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BACKGROUND: Early identification of patients requiring ventilator support will be beneficial for the outcomes of botulism. The present study aimed to establish a new scoring system to predict mechanical ventilation (MV) for botulism patients. METHODS: A single-center retrospective study was conducted to identify risk factors associated with MV in botulism patients from 2007 to 2022. Univariate analysis and multivariate logistic regression analysis were used to screen out risk factors for constructing a prognostic scoring system. The area under the receiver operating characteristic (ROC) curve was calculated. RESULTS: A total of 153 patients with botulism (66 males and 87 females, with an average age of 43 years) were included. Of these, 49 patients (32.0%) required MV, including 21 (13.7%) with invasive ventilation and 28 (18.3%) with non-invasive ventilation. Multivariate analysis revealed that botulinum toxin type, pneumonia, incubation period, degree of hypoxia, and severity of muscle involvement were independent risk factors for MV. These risk factors were incorporated into a multivariate logistic regression analysis to establish a prognostic scoring system. Each risk factor was scored by allocating a weight based on its regression coefficient and rounded to whole numbers for practical utilization ([botulinum toxin type A: 1], [pneumonia: 2], [incubation period ≤1 day: 2], [hypoxia <90%: 2], [severity of muscle involvement: grade II, 3; grade III, 7; grade IV, 11]). The scoring system achieved an area under the ROC curve of 0.82 (95% CI 0.75-0.89, P<0.001). At the optimal threshold of 9, the scoring system achieved a sensitivity of 83.7% and a specificity of 70.2%. CONCLUSION: Our study identified botulinum toxin type, pneumonia, incubation period, degree of hypoxia, and severity of muscle involvement as independent risk factors for MV in botulism patients. A score ≥9 in our scoring system is associated with a higher likelihood of requiring MV in botulism patients. This scoring system needs to be validated externally before it can be applied in clinical settings.
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Vascular dementia (VaD) is a prevalent form of dementia resulting from chronic cerebral hypoperfusion (CCH). However, the pathogenic mechanisms of VaD and corresponding therapeutic strategies are not well understood. Sirtuin 6 (SIRT6) has been implicated in various biological processes, including cellular metabolism, DNA repair, redox homeostasis, and aging. Nevertheless, its functional relevance in VaD remains unexplored. In this study, we utilized a bilateral common carotid artery stenosis (BCAS) mouse model of VaD to investigate the role of SIRT6. We detected a significant decrease in neuronal SIRT6 protein expression following CCH. Intriguingly, neuron-specific ablation of Sirt6 in mice exacerbated neuronal damage and cognitive deficits after CCH. Conversely, treatment with MDL-800, an agonist of SIRT6, effectively mitigated neuronal loss and facilitated neurological recovery. Mechanistically, SIRT6 inhibited excessive mitochondrial fission by suppressing the CCH-induced STAT5-PGAM5-Drp1 signaling cascade. Additionally, the gene expression of monocyte SIRT6 in patients with asymptomatic carotid stenosis showed a correlation with cognitive outcomes, suggesting translational implications in human subjects. Our findings provide the first evidence that SIRT6 prevents cognitive impairment induced by CCH, and mechanistically, this protection is achieved through the remodeling of mitochondrial dynamics in a STAT5-PGAM5-Drp1-dependent manner.
Assuntos
Disfunção Cognitiva , Dinaminas , Dinâmica Mitocondrial , Fator de Transcrição STAT5 , Sirtuínas , Idoso , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Isquemia Encefálica/complicações , Isquemia Encefálica/patologia , Isquemia Encefálica/metabolismo , Estenose das Carótidas/complicações , Estenose das Carótidas/metabolismo , Doença Crônica , Disfunção Cognitiva/patologia , Dinaminas/metabolismo , Dinaminas/genética , Camundongos Endogâmicos C57BL , Dinâmica Mitocondrial/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Transdução de Sinais/efeitos dos fármacos , Sirtuínas/metabolismo , Sirtuínas/genética , Fator de Transcrição STAT5/metabolismoRESUMO
What is already known about this topic?: Fatal poisonings caused by wild mushrooms containing amanita toxins pose a significant threat in the southern regions of China. These toxins primarily induce gastrointestinal symptoms initially, which are then followed by potentially life-threatening acute liver damage. What is added by this report?: This report contributes to the existing knowledge on these cases of poisoning by documenting the second occurrences in Hebei Province and the first occurrences in Xingtai City. Five individuals reported consuming wild mushrooms from the same origin, and laboratory tests confirmed the presence of α-amanitin in their blood samples. What are the implications for public health practice?: This underscores the risk associated with the collection and consumption of amanita toxin-containing mushrooms in Hebei. It is important to note that the identification of toxic and non-toxic mushrooms should not solely rely on personal experience or appearance.