Clocks & Sleep最新文献

{"title":"Impact of Varying Sleep Pressure on Daytime Sleep Propensity in Healthy Young and Older Adults.","authors":"Stella de Haan, Marine Dourte, Michele Deantoni, Mathilde Reyt, Marion Baillet, Christian Berthomier, Vincenzo Muto, Gregory Hammad, Christian Cajochen, Carolin F Reichert, Micheline Maire, Christina Schmidt, Svetlana Postnova","doi":"10.3390/clockssleep7010002","DOIUrl":"10.3390/clockssleep7010002","url":null,"abstract":"<p><p>Fixed sleep schedules with an 8 h time in bed (TIB) are used to ensure participants are well-rested before laboratory studies. However, such schedules may lead to cumulative excess wakefulness in young individuals. Effects on older individuals are unknown. We combine modelling and experimental data to quantify the effects of sleep debt on sleep propensity in healthy younger and older participants. A model of arousal dynamics was fitted to sleep data from 22 young (20-31 y.o.) and 26 older (61-82 y.o.) individuals (25 male) undertaking 10 short sleep-wake cycles during a 40 h napping protocol, following >1 week of fixed 8 h TIB schedules. Homeostatic sleep drive at the study start was varied systematically to identify best fits between observed and predicted sleep profiles for individuals and group averages. Daytime sleep duration was the same on the two days of the protocol within the groups but different between the groups (young: 3.14 ± 0.98 h vs. 3.06 ± 0.75 h, older: 2.60 ± 0.98 h vs. 2.37 ± 0.64 h). The model predicted an initial homeostatic drive of 11.2 ± 3.5% (young) and 10.1 ± 3.5% (older) above well-rested. Individual variability in first-day, but not second-day, sleep patterns was explained by the differences in the initial homeostatic drive for both age groups. Our study suggests that both younger and older participants arrive at the laboratory with cumulative sleep debt, despite 8 h TiB schedules, which dissipates after the first four sleep opportunities on the protocol. This has implications for protocol design and the interpretation of laboratory studies.</p>","PeriodicalId":33568,"journal":{"name":"Clocks & Sleep","volume":"7 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024988","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":"Changes in the Spatial Structure of Synchronization Connections in EEG During Nocturnal Sleep Apnea.","authors":"Maxim Zhuravlev, Anton Kiselev, Anna Orlova, Evgeniy Egorov, Oxana Drapkina, Margarita Simonyan, Evgenia Drozhdeva, Thomas Penzel, Anastasiya Runnova","doi":"10.3390/clockssleep7010001","DOIUrl":"10.3390/clockssleep7010001","url":null,"abstract":"<p><p>This study involved 72 volunteers divided into two groups according to the apnea-hypopnea index (AHI): AHI>15 episodes per hour (ep/h) (main group, n=39, including 28 men, median AHI 44.15, median age 47), 0≤AHI≤15ep/h (control group, n=33, including 12 men, median AHI 2, median age 28). Each participant underwent polysomnography with a recording of 19 EEG channels. Based on wavelet bicoherence (WB), the magnitude of connectivity between all pairs of EEG channels in six bands was estimated: Df1 0.25;1, Df2 1;4, Df3 4;8, Df4 8;12, Df5 12;20, Df6 20;30 Hz. In all six bands considered, we noted a significant decrease in symmetrical interhemispheric connections in OSA patients. Also, in the main group for slow oscillatory activity Df1 and Df2, we observe a decrease in connection values in the EEG channels associated with the central interhemispheric sulcus. In addition, patients with AHI>15 show an increase in intrahemispheric connectivity, in particular, forming a left hemisphere high-degree synchronization node (connections PzT3, PzF3, PzFp1) in the Df2 band. When considering high-frequency EEG oscillations, connectivity in OSA patients again shows a significant increase within the cerebral hemispheres. The revealed differences in functional connectivity in patients with different levels of AHI are quite stable, remaining when averaging the full nocturnal EEG recording, including both the entire sleep duration and night awakenings. The increase in the number of hypoxia episodes correlates with the violation of the symmetry of interhemispheric functional connections. Maximum absolute values of correlation between the apnea-hypopnea index, AHI, and the WB synchronization strength are observed for the Df2 band in symmetrical EEG channels C3C4 (-0.81) and P3P4 (-0.77). The conducted studies demonstrate the possibility of developing diagnostic systems for obstructive sleep apnea syndrome without using signals from the cardiovascular system and respiratory activity.</p>","PeriodicalId":33568,"journal":{"name":"Clocks & Sleep","volume":"7 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024985","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":"Impact of CPAP Therapy on Cognition and Fatigue in Patients with Moderate to Severe Sleep Apnea: A Longitudinal Observational Study.","authors":"Oumaïma Benkirane, Olivier Mairesse, Philippe Peigneux","doi":"10.3390/clockssleep6040051","DOIUrl":"10.3390/clockssleep6040051","url":null,"abstract":"<p><p>Continued solicitation of cognitive resources eventually leads to cognitive fatigue (CF), i.e., a decrease in cognitive efficiency that develops during sustained cognitive demands in conditions of constrained processing time, independently of sleepiness. The expression of CF and its impact on cognition are partly contingent upon prior sleep quality and its restorative effects. Sleep in obstructive sleep apnea (OSA) may be largely restored through the use of continuous positive airway pressure (CPAP) treatment, contributing to a gradual improvement in sleep quality. In this longitudinal observational study, we investigated immediate and longer-term behavioral effects of CPAP treatment on cognitive functioning, evaluating outcomes after the initiation of treatment, and at three and six months, in compliant CPAP-treated OSA patients. Results indicate that CPAP therapy significantly enhances subjective sleep quality and cognitive functions, including episodic memory, inhibition, sustained attention, working memory, and executive control. Noticeable performance improvements were observed in CF-inducing tasks, particularly after six months of CPAP use. Participants also reported substantial gains in quality of life, reduced daytime sleepiness, and improved mood. These results confirm that CPAP therapy not only alleviates immediate physiological disturbances associated with OSA, but also supports cognitive recovery and enhanced overall daily functioning.</p>","PeriodicalId":33568,"journal":{"name":"Clocks & Sleep","volume":"6 4","pages":"789-816"},"PeriodicalIF":2.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898692","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":"Multi-Night Home Assessment of Total Sleep Time Misperception in Obstructive Sleep Apnea with and Without Insomnia Symptoms.","authors":"Jasmin Kuhn, Laura R B Schiphorst, Bernice M Wulterkens, Jerryll Asin, Nanny Duis, Sebastiaan Overeem, Merel M van Gilst, Pedro Fonseca","doi":"10.3390/clockssleep6040050","DOIUrl":"10.3390/clockssleep6040050","url":null,"abstract":"<p><p>Total sleep time (TST) misperception has been reported in obstructive sleep apnea (OSA). However, previous findings on predictors were inconsistent and predominantly relied on single-night polysomnography, which may alter patients' sleep perception. We leveraged advances in wearable sleep staging to investigate predictors of TST misperception in OSA over multiple nights in the home environment. The study included 141 patients with OSA, 75 without insomnia symptoms (OSA group), and 66 with insomnia symptoms (OSA-I group). Objective TST was measured using a previously validated wrist-worn photoplethysmography and accelerometry device. Self-reported TST was assessed using a digital sleep diary. TST misperception was quantified with the misperception index (MI), calculated as (objective - self-reported TST)/objective TST. MI values differed significantly between the OSA (median = -0.02, IQR = [-0.06, 0.02]) and the OSA-I group (0.05, [-0.02, 0.13], <i>p</i> < 0.001). Multilevel modeling revealed that the presence of insomnia symptoms (β = 0.070, <i>p</i> < 0.001) and lower daily reported sleep quality (β = -0.229, <i>p</i> < 0.001) were predictive of higher MI (TST underestimation), while a higher apnea-hypopnea index (AHI) was predictive of lower MI (TST overestimation; β = -0.001, <i>p</i> = 0.006). Thus, insomnia symptoms and AHI are associated with TST misperception in OSA patients, but in opposite directions. This association extends over multiple nights in the home environment.</p>","PeriodicalId":33568,"journal":{"name":"Clocks & Sleep","volume":"6 4","pages":"777-788"},"PeriodicalIF":2.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898697","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":"Sex Differences in Sleep and Physical Activity Patterns in Autism Spectrum Disorder.","authors":"Véronique-Aurélie Bricout, Sandro Covain, Jacob Paterno, Michel Guinot","doi":"10.3390/clockssleep6040049","DOIUrl":"10.3390/clockssleep6040049","url":null,"abstract":"<p><p>Physical activity (PA) programs have been found to result in improved sleep in males with autism spectrum disorder (ASD), but little is known about the female characteristics. The aim of this work was to assess sex differences in sleep and PA indices using an accelerometer over 7 days and 7 nights. Sleep and PA variables were measured with questionnaires and with accelerometry in twenty-four children with ASD (16 boys, 10.3 ± 2.8; 8 girls, 11.1 ± 3.9). Some significant differences were reported between girls and boys. The total time in bed and wake time after sleep onset (WASO) were significantly higher in girls compared to boys (<i>p</i> < 0.01), whereas sleep efficiency was significantly lower in girls (<i>p</i> < 0.01). The results obtained from the sleep questionnaire (CSHQ) show averages above the threshold of 41 in both groups (the threshold indicates the presence of sleep disorders or low sleep quality). The number of daily steps was significantly lower in the girls' group (<i>p</i> < 0.01), and the PA volume for vigorous and strong vigorous intensities was significantly higher in the boys' group (<i>p</i> < 0.01 and <i>p</i> < 0.05, respectively). Our results show major alterations in girls, with a low level of PA and sleep alteration. PA is a relevant non-pharmacological approach to improve sleep quality and achieve sufficient sleep duration. However, particularly for girls with ASD, more personalized approaches to improve sleep may be needed to manage specific associated disorders.</p>","PeriodicalId":33568,"journal":{"name":"Clocks & Sleep","volume":"6 4","pages":"764-776"},"PeriodicalIF":2.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711139","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":"The Effect of Caffeine Exposure on Sleep Patterns in Zebrafish Larvae and Its Underlying Mechanism.","authors":"Yuanzheng Wei, Zongyu Miao, Huixin Ye, Meihui Wu, Xinru Wei, Yu Zhang, Lei Cai","doi":"10.3390/clockssleep6040048","DOIUrl":"10.3390/clockssleep6040048","url":null,"abstract":"<p><p>The effect of caffeine on the behavior and sleep patterns of zebrafish larvae, as well as its underlying mechanisms, has been a topic of great interest. This study aimed to investigate the impact of caffeine on zebrafish larval sleep/wake behavior and the expression of key regulatory genes such as cAMP-response element binding protein (CREB) and adenosine (ADA) in the sleep pathway. To begin, the study determined the optimal dose and duration of caffeine exposure, with the optimal doses found to be 31.25 μM, 62.5 μM, and 120 μM. Similarly, the optimal exposure time was established as no more than 120 h, ensuring a mortality rate of less than 10%. The confirmation of these conditions was achieved through the assessment of angiogenesis and the inflammatory reaction. As a result, the treatment time point of 24 h post-fertilization (hpf) was selected to examine the effects of caffeine on zebrafish larval sleep rhythm (48 h, with a light cycle of 14:10). Furthermore, the study analyzed the expression of clock genes (bmal1a, per1b, per2, per3, cry2), adenosine receptor genes (adora1a, adora1b, adora2aa, adora2ab, adora2b), and key regulatory factors (CREB and ADA). The research confirmed that caffeine could induce sleep pattern disorders, significantly upregulate adenosine receptor genes (adora1a, adora1b, adora2a, adora2ab, adora2b) (<i>p</i> < 0.05), and markedly decrease the total sleep time and sleep efficiency of the larvae. Additionally, the activity of ADA significantly increased during the exposure (<i>p</i> < 0.001), and the tissue-specific expression of CREB was also significantly increased, as assessed by immunofluorescence. Caffeine may regulate circadian clock genes through the ADA/ADORA/CREB pathway. These findings not only enhance our understanding of the effects of caffeine on zebrafish larvae but also provide valuable insights into the potential impact of caffeine on human behavior and sleep.</p>","PeriodicalId":33568,"journal":{"name":"Clocks & Sleep","volume":"6 4","pages":"749-763"},"PeriodicalIF":2.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711144","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":"Thirty-Fifth Annual Meeting of the Society for Light Treatment and Biological Rhythms (SLTBR), 20 June-22 June, Prague, Czech Republic.","authors":"Christian Cajochen","doi":"10.3390/clockssleep6040047","DOIUrl":"10.3390/clockssleep6040047","url":null,"abstract":"<p><p>I am delighted to introduce this collection of abstracts from our recent 35th Annual SLTBR Meeting in Prague [...].</p>","PeriodicalId":33568,"journal":{"name":"Clocks & Sleep","volume":"6 4","pages":"690-748"},"PeriodicalIF":2.1,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711149","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":"Are the Sleep-Wake Cycle and Sleep Duration Ethnically Determined? A Comparison of Tibetan and Japanese Children's Sleep.","authors":"Ping Su, Masako Taniike, Yuko Ohno, Ikuko Mohri","doi":"10.3390/clockssleep6040046","DOIUrl":"10.3390/clockssleep6040046","url":null,"abstract":"<p><strong>Background: </strong>Several environmental factors affect sleep. We investigated the sleep and sleep-related habits of preschool children living in Tibet and conducted an international comparison with those in Japan.</p><p><strong>Methods: </strong>We conducted a community-based cross-sectional study using the Chinese version of the Japanese Sleep Questionnaire for Preschoolers (JSQ-P-C) and compared the results with previous data on Japanese children.</p><p><strong>Results: </strong>The sleep status of 3113 children aged 3-6 years old in Qinghai province was evaluated. The average wake time and bedtime of the Tibetan children were 7:20 ± 0:31 and 21:16 ± 0:43, respectively. Their mean nocturnal sleep duration was 10.0 ± 0.7 h. In comparing 3-year-old children, the time for which they viewed TV in Tibet was shorter (65.5 ± 44.6 min) than that in Japan (149.7 ± 76.6 min), and the mother's bedtime was earlier in Tibet (21:28 ± 2:14) than in Japan (23:20 ± 1:05). However, the bedtime and sleep duration of the Tibetan children (21:17 ± 0:37 and 10.0 ± 0.7 h) were fairly similar to those of the Japanese children (21:24 ± 1:57 and 9.8 ± 0.8 h).</p><p><strong>Conclusions: </strong>The late bedtime and short nocturnal sleep duration of Tibetan toddlers were the same as those of Japanese toddlers despite considerable differences in their lifestyle and environment.</p>","PeriodicalId":33568,"journal":{"name":"Clocks & Sleep","volume":"6 4","pages":"682-689"},"PeriodicalIF":2.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710746","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":"Characteristics and Transition of Sleep-Wake Rhythm in Nursery School Children: The Importance of Nocturnal Sleep.","authors":"Takehiro Hasegawa, Shozo Murata, Tatsuo Kagimura, Kaoru Omae, Akiko Tanaka, Kaori Takahashi, Mika Narusawa, Yukuo Konishi, Kentaro Oniki, Teruhisa Miike","doi":"10.3390/clockssleep6040045","DOIUrl":"10.3390/clockssleep6040045","url":null,"abstract":"<p><p>In this study, we investigated the sleep-wake rhythm of nursery school children with the aim of supporting their health and mental/physical development. We analyzed 4881 children from infancy to 6 years of age, using 2 week sleep tables recorded by their guardians. The tables contained night bedtimes, wake times, nighttime/daytime sleep duration, and the differences in these between weekdays and weekends. The total sleep decrement of children with increasing age is attributed to a decrease in daytime sleep, while nighttime sleep duration remains almost unchanged at about 10 h, which is, therefore, referred to as the nighttime basic sleep duration (NBSD). Although bedtime stabilizes at around 9:30 p.m. by the age of 2, wake-up times tend to be before 7 a.m., which results in sleep insufficiency during weekdays. This lack of sleep is compensated for by long naps on weekdays and by catching up on sleep on weekend mornings, which may contribute to future social jet lag. Guardians are encouraged to know their children's exact NBSD and set an appropriate bedtime to be maintained on weekdays. This helps to prevent sleep debt and fosters a consistent daily rhythm of waking up at the same time both on weekdays and weekends. These conditions are believed to support mental/physical development and school and social adaptation.</p>","PeriodicalId":33568,"journal":{"name":"Clocks & Sleep","volume":"6 4","pages":"668-681"},"PeriodicalIF":2.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710802","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":"Use of Basket Trials to Solve Sleep Problems in Patients with Rare Diseases.","authors":"Lara C Pullen, Nick Bott, Cate McCanless, Amee Revana, Gunes Sevinc, Casey Gorman, Alexandra Duncan, Sarah Poliquin, Anna C Pfalzer, Katie Q Schmidt, E Robert Wassman, Chère Chapman, Maria Picone","doi":"10.3390/clockssleep6040044","DOIUrl":"10.3390/clockssleep6040044","url":null,"abstract":"<p><p>The need for sleep is universal, and the ability to meet this need impacts the quality of life for patients, families, and caregivers. Although substantial progress has been made in treating rare diseases, many patients have unmet medical sleep needs, and current regulatory policy makes it prohibitively difficult to address those needs medically. This opinion reviews the rare disease experience with sleep disorders and explores potential solutions. First, we provide case profiles for the rare diseases Wilson's Disease, Angelman Syndrome, and Prader-Willi Syndrome. These profiles highlight challenges in rare disease diagnosis and barriers to pinpointing disease pathophysiology, including biomarkers that intersect with sleep disorders. Second, we transition to a bird's eye view of sleep disorders and rare diseases by reporting input from a stakeholder discussion with the U.S. Food and Drug Administration regarding abnormal sleep patterns in various rare diseases. Last, in response to the profound unmet medical needs of patients with rare diseases and sleep disorders, we propose adapting and using the clinical trial design known as a \"basket trial\". In this case, a basket trial would include patients with different rare diseases but the same debilitating symptoms. This research approach has the potential to benefit many rare disease patients who are otherwise left with profound unmet medical needs.</p>","PeriodicalId":33568,"journal":{"name":"Clocks & Sleep","volume":"6 4","pages":"656-667"},"PeriodicalIF":2.1,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711065","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}