{"title":"The effect of fascial manipulation therapy on lower limb spasticity and ankle clonus in stroke patients.","authors":"Wenyan Li, Xin Liu, Yinghua Wen, Junying Wu, Federico Giordani, Carla Stecco","doi":"10.4081/ejtm.2024.12172","DOIUrl":"10.4081/ejtm.2024.12172","url":null,"abstract":"<p><p>Lower limb spasticity and clonus are common sequelae after cerebral stroke. An important part of their etiopathogenesis has been related to the peripheral component of spasticity. Rheological properties of the tissues seem to be involved. Several studies highlighted anatomical and functional changes in the connective structures. The fasciae might be implicated in the pathological process. Thus, this study intends to investigate the effect of the Fascial Manipulation (FM) technique on triceps surae in stroke patients through a clinical randomized controlled trial, to provide a reference for clinical treatment of lower limb spasticity and ankle clonus. A total of 40 patients with post-stroke ankle clonus were selected and divided into a control group and an observation group by random number table method, with 20 cases in each group. Both groups received conventional rehabilitation therapy, while the FM group received Fascial Manipulation based on conventional rehabilitation therapy. Before the first treatment and after 3 weeks of treatment, the Comprehensive Spasticity Scale (CSS), the Passive Range Of Motion (PROM), the simplified Fugl-Meyer motor function score (FMA), and the Modified Ashworth Scale (MAS) were used to assess the degree of ankle clonus, ankle passive range of motion, and lower limb motor function of the two groups of patients. Before treatment, there was no statistically significant difference between the control group and the FM group in terms of CSS, PROM, FMA, and MAS of the affected lower limbs (P>0.05). After 3 weeks of treatment, the CSS and MAS of the affected lower limbs in the control group and FM group decreased, while PROM and FMA increased compared to pre-treatment evaluation, with statistically significant differences (P<0.05). Moreover, the FM group showed a statistically significant decrease in CSS and MAS, as well as an increase in PROM and FMA, compared to the control group (P<0.05). Conclusions: Fascial manipulation in addition to conventional therapy can effectively reduce spasticity and ankle clonus in stroke patients in a short time, and improve the passive range of motion of the ankle joint and the function of lower limbs.</p>","PeriodicalId":46459,"journal":{"name":"European Journal of Translational Myology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493931","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}
Ester Tommasini, Sara Missaglia, Paola Vago, Christel Galvani, Claudio Pecci, Ermanno Rampinini, Andrea Bosio, Andrea Morelli, Andrea Bonanomi, Andrea Silvestrini, Alvaro Mordente, Daniela Tavian
{"title":"The time course of irisin release after an acute exercise: relevant implications for health and future experimental designs.","authors":"Ester Tommasini, Sara Missaglia, Paola Vago, Christel Galvani, Claudio Pecci, Ermanno Rampinini, Andrea Bosio, Andrea Morelli, Andrea Bonanomi, Andrea Silvestrini, Alvaro Mordente, Daniela Tavian","doi":"10.4081/ejtm.2024.12693","DOIUrl":"10.4081/ejtm.2024.12693","url":null,"abstract":"<p><p>This study aimed to analyze the acute impact of exercise on serum irisin levels in 22 young (YA, 24.6 ± 3.5 yrs) and in 12 middle-aged male adults (MA, 54.6 ± 5.7 yrs) 15 min and 24 h after an incremental cycling exercise test to exhaustion. ELISA assay was used for serum irisin detection. Circulating irisin increased significantly from baseline (9.0 ± 2.0 ng/ml) to 15 min post-exercise (10.2 ± 2.0 ng/ml, P < 0.001), but the greatest increment was detected after 24 h (13.5 ± 2.5 ng/ml, P < 0.001) reaching more than 50% of the basal release. Levels were significantly higher in YA (9.7 ± 1.7 to 11.1 ± 1.8 to 14.5 ± 2.2 ng/ml) than MA (7.6 ± 1.6 to 8.7 ± 1.5 to 11.8± 2.2 ng/ml) for all measured time-points (P < 0.05). Nevertheless, MA showed a comparable increase in serum irisin levels when compared to YA. These findings highlight the importance of acute physical exercise as a countermeasure against age-related deterioration of skeletal muscle mass and function in both YA and MA.</p>","PeriodicalId":46459,"journal":{"name":"European Journal of Translational Myology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471505","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":"Linc00513 sponges miR-7 to modulate TGF-β signaling in azoospermia.","authors":"Atoosa Etezadi, Adere Akhtare, Zahra Asadikalameh, Zeinab Hashem Aghaei, Paria Panahinia, Mozhgan Arman, Amene Abtahian, Fereshteh Faghih Khorasani, Vajihe Hazari","doi":"10.4081/ejtm.2024.12516","DOIUrl":"10.4081/ejtm.2024.12516","url":null,"abstract":"<p><p>Azoospermia, or the complete absence of sperm in the ejaculate, affects about 1% of men worldwide and is a significant fertility challenge. This study investigates Linc00513, a long non-coding RNA, and its potential role in regulating the TGF-β signaling pathway, a key player in spermatogenesis, in the context of azoospermia. We show that Linc00513 expression is significantly lower in testicular tissues from azoospermic patients than in HS1 controls. Linc00513 interacts directly with microRNA-7 (miR-7) via complementary base pairing, acting as a competing endogenous RNA (ceRNA). This interaction effectively inhibits miR-7's inhibitory action on the TGF-β receptor 1 (TGFBR1), a critical component of the TGF-β signaling cascade. Downregulating Linc00513 reduces TGFBR1 repression and increases TGF-β signaling in azoospermic testes. Functional assays with spermatogonial cell lines support these findings. Silencing Linc00513 leads to increased cell proliferation and decreased apoptosis, similar to TGF-β inhibition. Overexpression of miR-7 inhibits the effects of Linc00513 on TGF-β signaling. Our study sheds new light on how Linc00513, miR-7, and the TGF-β signaling pathway interact in azoospermia. Linc00513 regulates TGFBR1 expression and thus influences spermatogonial cell fate by acting as a miR-7 ceRNA. These findings identify a potential therapeutic target for azoospermia treatment, paving the way for future research into restoring fertility in affected individuals.</p>","PeriodicalId":46459,"journal":{"name":"European Journal of Translational Myology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477693","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":"Quantitative 3D-CT imaging of sarcopenia mitigation in the elderly: evidence from a case report.","authors":"Marco Quadrelli, Tommaso Baccaglini, Aldo Morra","doi":"10.4081/ejtm.2024.12715","DOIUrl":"10.4081/ejtm.2024.12715","url":null,"abstract":"<p><p>This case study examines the effectiveness of using combined CT imaging and 3D imaging in monitoring the prevention of sarcopenia through continuous daily exercises in an elderly patient. Using a 256-slice CT scanner with dose reduction technology and advanced muscle segmentation with the open-source software DAFNE, we compared changes in muscle mass and density in a 70-year-old patient in 2014 and in 2023. The obtained images allowed the creation of detailed 3D models for a more accurate and intuitive assessment of the leg musculature. Despite aging, the results of the scans performed at the beginning and end of the study period did not show significant changes in the patient's musculature, suggesting that a persistent Full-Body in-Bed Gym protocol (\"Gym Bed\" exercise routine) can effectively contribute to maintaining muscle mass and density in the elderly. These preliminary results highlight the potential of advanced imaging techniques not only to diagnose but also to quantify the effectiveness of non-pharmacological interventions against sarcopenia.</p>","PeriodicalId":46459,"journal":{"name":"European Journal of Translational Myology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471504","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}
Vincenzo Francavilla, Giuseppe Secolo, Marianna D'Armetta, Rosario Toscano, Angelo Campo, Valentina Catanzaro, Marina Manno, Innocenzo Secolo, Giuseppe Messina
{"title":"Onychocryptosis: a retrospective study of clinical aspects, inflammation treatment and pain management using Ozoile as a hydrogel and cream formulation.","authors":"Vincenzo Francavilla, Giuseppe Secolo, Marianna D'Armetta, Rosario Toscano, Angelo Campo, Valentina Catanzaro, Marina Manno, Innocenzo Secolo, Giuseppe Messina","doi":"10.4081/ejtm.2024.12487","DOIUrl":"10.4081/ejtm.2024.12487","url":null,"abstract":"<p><p>Ingrown toenails account for roughly 20% of all foot problems in primary care. It is most common in young men, with nail care habits and footwear being major contributors. Onychocryptosis is typically caused by self-treatment attempts to cure the condition in its early stages. Its clinical features are frequently confused with other osseous and soft tissue abnormalities. The goal of this study was to provide perspectives on the management of pain and inflammation in Onychocryptosis using an Ozoile-based hydrogel formulation in a semi-occlusive bandage for 14 days, while incorporating natural pharmacological solutions into established protocols. The primary outcomes measured were pain reduction on NRS and stadiation according to the Al Kline Classification. The reduction was statistically significant, with a mean decrease in VAS score from 10 to 4 (p < 0.05), and Al Kline classification decreased by an average of 1.6 stages. 42% of patients recovered within the first 15 days of treatment, and 93% by the end of the scheduled treatment.</p>","PeriodicalId":46459,"journal":{"name":"European Journal of Translational Myology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141459810","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":"Stretching exercises in managing spasticity: effectiveness, risks, and adjunct therapies.","authors":"Mostafa Mehraban Jahromi, Přemysl Vlček, Marcela Grünerová Lippertová","doi":"10.4081/ejtm.2024.12455","DOIUrl":"10.4081/ejtm.2024.12455","url":null,"abstract":"<p><p>Spasticity is a component of upper motor neuron disorders and can be seen in neurological conditions like stroke and multiple sclerosis. Although the incidence rate of spasticity is unknown, it can put pressure on the health condition of those with spasticity, and there is no absolute effective way to control it. In the past, stretching exercises were an accessible tool for physical therapists to manage and control spasticity, but opinions on the optimal dose, aftereffects, and mechanism of effects were controversial. Therefore, this article tries to provide an overview of the effectiveness and risks of stretching exercises. Furthermore, there are several adjunct therapies, such as brain stimulation and botulinum injection, that can increase the effectiveness of a simple stretch by increasing cortical excitability and reducing muscle tone and their role is evaluated in this regard. The results of this study propose that several prospective and case studies have demonstrated the benefits of stretching to control spasticity, but it seems that other methods such as casting can be more effective than a simple stretch. Therefore, it is better to use stretching in combination with other therapeutic regimes to increase its effectivity of it.</p>","PeriodicalId":46459,"journal":{"name":"European Journal of Translational Myology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318494","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":"Evaluation of the impact of oesophageal reflux disease on muscle fatigue.","authors":"Wenming Hong, Hao Wang, Xuheng Yu","doi":"10.4081/ejtm.2024.12243","DOIUrl":"10.4081/ejtm.2024.12243","url":null,"abstract":"<p><p>Gastroesophageal reflux disease (GERD) is a gastrointestinal tract disorder associated with regurgitation of gastric acid into the oesophagus. It can present itself as non-erosive reflux condition or erosive esophagitis. Our main objective was to evaluate the impact of oesophageal reflux disease on muscle fatigue among patients. The prospective study design was adopted using surveys performed at the South West China Medical University. All patients who were subjected to screening endoscopy at the South West China Medical University were prospectively enrolled in the study. Our study was conducted according to ethical guidelines involving animal and human subjects. Our study used Epworth Sleepiness Scale (ESS), Hospital Anxiety and Depression Scale (HADS), and the Multidimensional Fatigue Inventory (MFI) questionnaires to perform data collection on the levels of fatigue, depression, daytime hypersomnolence and anxiety. In the (HADS, Anxiety (β = 0.657, p < .001) and Depression (β = 2.927, p < .001) exhibited significant positive associations with the predicted fatigue. The Epworth Sleepiness Scale (ESS) showed no significant difference between individuals with and without reflux esophagitis (p = 0.787, power = 0.071). However, a significant difference was observed based on the presence of GERD symptoms (p = 0.003, power = 0.789), with higher mean scores for those with GERD symptoms (6.1±3.5) compared to those without (4.9±2.9). In MFI, significant differences were observed between the two groups for General and Physical Fatigue (p = 0.040, power = 0.823), Mental Fatigue (p = 0.002, power = 0.767), and MFI Total Score (p = 0.002, power = 0.981). In conclusion, GERD symptoms exhibited stronger associations with fatigue and daytime sleepiness than endoscopic findings, emphasizing the impact of symptomatic experiences on well-being.</p>","PeriodicalId":46459,"journal":{"name":"European Journal of Translational Myology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180252","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}
Ève Boissonnault, April Jeon, Michael C Munin, Mirko Filippetti, Alessandro Picelli, Chloe Haldane, Rajiv Reebye
{"title":"Assessing muscle architecture with ultrasound: implications for spasticity.","authors":"Ève Boissonnault, April Jeon, Michael C Munin, Mirko Filippetti, Alessandro Picelli, Chloe Haldane, Rajiv Reebye","doi":"10.4081/ejtm.2024.12397","DOIUrl":"10.4081/ejtm.2024.12397","url":null,"abstract":"<p><p>Botulinum Neurotoxin Type A (BoNT-A) injections using Ultrasound (US) guidance have led to research evaluating changes in muscle architecture. Controversy remains as to what constitutes increased Echo-Intensity (EI) in spastic muscles and whether this may affect outcomes. We aim to provide a narrative review of US muscle architecture changes following Central Nervous System (CNS) lesions and explore their relationship to spasticity. Medline, CINAHL, and Embase databases were searched with keywords: ultrasonography, hypertonia, spasticity, fibrosis, and Heckmatt. Three physicians reviewed the results of the search to select relevant papers. Reviews identified in the search were used as a resource to identify additional studies. A total of 68 papers were included. Four themes were identified, including histopathological changes in spastic muscle, effects of BoNT-A on the muscle structure, available US modalities to assess the muscle, and utility of US assessment in clinical spasticity. Histopathological studies revealed atrophic and fibro-fatty changes after CNS lesions. Several papers described BoNT-A injections contributing to those modifications. These changes translated to increased EI. The exact significance of increased muscle EI remains unclear. The Modified Heckmatt Scale (MHS) is a validated tool for grading muscle EI in spasticity. The use of the US may be an important tool to assess muscle architecture changes in spasticity and improve spasticity management. Treatment algorithms may be developed based on the degree of EI. Further research is needed to determine the incidence and impact of these EI changes in spastic muscles.</p>","PeriodicalId":46459,"journal":{"name":"European Journal of Translational Myology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180294","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}
Paul Dowling, Stephen Gargan, Margit Zweyer, Michael Henry, Paula Meleady, Dieter Swandulla, Kay Ohlendieck
{"title":"Proteomic reference map for sarcopenia research: mass spectrometric identification of key muscle proteins located in the sarcomere, cytoskeleton and the extracellular matrix.","authors":"Paul Dowling, Stephen Gargan, Margit Zweyer, Michael Henry, Paula Meleady, Dieter Swandulla, Kay Ohlendieck","doi":"10.4081/ejtm.2024.12564","DOIUrl":"10.4081/ejtm.2024.12564","url":null,"abstract":"<p><p>Sarcopenia of old age is characterized by the progressive loss of skeletal muscle mass and concomitant decrease in contractile strength. Age-related skeletal muscle dysfunctions play a key pathophysiological role in the frailty syndrome and can result in a drastically diminished quality of life in the elderly. Here we have used mass spectrometric analysis of the mouse hindlimb musculature to establish the muscle protein constellation at advanced age of a widely used sarcopenic animal model. Proteomic results were further analyzed by systems bioinformatics of voluntary muscles. In this report, the proteomic survey of aged muscles has focused on the expression patterns of proteins involved in the contraction-relaxation cycle, membrane cytoskeletal maintenance and the formation of the extracellular matrix. This includes proteomic markers of the fast versus slow phenotypes of myosin-containing thick filaments and actin-containing thin filaments, as well as proteins that are associated with the non-sarcomeric cytoskeleton and various matrisomal layers. The bioanalytical usefulness of the newly established reference map was demonstrated by the comparative screening of normal versus dystrophic muscles of old age, and findings were verified by immunoblot analysis.</p>","PeriodicalId":46459,"journal":{"name":"European Journal of Translational Myology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088607","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}
Paul Dowling, Stephen Gargan, Margit Zweyer, Michael Henry, Paula Meleady, Dieter Swandulla, Kay Ohlendieck
{"title":"Proteomic reference map for sarcopenia research: mass spectrometric identification of key muscle proteins of organelles, cellular signaling, bioenergetic metabolism and molecular chaperoning.","authors":"Paul Dowling, Stephen Gargan, Margit Zweyer, Michael Henry, Paula Meleady, Dieter Swandulla, Kay Ohlendieck","doi":"10.4081/ejtm.2024.12565","DOIUrl":"10.4081/ejtm.2024.12565","url":null,"abstract":"<p><p>During the natural aging process, frailty is often associated with abnormal muscular performance. Although inter-individual differences exit, in most elderly the tissue mass and physiological functionality of voluntary muscles drastically decreases. In order to study age-related contractile decline, animal model research is of central importance in the field of biogerontology. Here we have analyzed wild type mouse muscle to establish a proteomic map of crude tissue extracts. Proteomics is an advanced and large-scale biochemical method that attempts to identify all accessible proteins in a given biological sample. It is a technology-driven approach that uses mass spectrometry for the characterization of individual protein species. Total protein extracts were used in this study in order to minimize the potential introduction of artefacts due to excess subcellular fractionation procedures. In this report, the proteomic survey of aged muscles has focused on organellar marker proteins, as well as proteins that are involved in cellular signaling, the regulation of ion homeostasis, bioenergetic metabolism and molecular chaperoning. Hence, this study has establish a proteomic reference map of a highly suitable model system for future aging research.</p>","PeriodicalId":46459,"journal":{"name":"European Journal of Translational Myology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088680","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}