Placentas in Singleton Pregnancies After Assisted Reproductive Technology Treatment of Endometriosis-Related Infertility.","authors":"Stipe Dumancic, Marinela Bakotin Jakovac, Marko Drazen Mimica, Sandra Zekic Tomas, Jelena Marusic","doi":"10.3390/life15020240","DOIUrl":"10.3390/life15020240","url":null,"abstract":"<p><p>A eutopic endometrium in endometriosis shows altered immune responses, including abnormalities of NK cells and expression of plasma cells, related to reproductive issues. This study investigated the counts of CD56-positive NK cells and CD138-positive plasma cells in the basal decidua of term placentas in singleton pregnancies after endometriosis-related infertility conceived by assisted reproductive technology (ART). This single-center, case-control study involved immunohistochemical analysis of CD56-positive NK cells and CD138-positive plasma cells in basal decidua using primary monoclonal mouse antibodies, followed by secondary antibodies using a standardized protocol. CD56 and CD138 immunohistochemically positive cells were reported as the total cell count for each studied antibody expressed per 1 mm² of basal decidua (Olympus BX46 and Olympus Image Analyzer). Placental samples containing basal decidua from 36 participants with endometriosis-related infertility who conceived by ART, 31 participants with male factor infertility who conceived by ART and 40 healthy controls were included. Endometriosis decidua showed the lowest median count of CD56-positive NK cells (11.5 / mm², <i>p</i> = 0.039) in BD compared to male factor group (25 / mm²) and healthy controls (24.5 / mm²). No differences were found for CD138-positive plasma cells counts between study groups. Basal decidua in pregnancies after endometriosis-related infertility showed reduced total count of CD56-positive NK cells, without differences in the CD138-positive plasma cell counts compared to control groups. Future studies should investigate how changes in NK cells throughout pregnancy affect the development of perinatal complications and placental pathologies in women with endometriosis, which could uncover potential diagnostic and therapeutic targets.</p>","PeriodicalId":56144,"journal":{"name":"Life-Basel","volume":"15 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11856745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Decade of Progress in Ultrasound Assessments of Subcutaneous and Total Body Fat: A Scoping Review.","authors":"Monica Neagu, Adrian Neagu","doi":"10.3390/life15020236","DOIUrl":"10.3390/life15020236","url":null,"abstract":"<p><p>Body composition assessment by ultrasonography is a vivid research field. Ultrasound (US) can be used to quantify subcutaneous and visceral fat, to evaluate the quantity and quality of skeletal muscle, and to infer intracellular fat content. This scoping review aimed to summarize recent advancements in subcutaneous fat estimation using US and related applications. A systematic search was conducted on PubMed, MEDLINE, Scopus, Google Scholar, and Web of Science to identify original articles published in English between 1 January 2014 and 20 December 2024. A total of 1869 articles were screened based on their titles and abstracts, and 283 were retrieved for full-text evaluation. Our search and selection strategy resulted in 89 eligible documents. The literature discussed in this review suggests that US is a reliable and valid technique for measuring subcutaneous fat thickness at selected anatomic locations. Standardized measurement protocols enabled accurate subcutaneous adipose tissue (SAT) patterning in various populations (e.g., athletes, children, adults, and patients with anorexia nervosa). Further research is warranted to establish clinically relevant cutoff values. US-derived SAT thicknesses can also provide whole-body fat estimates of fat mass (FM), fat-free mass (FFM), and body fat percentage (%BF). To this end, prediction formulas were developed to ensure agreement with criterion measures given by laboratory techniques, or multicompartment models based on combinations thereof. The resulting assessments of global adiposity were reliable but inaccurate in certain populations (e.g., overweight and obese). Nevertheless, due to its high reliability, US might be used to track changes in body fat content during nutritional and/or lifestyle interventions. Future investigations will be needed to evaluate its accuracy in this respect and to improve the validity of whole-body fat estimation compared to multicompartment models.</p>","PeriodicalId":56144,"journal":{"name":"Life-Basel","volume":"15 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11856862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anatomical-Based Filler Injection Diagnosis to Treatment Techniques: Infraorbital Groove and Hollowness.","authors":"Gi-Woong Hong, Wonseok Choi, Song-Eun Yoon, Jovian Wan, Kyu-Ho Yi","doi":"10.3390/life15020237","DOIUrl":"10.3390/life15020237","url":null,"abstract":"<p><p>Infraorbital groove and hollowness are common aging-related anatomical changes in the periorbital region, leading to a sunken and tired appearance. These conditions are caused by the progressive loss of volume in the deep fat pads, including the sub-orbicularis oculi fat (SOOF) and malar fat, along with skin thinning and decreased elasticity. Filler injections, particularly hyaluronic acid-based fillers, are the preferred treatment to restore volume and smooth the under-eye area. Proper diagnosis, understanding of anatomical variations, and accurate injection techniques are essential to avoid complications and achieve natural, esthetically pleasing outcomes. Treatments should consider the patient's unique anatomy and potential adjunctive procedures to ensure balanced and harmonious facial rejuvenation.</p>","PeriodicalId":56144,"journal":{"name":"Life-Basel","volume":"15 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11856387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin C: From Self-Sufficiency to Dietary Dependence in the Framework of Its Biological Functions and Medical Implications.","authors":"Andrei Cristian Grădinaru, Setalia Popa","doi":"10.3390/life15020238","DOIUrl":"10.3390/life15020238","url":null,"abstract":"<p><p>Vitamin C is an organic compound biosynthesized in plants and most vertebrates. Since its discovery, the benefits of vitamin C use in the cure and prevention of various pathologies have been frequently reported, including its anti-oxidant, anti-inflammatory, anticoagulant, and immune modulatory properties. Vitamin C plays an important role in collagen synthesis and subsequent scurvy prevention. It is also required in vivo as a cofactor for enzymes involved in carnitine and catecholamine norepinephrine biosynthesis, peptide amidation, and tyrosine catabolism. Moreover, as an enzymatic cofactor, vitamin C is involved in processes of gene transcription and epigenetic regulation. The absence of the synthesis of L-gulono-1,4-lactone oxidase, a key enzyme in the pathway of vitamin C synthesis, is an inborn metabolism error in some fishes and several bird and mammalian species, including humans and non-human primates; it is caused by various changes in the structure of the original <i>GULO</i> gene, making these affected species dependent on external sources of vitamin C. The evolutionary cause of <i>GULO</i> gene pseudogenization remains controversial, as either dietary supplementation or neutral selection is evoked. An evolutionary improvement in the control of redox homeostasis was also considered, as potentially toxic H₂O₂ is generated as a byproduct in the vitamin C biosynthesis pathway. The inactivation of the <i>GULO</i> gene and the subsequent reliance on dietary vitamin C may have broader implications for aging and age-related diseases, as one of the most important actions of vitamin C is as an anti-oxidant. Therefore, an important aim for medical professionals regarding human and animal health should be establishing vitamin C homeostasis in species that are unable to synthesize it themselves, preventing pathologies such as cardiovascular diseases, cognitive decline, and even cancer.</p>","PeriodicalId":56144,"journal":{"name":"Life-Basel","volume":"15 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11856994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Prognostic Power of Three-Dimensional Speckle-Tracking Echocardiography-Derived Peak Left Atrial Reservoir Global Longitudinal Strain in Healthy Adults-An Analysis from the MAGYAR-Healthy Study.","authors":"Attila Nemes, Dorottya Lilla Olajos, Alexandru Achim, Zoltán Ruzsa, Nóra Ambrus, Csaba Lengyel","doi":"10.3390/life15020232","DOIUrl":"10.3390/life15020232","url":null,"abstract":"<p><p><b>Introduction:</b> The contraction-relaxation pattern of the left atrial (LA) walls is opposite to that detected in the left ventricle, which includes thinning in radial, lengthening in longitudinal, and widening in circumferential directions in the systolic reservoir phase of LA function as measured by three-dimensional speckle-tracking echocardiography (3DSTE). Global longitudinal strain (GLS) is a quantitative feature of longitudinal wall contraction referring to the whole LA. The present study aims to clarify the expected prognostic impact of peak LA-GLS as assessed by 3DSTE in healthy participants during a long-term follow-up period. <b>Methods:</b> The study consisted of 142 healthy adults (with an average age of 32.1 ± 12.7 years; 72 of the participants were men), in whom complete two-dimensional Doppler echocardiography and 3DSTE were performed on a voluntary basis. <b>Results:</b> Thirteen adults suffered from a cardiovascular event, including two cardiac deaths during a mean follow-up of 8.35 ± 4.20 years. Peak LA-GLS ≥ 20.9%, as assessed by 3DSTE, was found to be a significant predictor for cardiovascular event-free survival by using ROC analysis (specificity 74%, sensitivity 62%, area under the curve 0.69, <i>p</i> = 0.025). Healthy individuals with peak LA-GLS < 20.9% had a lower LV-EF and a significantly higher ratio of cardiovascular events compared to cases with peak LA-GLS ≥ 20.9%. Subjects who experienced cardiovascular events had lower peak LA-GLS and the ratio of subjects with peak LA-GLS < 20.9% proved to be significantly increased compared to that of cases without cardiovascular events. <b>Conclusions:</b> 3DSTE-derived peak LA-GLS representing LA lengthening in the end-systolic reservoir phase of LA function predicts future cardiovascular events in healthy adults.</p>","PeriodicalId":56144,"journal":{"name":"Life-Basel","volume":"15 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11856474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}