Tremor and Other Hyperkinetic Movements最新文献

{"title":"Phenomenology and Physiology of Tacrolimus Induced Tremor.","authors":"Aparna Wagle Shukla, Caroline Lunny, Ibrahim Hisham, Jackson Cagle, Joyce Malea, Alfonso Santos, Ashutosh M Shukla","doi":"10.5334/tohm.725","DOIUrl":"https://doi.org/10.5334/tohm.725","url":null,"abstract":"Background: Tacrolimus is a potent immunosuppressant drug commonly used after solid organ transplant surgery. The use of this drug is frequently associated with the emergence of tremors. There is little information on the clinical and physiological characteristics of tacrolimus-induced tremors. Characterizing these tremors is essential as they can promote the development of specific therapies. Methods: We describe four patients placed on tacrolimus immunosuppressant therapy following kidney transplant surgery and who developed tremors impacting their daily functional activities. We describe the clinical and physiological characteristics of the tremor and the response generated after a limb cooling test. Results: A postural and kinetic tremor mainly involving the distal hands was observed in our cohort. In the accelerometer-based assessment, the tremor amplitude was noted to be mild to moderate, and the frequency was 5–6 Hz. Cooling the forearm and the hand led to a temporary albeit significant reduction of tremor amplitude (p = 0.03). Limb cooling lowered the tremor frequency by 1 Hz in two patients with no change in the other two patients, and the statistical comparison was not significant (p > 0.05). Conclusions: Limb cooling may be pursued as a therapeutic option for addressing tacrolimus-induced tremor, as the patients in our cohort benefitted from temporary tremor suppression.","PeriodicalId":23317,"journal":{"name":"Tremor and Other Hyperkinetic Movements","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9912847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10859382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progressive Multifocal Encephalopathy Holmes Tremor Successfully Treated with Bilateral Deep Brain Stimulation.","authors":"Talita D Rosa,&nbsp;Laura Dixon,&nbsp;Muhammad Ismail Khalid Yousaf,&nbsp;Victoria Holiday,&nbsp;Ajmal Zemmar,&nbsp;Joseph Neimat,&nbsp;Peter Hedera","doi":"10.5334/tohm.781","DOIUrl":"https://doi.org/10.5334/tohm.781","url":null,"abstract":"<p><strong>Background: </strong>We report a patient with bilateral HT treated with DBS.</p><p><strong>Case report: </strong>A 58-year-old man diagnosed with HIV/AIDS and progressive multifocal leukoencephalopathy (PML) presented with 20 years of bilateral arm tremor refractory to therapy. DBS was implanted on the left ventral intermediate nucleus and posterior subthalamic area (VIM/PSA). One year later, a right VIM/PSA DBS was implanted. At twelve months, there were no significant side-effects. With his DBS turned off and on, the Fahn-Tolosa-Marin scale was rated 82 and 58, respectively.</p><p><strong>Discussion: </strong>To our knowledge, this is the first report of bilateral DBS VIM/PSA treating HT with no significant side effects.</p><p><strong>Highlights: </strong>We report a successful treatment using deep brain stimulation of bilateral Holmes tremor that was caused by progressive multifocal encephalopathy. The patient achieved 30% improvement in tremor control with a meaningful improvement in his activities of daily living.</p>","PeriodicalId":23317,"journal":{"name":"Tremor and Other Hyperkinetic Movements","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10473162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10532737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is Behavioural Therapy a New Treatment Option for Task-Specific Dystonia in Athletes? A Case Series.","authors":"Marleen Ieke Tibben,&nbsp;Erik van Wensen,&nbsp;Beorn Nijenhuis,&nbsp;Johannes Zwerver","doi":"10.5334/tohm.737","DOIUrl":"https://doi.org/10.5334/tohm.737","url":null,"abstract":"<p><strong>Background: </strong>Task-specific dystonia is a movement disorder of the central nervous system characterized by focal involuntary spasms and muscle contractions, which can negatively affect performance of a specific task. It can affect a wide range of fine motor skills, also in athletes. Current management of task-specific dystonia includes mainly prescribing drugs, exercise therapy or botulinum injections to the affected muscles. Psychological interventions for athletes suffering from task-specific dystonia have not been described extensively so far.</p><p><strong>Methods: </strong>We present a case-series of 4 different advanced skill-level athletes with suspected task-specific dystonia, which had a major impact on their performance. They all received treatment consisting of a combination of standardized behavioural therapy and relaxation techniques in the form of hypnosis in a total of 8 sessions in a 16-week time period.</p><p><strong>Results: </strong>After treatment, all athletes returned to their original high level of sport performance without further symptoms of their suspected task-specific dystonia.</p><p><strong>Discussion: </strong>Behavioural therapy in combination with a relaxation technique seems to be a safe and promising treatment for athletes with suspected task-specific dystonia. Further studies in a larger, preferably randomized controlled trial, are warranted to evaluate if this treatment strategy is effective in athletes with suspected task-specific dystonia.</p>","PeriodicalId":23317,"journal":{"name":"Tremor and Other Hyperkinetic Movements","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10178567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10061733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcutaneous Afferent Patterned Stimulation for Essential Tremor: Real-World Evidence with Long Term Follow-Up.","authors":"Chiahao Lu,&nbsp;Dhira Khosla,&nbsp;Alexander Kent,&nbsp;Helen M Bronte-Stewart,&nbsp;Kathryn H Rosenbluth","doi":"10.5334/tohm.775","DOIUrl":"https://doi.org/10.5334/tohm.775","url":null,"abstract":"<p><strong>Background: </strong>Transcutaneous afferent patterned stimulation (TAPS) is a non-invasive neuromodulation therapy for the treatment of hand tremor in patients with essential tremor (ET). This retrospective post-market analysis evaluated the usage, effectiveness, and safety of TAPS in patients using TAPS beyond a 90-day trial period in a real-world setting.</p><p><strong>Methods: </strong>Study personnel screened a manufacturer's database for TAPS devices that had been prescribed for the treatment of ET and used beyond a 90-day trial period between August 2019 and January 2023. The device logs were collected to extract the therapy usage, accelerometry measurements, and on-board ratings of tremor improvement. Study personnel also evaluated results of a voluntary survey requested by the manufacturer after the 90-day trial period. Adverse events were assessed from patients' complaints reported to the manufacturer.</p><p><strong>Results: </strong>A total of 1,223 patients in the manufacturer's database met the study criteria. The patients had used therapy between 90 and 1,233 days, with average usage of 5.6 sessions per week. Accelerometry data indicated 89% of patients experienced tremor improvement, with an average 64% improvement. 63% of patients rated at least half of their sessions as improved. No significant habituation was observed in patients who used therapy for more than one year. Approximately 62% of survey respondents either had reduced medication or planned to consult physicians about their medication usage. No serious safety events were reported, and 10% of patients reported minor safety complaints.</p><p><strong>Discussion: </strong>The analysis demonstrates the real-world effectiveness and safety of TAPS beyond a 90-day trial period over a longer timeframe and in a larger population size than previously published evidence.</p>","PeriodicalId":23317,"journal":{"name":"Tremor and Other Hyperkinetic Movements","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10473165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10182129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter response: Intra-familial phenotype variability in Late-Onset Tay-Sachs disease.","authors":"Giulietta Maria Riboldi,&nbsp;Heather Lau","doi":"10.5334/tohm.756","DOIUrl":"https://doi.org/10.5334/tohm.756","url":null,"abstract":"","PeriodicalId":23317,"journal":{"name":"Tremor and Other Hyperkinetic Movements","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9983494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10849019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upper Limb Function but Not Proprioception is Impaired in Essential Tremor: A Between-Groups Study and Causal Mediation Analysis.","authors":"Annie A Butler,&nbsp;Joanna Diong,&nbsp;Kajsa Lidman,&nbsp;Johanna Adler,&nbsp;Daniel L Wardman,&nbsp;Simon C Gandevia,&nbsp;Martin E Héroux","doi":"10.5334/tohm.731","DOIUrl":"https://doi.org/10.5334/tohm.731","url":null,"abstract":"<p><strong>Background: </strong>Essential tremor (ET) is characterized by abnormal oscillatory muscle activity and cerebellar involvement, factors that can lead to proprioceptive deficits, especially in active tasks. The present study aimed to quantify the severity of proprioceptive deficits in people with ET and estimate how these contribute to functional impairments.</p><p><strong>Methods: </strong>Upper limb sensory, proprioceptive and motor function was assessed inindividuals with ET (n = 20) and healthy individuals (n = 22). To measure proprioceptive ability, participants discriminated the width of grasped objects and the weight of objects liftedwith the wrist extensors. Causal mediation analysis was used to estimate the extentthat impairments in upper limb function in ET was mediated by proprioceptive ability.</p><p><strong>Results: </strong>Participants with ET had impaired upper limb function in all outcomes, and had greater postural and kinetic tremor. There were no differences between groups in proprioceptive discrimination of width (between-group mean difference [95% CI]: 0.32 mm [-0.23 to 0.87 mm]) or weight (-1.12 g [-7.31 to 5.07 g]). Causal mediation analysis showed the effect of ET on upper limb function was not mediated by proprioceptive ability.</p><p><strong>Conclusions: </strong>Upper limb function but not proprioception was impaired in ET. The effect of ET on motor function was not mediated by proprioception. These results indicate that the central nervous system of people with ET is able to accommodate mild to moderate tremor in active proprioceptive tasks that rely primarily on afferent signals from muscle spindles.</p>","PeriodicalId":23317,"journal":{"name":"Tremor and Other Hyperkinetic Movements","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9404175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol and Ganaxolone Suppress Tremor via Extra-Synaptic GABA_A Receptors in the Harmaline Model of Essential Tremor.","authors":"Adrian Handforth,&nbsp;Hovsep P Kosoyan,&nbsp;Pournima A Kadam,&nbsp;Ram P Singh","doi":"10.5334/tohm.760","DOIUrl":"https://doi.org/10.5334/tohm.760","url":null,"abstract":"<p><strong>Background: </strong>A long-standing question is why essential tremor often responds to non-intoxicating amounts of alcohol. Blood flow imaging and high-density electroencephalography have indicated that alcohol acts on tremor within the cerebellum. As extra-synaptic δ-subunit-containing GABA_A receptors are sensitive to low alcohol levels, we wondered whether these receptors mediate alcohol's anti-tremor effect and, moreover, whether the δ-associated GABA_A receptor α6 subunit, found abundantly in the cerebellum, is required.</p><p><strong>Methods: </strong>We tested the hypotheses that low-dose alcohol will suppress harmaline-induced tremor in wild-type mice, but not in littermates lacking GABA_A receptor δ subunits, nor in littermates lacking α6 subunits. As the neurosteroid ganaxolone also activates extra-synaptic GABA_A receptors, we similarly assessed this compound. The harmaline mouse model of essential tremor was utilized to generate tremor, measured as a percentage of motion power in the tremor bandwidth (9-16 Hz) divided by background motion power at 0.25-32 Hz.</p><p><strong>Results: </strong>Ethanol, 0.500 and 0.575 g/kg, and ganaxolone, 7 and 10 mg/kg, doses that do not impair performance in a sensitive psychomotor task, reduced harmaline tremor compared to vehicle-treated controls in wild-type mice but failed to suppress tremor in littermates lacking the δ or the α6 GABA_A receptor subunit.</p><p><strong>Discussion: </strong>As cerebellar granule cells are the predominant brain site intensely expressing GABA_A receptors containing both α6 and δ subunits, these findings suggest that this is where alcohol acts to suppress tremor. It is anticipated that medications designed specifically to target α6βδ-containing GABA_A receptors may be effective and well-tolerated for treating essential tremor.</p><p><strong>Highlights: </strong>How does alcohol temporarily ameliorate essential tremor? This study with a mouse model found that two specific kinds of GABA receptor subunits were needed for alcohol to work. As receptors with both these subunits are found mainly in cerebellum, this work suggests this is where alcohol acts to suppress tremor.</p>","PeriodicalId":23317,"journal":{"name":"Tremor and Other Hyperkinetic Movements","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10198231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9687008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Task Specific Tremor in Parkinson's Disease Responds to Apomorphine.","authors":"William G Ondo,&nbsp;Vindhya Koneru,&nbsp;Chia Arif","doi":"10.5334/tohm.764","DOIUrl":"https://doi.org/10.5334/tohm.764","url":null,"abstract":"<p><strong>Background: </strong>Task specific tremor (TST) is a poorly understood entity without any standard treatments, that may subsequently develop tremor during additional tasks, later develop postural/kinetic tremor (essential tremor criteria), and later develop Parkinson's disease. The pathophysiology is not understood as it has features of tremor, dystonia, and parkinsonism.</p><p><strong>Objectives: </strong>To assess response of TST to apomorphine and thus infer pathophysiology.</p><p><strong>Methods: </strong>We administered sublingual apomorphine to 8 patients diagnosed with Parkinson's disease based on clinical criteria and dopamine imaging, who all initially presented with TST and later presented other parkinsonian signs and dopamine imaging deficits.</p><p><strong>Results: </strong>Apomorphine improved TST, which was refractory to oral levodopa and other tremor therapies, in 6/8 subjects.</p><p><strong>Discussion: </strong>These results offer a treatment option for TST, which is usually refractory to other pharmacologic treatments, in patients with other parkinsonian features, and infers a dopaminergic pathophysiology of TST.</p>","PeriodicalId":23317,"journal":{"name":"Tremor and Other Hyperkinetic Movements","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10237238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10044410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brief Submotor-Threshold Electrical Stimulation Applied Synchronously Over Wrist Flexor and Extensor Muscles does Not Suppress Essential Tremor, Independent of Stimulation Frequency.","authors":"Christian Metzner,&nbsp;Adam Stringham,&nbsp;Brenna Hislop,&nbsp;Joseph Bonham,&nbsp;Larrisa Chatterton,&nbsp;Ryan DeFigueiredo,&nbsp;Steven K Charles","doi":"10.5334/tohm.740","DOIUrl":"https://doi.org/10.5334/tohm.740","url":null,"abstract":"<p><strong>Background: </strong>Electrical stimulation of muscles below motoneuron threshold has shown potential as a low-cost and minimally invasive treatment for Essential Tremor (ET). Prior studies have stimulated wrist flexor and extensor muscles synchronously with diverging results, calling for further investigation. Also, prior studies have only used a narrow range of stimulation parameters, so stimulation parameters have not been optimized. Our purpose was to further investigate synchronous submotor stimulation and identify the effect of stimulation frequency on tremor suppression.</p><p><strong>Methods: </strong>We quantified the effect of brief, synchronous stimulation at 15 different frequencies from 10-150 Hz applied over wrist flexors and extensors on both tremor power and frequency in 20 ET patients. We compared tremor power and frequency from hand acceleration and sEMG between pre-, per-, and post-stimulation phases.</p><p><strong>Results: </strong>Our stimulation paradigm did not result in significant tremor suppression or tremor frequency changes at any tested stimulation frequency, showing no significant interaction between phase and stimulation frequency for tremor power measured by either hand acceleration (p = 0.69) or sEMG (p = 0.07). Additionally, the effect of phase interacting with stimulation frequency on tremor frequency was statistically insignificant for acceleration (p = 0.64) and sEMG (p = 0.37).</p><p><strong>Discussion: </strong>We conclude that brief synchronous submotor-threshold stimulation does not reduce tremor in ET patients, independent of stimulation frequency (from 10 to 150 Hz). Our results are consistent with the hypothesis that brief submotor-threshold stimulation suppresses tremor via reciprocal inhibition, which requires asynchronous stimulation. In contrast, it is hypothesized that synchronous stimulation might require longer stimulation durations to affect supraspinal tremor networks.</p><p><strong>Highlights: </strong>We studied the effects of synchronous submotor electrical stimulation over wrist flexor and extensor muscles on Essential Tremor. Our results indicate that suppressing tremor with brief synchronous stimulation is ineffective. Based on recently hypothesized mechanisms of peripheral tremor suppression, we hypothesize that asynchronous stimulation or long-duration synchronous stimulation are more effective approaches to peripheral tremor suppression.</p>","PeriodicalId":23317,"journal":{"name":"Tremor and Other Hyperkinetic Movements","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10473161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10532738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and Management of Persistent Stimulation-Induced Dyskinesia Associated with STN DBS: The See-Saw Dilemma.","authors":"Matthew A Remz,&nbsp;Joshua K Wong,&nbsp;Justin D Hilliard,&nbsp;Tracy Tholanikunnel,&nbsp;Ashley E Rawls,&nbsp;Michael S Okun","doi":"10.5334/tohm.780","DOIUrl":"https://doi.org/10.5334/tohm.780","url":null,"abstract":"<p><strong>Clinical vignette: </strong>A 73-year-old woman with Parkinson's disease (PD) underwent implantation of bilateral subthalamic nucleus deep brain stimulators (STN-DBS) to address bilateral upper extremity medication-refractory tremor. Post-operatively, she experienced a \"see-saw effect\" where small increases in stimulation resulted in improvement in one symptom (tremor) with concurrent worsening in another (dyskinesia).</p><p><strong>Clinical dilemma: </strong>SID is usually considered a positive predictor of DBS outcome. However, there are cases where SID cannot be optimized. Lead location and pre-operative characteristics may contribute to this adverse effect. If the combination of programming and medication adjustments fails to resolve SID, what can be done to \"rescue\" the outcome?</p><p><strong>Clinical solution: </strong>Management of SID requires a gradual and steadfast programming approach. Post-operative lead localization can guide advanced programming and decision-making. Rescue surgical interventions may be considered.</p><p><strong>Gap in knowledge: </strong>In cases where SID is persistent despite deploying persistent optimization strategies, there is limited guidance on next steps.</p>","PeriodicalId":23317,"journal":{"name":"Tremor and Other Hyperkinetic Movements","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10473163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10227309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}