Life最新文献

{"title":"Determinants of Human Asymmetry: Does Asymmetrical Retinal Vasculature Predict Asymmetry Elsewhere in the Body?","authors":"Doris Plećaš, Vesna Gotovac Đogaš, O. Polašek, Jelena Škunca Herman","doi":"10.3390/life14080929","DOIUrl":"https://doi.org/10.3390/life14080929","url":null,"abstract":"The aim of this study was to explore retinal vasculature asymmetry (ReVA) patterns in subjects from the islands of Vis and Korcula and the city of Split, Croatia. Asymmetry estimates were based on topographic image analysis of non-mydriatic retinal fundus photographs and compared with nine ophthalmic measurements, three Doppler-based pressure indices and eight frequencies of audiometry. ReVA was also correlated to the genomic runs of homozygosity (ROHs) and used in a Cox regression survival model, where we adjusted for the effects of sex, age and comorbidity. In 1873 subjects, ReVA estimates were significantly correlated with most ophthalmic asymmetry measures, less strongly with the ankle–brachial pressure index and only modestly with higher-amplitude audiometry asymmetries (lowest p = 0.020). ReVA was significantly correlated with the number of ROHs (r = 0.229, p < 0.001) but less strongly with the ROH length (r = 0.101, p < 0.001). The overlap of asymmetries was low, with only 107 subjects (5.7% of the total sample) who had two or more instances in which they were among the top 10%. Multiple asymmetries did not affect survival (HR = 0.74, 95% confidence intervals 0.45–1.22). Retinal vasculature asymmetry is a poor predictor of asymmetry elsewhere in the body. Despite its existence and apparent association with comorbidities, the observed extent of retinal vasculature asymmetry did not affect the lifespan in this population.","PeriodicalId":18182,"journal":{"name":"Life","volume":"60 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141807562","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":"Effects of Endurance Training on Antioxidant and Hormonal Status in Peripheral Blood of Young Healthy Men","authors":"S. Stojiljković, L. Gavrilović, S. Pejić, S. Pajović, M. Macura, Dragan Nikolic, S. Bubanj, V. Stojiljkovic","doi":"10.3390/life14080921","DOIUrl":"https://doi.org/10.3390/life14080921","url":null,"abstract":"(1) Background: Physical activity may cause an imbalance in the major functions of the human body. This study aimed to investigate the effects of endurance running training on the parameters of the antioxidant defense system (SOD, CAT, GPx, GR, GSH), LPO (malondialdehyde, MDA), and stress hormones (A, NA) in young healthy, previously untrained men. (2) Methods: The training program was as follows: 8 weeks of running, three times per week; the duration of a single session was 30–70 min, the intensity was twice a week in the so-called extensive endurance zone, and once a week in the anaerobic threshold zone. Blood samples were collected from the subjects, before and after the running program. (3) Results: The training program resulted in a significant increase in maximal oxygen consumption (p < 0.001). The activities of SOD, GPx, and GR also increased significantly (p < 0.05, p < 0.01, and p < 0.05, respectively), while CAT activity and GSH and MDA concentrations remained unchanged. The concentration of A decreased (p < 0.05), while the NA concentration increased significantly (p < 0.05). SOD, GPx, GR, and NA positively correlated with VO2max (p < 0.05, p < 0.001, p < 0.01, p < 0.05, respectively), while a negative correlation was detected between A and VO2max (p < 0.05). (4) Conclusions: These results indicate that there is no persistent oxidative stress in response to the applied 8-week running program, probably due to exercise-induced protective alterations in the antioxidant defense system. Furthermore, adaptations occurred at the hormonal level, making the organism more ready for a new challenge.","PeriodicalId":18182,"journal":{"name":"Life","volume":"27 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141808770","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":"Resistome Signature and Antibiotic Resistance Mechanisms in Rhizospheric Soil Bacteriomes of Mecca Region, Saudi Arabia: Insights into Impact on Human Health","authors":"R. Jalal, H. Sonbol","doi":"10.3390/life14080928","DOIUrl":"https://doi.org/10.3390/life14080928","url":null,"abstract":"The objective of this investigation is to ascertain the distinctive profile of the rhizospheric soil resistome within the Mecca region, while also evaluating the potential risks associated with the horizontal transfer of resistome determinants to the open environment and human clinical isolates. We have made metagenomic whole-genome shotgun sequencing for rhizospheric microbiomes of two endemic plants, namely Moringa oleifera and Abutilon fruticosum. The rhizospheric resistomes of the two plants and the abundance of antibiotic resistance genes (ARGs) were identified by cross-referencing encoded proteins with the comprehensive antibiotic resistance database (CARD). The identified ARGs were then analyzed for their antimicrobial resistance (AMR) mechanisms. Predominantly within this soil are the two bacterial species Pseudomonas aeruginosa and Mycobacterium tuberculosis. These opportunistic human pathogens are implicated in respiratory infections and are correlated with heightened mortality rates. The most prevalent array of ARGs existing in this soil comprises mexA, mexC, mexE, and cpxR, associated with mechanisms of antibiotic active efflux, along with ACC(2), ACC(3), AAC(6), and APH(6), in addition to arr1, arr3, arr4, iri, rphA, and rphB, implicated in antibiotic inactivation. Furthermore, vanS, vanR, and vanJ are identified for antibiotic target alteration, while rpoB2 and RbpA are noted for antibiotic target replacement and protection, respectively. These mechanisms confer resistance against a diverse spectrum of drug classes encompassing fluoroquinolones, aminoglycosides, glycopeptides, and rifampicins. This study underscores the potential hazards posed to human health by the presence of these pathogenic bacteria within the rhizospheric soil of the Mecca region, particularly in scenarios where novel ARGs prevalent in human populations are harbored and subsequently transmitted through the food chain to human clinical isolates. Consequently, stringent adherence to good agricultural and food transportation practices is imperative, particularly with regard to edible plant parts and those utilized in folkloric medicine.","PeriodicalId":18182,"journal":{"name":"Life","volume":"30 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141810207","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":"The Brain–Heart Axis: An Umbrella Review on Impact of Psychiatric Disease on Incidence, Management, and Outlook of Cardiovascular Disease","authors":"Marianna Mazza, Giuseppe Biondi-Zoccai, Francesco Maria Lisci, Caterina Brisi, Greta Sfratta, Sara Rossi, G. Traversi, Eleonora Gaetani, Roberto Pola, Sofia Morini, Enrico Romagnoli, B. Simeoni, M. Covino, G. Marano","doi":"10.3390/life14080919","DOIUrl":"https://doi.org/10.3390/life14080919","url":null,"abstract":"Psychiatric conditions, such as depression, anxiety, bipolar disorder, and schizophrenia, are increasingly recognized as significant risk factors for cardiovascular disease (CVD). This review systematically analyzes evidence from various databases to provide a comprehensive understanding of the impact of psychiatric illnesses on the incidence, management, and prognosis of CVD. Key findings suggest a bidirectional relationship between psychiatric disorders and CVD, indicating that mental health conditions can predispose individuals to CVD, while CVD can exacerbate or trigger psychiatric symptoms. The review explores the underlying mechanisms of these associations, including behavioral factors, stress responses, and medication side effects. It also examines the challenges in managing CVD patients with comorbid psychiatric conditions, emphasizing the importance for integrated care approaches. This review underscores the necessity of considering mental health as an integral component of cardiovascular care and calls for further research to develop tailored management strategies for these complex conditions, ultimately aiming to improve patient outcomes and quality of life. This comprehensive analysis provides valuable insights for future investigations and guides clinicians in optimizing care for patients with both psychiatric and cardiovascular conditions.","PeriodicalId":18182,"journal":{"name":"Life","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141813242","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":"Sensitization to Lanolin in North-Eastern Italy, 1997–2021: Prevalence, Risk Factors and the Impact of Occupation","authors":"Luca Cegolon, F. Larese Filon","doi":"10.3390/life14080916","DOIUrl":"https://doi.org/10.3390/life14080916","url":null,"abstract":"Background: Direct skin contact with items containing lanolin can induce sensitization and development of contact dermatitis (CD). This multi-centric study investigated prevalence of lanolin sensitization among 30,269 outpatients from North-Eastern Italy patch tested during 1997–2021. Methods: European baseline and extended Triveneto series were applied on the upper part of patients’ back and removed after 48 h. Risk factors for lanolin sensitization were investigated by multiple logistic regression analysis, reporting adjusted odds ratios (aOR) with 95% confidence interval (95%CI). Results. Overall lanolin patch test positive ratio (PTPR) was 1.64% (=501/30,629), with variability over time and by research center. The body area most frequently affected by CD were hands (36.32%), followed by face (19.52%) and legs (8.09%), with a lanolin PTPR of 1.68%, 1.37% and 3.07%, respectively. Prevalence of occupational CD was 8.24%, and 1.83% patients with occupational CD patch tested positive against lanolin. Lanolin sensitization was significantly higher in males (aOR = 1.34; 95%CI: 1.08; 1.65) and among patients with leg CD aged 49–60 years (aOR = 2.34; 95%CI: 1.20; 4.57) or older than 60 (aOR = 4.21; 95%CI: 2.59; 6.85). Sub-group analysis confirmed the significantly higher sensitization rate of older patients with leg CD, with much stronger effect size in females 61+ years old (aOR = 5.33; 95%CI 2.87; 9.89) than males in the same age group (aOR = 2.92; 95%CI: 1.34; 6.39). Moreover, female house painters were more likely to test positive to lanolin. Conclusions: The variability of lanolin PTPR over time and by research center endorsed the ongoing debate on the relevance of the respective skin reaction. Clinicians assessing patients with dermatitis should collect information on potential risk factors for lanolin sensitization, particularly use of skin care products containing the hapten. Occupational exposure to lanolin-containing varnishes should also be considered.","PeriodicalId":18182,"journal":{"name":"Life","volume":"34 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141814317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Role of Susceptibility Inducing Cofactors and of Acetaminophen in the Etiology of Autism Spectrum Disorder","authors":"John P. Jones, Lauren Williamson, Zacharoula Konsoula, Rachel Anderson, Kathryn J. Reissner, William Parker","doi":"10.3390/life14080918","DOIUrl":"https://doi.org/10.3390/life14080918","url":null,"abstract":"More than 20 previously reported lines of independent evidence from clinical observations, studies in laboratory animal models, pharmacokinetic considerations, and numerous temporal and spatial associations indicate that numerous genetic and environmental factors leading to inflammation and oxidative stress confer vulnerability to the aberrant metabolism of acetaminophen during early development, leading to autism spectrum disorder (ASD). Contrary to this conclusion, multivariate analyses of cohort data adjusting for inflammation-associated factors have tended to show little to no risk of acetaminophen use for neurodevelopment. To resolve this discrepancy, here we use in silico methods to create an ideal (virtual) population of 120,000 individuals in which 50% of all cases of virtual ASD are induced by oxidative stress-associated cofactors and acetaminophen use. We demonstrate that Cox regression analysis of this ideal dataset shows little to no risk of acetaminophen use if the cofactors that create aberrant metabolism of acetaminophen are adjusted for in the analysis. Further, under-reporting of acetaminophen use is shown to be a considerable problem for this analysis, leading to large and erroneously low calculated risks of acetaminophen use. In addition, we argue that factors that impart susceptibility to acetaminophen-induced injury, and propensity for acetaminophen use itself, can be shared between the prepartum, peripartum, and postpartum periods, creating additional difficulty in the analysis of existing datasets to determine risks of acetaminophen exposure for neurodevelopment during a specific time frame. It is concluded that risks of acetaminophen use for neurodevelopment obtained from multivariate analysis of cohort data depend on underlying assumptions in the analyses, and that other evidence, both abundant and robust, demonstrate the critical role of acetaminophen in the etiology of ASD.","PeriodicalId":18182,"journal":{"name":"Life","volume":"129 42","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141811308","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":"Acute Effects of Breath-Hold Conditions on Aerobic Fitness in Elite Rugby Players","authors":"Wendi Wang, Dongzhe Wu, Hao Wang, Zhiqiang Zhang, Xuming Jiang, Shufeng Li, Yongjin Shi, Xiaolin Gao","doi":"10.3390/life14080917","DOIUrl":"https://doi.org/10.3390/life14080917","url":null,"abstract":"The effects of face immersion and concurrent exercise on the diving reflex evoked by breath-hold (BH) differ, yet little is known about the combined effects of different BH conditions on aerobic fitness in elite athletes. This study aimed to assess the acute effects of various BH conditions on 18 male elite rugby players (age: 23.5 ± 1.8 years; height: 183.3 ± 3.4 cm; body mass: 84.8 ± 8.5 kg) and identify the BH condition eliciting the greatest aerobic fitness activation. Participants underwent five warm-up conditions: baseline regular breathing, dynamic dry BH (DD), static dry BH (SD), wet dynamic BH (WD), and wet static BH (WS). Significant differences (p < 0.05) were found in red blood cells (RBCs), red blood cell volume (RGB), and hematocrit (HCT) pre- and post-warm-up. Peak oxygen uptake (VO2peak) and relative oxygen uptake (VO2/kgpeak) varied significantly across conditions, with BH groups showing notably higher values than the regular breathing group (p < 0.05). Interaction effects of facial immersion and movement conditions were significant for VO2peak, VO2/kgpeak, and the cardiopulmonary optimal point (p < 0.05). Specifically, VO2peak and peak stroke volume (SVpeak) were significantly higher in the DD group compared to that in other conditions. Increases in VO2peak were strongly correlated with changes in RBCs and HCT induced by DD warm-up (r∆RBC = 0.84, r∆HCT = 0.77, p < 0.01). In conclusion, DD BH warm-up appears to optimize subsequent aerobic performance in elite athletes.","PeriodicalId":18182,"journal":{"name":"Life","volume":"134 27","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141811207","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":"Differentiating Gliosarcoma from Glioblastoma: A Novel Approach Using PEACE and XGBoost to Deal with Datasets with Ultra-High Dimensional Confounders","authors":"A. Saki, U. Faghihi, Ismaila Baldé","doi":"10.3390/life14070882","DOIUrl":"https://doi.org/10.3390/life14070882","url":null,"abstract":"In this study, we used a recently developed causal methodology, called Probabilistic Easy Variational Causal Effect (PEACE), to distinguish gliosarcoma (GSM) from glioblastoma (GBM). Our approach uses a causal metric which combines Probabilistic Easy Variational Causal Effect (PEACE) with the XGBoost, or eXtreme Gradient Boosting, algorithm. Unlike prior research, which often relied on statistical models to reduce dataset dimensions before causal analysis, our approach uses the complete dataset with PEACE and the XGBoost algorithm. PEACE provides a comprehensive measurement of direct causal effects, applicable to both continuous and discrete variables. Our method provides both positive and negative versions of PEACE together with their averages to calculate the positive and negative causal effects of the radiomic features on the variable representing the type of tumor (GSM or GBM). In our model, PEACE and its variations are equipped with a degree d which varies from 0 to 1 and it reflects the importance of the rarity and frequency of the events. By using PEACE with XGBoost, we achieved a detailed and nuanced understanding of the causal relationships within the dataset features, facilitating accurate differentiation between GSM and GBM. To assess the XGBoost model, we used cross-validation and obtained a mean accuracy of 83% and an average model MSE of 0.130. This performance is notable given the high number of columns and low number of rows (code on GitHub).","PeriodicalId":18182,"journal":{"name":"Life","volume":"6 13","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141642428","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":"Comparative Proteomic Analysis of Type 2 Diabetic versus Non-Diabetic Vitreous Fluids","authors":"Abdulaziz H. Alanazi, Shengshuai Shan, S. P. Narayanan, P. R. Somanath","doi":"10.3390/life14070883","DOIUrl":"https://doi.org/10.3390/life14070883","url":null,"abstract":"Background: Diabetic retinopathy (DR) is a leading cause of vision loss, with complex mechanisms. The study aimed to comprehensively explore vitreous humor of diabetic and non-diabetic individuals, paving the way for identifying the potential molecular mechanisms underlying DR. Methods: Vitreous samples from type 2 diabetic and non-diabetic subjects, collected post-mortem, were analyzed using liquid chromatography–mass spectrometry. Pathway enrichment and gene ontology analyses were conducted to identify dysregulated pathways and characterize protein functions. Results: Pathway analysis revealed dysregulation in multiple metabolic and signaling pathways associated with diabetes, including glycerolipid metabolism, histidine metabolism, and Wnt signaling. Gene ontology analysis identified proteins involved in inflammation, immune response dysregulation, and calcium signaling. Notably, proteins such as Inositol 1,4,5-trisphosphate receptor type 2 (ITPR2), Calcium homeostasis endoplasmic reticulum protein (CHERP), and Coronin-1A (CORO1A) were markedly upregulated in diabetic vitreous, implicating aberrant calcium signaling, inflammatory responses, and cytoskeletal reorganization in DR. Conclusions: Our study provides valuable insights into the intricate mechanisms underlying DR and highlights the significance of inflammation, immune dysregulation, and metabolic disturbances in disease progression. Identification of specific proteins as potential biomarkers underscores the multifactorial nature of DR. Future research in this area is vital for advancing therapeutic interventions and translating findings into clinical practice.","PeriodicalId":18182,"journal":{"name":"Life","volume":"74 14","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141643228","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":"Influence of Diet on Reproducible Corticosterone Levels in a Mouse Model of Maternal Separation with Early Weaning","authors":"Jamie Y. Choe, Michael Donkor, Roland J. Thorpe, Michael S. Allen, Nicole R. Phillips, Harlan P. Jones","doi":"10.3390/life14070880","DOIUrl":"https://doi.org/10.3390/life14070880","url":null,"abstract":"Maternal separation with early weaning (MSEW) is a popular early life stress (ELS) model in rodents, which emulates childhood neglect through scheduled mother-offspring separation. Although variations of ELS models, including maternal separation and MSEW, have been published for the mouse species, the reported results are inconsistent. Corticosterone is considered the main stress hormone involved in regulating stress responses in rodents—yet generating a robust and reproducible corticosterone response in mouse models of ELS has been elusive. Considering the current lack of standardization for MSEW protocols, these inconsistent results may be attributed to variations in model methodologies. Here, we compared the effects of select early wean diet sources—which are the non-milk diets used to complete early weaning in MSEW pups—on the immediate stress phenotype of C57BL/6J mice at postnatal day 21. Non-aversive handling was an integral component of our modified MSEW model. The evaluation of body weight and serum corticosterone revealed the early wean diet to be a key variable in the resulting stress phenotype. Interestingly, select non-milk diets facilitated a stress phenotype in which low body weight was accompanied by significant corticosterone elevation. Our data indicate that dietary considerations are critical in MSEW-based studies and provide insight into improving the reproducibility of key stress-associated outcomes as a function of this widely used ELS paradigm.","PeriodicalId":18182,"journal":{"name":"Life","volume":"18 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141646496","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}