{"title":"Adverse Health Effects and Perceived Musculoskeletal Pain in the Sawmill Workers of West Bengal, India.","authors":"Banibrata Das","doi":"10.1177/07482337231210331","DOIUrl":"10.1177/07482337231210331","url":null,"abstract":"<p><p>The present study aimed to determine the prevalence of musculoskeletal pain, unfavorable working conditions, and assessment of occupational injuries among sawmill workers. The Nordic Musculoskeletal Questionnaire, measurement of handgrip strength, working environment, and occupational injuries were assessed among 135 sawmill workers participating in the study. The data showed that sawmill workers complained of discomfort (pain) felt primarily in the low back region of the body followed by the shoulders, hands, knees, upper back, and wrist. This study indicated that sawmill workers had less handgrip strength due to more intense manual work than control subjects. Based on the results of this study, it was concluded that sawmill workers were highly affected due to working in an awkward posture with manual material handling for an extended period of time and that these factors may lead to work-related musculoskeletal disorders as well as occupational injuries. Proper training, a proper work-rest schedule, and modifications of some working procedures may reduce injuries and work-related musculoskeletal pain.</p>","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"9-22"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50158846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Toxic potential assessment of hair dye developer 2,4,5,6-tetraaminopyrimidine sulfate exposed under ambient UVB radiation.","authors":"Saumya Shukla, Priyanka Chauhan, Prakriti Gaur, Priyanka Rana, Sunil Kumar Patel, Deepti Chopra, Apeksha Vikram, Gaurav Prajapati, Akhilesh Kumar Yadav, Sumana Y Kotian, Lakshmi Bala, Ashish Dwivedi, Aradhana Mishra","doi":"10.1177/07482337231209352","DOIUrl":"10.1177/07482337231209352","url":null,"abstract":"<p><p>Synthetic cosmetics, particularly hair dyes, are becoming increasingly popular among people of all ages and genders. 2,4,5,6-tetraaminopyrimidine sulfate (TAPS) is a key component of oxidative hair dyes and is used as a developer in several hair dyes. TAPS has previously been shown to absorb UVB strongly and degrade in a time-dependent manner, causing phototoxicity in human skin cells. However, the toxic effects of UVB-degraded TAPS are not explored in comparison to parent TAPS. Therefore, this research work aims to assess the toxicity of UVB-degraded TAPS than TAPS on two different test systems, that is, HaCaT (mammalian cell) and <i>Staphylococcus aureus</i> (a bacterial cell). Our result on HaCaT has illustrated that UVB-degraded TAPS is less toxic than parent TAPS. Additionally, UVB-exposed TAPS and parent TAPS were given to <i>S. aureus,</i> and the bacterial growth and their metabolic activity were assessed via CFU and phenotype microarray. The findings demonstrated that parent TAPS reduced bacterial growth via decreased metabolic activity; however, bacteria easily utilized the degraded TAPS. Thus, this study suggests that the products generated after UVB irradiation of TAPS is considered to be safer than their parent TAPS.</p>","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"1-8"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50158848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A plasmid containing the human metallothionein-II gene selectively distinguishes trivalent lanthanum from several divalent heavy metal cations during monoclonal antibody-assisted agarose gel electrophoresis.","authors":"Dennis C Wooten","doi":"10.1177/07482337231222354","DOIUrl":"10.1177/07482337231222354","url":null,"abstract":"<p><p>Trivalent lanthanide ions are known for their ability to interact with calcium-binding sites in various proteins. There is a need to assess the bioavailability of lanthanides and other heavy metals introduced into the body as components of implants or as contrast agents. This study aimed to develop a method to address bioavailability and/or presence of trivalent lanthanide ions by examining electrophoretic mobility in an agarose gel of a plasmid harboring the human metallothionein-II gene (<i>hMT-II</i>). Mobility of the plasmid was specifically altered by a monoclonal antibody raised against the zinc-binding transcription factor that controls the activity of the <i>hMT-II</i> gene. This study showed that the plasmid acquired a lanthanide-specific mobility pattern that allowed the presence of lanthanide ions to be readily determined in a 0.8% agarose gel. These findings suggest that this plasmid/monoclonal antibody combination under selected conditions may be useful in industrial, environmental, and biomedical settings to identify, separate, or capture lanthanide ions in complex mixtures that contain an array of metal ions.</p>","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"69-74"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138806156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biomarkers of oral subacute toxicity of deltamethrin in exposed male Albino rats.","authors":"Rania Elbanna, Khaled A Osman, Maher S Salama","doi":"10.1177/07482337231209360","DOIUrl":"10.1177/07482337231209360","url":null,"abstract":"<p><p>Deltamethrin is one of the most effective pyrethroid compounds, widely employed in veterinary medicine, public health, and farming. Deltamethrin-triggered oxidative stress largely causes serious harm to an organism. Acute toxicity of this compound was extensively investigated, while less information is available on its oral sub-acute effects. This study assessed, in the male Albino rats, the effects of oral gavage of either 0.874 mg/kg (0.01 LD<sub>50</sub>) or 8.740 mg/kg (0.10 LD<sub>50</sub>) of deltamethrin for successive 14 days to investigate its effects on biomarkers and to detect the tissue injury in rats following subacute deltamethrin treatment. It was found that levels of glutathione peroxidase, superoxide dismutase, and catalase in the brain, kidney, and liver, alkaline phosphatase (ALP), and uric acid in serum, hematocrit, mean corpuscular volume (MCV), white blood cells (WBC)s, eosinophils, and basophils were significantly reduced compared with untreated rats. However, when rats were treated with deltamethrin for successive 14 days, alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities in serum and the levels of thiobarbituric acid reactive substances (TBARs) in brain, kidney, and liver, red blood cell distribution width (RDW-CV), total protein, monocytes, and basophils and the ratios of neutrophils to lymphocytes, an aggregated marker of systemic inflammation and systemic immune inflammation indexes, significantly increased compared with the control group. Histologic lesions were observed in the liver, kidney, brain, testis, and epidemies in rats exposed to subacute deltamethrin for 14 days, and most tissues of rats treated with 0.10 LD<sub>50</sub> of deltamethrin were more affected than those treated with 0.01 LD<sub>50</sub>. These findings strongly suggest that subacute exposure to deltamethrin caused significant systemic toxicity through oxidative stress resulting in biochemical and histological changes in the studied tissues. These findings highlight the potential harmful effects of deltamethrin and emphasize the importance of understanding the subacute effects of this compound, particularly in the context of veterinary medicine, public health, and farming.</p>","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"735-753"},"PeriodicalIF":1.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50158847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sheunesu Ngwenya, Ntsieni S Mashau, Sphiwe E Mhlongo, Afsatou N Traoré
{"title":"A systematic review of the risk management frameworks for potentially toxic chemical elements.","authors":"Sheunesu Ngwenya, Ntsieni S Mashau, Sphiwe E Mhlongo, Afsatou N Traoré","doi":"10.1177/07482337231209092","DOIUrl":"10.1177/07482337231209092","url":null,"abstract":"<p><p>In the last 50 years, various frameworks have been used to control and manage potentially toxic chemical risks; however, these chemicals continue to negatively impact environmental and human health. This work was intended to provide a systematic review of the literature on essential aspects of current risk management frameworks for potentially toxic chemicals. The frameworks were reviewed using Organisation for Economic Co-operation and Development (OECD) principles that focus on elements, successes, shortcomings, similarities, and dissimilarities premised on the experiences of many countries. Keywords such as heavy metals, health risk, industrial chemicals, potentially toxic elements, chemical pollutants, and risk management framework were utilised to search the literature from databases and other sources. Ten risk framework documents selected from an initial yield of 1349 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow processes met the inclusion criteria. The key elements of risk frameworks that were identified included the risk assessment paradigm, iteration, tiered approach, weight of evidence, uncertainty analysis, and multi-criteria decision analysis among others. Notable gaps in risk frameworks that required improvements to effectively manage health risks posed by potentially toxic chemicals were identified. While existing risk frameworks have made significant contributions to human health and environmental protection, new and comprehensive frameworks are needed to address the novel and dynamic risks posed by toxic industrial chemicals. Also, there is a need to promote the use of risk management frameworks in developing countries through technology transfer and the provision of financial assistance to improve environmental and public health protection from toxic chemicals.</p>","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"679-686"},"PeriodicalIF":1.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10655695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49682641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Murat Alagöz, Selma Yazar, Hale Secilmis Canbay, Abdullah Acıkgöz, Burcin S Corba
{"title":"Associations of semen quality with pyrethroids in semen and urine samples of men with oligozoospermia: A cross-sectional study in Samsun, Turkey.","authors":"Murat Alagöz, Selma Yazar, Hale Secilmis Canbay, Abdullah Acıkgöz, Burcin S Corba","doi":"10.1177/07482337231209356","DOIUrl":"10.1177/07482337231209356","url":null,"abstract":"<p><p>Pyrethroids (PYRs) may act as endocrine disrupters and lead to infertility. The aim of the study was to analyze the levels of anti-androgenic PYRs (cypermethrin, deltamethrin, and permethrin) and 3-phenoxy benzoic acid (3-PBA), a general metabolite of PYRs, in both semen and urine samples of men with oligozoospermia. The PYRs and 3-PBA metabolite levels in the semen and urine samples of the men were analyzed through GC-MS. The results indicated that the levels of PYRs in the semen samples of the infertile group were significantly higher than those of the fertile group. It was determined that cypermethrin exposure was associated with changes in sperm count and total sperm motility, while permethrin, deltamethrin, and 3-PBA levels were associated with changes in sperm morphology. It was determined that there was a significant negative correlation between semen deltamethrin levels and sperm morphology and sperm count. In addition, exposure of these patients to deltamethrin (range; 1.53-8.02 µg/l) and having farmer parents were determined to increase the risk of infertility. In conclusion, the findings of this study showed that exposure to environmental PYRs may adversely affect semen quality, especially in terms of sperm morphology, in men with oligozoospermia.</p>","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"754-761"},"PeriodicalIF":1.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49682642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chandrika Moudgal, Lennart T Anger, Wolfgang Muster, Ruthi Nguyen, Fjodor Melnikov, Vishal B Siramshetty, Jessica Graham
{"title":"The application of acute oral toxicity computational models in dangerous goods classification.","authors":"Chandrika Moudgal, Lennart T Anger, Wolfgang Muster, Ruthi Nguyen, Fjodor Melnikov, Vishal B Siramshetty, Jessica Graham","doi":"10.1177/07482337231209091","DOIUrl":"10.1177/07482337231209091","url":null,"abstract":"<p><p>Acute oral toxicity (AOT) data inform the acute toxicity potential of a compound and guides occupational safety and transportation practices. AOT data enable the categorization of a chemical into the appropriate AOT Globally Harmonized System (GHS) category based on the severity of the hazard. AOT data are also utilized to identify compounds that are Dangerous Goods (DGs) and subsequent transportation guidance for shipping of these hazardous materials. Proper identification of DGs is challenging for novel compounds that lack data. It is not feasible to err on the side of caution for all compounds lacking AOT data and to designate them as DGs, as shipping a compound as a DG has cost, resource, and time implications. With the wealth of available historical AOT data, AOT testing approaches are evolving, and in silico AOT models are emerging as tools that can be utilized with confidence to assess the acute toxicity potential of de novo molecules. Such approaches align with the 3R principles, offering a reduction or even replacement of traditional in vivo testing methods and can also be leveraged for product stewardship purposes. Utilizing proprietary historical in vivo AOT data for 210 pharmaceutical compounds (PCs), we evaluated the performance of two established in silico AOT programs: the Leadscope AOT Model Suite and the Collaborative Acute Toxicity Modeling Suite. These models accurately identified 94% and 97% compounds that were not DGs (GHS categories 4, 5, and not classified (NC)) suggesting that the models are fit-for-purpose in identifying PCs with low acute oral toxicity potential (LD50 >300 mg/kg). Utilization of these models to identify compounds that are not DGs can enable them to be de-prioritized for in vivo testing. This manuscript provides a detailed evaluation and assessment of the two models and recommends the most suitable applications of such models.</p>","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"687-699"},"PeriodicalIF":1.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49682644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inorganic arsenic-mediated upregulation of TUG1 promotes apoptosis in human bronchial epithelial cells by activating the p53 signaling pathway.","authors":"Qian Chen, Mingjun Sun, Huirong Cheng, Jun Qi, Jingwen Tan, Yun Gu, Tianle Yu, Ming Li, Hao Xu, Yuefeng He, Weihua Wen","doi":"10.1177/07482337231209349","DOIUrl":"10.1177/07482337231209349","url":null,"abstract":"<p><p>Exposure to arsenic, an environmental contaminant, is known to cause arsenicosis and cancer. Although considerable research has been conducted to understand the underlying mechanism responsible for arsenic-induced cancers, the precise molecular mechanisms remain unknown, especially at the epigenetic regulation level. Long non-coding RNAs (LncRNAs) that have been shown to mediate various biological processes, including proliferation, apoptosis, necrosis, and mutagenesis. There are few studies on LncRNAs and biological damage caused by environmental pollutants. The LncRNAs taurine upregulated gene 1 (TUG1) regulates cell growth both in vitro and in vivo, and contributes its oncogenic role. However, the precise roles and related mechanisms of arsenic-induced cell apoptosis are still not fully understood owing to controversial findings in the literature. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed higher expression levels of TUG1 in people occupationally exposed to arsenic than in individuals living away from the source of arsenic exosure (<i>N</i> = 25). In addition, the results suggested that TUG1 was involved in arsenic-induced apoptosis. Furthermore, knockdown experiments showed that silencing of TUG1 markedly inhibited proliferation, whereas depletion of TUG1 led to increased apoptosis. The TUG1-small interfering RNA (siRNA) combination with arsenic (3 μM/L) slightly increased apoptosis compared with the TUG1-siRNA. Additionally, the knockdown experiments showed that the silencing of TUG1 by siRNA inhibited proliferation and promoted apoptosis by inducing p53, p-p53 (ser392), FAS, BCL2, MDM2, cleaved-caspase7 proteins in 16HBE cells. These results indicated that arsenic mediates the upregulation of TUG1 and induces cell apoptosis via activating the p53 signaling pathway.</p>","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"700-711"},"PeriodicalIF":1.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49682643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of silver nanoparticles prepared by aqueous extract of <i>Ferula communis</i> on the developing mouse embryo after maternal exposure.","authors":"Amin A Seleem, Belal Hm Hussein","doi":"10.1177/07482337231209094","DOIUrl":"10.1177/07482337231209094","url":null,"abstract":"<p><p>Green synthesis of silver nanoparticles (AgNPs) from aqueous silver nitrate has been achieved using an extract of <i>Ferula communis</i> leaf as a capping, reducing, and stabilizing agent. The formation and stability of the green synthesized silver nanoparticles in the colloidal solution were monitored by absorption measurements. Silver nanoparticles were characterized by different analyses such as X-ray diffraction (XRD), energy dispersive spectroscopy (EDS), and FT-IR spectroscopy. The average particle size of silver nanoparticles was determined by high-resolution transmission electron microscopy (HRTEM) and scanning electron microscopy (SEM) analyses. In this experiment, pregnant female mice were divided into four groups (G); G1 was the control and received phosphate-buffered saline, G2 received orally aqueous extract of <i>F. communis</i> leaf<i>,</i> G3 received orally AgNPs chemically prepared by NaBH<sub>4</sub>, and G4 received orally AgNPs prepared by aqueous extract of <i>F. communis</i> leaf<i>.</i> The diameter of AgNPs was 20 nm. AgNPs exhibited good catalytic reduction ability toward methyl orange in the presence of sodium borohydride with a rate constant of 2.95 x 10<sup>-4</sup> s<sup>-1</sup>. The results revealed the occurrence of resorbed embryos in G2, G3, and G4 with different percentages. The livers of mothers and embryos at E14.5 in G2, G3, and G4 showed different levels of histopathological alteration and increase in GFAP and CTGF expressions compared with the control group. The study concluded that the oral administration of small-sized AgNPs (20 nm) prepared by <i>Ferula</i> extract had less toxicity than those prepared by the chemical method.</p>","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"712-734"},"PeriodicalIF":1.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49692531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B Baali, L Kirane-Amrani, L Tichati, R Soual, K Ouali
{"title":"Lipid peroxidation and changes in major antioxidant markers in copper quinolate fungicide-exposed rats.","authors":"B Baali, L Kirane-Amrani, L Tichati, R Soual, K Ouali","doi":"10.1177/07482337231203075","DOIUrl":"10.1177/07482337231203075","url":null,"abstract":"<p><p>The present study investigated the toxic effects of sub-chronic exposure to copper quinolate (CuQ) fungicide on liver and kidney function. Twenty-four adult male Wistar rats were equally divided into a control group, and three treated groups received, respectively, by oral gavage, three increasing doses of CuQ: 47; 67.1; and 94 mg/kg b.w corresponding, respectively, LD<sub>50</sub>/100, LD<sub>50</sub>/70, and LD<sub>50</sub>/50 daily for 8 weeks. CuQ resulted in a significant increase in the serum enzymatic activity of aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and the serum levels of urea, creatinine, uric acid, and malondialdehyde, along with a marked decrease in alanine aminotransferase (ALT) activity, and the contents of total protein and albumin compared to those of the control group. Furthermore, glutathione content and the enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione peroxidase (GPx) decreased significantly in a dose-dependent manner with respect to CuQ. The adverse effects of CuO were supported by the histopathological evaluations of liver and kidney tissues. Conclusively, sub-chronic CuQ exposure was shown to induce kidney and liver oxidative damage and dysfunction.</p>","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"664-678"},"PeriodicalIF":1.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41145029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}