{"title":"Physicians’ Perception and Practice of Prescribing Vitamin B Combination versus Antiepileptic Drugs for Diabetic Neuropathy: Content Validity, Reliability and Pilot Study","authors":"Narmin Essa, M. Aladul","doi":"10.31351/vol32iss1pp202-218","DOIUrl":"https://doi.org/10.31351/vol32iss1pp202-218","url":null,"abstract":"Background: Diabetic neuropathy (DN) is the most common complication of diabetes mellitus causing increased morbidity and mortality. Although international guidelines did not include vitamins and dietary supplements in any line of management, these agents were prescribed by a significant number of physicians either as preventive or treatment of DN. This study aimed to develop a validated questionnaire that examines the physicians’ perception and practice towards prescribing vitamins or dietary supplements for DN treatment. \u0000Method: The questionnaire was developed upon literature review via PubMed, Medline, Web of Science, Scopus, and Google Scholar. The questionnaire was revised upon experts’ views and opinions. The constructed questionnaire was validated by the means of content validity and internal consistency. Finally, the developed questionnaire was piloted in a small representative sample of the original future aimed research target population, to test its applicability and feasibility. \u0000Results: A total of 19 items questionnaire were developed in two domains (perception and practice). Content validity analysis results met a satisfactory level, in which the S-CVI/UA value was 0.84 and 0.89 for clarity and relevance respectively. The questionnaire also showed good reliability, in which the Cronbach’s alphas was 0.824. \u0000Conclusion: This study showed the ability to construct a questionnaire with good levels of content validity and reliability that can cover different aspects of the current state of perception and practice among physicians regarding the management of DN.","PeriodicalId":14509,"journal":{"name":"Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512)","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72945102","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":"Chitosan- (Prunus avium) Gum Nanocapsules Loaded with Orange Peel Extract","authors":"Tahani Alidee, H. Habbal, F. Karabet","doi":"10.31351/vol32iss1pp194-201","DOIUrl":"https://doi.org/10.31351/vol32iss1pp194-201","url":null,"abstract":"The orange peel extract (OE) is an additive material that has been used widely as a natural antioxidant source and bioactive compounds in Pharmaceutical and food sector. The poor stability and degradation of this extract were considered problems in the industry. New technologies have been introduced recently to prevent this degradation as encapsulation. \u0000In this work, chitosan (CS) and Prunus avium gum (PG) were proposed as promising based materials for encapsulation OE via ionic gelation method. The effect of different ratios of CS: PG and CS: OE on encapsulation efficiency (EE %) and the capsules size were investigated. The EE% of CS-PG was ranged from 60.63 to 87.06 % with a size range of 40 to 95nm according to Atomic Force Microscope (AFM) images. The formulation with the highest EE% was chosen to be characterized by FTIR, scanning electron microscope (SEM), and in vitro release study. The FTIR spectra confirm the cross-linking between the NH3+ group in CS and the negative functional group (-COO-) in PG. According to SEM micrographs, the capsules showed a spongy porous structure. The in vitro release study indicated that the release of OE from CS-PG matrix in the acidic and neutral medium was 55.15 and 52.67% respectively after incubation for 240 minutes. This study found that CS-PG can be used as an effective wall matrix for encapsulating OE and delivering it into the gastrointestinal system.","PeriodicalId":14509,"journal":{"name":"Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512)","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88889820","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}
Ruaa Mohammed Ibrahim, Dhuha Abdul Saheb Alshammaa
{"title":"Pharmacological aspects of Borago officinalis (Borage): A review article","authors":"Ruaa Mohammed Ibrahim, Dhuha Abdul Saheb Alshammaa","doi":"10.31351/vol32iss1pp1-13","DOIUrl":"https://doi.org/10.31351/vol32iss1pp1-13","url":null,"abstract":"Abstract: \u0000Borago officinalis is highly interesting amongst nutritional and medical source relate to its high composition of some useful phytochemical compound. It is great plants with bright blue star-shaped flowers present in most world regions and usually known as borage. The Borago phytochemical analysis showed the presence of alkaloids, tannins, flavonoids, phenolic acids, essential oil, vitamins and others. Borage is cultivated all over the world and used in traditional medicine as a demulcent, diuretic, emollient, tonic, expectorant, for the treatment of coughs, inflammation and swelling, and other diseases. In herbal medicine, Borage seed oil (BSO) has been utilized for many progressive illnesses as a treatment agent. The BSO compounds include p-simen-8-L, ?-caryophyllene, sesquiterpenes, monoterpenes, alpha-linoleic, gammalinoleic and linoleic acid. BSO is famed to be the richest vegetable origin of gamma (?)-linoleic acid (GLA). Borage officinalis possess different pharmacological properties including antinociceptive, antioxidant, radioprotective, memory improving, hepatoprotective, antinflammatory, and analgesic effects.","PeriodicalId":14509,"journal":{"name":"Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512)","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91538224","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 Protective Effects of N-acetylcysteine against 5-Fluorouracil Induced Intestinal Toxicity in Albino Rats","authors":"M. Al-Hamdany, A. Al-Hubaity","doi":"10.31351/vol32iss1pp40-44","DOIUrl":"https://doi.org/10.31351/vol32iss1pp40-44","url":null,"abstract":"5-fluorouracil (5-FU) is a is Pyrimidine analogue widely used in the treatment of various malignancies It belongs to the antimetabolites family that acts during the S-phase of the cell cycle thus it prevents DNA synthesis.N-acetylcysteine is nutritional complement acts as antioxidant.The purpose of the current study is to investigate whether there is a protective role of N-acetylcystein against intestinal toxicity induced by 5-fluorouracil in albino rats.18 healthy adult rats were distributed into 3 groups of 6 rats for each. Group A as a control group.Group B injected with 5-FU (20 mgs dissolved in 2ml normal saline per kilogram body weight intraperitoneally for 7 successive days while Group C received N-acetylcysteine 200 mg per kilogram body weight 24 hour prior to FU injections for 7 consecutive days. The animals were sacrificed specimens of intestine (colon) tissue of the three groups were removed and prepared for light microscopic examination.The sections were stained with Harris Hematoxylin and Eosin (H&E) stain and Masson's trichrome stain. Results showed increase in the depth of the colonic crypts in group B rats as compared to the control group, mucinous degeneration of the intestinal mucosal cells along with necrosis, and inflammatory cells infiltration in the lamia propria. The appearance of the crypts is nearly normal in group C with reduction in the depth and normal columnar epithelium lining the crypts the study concluded that 5-FU seriously affects the structure of the intestinal tissue and pretreatment with NAC protects the intestinal tissue against the toxic effects provoked by 5FU via antioxidant effect.","PeriodicalId":14509,"journal":{"name":"Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512)","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73174982","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}
D. Pozdnyakov, S. Adzhiakhmetova, N. Chervonnaya, S. Oganesyan
{"title":"Lipid -Lowering Effect of Polysaccharide (Pectin) of Viscum album L. Plant in Rats","authors":"D. Pozdnyakov, S. Adzhiakhmetova, N. Chervonnaya, S. Oganesyan","doi":"10.31351/vol32iss1pp75-83","DOIUrl":"https://doi.org/10.31351/vol32iss1pp75-83","url":null,"abstract":"Disturbances of lipid metabolism is a predisposing factor of cardiovascular diseases, which are accompanied by high mortality rates of the population - ischemic heart disease and ischemic stroke. Plant polysaccharides can be promising remedies for correction of lipid imbalance. \u0000In this regard, the aim of the study was to assess the hypolipidemic activity of polysaccharides isolated from the leaves of mistletoe. \u0000The test-object was the leaves of the white mistletoe (Viscum album L.) growing on the apple (Malus domestica Borkh.), and the pear (Pyrus communis L.). Polysaccharides (water-soluble polysaccharides and pectin substances) were quantitatively determined by the gravimetric method followed by reprecipitation from ethanol. The qualitative composition was evaluated by thin layer chromatography. Functional groups in polysaccharides were determined by titrimetric method. The hypolipidemic activity of the obtained polysaccharides was determined under oral administration at a dose of 100 mg / kg in Wistar rats by the change of the concentration of total cholesterol, triglycerides, LDL and HDL cholesterol. The change of the content of cholesteryl ester transfer protein and Niemann-Pick C1-Like1 protein was also determined. \u0000As a result, it was found that among the polysaccharides in the leaves of mistletoe, pectin substances are predominate, which belong to the group of low-esterified pectins. A significant content of free carboxyl groups in pectins from the leaves of mistletoe was also found. The study of hypolipidemic activity showed that, among the polysaccharides of mistletoe leaves, pectin substances exert a more pronounced effect on lipid metabolism, the use of which reduced the content of triglycerides, total cholesterol and LDL cholesterol with an increase in LDL cholesterol in rats, probably due to a decrease in the activity of cholesteryl ester transfer protein and Niemann-Pick C1-Like1 protein. At the same time, at the level of the trend, mistletoe pectins showed a higher level of activity than analogous compounds obtained from the leaves of host-plants. It should be noted that the severity of the pharmacological effect of mistletoe pectins did not depend on the host-plants. \u0000Thus, based on the obtained results, it can be assumed that pectins obtained from the mistletoe leaves can be a potentially effective and safety hypolipidemic agent.","PeriodicalId":14509,"journal":{"name":"Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512)","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73828826","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":"Role of Fasting Mimicking Diet in Farnesoid x Receptor for Suppressing Epithelial-to-Mesenchymal Transition, Cell Cycle Progression, and Viability of Prostate Cancer Cells","authors":"W. Al-khfajy, I. Arif, Basma T. Al-sudani","doi":"10.31351/vol32iss1pp115-124","DOIUrl":"https://doi.org/10.31351/vol32iss1pp115-124","url":null,"abstract":"The systemic and resistant nature of metastatic castration-resistant prostate cancers (mCRPC) renders it largely incurable even after intensive multimodal therapy. Proliferation, survival, and epithelial-mesenchymal transition (EMT) are three fundamental events that are deeply linked to carcinogenesis. Hence, it is necessary to find a new combination of several therapies, targeting those vital mechanisms without causing side effects. Significant research works have shown differential low expression of the metabolic Farnesoid X receptor (FXR) in primary and metastatic prostate cancer suggesting their importance in prostate pathogenesis. Obticholic acid (INT 747), a potent FXR agonist is widely used in primary biliary cholangitis, and Fasting mimicking Diet (FMD) both were drastically showed effects on different cancer progression. We hypothesized that FXR and FMD may inhibit proliferation and the metastatic phenotype in PC-3 prostate cancer cells. Analyses of the cell viability, cell cycle, migration, and matrigel invasion assays were performed to elucidate how INT 747 and /or FMD functions in prostate cancer. In this study, INT 747 treatment caused apoptotic morphological changes and significantly reduced the survival of PC-3 cells incubated in normal mediums. Furthermore, we showed that the combination of the INT 747 and FMD was much more harmful to cancer cells than the treatment with INT 747 or FMD alone. Moreover, our study showed that INT 747 either alone or combined with FMD robustly induced cell cycle arrest at the S phase. Interestingly, the combination treatment on PC-3 cells not only showed several lines of evidence of apoptotic cells death but also inhibited carcinogenic potential as evaluated by impairment of spheroid formation capacity and delayed wound healing and matrigel invasion. At the cellular level, FXR activation resulted in down-regulation of procaspase -3, vimentin, and MMP9, which triggers apoptotic cell death, cell cycle arrest, and switch from mesenchymal to an epithelial phenotype. Collectively, FXR activation alone markedly decreases, and when combined with FMD abrogates the survival and carcinogenic potential of metastatic prostate cancer cells. \u0000 ","PeriodicalId":14509,"journal":{"name":"Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512)","volume":"357 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82624025","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 Ameliorating Effect of Oral Paquinimod Administration against Imiquimod Induced Psoriasis-like Inflammation in Mice","authors":"R. Khaleel, M. Zalzala","doi":"10.31351/vol32iss1pp92-99","DOIUrl":"https://doi.org/10.31351/vol32iss1pp92-99","url":null,"abstract":" \u0000 Psoriasis is a chronic, inflammatory condition that primarily affects the skin, hair, and joints and is associated with significant humanistic and economic consequences. Psoriasis was induced in mice in this work using an imiquimod 5% cream, an immune response modifier that can cause psoriasis-like skin inflammation when given orally. Paquinimod is prepared as a suspension and has been orally given to mice before imiquimod application. The current study found that paquinimod suspension reduced psoriasis area and severity index, spleen index, skin thickness ,TNF-α,IL-23,IL17 level and gene expression of TNF-α,Nf-KB,IL-1B,IL-17in the (Paquinimod suspension+imiquimod) group substantially more than the (vehicle suspension+imiquimod) groups.","PeriodicalId":14509,"journal":{"name":"Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512)","volume":"83 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90470669","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":"Preparation and in Vitro Evaluation for Different Types of Ondansetron Hydrochloride Transdermal Patches","authors":"Karima Abd allatif, Jameela Ali Hasian","doi":"10.31351/vol32iss1pp147-155","DOIUrl":"https://doi.org/10.31351/vol32iss1pp147-155","url":null,"abstract":"This research aims to develop transdermal patches of Ondansetron hydrochloride (OSH) with different types of polymers, ethyl cellulose and, polyvinyl pyrrolidone k30 in a ratio (3:0.5,3:1,3:2,2:1,1:1) with propylene glycol 20%w/w as a plasticizer. Prepared transdermal patches were evaluated for physical properties. The compatibility between the drug and excipients was studied by Differential scanning calorimetry (DSC), where there is no interaction between the drug and polymers. From the statistical study, there is a statistical difference between all the prepared formulations p<0.05. In-vitro Release study of transdermal patches was performed by using a paddle over the disc. The release profile of OSH followed Korsmeyer - Peppas Model in P2, P4 formulations and, Higuchi Model in P1, P3, P5 formulations. The best formulation P6 carrying EC:PVP in ratio1:1 released 96.47% of ondansetron hydrochloride during 12 h. The release profile of P6 followed the Higuchi model and correlation coefficient (r2 = 0.9815)","PeriodicalId":14509,"journal":{"name":"Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512)","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87294491","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":"Autophagy or Apoptosis: Anticancer Molecular Mechanism of Epigallocatechin Gallate with Natural Polyphenol Effect on HepG2 Cells Viability","authors":"R. Hafidh, Z. Ali, A. Abdulamir","doi":"10.31351/vol32iss1pp167-176","DOIUrl":"https://doi.org/10.31351/vol32iss1pp167-176","url":null,"abstract":"Background: The anticancer impact of Epigallocatechin gallate (EGCG) the highly active polyphenol of green tea was abundantly studied. Though, the exact mechanism of its cytotoxicity is still under investigation. Objectives: Hence, the current study designed to investigate the molecular target of EGCG in HepG2 cells on thirteen autophagy- and/or apoptosis- related genes. Methods: The apoptosis detection analyses such as flow cytometry and dual apoptosis assay were used. The genes expression profile was explored by the real-time quantitative-PCR. Results: EGCG increases G0/G1 cell cycle arrest and the real-time apoptosis markers proteins leading to stimulate apoptosis in 70% of the treated HepG2 cells. The up-regulation was recorded in two of autophagy inhibitory genes (FOS-1, FOS-2) and apoptosis inducer gene (DDIT3). While the other ten genes expressed down-regulation after treatment. The down regulation was manifested in the genes of mitochondrial autophagy marker proteins (BNIP3, BNIP3L, and NBR1), the autophagy regulator genes (BIRC5, MAPK9), and the gene that implicated in protein biosynthesis and protein modification (ITGB1). The genes that have pro-apoptotic function in cells (CAPNS1, CFLAR, EIF4G, and RB1) were also showed down-regulation after treatment. Conclusion: Thus, the results demonstrated a potential effect of EGCG to induce apoptosis rather than autophagy in the treated HepG2 cells that could play a good target for therapy. ","PeriodicalId":14509,"journal":{"name":"Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88140569","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}
L. Oktavia, Evana Evana, Reza Fahardita, A. Agusta
{"title":"Optimization of Bis-anthraquinones Production from Endophytic Fungi Diaporthe sp. GNBP-10","authors":"L. Oktavia, Evana Evana, Reza Fahardita, A. Agusta","doi":"10.31351/vol32iss1pp160-166","DOIUrl":"https://doi.org/10.31351/vol32iss1pp160-166","url":null,"abstract":"Bis-anthraquinones with a unique molecular backbone, (+)-2,2’-epicytoskyrin A (epi) and (+)-1,1′-bislunatin (bis), was produced by endophytic fungi Diaporthe sp GNBP-10 associated with Gambir plant (Uncaria gambier). Epi and bis possess robust antimicrobial activity toward various pathogens. This study focus on knowing the optimum condition of epi and bis production from Diaporthe sp GNBP-10. A series of culture media with various nutrient compositions was investigated in epi and bis production. The content of epi and bis was determined by measuring the area under the curve from TLC-densitometric (scanner) experiment. The linear regression analysis was then applied to obtain the results. The optimized epi and bis production was observed in liquid media 3 containing potato starch and dextrose with the amount of epi produced is 0.484mg while bis content is 0.163mg. The presence of carbohydrates, whether simple sugar or carbohydrate complex, plays an essential role in the bis-anthraquinones production from Diaphorthe sp culture. The presence of minerals and excessive protein sources did not significantly affect bis-anthraquinones production. \u0000Keywords: bis-anthraquinone, Diaporthe sp, culture media, regression, TLC scanner","PeriodicalId":14509,"journal":{"name":"Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512)","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80857935","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}