Non cognitive symptoms are almost always present in dementia with important consequences for patients and caregivers quality of life. Behavioural and Psychological Symptoms of Dementia (BPSD) are heterogeneous and varied in relation to the stage of the demetia and to the aetiology. Treatment of behavioral and psychological symptoms of dementia represent an important challenge, and non pharmacological and pharmacological approach needs. Antidepressant and neuroleptics are the most frequently used drugs in the treatment of BPSD, even if the number of well designed controlled studies are limited. A variety of different forms of environmental and rehabilitative interventions showed efficacy on BPSD.
{"title":"Behavioural and psychological symptoms of dementia: clinical aspects","authors":"A. Bianchetti, M. Trabucchi","doi":"10.1002/NRC.20031","DOIUrl":"https://doi.org/10.1002/NRC.20031","url":null,"abstract":"Non cognitive symptoms are almost always present in dementia with important consequences for patients and caregivers quality of life. Behavioural and Psychological Symptoms of Dementia (BPSD) are heterogeneous and varied in relation to the stage of the demetia and to the aetiology. Treatment of behavioral and psychological symptoms of dementia represent an important challenge, and non pharmacological and pharmacological approach needs. Antidepressant and neuroleptics are the most frequently used drugs in the treatment of BPSD, even if the number of well designed controlled studies are limited. A variety of different forms of environmental and rehabilitative interventions showed efficacy on BPSD.","PeriodicalId":19198,"journal":{"name":"Neuroscience Research Communications","volume":"16 1","pages":"173-183"},"PeriodicalIF":0.0,"publicationDate":"2004-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78935268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Here we summarise current knowledge about biological markers available for early Alzheimer Disease detection. In fact delineating disease process from “normal ageing” may be difficult in the very early stages; in later stages of the disease distinguishing Dementia of Alzheimer Type from a number of neurodegenerative diseases associated with dementia may also be troublesome.
{"title":"Advance on the diagnostic potential of biological markers in the early detection of Alzheimer Disease","authors":"B. Borroni, M. Diluca, F. Cattabeni, A. Padovani","doi":"10.1002/NRC.20036","DOIUrl":"https://doi.org/10.1002/NRC.20036","url":null,"abstract":"Here we summarise current knowledge about biological markers available for early Alzheimer Disease detection. In fact delineating disease process from “normal ageing” may be difficult in the very early stages; in later stages of the disease distinguishing Dementia of Alzheimer Type from a number of neurodegenerative diseases associated with dementia may also be troublesome.","PeriodicalId":19198,"journal":{"name":"Neuroscience Research Communications","volume":"58 1","pages":"232-245"},"PeriodicalIF":0.0,"publicationDate":"2004-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74210657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Age has a powerful effect on enhanced susceptibility to cardiovascular diseases, stroke, cognitive impairment and neurodegenerative diseases and a condition of increased oxidative stress status seems to be the link factor. In this paper we briefly reviewed the more recently reports on the role of oxidative stress in aging and age-related diseases with a specific focus on mild cognitive impairment and Alzheimer's disease. The role of antioxidant therapy and/or supplementation and the importance of an antioxidant rich diet are then discussed.
{"title":"Oxidative stress in Alzheimer's disease: a selective status report","authors":"P. Mecocci, F. Mangialasche, M. Polidori","doi":"10.1002/NRC.20034","DOIUrl":"https://doi.org/10.1002/NRC.20034","url":null,"abstract":"Age has a powerful effect on enhanced susceptibility to cardiovascular diseases, stroke, cognitive impairment and neurodegenerative diseases and a condition of increased oxidative stress status seems to be the link factor. In this paper we briefly reviewed the more recently reports on the role of oxidative stress in aging and age-related diseases with a specific focus on mild cognitive impairment and Alzheimer's disease. The role of antioxidant therapy and/or supplementation and the importance of an antioxidant rich diet are then discussed.","PeriodicalId":19198,"journal":{"name":"Neuroscience Research Communications","volume":"76 1","pages":"202-212"},"PeriodicalIF":0.0,"publicationDate":"2004-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81627628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Bossù, A. Ciaramella, M. Moro, G. Spalletta, C. Caltagirone
SUMMARY Alzheimer’s Disease (AD) is a neurodegenerative disorder characterised by abnormal fibrillar deposits of amyloid beta peptides (AP), which are suggested to play a pivotal role in driving disease pathogenesis. Although the aetiology of AD is still unknown, a perturbation of the immune system has been widely demonstrated in both animal experimental models and patients. The most studied aspect of immune reaction in AD is inflammation, which has been described to be implied in its pathogenic processes. Moreover, a growing body of evidence, indicating that the triggering of the specific AP immune response can be effective in reducing AD symptoms, suggest that a dysregulated network of innate and adaptive immune mechanisms could be critical in AD pathogenic process. The present short review, aimed to summarise some of the principal research studies on immune activation in AD, has the intent to provide suggestions useful to formulate new immune-therapeutic strategies for pathology treatment.
{"title":"Alzheimer's disease and immune activation: A translational perspective","authors":"P. Bossù, A. Ciaramella, M. Moro, G. Spalletta, C. Caltagirone","doi":"10.1002/NRC.20033","DOIUrl":"https://doi.org/10.1002/NRC.20033","url":null,"abstract":"SUMMARY Alzheimer’s Disease (AD) is a neurodegenerative disorder characterised by abnormal fibrillar deposits of amyloid beta peptides (AP), which are suggested to play a pivotal role in driving disease pathogenesis. Although the aetiology of AD is still unknown, a perturbation of the immune system has been widely demonstrated in both animal experimental models and patients. The most studied aspect of immune reaction in AD is inflammation, which has been described to be implied in its pathogenic processes. Moreover, a growing body of evidence, indicating that the triggering of the specific AP immune response can be effective in reducing AD symptoms, suggest that a dysregulated network of innate and adaptive immune mechanisms could be critical in AD pathogenic process. The present short review, aimed to summarise some of the principal research studies on immune activation in AD, has the intent to provide suggestions useful to formulate new immune-therapeutic strategies for pathology treatment.","PeriodicalId":19198,"journal":{"name":"Neuroscience Research Communications","volume":"37 1","pages":"193-201"},"PeriodicalIF":0.0,"publicationDate":"2004-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87080565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Serra, R. Perri, G. Carlesimo, L. Fadda, S. Lorusso, A. Padovani, C. Pettenati, Maia Vegliante, C. Caltagirone
Objective: Aim of this study was to compare ADAS-Cog and MDB, instruments usually used in cognitive assessment of AD patients, relative to: 1) diagnostic sensitivity for dementia of AD; 2) ability to rate the progression of cognitive decline and ability to detect the qualitative characteristics of cognitive decline. Material and methods: A sample of 54 AD patients was submitted to a cognitive assessment with both battery at time of study entry (T 0) and after 12 months (T 12). Results: This study showed: 1) a better diagnostic sensitivity of MDB respect to ADAS-Cog in diagnosing patients affected by mild to moderate levels of AD; 2) a better sensitivity of ADAS-Cog to follow the cognitive decline over a twelve-months period Conclusion: These results supports the use of the MDB in the screening phase of AD patients and of ADAS-Cog to follow the progression of cognitive decline over time.
{"title":"ADAS-CoG and mental deterioration battery: Different instruments for different aspects of cognitive decline in Alzheimer's disease","authors":"L. Serra, R. Perri, G. Carlesimo, L. Fadda, S. Lorusso, A. Padovani, C. Pettenati, Maia Vegliante, C. Caltagirone","doi":"10.1002/NRC.20032","DOIUrl":"https://doi.org/10.1002/NRC.20032","url":null,"abstract":"Objective: Aim of this study was to compare ADAS-Cog and MDB, instruments usually used in cognitive assessment of AD patients, relative to: 1) diagnostic sensitivity for dementia of AD; 2) ability to rate the progression of cognitive decline and ability to detect the qualitative characteristics of cognitive decline. Material and methods: A sample of 54 AD patients was submitted to a cognitive assessment with both battery at time of study entry (T 0) and after 12 months (T 12). Results: This study showed: 1) a better diagnostic sensitivity of MDB respect to ADAS-Cog in diagnosing patients affected by mild to moderate levels of AD; 2) a better sensitivity of ADAS-Cog to follow the cognitive decline over a twelve-months period Conclusion: These results supports the use of the MDB in the screening phase of AD patients and of ADAS-Cog to follow the progression of cognitive decline over time.","PeriodicalId":19198,"journal":{"name":"Neuroscience Research Communications","volume":"10 1","pages":"184-192"},"PeriodicalIF":0.0,"publicationDate":"2004-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85441066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This review discusses the phosphorylation of the Amyloid Precursor Protein (APP) and the possible role of this phosphorylation in Alzheimer's disease (AD). AD is a neurodegenerative disorder characterized by the deposition of β-amyloid plaques in the brain parenchyma and neurofibrillary tangles comprised of hyperphosphorylated tau. APP plays a primary role in the pathogenesis of AD, because its processing generates the amyloid beta peptide (Aβ), the core of the amyloid plaque. APP has a large N-terminal extracellular domain and a short intracellular C-terminal domain that can be phosphorylated by various protein kinases. This review summarized recent work describing the phsphorylation of APP and the downstream events induced by this phosphorylation as well as the impact of APP phosphorylation on APP function and on the production of Aβ peptide.
{"title":"Phosphorylation of the amyloid precursor protein (APP): Is this a mechanism in favor or against Alzheimer's disease?","authors":"L. Pastorino, K. Lu","doi":"10.1002/NRC.20035","DOIUrl":"https://doi.org/10.1002/NRC.20035","url":null,"abstract":"This review discusses the phosphorylation of the Amyloid Precursor Protein (APP) and the possible role of this phosphorylation in Alzheimer's disease (AD). AD is a neurodegenerative disorder characterized by the deposition of β-amyloid plaques in the brain parenchyma and neurofibrillary tangles comprised of hyperphosphorylated tau. APP plays a primary role in the pathogenesis of AD, because its processing generates the amyloid beta peptide (Aβ), the core of the amyloid plaque. APP has a large N-terminal extracellular domain and a short intracellular C-terminal domain that can be phosphorylated by various protein kinases. This review summarized recent work describing the phsphorylation of APP and the downstream events induced by this phosphorylation as well as the impact of APP phosphorylation on APP function and on the production of Aβ peptide.","PeriodicalId":19198,"journal":{"name":"Neuroscience Research Communications","volume":"70 1","pages":"213-231"},"PeriodicalIF":0.0,"publicationDate":"2004-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76317721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The author describes a refiguration of medical thought which originate from non linear dynamics and chaos theory. The coupling of computer science and these new theoretical bases allows the creation of “intelligent” agents (Artificial Adaptive Systems AAS) able to adapt themselves dynamically to problem of high complexity like Alzheimer Disease. ASS are able to reproduce the dynamical interactio of multiple factors simultaneously, allowing the study of complexity; they can also draw conclusions on individual basis and not as average trends. In the last years of co-operation between ITINAD, Bracco Medical Department and Semeion Research Centre different kinds of experiments have been performed with ANNs in Alzheimer Disease context. The specific application of ANN in most cases is original, and has followed two principal aims: –prediction of outcome or diagnosis in individual patients; –data mining of complex data sets. Several examples of applications will be described.
{"title":"The potential role played by artificial adaptive systems in enhancing our understanding of Alzheimer disease: The experience gained within Italian Interdisciplinary network on Alzheimer disease","authors":"E. Grossi, M. Buscema","doi":"10.1002/NRC.20037","DOIUrl":"https://doi.org/10.1002/NRC.20037","url":null,"abstract":"The author describes a refiguration of medical thought which originate from non linear dynamics and chaos theory. The coupling of computer science and these new theoretical bases allows the creation of “intelligent” agents (Artificial Adaptive Systems AAS) able to adapt themselves dynamically to problem of high complexity like Alzheimer Disease. ASS are able to reproduce the dynamical interactio of multiple factors simultaneously, allowing the study of complexity; they can also draw conclusions on individual basis and not as average trends. In the last years of co-operation between ITINAD, Bracco Medical Department and Semeion Research Centre different kinds of experiments have been performed with ANNs in Alzheimer Disease context. The specific application of ANN in most cases is original, and has followed two principal aims: –prediction of outcome or diagnosis in individual patients; –data mining of complex data sets. Several examples of applications will be described.","PeriodicalId":19198,"journal":{"name":"Neuroscience Research Communications","volume":"23 1","pages":"246-268"},"PeriodicalIF":0.0,"publicationDate":"2004-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75483979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Jang, M. Shin, Hyun-kyung Chang, Taeck-Hyun Lee, Hee-Hyuk Lee, Mal-Soon Shin, Chang-Ju Kim, J. Kang, Seon-Pyo Hong, Sonhae Cho
Nitric oxide is synthesized from L-arginine by nitric oxide synthase (NOS), and it is a free radical with signaling functions. Neuronal nitric oxide synthase (nNOS) is mainly expressed in the central nervous system, and it has been implicated in the pathogenesis of brain injury such as ischemia. In the present study, the effects of 7-nitroindazole, which specifically inhibits nNOS, on apoptosis and cell proliferation int he dentate gyrus after transient global ischemia in gerbils were investigated. Enhanced apoptotic neuronal cell death and cell proliferation were observed in the dentate gyrus of ischemic gerbils. However, 7-nitroindazole suppressed the ischemia-induced apoptosis and cell proliferation. These results suggest that 7-nitroindazole has an inhibitive effect on apoptosis and cell proliferation following transient global ischemia. The present study shows that nitric oxide, the synthesis of which is augmented by ischemia, plays an important role in the regulation of apoptosis and cell proliferation following ischemic injury.
{"title":"7-Nitroindazole reduces ischemia-induced increment of apoptosis and cell proliferation in the dentate gyrus of rats","authors":"M. Jang, M. Shin, Hyun-kyung Chang, Taeck-Hyun Lee, Hee-Hyuk Lee, Mal-Soon Shin, Chang-Ju Kim, J. Kang, Seon-Pyo Hong, Sonhae Cho","doi":"10.1002/NRC.20030","DOIUrl":"https://doi.org/10.1002/NRC.20030","url":null,"abstract":"Nitric oxide is synthesized from L-arginine by nitric oxide synthase (NOS), and it is a free radical with signaling functions. Neuronal nitric oxide synthase (nNOS) is mainly expressed in the central nervous system, and it has been implicated in the pathogenesis of brain injury such as ischemia. In the present study, the effects of 7-nitroindazole, which specifically inhibits nNOS, on apoptosis and cell proliferation int he dentate gyrus after transient global ischemia in gerbils were investigated. Enhanced apoptotic neuronal cell death and cell proliferation were observed in the dentate gyrus of ischemic gerbils. However, 7-nitroindazole suppressed the ischemia-induced apoptosis and cell proliferation. These results suggest that 7-nitroindazole has an inhibitive effect on apoptosis and cell proliferation following transient global ischemia. The present study shows that nitric oxide, the synthesis of which is augmented by ischemia, plays an important role in the regulation of apoptosis and cell proliferation following ischemic injury.","PeriodicalId":19198,"journal":{"name":"Neuroscience Research Communications","volume":"48 1","pages":"164-172"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84162296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We investigated whether the role of the astrocytic glutamate transporter GLT-1 is reversed when the ionic gradient across plasma membrane has collapsed, and if so, whether the reversal is crucial to neuronal death. To estimate the direction of glutamate transport by GLT-1, Na+ movement coupled with glutamate transport in astrocytes was analyzed in mixed astrocyte/neuron cultures. The rise in astrocytic intracellular Na+ due to glutamate exposure was suppressed by co-treatment with dihydrokainate (DHK). In contrast, the ouabain-induced rise in Na+ was significantly enhanced by DHK, suggesting that the role of GLT-1 was reversed. We then analyzed whether the reversal increased the amount of extracellular glutamate, and was crucial to excitotoxic neuronal death. Ouabain treatment resulted in a marked rise in glutamate and in neuronal death, and both the rise and cell death were significantly attenuated by DHK treatment.
{"title":"Ouabain‐induced reversal of astrocytic GLT‐1 crucial to neuronal death in neuron/astrocyte co‐cultures","authors":"Motoki Tanaka, K. Kawahara, Rui Hosoya, Tatsuro Kosugi, Takayuki Nakajima, Takeshi Yamada","doi":"10.1002/NRC.20029","DOIUrl":"https://doi.org/10.1002/NRC.20029","url":null,"abstract":"We investigated whether the role of the astrocytic glutamate transporter GLT-1 is reversed when the ionic gradient across plasma membrane has collapsed, and if so, whether the reversal is crucial to neuronal death. To estimate the direction of glutamate transport by GLT-1, Na+ movement coupled with glutamate transport in astrocytes was analyzed in mixed astrocyte/neuron cultures. The rise in astrocytic intracellular Na+ due to glutamate exposure was suppressed by co-treatment with dihydrokainate (DHK). In contrast, the ouabain-induced rise in Na+ was significantly enhanced by DHK, suggesting that the role of GLT-1 was reversed. We then analyzed whether the reversal increased the amount of extracellular glutamate, and was crucial to excitotoxic neuronal death. Ouabain treatment resulted in a marked rise in glutamate and in neuronal death, and both the rise and cell death were significantly attenuated by DHK treatment.","PeriodicalId":19198,"journal":{"name":"Neuroscience Research Communications","volume":"17 1","pages":"150-163"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76824984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Embryonic stem (ES) cells are pluripotent cells that are derived from the inner cell mass of blastocysts. We produced neuronal cells by directed differentiation of a newly established murine ES cell line in vitro (Royan B1). Immunohistochemistry, scanning electron microscopy, Campenot's assay and electrophysiology were used to evaluate the differentiated neurons. Antibodies against microtubule-associated protein (MAP2), glutamic acid decarboxylase (GAD) and tyrosine hydroxylase (TH) antigens showed that the cells had GABAergic and dopaminergic characteristics. The Campenot's assay revealed there were a number of peripheral nerveous system related neurons but they were rare. The cells also produced action potentials and responded to electrical stimulation by expressing calcium channels in the processes. We showed therefore that functional neurons can be generated by directed differentiation from embryonic stem cells in vitro.
{"title":"Differentiation of Embryonic Stem Cells into Functional Neurons In Vitro","authors":"H. Baharvand, J. Power, N. Ozsarac, K. Matthaei","doi":"10.1002/NRC.20027","DOIUrl":"https://doi.org/10.1002/NRC.20027","url":null,"abstract":"Embryonic stem (ES) cells are pluripotent cells that are derived from the inner cell mass of blastocysts. We produced neuronal cells by directed differentiation of a newly established murine ES cell line in vitro (Royan B1). Immunohistochemistry, scanning electron microscopy, Campenot's assay and electrophysiology were used to evaluate the differentiated neurons. Antibodies against microtubule-associated protein (MAP2), glutamic acid decarboxylase (GAD) and tyrosine hydroxylase (TH) antigens showed that the cells had GABAergic and dopaminergic characteristics. The Campenot's assay revealed there were a number of peripheral nerveous system related neurons but they were rare. The cells also produced action potentials and responded to electrical stimulation by expressing calcium channels in the processes. We showed therefore that functional neurons can be generated by directed differentiation from embryonic stem cells in vitro.","PeriodicalId":19198,"journal":{"name":"Neuroscience Research Communications","volume":"20 1","pages":"130-138"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79666449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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