Bişar Ergün, Begüm Ergan, Murat Küçük, Mehmet Nuri Yakar, Mehmet Celal Öztürk, Ferhan Demirer Aydemir, Özlem Öner, Volkan Hanci, Bilgin Cömert, Ali Necati Gökmen
{"title":"Is serum magnesium level associated with atrial fibrillation in the mixed medical/surgical intensive care unit setting?","authors":"Bişar Ergün, Begüm Ergan, Murat Küçük, Mehmet Nuri Yakar, Mehmet Celal Öztürk, Ferhan Demirer Aydemir, Özlem Öner, Volkan Hanci, Bilgin Cömert, Ali Necati Gökmen","doi":"10.1684/mrh.2023.0506","DOIUrl":"https://doi.org/10.1684/mrh.2023.0506","url":null,"abstract":"<p><strong>Background: </strong>Although low serum magnesium level is a a relatively common problem in mixed medical/surgical intensive care units (ICUs), its association with new-onset atrial fibrillation (NOAF) has been studied to a lesser extent. We aimed to investigate the effect of magnesium levels on the development of NOAF in critically ill patients admitted to the mixed medical/surgical ICU.</p><p><strong>Methods: </strong>A total of 110 eligible patients (45 female, 65 male) were included in this case-control study. The age and sex-matched control group (n = 110) included patients with no atrial fibrillation from admission to discharge or death.</p><p><strong>Results: </strong>The incidence of NOAF was 2.4% (n = 110) between January 2013 and June 2020. At NOAF onset or the matched time point, median serum magnesium levels were lower in the NOAF group than in the control group (0.84 [0.73-0.93] vs. 0.86 [0.79-0.97] mmol/L; p = 0.025). At NOAF onset or the matched time point, 24.5% (n = 27) in the NOAF group and 12.7% (n = 14) in the control group had hypomagnesemia (p = 0.037). Based on Model 1, multivariable analysis demonstrated magnesium level at NOAF onset or the matched time point (OR: 0.07; 95%CI: 0.01-0.44; p = 0.004), acute kidney injury (OR: 1.88; 95%CI: 1.03-3.40; p = 0.039), and APACHE II (OR: 1.04; 95% CI: 1.01-1.09; p = 0.046) as factors independently associated with an increased risk of NOAF. Based on Model 2, multivariable analysis demonstrated hypomagnesemia at NOAF onset or the matched time point (OR: 2.52; 95% CI: 1.19-5.36; p = 0.016) and APACHE II (OR: 1.04; 95%CI: 1.01-1.09; p = 0.043) as factors independently associated with an increased risk of NOAF. In multivariate analysis for hospital mortality, NOAF was an independent risk factor for hospital mortality (OR: 3.22; 95% CI: 1.69-6.13, p<0.001).</p><p><strong>Conclusion: </strong>The development of NOAF in critically ill patients increases mortality. Critically ill patients with hypermagnesemia should be carefully evaluated for risk of NOAF.</p>","PeriodicalId":18159,"journal":{"name":"Magnesium research","volume":"35 3","pages":"96-107"},"PeriodicalIF":3.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9385896","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":"Magnesemia in COVID-19 ICU patients: the relationship between serum magnesium level and mortality","authors":"Bilge Banu Taşdemir Mecit, Semiha Orhan","doi":"10.1684/mrh.2022.0504","DOIUrl":"https://doi.org/10.1684/mrh.2022.0504","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the relationship between serum magnesium (Mg) levels at the time of admission and survival in COVID-19 patients followed in the intensive care unit (ICU).</p><p><strong>Methods: </strong>In total, 461 patients over the age of 18 diagnosed with the COVID-19, followed in the COVID-19 ICU of our hospital, were included. Patients whose files could not be accessed were excluded. Data on patients' demographics, clinical features, and laboratory data were compared according to the Mg levels measured during their admission to the ICU. The patients were divided into five groups according to their Mg level: Group 1 (<1.8 mg/dL), Group 2 (1.8-<2 mg/dL), Group 3 (2-<2.2 mg/dL), Group 4 (2.2-<2.4 mg/dL), and Group 5 (>2.4 mg/dL).</p><p><strong>Results: </strong>For patients with Mg value of <2 mg/dL, the proportion of males to females was roughly equal, however, the proportion of males was higher in other groups (p = 0.004). Overall, hypertension was the most common comorbid disease in patients, followed by diabetes mellitus in 32.1%. The latter was observed more frequently in Group 1 (<1.8 mg/dL) compared to the other groups (51.3%, p = 0.008). No significant difference was determined between the groups regarding laboratory values and treatments administered. Requirement of mechanical ventilation was significantly higher in Groups 1 (<1.8 mg/dL) and 5 (>2.4 mg/dL) than in other groups (p = 0.008). However, although mortality was also high in these groups, the difference was not statistically significant (p = 0.067).</p><p><strong>Conclusion: </strong>A correlation between serum Mg levels and mortality was not observed, but mortality and the need for mechanical ventilation were higher in groups with Mg levels <1.8 mg/dL and >2.4 mg/dL compared to other groups. We believe that it is critical to measure serum Mg levels while supporting COVID-19 patients with Mg in the ICU.</p>","PeriodicalId":18159,"journal":{"name":"Magnesium research","volume":"35 3","pages":"80-87"},"PeriodicalIF":3.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9369462","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":"Development of a bio-relevant pH gradient dissolution method for a high-dose, weakly acidic drug, its optimization and IVIVC in Wistar rats: a case study of magnesium orotate dihydrate","authors":"Hitesh Verma, Rajeev Garg","doi":"10.1684/mrh.2022.0505","DOIUrl":"https://doi.org/10.1684/mrh.2022.0505","url":null,"abstract":"<p><p>Magnesium orotate dihydrate (MOD) is a weakly acidic drug (pKa 2.83) which belongs to Biopharmaceutical Classification System (BCS) Class I at a dose of 500 mg and to BCS Class II at a dose of 1,000 mg. It is clinically prescribed at a dose of 3,000 mg (in two to three divided doses). The aim of the present study was to develop a bio-relevant pH gradient dissolution method for MOD in order to evaluate whether its clinically practiced therapeutic dose may be absorbed or not. The developed method revealed that MOD undergoes slow, but complete dissolution within 180 minutes, corresponding to the time to achieve maximum serum concentration (Tmax) in vivo. Optimization studies revealed that a rotational speed of 75 rpm provided reliable results (relative standard deviation of less than 20% up to a 10-minute time point, and less than 10% for the other time points), and MOD underwent complete dissolution within the testing timeframe at this rotational speed. Based on a pharmacokinetics study and the Wagner Nelson method, the relative extent of MOD absorption, when administered at a high dose equivalent to a human dose of 1,524 mg in Wistar rats in comparison to its oral suspension, was greater than 90%. In vitro – in vivo correlation, established through a deconvolution method, showed excellent correlation between percent of drug dissolved and percent of drug absorbed (R² = 0.9303). Therefore, even when MOD is administered at a single high dose, it can undergo slow but complete dissolution and absorption in vivo.</p>","PeriodicalId":18159,"journal":{"name":"Magnesium research","volume":"35 3","pages":"88-95"},"PeriodicalIF":3.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9385894","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}
Marcio Tadashi Hoshino, Matheus Gomes Bochio, Juliandra Spagnol Bonache, Larissa Ludwig, Michel Leandro de Campos, Guilherme Luz Emerick
{"title":"Plasma and erythrocyte magnesium levels: from validation of the method to analysis in volunteers diagnosed to migraine","authors":"Marcio Tadashi Hoshino, Matheus Gomes Bochio, Juliandra Spagnol Bonache, Larissa Ludwig, Michel Leandro de Campos, Guilherme Luz Emerick","doi":"10.1684/mrh.2022.0502","DOIUrl":"https://doi.org/10.1684/mrh.2022.0502","url":null,"abstract":"<p><p>Deficiency of serum magnesium is associated with the incidence of migraine attacks. The present study aimed to evaluate plasma and erythrocyte magnesium levels in a group of patients diagnosed with migraine. Human donors were selected from basic health units (migraine, n = 25) and from a collection and transfusion unit (control, n = 25), both located in the city of Sinop, Brazil. Plasma and erythrocyte magnesium were assessed using flame atomic absorption. Plasma magnesium concentration was significantly lower in the migraine group (0.172 ± 0.018) compared to the control group (0.197 ± 0.020 mg/L), and erythrocyte magnesium concentration was also lower in the migraine group (0.393 ± 0.053 mg/L) compared to the control group (0.432 ± 0.056 mg/L). The method for analysis of magnesium in human plasma and erythrocytes by flame atomic absorption was shown to be in accordance with validation guidelines. This study shows that plasma and erythrocyte magnesium levels were significantly lower in volunteers diagnosed with migraine compared to healthy volunteers. Furthermore, erythrocyte magnesium proved to be a better marker than plasma magnesium for patients with migraine.</p>","PeriodicalId":18159,"journal":{"name":"Magnesium research","volume":"35 2","pages":"51-61"},"PeriodicalIF":3.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10572692","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}
Sara Saba, Fakhrudin Faizi, Mojtaba Sepandi, Batool Nehrir
{"title":"Effect of short-term magnesium supplementation on anxiety, depression and sleep quality in patients after open-heart surgery","authors":"Sara Saba, Fakhrudin Faizi, Mojtaba Sepandi, Batool Nehrir","doi":"10.1684/mrh.2022.0503","DOIUrl":"https://doi.org/10.1684/mrh.2022.0503","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to evaluate the effect of magnesium supplementation on anxiety, depression and sleep quality of patients after openheart surgery.</p><p><strong>Materials and methods: </strong>Based on a clinical trial, 60 candidates for open-heart surgery were separated into control and intervention groups. In the intervention group, 500 mg of magnesium was administered daily in the form of two 250-mg magnesium oxide tablets for five days, and routine care was performed in the control group. Patients’ demographic information and assessment based on the Hospital Anxiety and Depression Scale (HADS) and Petersburg Sleep Quality Inventory (PSQI) were documented at the beginning of the study, after surgery and endotracheal intubation, and at the end of the study. Data were statistically analysed using Stata software version 13.</p><p><strong>Results: </strong>After the intervention, the mean level of magnesium in the intervention group was significantly higher (p=0.001). At the end of the study, the mean level of anxiety and depression was significantly lower in the intervention group than the control group (p=0.007), moreover, mean sleep quality improved in the intervention group (8.3 ± 2.1) compared to the control group (10.3 ± 2.0) (p=0.001).</p><p><strong>Conclusion: </strong>Due to the effects of magnesium supplementation in patients after heart surgery, it is recommended that this supplement be included in the treatment plan in order to prevent anxiety and depression in these patients after surgery and improve their quality of sleep.</p>","PeriodicalId":18159,"journal":{"name":"Magnesium research","volume":" ","pages":"62-70"},"PeriodicalIF":3.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40690266","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}
Xiao-Li Liu, Si-Qiong Wang, Mei-Jing Ji, Xiao-Ming Wang, Jing Sun, Meng-Meng Zhang, Chun-Ming Ma
{"title":"Hypomagnesemia is associated with increased mortality in the short-term but not the long-term in community-acquired pneumonia patients with type 2 diabetes","authors":"Xiao-Li Liu, Si-Qiong Wang, Mei-Jing Ji, Xiao-Ming Wang, Jing Sun, Meng-Meng Zhang, Chun-Ming Ma","doi":"10.1684/mrh.2022.0499","DOIUrl":"https://doi.org/10.1684/mrh.2022.0499","url":null,"abstract":"<p><strong>Introduction: </strong>The present study explored the relationship between hypomagnesemia and outcome in community-acquired pneumonia (CAP) patients with type 2 diabetes mellitus (T2DM).</p><p><strong>Methods: </strong>The study was a retrospective cohort study, conducted on adult CAP patients with T2DM at The First Hospital of Qinhuangdao between January 2015 and December 2018. The primary outcome was all-cause deaths.</p><p><strong>Results: </strong>In total, 480 CAP inpatients with T2DM were enrolled, and 71 patients (14.8%) had hypomagnesemia on admission. After one month and three months of follow-up, the hypomagnesemia group had a higher mortality rate than the normal magnesium group (p<0.05). After six months of follow-up, the mortality rate remained higher in the hypomagnesemia group, however, this was not statistically significant (χ²=2.799, p=0.094). After 12 months and 24 months of follow-up, the mortality rates were similar between the hypomagnesemia and normal magnesium groups (p<0.05). Based on multiple logistic regression analysis, hypomagnesemia was an independent risk factor for one-monthmortality(OR=3.858,95% CI: 1.637~9.088, p=0.002), three-month mortality (OR=3.083, 95% CI: 1.434~6.627, p=0.004) and six-month mortality (OR=2.551, 95% CI: 1.209~5.383, p=0.014).</p><p><strong>Conclusions: </strong>Hypomagnesemia is common in CAP inpatients with T2DM. Moreover, in these patients, hypomagnesemia at admission is associated with increased mortality in the short-term but not the long-term.</p>","PeriodicalId":18159,"journal":{"name":"Magnesium research","volume":" ","pages":"33-38"},"PeriodicalIF":3.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40675415","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":"Oral magnesium sulphate administration in rats with minimal hepatic encephalopathy: NMR-based metabolic characterization of the brain","authors":"Xue-Fei Liu, Jin-Jin Lu, Ying Li, Xiu-Ying Yang, Jin-Wei Qiang","doi":"10.1684/mrh.2022.0500","DOIUrl":"https://doi.org/10.1684/mrh.2022.0500","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the metabolic changes in rats with minimal hepatic encephalopathy (MHE) treated with oral magnesium sulphate administration.</p><p><strong>Materials and methods: </strong>A total of 30 Sprague-Dawley rats were divided into a control group and MHE group (further divided into an MHE group and an MHE-Mg group treated with oral administration of 124 mg/kg/day magnesium sulphate). Morris water maze (MWM), Y maze and narrow beam walking (NBW) were used to evaluate cognitive and motor functions. Brain manganese and magnesium content were measured. The metabolic changes in rats with MHE were investigated using hydrogen-nuclear magnetic resonance. Metabolomic signatures were identified with enrichment and pathway analysis.</p><p><strong>Results: </strong>A significantly decreased number of entries into the MWM within the range of interest, longer latency and total time during NBW, and higher brain manganese content were found in rats with MHE. After magnesium sulphate treatment, the rats with MHE had better behavioural performance and lower brain manganese content. The 25 and 26 metabolomic signatures were identified in the cortex and striatum of rats with MHE. The pathway analysis revealed alanine, aspartate and glutamate metabolism as the major abnormal metabolic pathways associated with these metabolomic signatures.</p><p><strong>Conclusion: </strong>Alanine, aspartate and glutamate metabolism are major abnormal metabolic pathways in rats with MHE, which could be restored by magnesium sulphate treatment.</p>","PeriodicalId":18159,"journal":{"name":"Magnesium research","volume":" ","pages":"39-50"},"PeriodicalIF":3.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40675416","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":"Corrigendum to \"biopharmaceutics classification and pharmacokinetics study of magnesium orotate\" (Mag Res 2019;32:132-42)","authors":"Hitesh Verma, Rajeev Garg","doi":"10.1684/mrh.2022.0496","DOIUrl":"https://doi.org/10.1684/mrh.2022.0496","url":null,"abstract":"","PeriodicalId":18159,"journal":{"name":"Magnesium research","volume":" ","pages":"27-28"},"PeriodicalIF":3.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33498375","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}
Hyun-Jung Shin, Jiwon Han, Subin Yim, Sang-Hwan Do
{"title":"Incidence of ionized hypomagnesemia in adult patients undergoing noncardiac major surgery: a prospective observational trial","authors":"Hyun-Jung Shin, Jiwon Han, Subin Yim, Sang-Hwan Do","doi":"10.1684/mrh.2022.0498","DOIUrl":"https://doi.org/10.1684/mrh.2022.0498","url":null,"abstract":"<p><strong>Background: </strong>The present study aimed to investigate the incidence of preoperative ionized hypomagnesemia and compare with that of total hypomagnesemia.</p><p><strong>Methods: </strong>This prospective observational study included 536 patients aged >20 years who were scheduled for elective surgery. Total and ionized magnesium levels were evaluated before and after the surgery. Based on these levels, patients were classified into the following groups: ionized hypo- (<0.42 mmol/L), normo- (0.42-0.59 mmol/L) and hypermagnesemia (>0.59 mmol/L), as well as total hypo- (<1.9 mg/dL[0.78 mmol/L]), normo- (1.9-2.7 mg/dL[0.78-1.11 mmol/L]) and hypermagnesemia (>2.7 mg/dL [1.11 mmol/L]). The primary objective was to establish the incidence of preoperative ionized hypomagnesemia.</p><p><strong>Results: </strong>There was a marked difference between the incidence of preoperative ionized and total hypomagnesemia (28% vs. 19%; p<0.001). The postoperative values of ionized magnesium, ionized calcium, and albumin were significantly lower than the respective preoperative values (p<0.001 for all three variables).</p><p><strong>Conclusion: </strong>The incidence of hypomagnesemia, determined by ionized magnesium concentration, was higher than that determined by total magnesium concentration.</p>","PeriodicalId":18159,"journal":{"name":"Magnesium research","volume":" ","pages":"11-17"},"PeriodicalIF":3.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33498377","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}
Loyara Rocha Miranda Teixeira, Andrea Castro Perez, Thiago Roberto Lima Romero, Igor Dimitri Gama Duarte
{"title":"Magnesium sulphate activates the L-arginine/NO/cGMP pathway to induce peripheral antinociception in mice","authors":"Loyara Rocha Miranda Teixeira, Andrea Castro Perez, Thiago Roberto Lima Romero, Igor Dimitri Gama Duarte","doi":"10.1684/mrh.2022.0495","DOIUrl":"https://doi.org/10.1684/mrh.2022.0495","url":null,"abstract":"<p><p>In the present study, we investigated whether magnesium sulphate activates the L-arginine/NO/cGMP pathway and elicits peripheral antinociception. The male Swiss mice paw pressure test was performed with hyperalgesia induced by intraplantar injection of prostaglandin E2. All drugs were administered locally into the right hind paw of animals. Magnesium sulphate (20, 40, 80 and 160 μg/paw) induced an antinociceptive effect. The dose of 80 μg/paw elicited a local antinociceptive effect that was antagonized by the non-selective NOS inhibitor, L-NOArg, and by the selective neuronal NOS inhibitor, L-NPA. The inhibitors, L-NIO and L-NIL, selectively inhibited endothelial and inducible NOS, respectively, but were ineffective regarding peripheral magnesium sulphate injection. The soluble guanylyl cyclase inhibitor, ODQ, blocked the action of magnesium sulphate, and the cGMP-phosphodiesterase inhibitor, zaprinast, enhanced the antinociceptive effects of intermediate dose of magnesium sulphate. Our results suggest that magnesium sulphate stimulates the NO/cGMP pathway via neuronal NO synthase to induce peripheral antinociceptive effects.</p>","PeriodicalId":18159,"journal":{"name":"Magnesium research","volume":" ","pages":"1-10"},"PeriodicalIF":3.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33498374","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}