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Malignant hyperthermia (MH) is a potentially fatal inherited pharmacogenetic disorder related to pathogenic variants in the RYR1, CACNA1S, or STAC3 genes. Early recognition of the occurrence of MH and prompt medical treatment are indispensable to ensure a positive outcome. The purpose of this study was to provide valuable information for the early identification of MH by summarizing epidemiological and clinical features of MH. This scoping review followed the methodological framework recommended by Arksey and O'Malley. PubMed, Embase, and Web of science databases were searched for studies that evaluated the epidemical and clinical characteristics of MH. A total of 37 studies were included in this review, of which 26 were related to epidemiology and 24 were associated with clinical characteristics. The morbidity of MH varied from 0.18 per 100 000 to 3.9 per 100 000. The mortality was within the range of 0%-18.2%. Identified risk factors included sex, age, disorders associated with MH, and others. The most frequent initial clinical signs included hyperthermia, sinus tachycardia, and hypercarbia. The occurrence of certain signs, such as hypercapnia, delayed first temperature measurement, and peak temperature were associated with poor outcomes. The epidemiological and clinical features of MH varied considerably and some risk factors and typical clinical signs were identified. The main limitation of this review is that the treatment and management strategies were not assessed sufficiently due to limited information.
Assuntos
Hipertermia Maligna , Humanos , Hipertermia Maligna/diagnóstico , Hipertermia Maligna/epidemiologia , Hipertermia Maligna/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Fatores de Risco , Medição de RiscoRESUMO
The topological transport of Lamb wave in phononic crystal slabs provides a great potential in reinforcing nondestructive testing, high sensitivity sensing, and information processing. In this paper, the authors investigate the pseudospins edge states of fundamental antisymmetric Lamb waves in a snowflakelike phononic slab. Significantly, the fourfold Dirac degeneracy for antisymmetric Lamb mode is accidentally formed at the Γ point with the critical angle of the snowflakelike holes, which does not require the folding of the lattices. Meanwhile, based on the rotating-scatterer mechanism, the mirror symmetry is broken and the topological multipole phase transitions are well induced during the gradual change of the scattering strength among the scatterers with the rotation angle. The topologically protected edge states and its unidirectional robust propagation are further demonstrated. The proposed topological phononic slabs will be a more hopeful option to apply in engineering practices.
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Background: Malignant hyperthermia (MH) is a hypermetabolic syndrome with high mortality rates. Early detection and prompt intravenous administration of dantrolene are crucial for effective management of MH. However, there is currently a lack of comprehensive nationwide surveys on the availability of dantrolene and anesthesiologists' understanding of MH in China. Methods: A nationwide survey was conducted between January 2022 and June 2022. Online questionnaires on the cognition of MH among anesthesiologists in China were sent through social platforms to anesthesiologists in mainland China. Data regarding participants' perception of MH-related knowledge, availability of domestic dantrolene, and reported MH cases were collected in this study. Results: Responses were collected from a total of 11,354 anesthesiologists representing 31 provinces across the Chinese mainland. Among the 11 scoring questions, the highest accuracy rates were observed for the question regarding therapeutic drugs for MH (99.3%) and the characteristics of MH (98.0%). Conversely, the question pertaining to the earliest clinical signs of MH had the lowest accuracy rate (23.5%). Significant variations were observed in the scores among different professional titles (P=0.003), academic degree (P<0.001), hospital classification (P<0.001), and urban hierarchy (P<0.001). Of the respondents, 919 (8.1%) anesthesiologists reported dantrolene availability in their hospitals, and 631 (5.6%) indicated unclear. A total of 136 hospitals in this survey reported at least one previous case of MH. Conclusion: Mainland China faces challenges such as insufficient experience in diagnosing and treating MH, as well as difficulty in obtaining dantrolene. To improve the public awareness of MH, it is imperative to establish and promote a refined MH training system. Additionally, a streamlined and rapid dantrolene linkage emergency system should be implemented to ensure prompt access to the drug.
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The remarkable properties of topological insulators have inspired numerous studies on topological transport for bulk waves, but the demonstrations of topological edge states with tunable frequency are few attempts. Here, we report on the active frequency tunability of topologically protected edge states for in-plane bulk waves by applying a thermal field. We find that the center frequency of topological band gap is shifted down and the band width is enlarged as the temperature increases. Meanwhile, the frequency range of topologically protected edge states is also shifted to low frequency region with the higher temperature. Furthermore, the robust propagation of in-plane bulk waves along a desired path is demonstrated within different frequency bands. The tunable frequency for both topological band gaps and topologically protected edge states achieves the active control of the transport for in-plane bulk waves, which may dramatically facilitate practical applications of novel phononic devices.
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Despite promising preclinical data, few novel stroke therapies have shown efficacy in man. Efforts to improve standards in conduct and reporting of preclinical research are ongoing. In clinical trials, inconsistency in outcome measures led to regulatory agencies and funders mandating use of a core set of functional outcomes. Our aim was to describe functional outcome measures in preclinical stroke and vascular cognitive impairment (VCI) studies. From 14 high impact journals (January 2005-December 2015 inclusive), 91,956 papers were screened with 1302 full texts analyzed for stroke (ischemic and hemorrhagic) and 56 for VCI studies. In total, 636 (49%) stroke and 37 (66%) VCI papers reported functional outcome measures. There were 74 different functional assessments reported in stroke and 20 in VCI studies. Neurological deficit scores (74%) and Morris water maze (60%) were most commonly used in stroke and VCI, respectively. However, inconsistencies in methods used to assess and score recovery were noted. Neurological and behavioural functional outcome measures are increasingly used in preclinical stroke or VCI studies; however, there is substantial variation in methods. A strict standardized outcome set may not be suitable for translational work, but greater consistency in choice, application and reporting of outcomes may improve the science.
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Demência Vascular , Modelos Animais de Doenças , Recuperação de Função Fisiológica , Acidente Vascular Cerebral , AnimaisRESUMO
Parkinson's disease (PD) is a common neurodegenerative disorder that affects ~2% of the human population aged >65. αsynuclein serves a role in the pathogenesis of PD as it is a primary component of Lewy bodies, a pathological feature of PD. Endosomallysosomal dysfunction may be a key factor involved in the pathophysiology of PD, and may cause PDassociated neurodegeneration via αsynucleindependent and independent mechanisms. The D620N mutation in the endosomallysosomal gene, vacuolar protein sortingassociated protein 35 (VPS35), has been linked to PD. To clarify the underlying cellular mechanism of the VPS35 D620N mutation in PD, cell growth and endosomallysosomal functions were investigated in Saccharomyces cerevisiae (sc) yeast cells that exhibited various expression levels of scVPS35, in the presence or absence of nontoxic expression levels of αsynuclein. Overexpression of the scVPS35 D686N mutation (the yeast equivalent of D620N) did not lead to toxicity in yeast. However, the coexpression of high copy numbers of scVPS35 D686N and low copy numbers of αsynuclein caused toxicity, whereas the coexpression of scVPS35 wildtype and αsynuclein did not. In addition, the scVPS35 D686N mutant enhanced αsynuclein aggregation. Fragmentation of vacuoles and subsequent inhibition of lysosome function was evident in yeast cells bearing the scVPS35 mutant. The results of the present study suggested that αsynuclein and scVPS35 were interlinked via the endosomallysosome pathway, which is important for the pathogenesis of PD.
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Viabilidade Microbiana/genética , Mutação , Doença de Parkinson/genética , Proteínas de Transporte Vesicular/genética , Leveduras/genética , Leveduras/metabolismo , alfa-Sinucleína/metabolismo , Humanos , Lisossomos , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Agregados Proteicos , Agregação Patológica de Proteínas , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Transporte Vesicular/metabolismoRESUMO
Huntington's disease is an autosomal-dominant neurodegenerative disorder, with chorea as the most prominent manifestation. The disease is caused by abnormal expansion of CAG codon repeats in the IT15 gene, which leads to the expression of a glutamine-rich protein named mutant Huntingtin (Htt). Because of its devastating disease burden and lack of valid treatment, development of more effective therapeutics for Huntington's disease is urgently required. Xyloketal B, a natural product from mangrove fungus, has shown protective effects against toxicity in other neurodegenerative disease models such as Parkinson's and Alzheimer's diseases. To identify potential neuroprotective molecules for Huntington's disease, six derivatives of xyloketal B were screened in a Caenorhabditis elegans Huntington's disease model; all six compounds showed a protective effect. Molecular docking studies indicated that compound 1 could bind to residues GLN369 and GLN393 of the mutant Htt protein, forming a stable trimeric complex that can prevent the formation of mutant Htt aggregates. Taken together, we conclude that xyloketal derivatives could be novel drug candidates for treating Huntington's disease. Molecular target analysis is a good method to simulate the interaction between proteins and drug compounds. Further, protective candidate drugs could be designed in future using the guidance of molecular docking results.
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Caenorhabditis elegans/metabolismo , Modelos Animais de Doenças , Proteína Huntingtina/metabolismo , Doença de Huntington/metabolismo , Fármacos Neuroprotetores/farmacologia , Agregados Proteicos/efeitos dos fármacos , Piranos/química , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Caenorhabditis elegans/genética , Proteína Huntingtina/química , Proteína Huntingtina/genética , Doença de Huntington/tratamento farmacológico , Doença de Huntington/prevenção & controle , Simulação de Acoplamento Molecular , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Agregados Proteicos/genética , Piranos/farmacologia , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/químicaRESUMO
Mutations in the TARDBP gene, which encodes the Tar DNA binding protein, have been shown to causes of both familial amyotrophic lateral sclerosis (FALS) and sporadic ALS (SALS). Recently, several novel TARDBP exon 6 mutants have been reported in patients with ALS in Europe and America but not in Asia. To further examine the spectrum and frequency of TARDBP exon 6 mutations, we investigated their frequency in ethnic Chinese patients with sporadic ALS. TARDBP exon 6 was screened by direct sequencing in 207 non-SOD1 SALS patients and 230 unrelated healthy controls but no mutations were identified. Our data indicate that exon 6 mutations in TARDBP are not a common cause of SALS in Han Chinese population from Southern Mainland China.