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Thousands of Down syndrome cell adhesion molecule (Dscam1) isoforms and â¼60 clustered protocadhrein (cPcdh) proteins are required for establishing neural circuits in insects and vertebrates, respectively. The strict homophilic specificity exhibited by these proteins has been extensively studied and is thought to be critical for their function in neuronal self-avoidance. In contrast, significantly less is known about the Dscam1-related family of â¼100 shortened Dscam (sDscam) proteins in Chelicerata. We report that Chelicerata sDscamα and some sDscamß protein trans interactions are strictly homophilic, and that the trans interaction is meditated via the first Ig domain through an antiparallel interface. Additionally, different sDscam isoforms interact promiscuously in cis via membrane proximate fibronectin-type III domains. We report that cell-cell interactions depend on the combined identity of all sDscam isoforms expressed. A single mismatched sDscam isoform can interfere with the interactions of cells that otherwise express an identical set of isoforms. Thus, our data support a model by which sDscam association in cis and trans generates a vast repertoire of combinatorial homophilic recognition specificities. We propose that in Chelicerata, sDscam combinatorial specificity is sufficient to provide each neuron with a unique identity for self-nonself discrimination. Surprisingly, while sDscams are related to Drosophila Dscam1, our results mirror the findings reported for the structurally unrelated vertebrate cPcdh. Thus, our findings suggest a remarkable example of convergent evolution for the process of neuronal self-avoidance and provide insight into the basic principles and evolution of metazoan self-avoidance and self-nonself discrimination.
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Proteínas de Artrópodos/metabolismo , Artrópodos/metabolismo , Animales , Proteínas de Artrópodos/genética , Artrópodos/clasificación , Artrópodos/genética , Moléculas de Adhesión Celular/química , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Comunicación Celular , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Neuronas/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismoRESUMEN
Traumatic brain injury is one of the major causes of morbidity and mortality worldwide. With the development of bile acids as a potential treatment, to identify the influence of traumatic brain injury on bile acid metabolism shows growing importance. This present study did a preliminary exploration of the bile acid profile alteration among traumatic brain injury patients. In total, 14 patients and 7 healthy volunteers were enrolled. The bile acid profile of the blood samples were detected by an Ultra-performance Liquid Chromatography Mass Spectrometer/Mass Spectrometer system. It was found that 6 bile acids were statistically decreased in traumatic brain injury patients comparing with healthy volunteers: glycocholic acid (median level 44.4â ng/ml vs 98.7â ng/ml, pâ =â 0.003), taurocholic acid (median level 10.9â ng/ml vs 19.5â ng/ml, pâ =â 0.006), glycoursodeoxycholic acid (median level 17.4â ng/ml vs 71.4â ng/ml, pâ =â 0.001), ursodeoxycholic acid (median level <1â ng/ml vs 32.4â ng/ml, pâ =â 0.002), taurochenodeoxycholic acid (median level <1â ng/ml vs 53.6â ng/ml, pâ =â 0.003) and glycochenodeoxycholic acid (GCDCA, median level 160â ng/ml vs 364â ng/ml, p<0.001). In conclusion, traumatic brain injury events are able to induce bile acid metabolism alteration in plasma and might cause reduction in glycocholic, taurocholic, glycoursodeoxycholic, ursodeoxycholic, taurochenodeoxycholic and glycochenodeoxycholic acid levels.
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BACKGROUND: Chronic subdural hematoma (CSDH) is a common illness in neurosurgical practice with a substantial recurrence rate. Previous studies found that serum lipids were associated with the risk of stroke and subarachnoid hemorrhage. In the current study, we aimed to identify the relationship between serum lipids and CSDH recurrence. METHODS: The medical records of 274 consecutive surgical patients with CSDH in our department were reviewed and analyzed. Patients were separated into recurrence and non-recurrence groups. Univariable and multivariable Cox proportional hazards regression analyses were performed to identify serum lipids (triglycerides, total cholesterol, LDL, HDL) and other potential predictors associated with CSDH recurrence, and the performance of predictors was assessed with receiver operating characteristic (ROC) curve. RESULTS: Of the 274 patients included in the study, 42 (15.3%) experienced at least 1 recurrence of CSDH. Univariate analysis showed that age, hypertension, diabetes mellitus, anticoagulant use, triglycerides, HDL, and midline shift were all significantly associated with CSDH recurrence. Multivariable Cox regression analysis found that only age, diabetes mellitus, midline shift, and HDL level were independent risk factors for CSDH recurrence. A higher HDL level (HR = 0.929, 95% CI 0.905-0.953) was significantly associated with a lower risk of recurrence, and ROC curve analysis revealed that the optimal HDL cut-off value as a predictor was 37.45 mg/dl. CONCLUSIONS: Low level of high-density lipoprotein is significantly associated with recurrence of chronic subdural hematoma.
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Hematoma Subdural Crónico/sangre , Lipoproteínas HDL/sangre , Adulto , Anciano , Femenino , Hematoma Subdural Crónico/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , RecurrenciaRESUMEN
Traumatic axonal injury (TAI) is a major cause of death and disability among patients with severe traumatic brain injury (TBI); however, no effective therapies have been developed to treat this disorder. Neuroinflammation accompanying microglial activation after TBI is likely to be an important factor in TAI. In this review, we summarize the current research in this field, and recent studies suggest that microglial activation plays an important role in TAI development. We discuss several drugs and therapies that may aid TAI recovery by modulating the microglial phenotype following TBI. Based on the findings of recent studies, we conclude that the promotion of active microglia to the M2 phenotype is a potential drug target for the treatment of TAI.
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Lesión Axonal Difusa/tratamiento farmacológico , Microglía/efectos de los fármacos , Animales , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Encefalitis/tratamiento farmacológico , Encefalitis/etiología , HumanosRESUMEN
Post-traumatic hydrocephalus is a common complication secondary to traumatic brain injury. It can cause cerebral metabolic impairment and dysfunction. Therefore, timely treatment with shunt implantation is necessary. However, the outcomes of shunt surgery in patients with post-traumatic hydrocephalus combined with disturbance of consciousness are doubtful. The objective was to develop a predictive model that uses the information available before surgery to predict the outcome of shunt implantation in such patients. Retrospectively collected data were used to develop a clinical prediction model. The model was derived from 59 patients using logistic regression analysis, and then it was evaluated by the area under the receiver operating characteristic curve and Hosmer-Lemshow test. A validation cohort verified the model. Four independent predictors were identified: age < 50 years, mild hydrocephalus, Glasgow Coma Scale scores 9-12 at the time of injury, and time interval from trauma to shunting < 3 months. We calculated the total score and defined the patients into three groups: low-probability (0-10 points), medium-probability (11-16 points), and high-probability (17-30 points). The rates of improved outcomes in the three groups were 14.3%, 52.6%, and 94.7%, respectively (P < 0.0001). The correlative rates of the validation cohort were 21.4%, 54.5%, and 85.7%. The prognostic model showed good discrimination (area under the receiver operating characteristic curve = 0.869) and calibration (Hosmer-Lemshow test, P = 0.391). The developed predictive model can identify patients with post-traumatic hydrocephalus combined with disturbance of consciousness who can benefit from shunt implantation. Therefore, our prognostic model can predict the outcomes of patients with post-traumatic hydrocephalus and disturbance of consciousness after shunt surgery.
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Lesiones Traumáticas del Encéfalo/diagnóstico , Lesiones Traumáticas del Encéfalo/cirugía , Derivaciones del Líquido Cefalorraquídeo , Trastornos de la Conciencia/cirugía , Hidrocefalia/cirugía , Anciano , Lesiones Traumáticas del Encéfalo/complicaciones , Trastornos de la Conciencia/etiología , Femenino , Humanos , Hidrocefalia/etiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Cranioplasty is a common procedure in neurosurgical practice. However, some complications may occur after the operation. We here presented a case of bilateral skull defect and underwent cranioplasty with polyetheretherketone (PEEK) prosthesis. The patient developed epidural effusion on both sides 7 days after surgery. The effusion was light yellow and transparent, and laboratory examinations revealed normal glucose level, negative bacteriological results, and increased IgG protein concentration. The effusion disappeared after treatment with dexamethasone and drainage. We speculated that the epidural effusion was because of delayed type allergic reactions after PEEK cranioplasty. However, further studies are needed to investigate its related mechanisms.
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Materiales Biocompatibles/efectos adversos , Hipersensibilidad/etiología , Cetonas/efectos adversos , Polietilenglicoles/efectos adversos , Prótesis e Implantes/efectos adversos , Cráneo/cirugía , Adulto , Benzofenonas , Espacio Epidural , Humanos , Hipersensibilidad/terapia , Cetonas/inmunología , Masculino , Polímeros , Complicaciones Posoperatorias/etiología , Procedimientos de Cirugía Plástica/efectos adversos , Cráneo/lesionesRESUMEN
BACKGROUND: Hypopituitarism is a common but potentially undiagnosed complication in patients who suffer traumatic brain injury (TBI). The identification of risk factors of hypopituitarism after TBI is vital to establish a rational testing approach for these patients. METHODS: The authors retrospectively reviewed the case records of patients with TBI, who underwent pituitary function evaluation in our department between January 2014 and December 2016. RESULTS: In all, 193 patients (66.3% male) hospitalized with TBI were included in this study. Anterior hypopituitarism was observed in 33 (17.1%) patients, with 4.7% of the patients having multiple pituitary axes dysfunction. Patients with hypopituitarism had a longer length of ICU stay (8.7â±â5.5 versus 3.3â±â4.6, Pâ<â0.001), longer length of total hospital stay (28.7â±â20.1 versus 21.0â±â15.8, Pâ=â0.011), and lower Glasgow coma scale (GCS) on admission (9.1â±â3.5 versus 11.8â±â3.6, Pâ<â0.001) than those without the condition. Length of ICU stay (Pâ=â0.004, ORâ=â1.253) and intracranial hypertension (Pâ=â0.027, ORâ=â3.206) were independent risk factors for posttraumatic hypopituitarism. CONCLUSIONS: The prevalence of anterior hypopituitarism was estimated to be 17.1%. Patients with intracranial hypertension and longer length of ICU stay are at risk of hypopituitarism. Routine pituitary function evaluation is indicated for this group of patients.
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Lesiones Traumáticas del Encéfalo/complicaciones , Hipopituitarismo/etiología , Adulto , Femenino , Escala de Coma de Glasgow , Humanos , Hipopituitarismo/epidemiología , Tiempo de Internación , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Hyperbaric oxygen therapy (HBOT) is an efficient therapeutic option to improve progress of lots of diseases especially hypoxia-related injuries, and has been clinically established as a wide-used therapy for patients with carbon monoxide poisoning, decompression sickness, arterial gas embolism, problematic wound, and so on. In the liver, most studies positively evaluated HBOT as a potential therapeutic option for liver transplantation, acute liver injury, nonalcoholic steatohepatitis, fibrosis and cancer, especially for hepatic artery thrombosis. This might mainly attribute to the anti-oxidation and anti-inflammation of HBOT. However, some controversies are existed, possibly due to hyperbaric oxygen toxicity. This review summarizes the current understandings of the role of HBOT in liver diseases and hepatic regeneration. Future understanding of HBOT in clinical trials and its in-depth mechanisms may contribute to the development of this novel adjuvant strategy for clinical therapy of liver diseases.
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Oxigenoterapia Hiperbárica , Hepatopatías/terapia , Humanos , Regeneración HepáticaRESUMEN
BACKGROUND: Chronic subdural hematoma (CSDH) is a common disease in neurosurgical practice with substantial recurrence rate. We aimed to estimate recurrence rate of CSDH and to identify risk factors for CSDH recurrence. METHODS: We retrospectively studied consecutive cases with CSDH and performed surgical therapy in our hospital. Univariate and multivariate logistic regression analyses were performed to identify factors associated with recurrence of CSDH. RESULTS: A total of 226 patients with CSDH were included; 34 patients recurred after surgery with a recurrence rate of 15.0%. Univariate analysis showed that the recurrence group had more patients with homogenous hyper-dense hematoma (20.6 vs 6.3%, p = 0.035) and shorter duration of subdural drainage post-surgery (1.2 ± 1.4 vs 1.5 ± 0.9, p = 0.022) than the non-recurrence group. Logistic regression analysis revealed that duration of subdural drainage (OR = 0.66, p = 0.05) and hyper-dense of hematoma (OR = 4.94, p = 0.012) were independent predictors for CSDH recurrence. CONCLUSIONS: Homogenous hyper-dense of hematoma and duration of subdural drainage post-surgery were independent predictors for CSDH recurrence; longer duration of postoperative subdural drainage was associated with lower risk of recurrence.
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Hematoma Subdural Crónico/epidemiología , Complicaciones Posoperatorias/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Drenaje/efectos adversos , Femenino , Hematoma Subdural Crónico/cirugía , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , RecurrenciaRESUMEN
BACKGROUND: Intracranial pressure (ICP) monitoring is widely used in the management of patients with severe traumatic brain injury (TBI). However, there is limited evidence about the efficacy of ICP monitoring in older subjects (aged ≥65 years). This study evaluated the effect of intraventricular ICP monitoring on the outcome of older adults suffering from a severe TBI. METHODS: This prospective, observational study included 166 older TBI patients (aged ≥65 years) with Glasgow Coma scale (GCS) scores lower than 9 at admission. The study cohort was divided into two groups, intraventricular ICP monitoring and non-ICP monitoring. The primary outcome was in-hospital mortality. The secondary outcomes included the Glasgow Outcome Scale (GOS) score 6 months after injury, the ICU and total hospital lengths of stay, and mechanical ventilation days. RESULTS: There were 80 patients in the intraventricular ICP monitoring group and 86 patients in non-ICP monitoring group. There was no statistical difference between groups in demographics and severity of head injury. Patients treated with intraventricular ICP monitoring had lower in-hospital mortality (33.8 % vs 51.2 %, P < 0.05), a higher 6-month GOS score (3.0 ± 1.4 vs 2.5 ± 1.2 P < 0.05), and a lower dosage (514 ± 246 g vs 840 ± 323 g, P < 0.0001) and shorter duration (7.2 ± 3.6 days vs 8.4 ± 4.3 days, P < 0.01) of mannitol use. However, the ICU length of stay (14.3 ± 6.4 days vs 11.6 ± 5.8 days, P < 0.01) and mechanical ventilation days (6.7 ± 3.5 days vs 5.6 ± 2.4 days, P < 0.05) were longer in the ICP monitoring group. The total length of hospital stay did not differ between the two groups (28.5 ± 12.1 days vs 26.1 ± 13.5 days, P = 0.23). CONCLUSIONS: Intraventricular ICP monitoring may have beneficial effects on the decreased in-hospital mortality and improved 6-month outcome of older patients with severe TBI. However, given that this was an observational study conducted in a single institution, further well-designed randomized control trials are needed to evaluate the effect of intraventricular ICP monitoring on the outcome of older severe TBI patients.
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Lesiones Traumáticas del Encéfalo/terapia , Presión Intracraneal , Monitoreo Fisiológico/métodos , Respiración Artificial/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Lesiones Traumáticas del Encéfalo/fisiopatología , Femenino , Escala de Coma de Glasgow , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación/estadística & datos numéricos , Masculino , Manitol/administración & dosificación , Estudios ProspectivosRESUMEN
PURPOSE: It is becoming increasingly clear that genetic factors play a role in traumatic brain injury (TBI), whether in modifying clinical outcome after TBI or determining susceptibility to it. MicroRNAs are small RNA molecules involved in various pathophysiological processes by repressing target genes at the post- transcriptional level, and TBI alters microRNA expression levels in the hippocampus and cortex. This study was designed to detect differentially expressed microRNAs in the cerebrospinal fluid (CSF) of TBI patients remaining unconscious two weeks after initial injury and to explore related single nucleotide polymorphisms (SNPs). METHODS: We used a microarray platform to detect differential microRNA expression levels in CSF samples from patients with post-traumatic coma compared with samples from controls. A bioinformatic scan was performed covering microRNA gene promoter regions to identify potential functional SNPs. RESULTS: Totally 26 coma patients and 21 controls were included in this study, with similar distribution of age and gender between the two groups. Microarray showed that fourteen microRNAs were differentially expressed, ten at higher and four at lower expression levels in CSF of traumatic coma patients compared with controls (p<0.05). One SNP (rs11851174 allele: C/T) was identified in the motif area of the microRNA hsa-miR-431-3P gene promoter region. CONCLUSION: The altered microRNA expression levels in CSF after brain injury together with SNP identified within the microRNA gene promoter area provide a new perspective on the mechanism of impaired consciousness after TBI. Further studies are needed to explore the association between the specific microRNAs and their related SNPs with post-traumatic unconsciousness.
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Lesiones Traumáticas del Encéfalo/líquido cefalorraquídeo , Biología Computacional , MicroARNs/líquido cefalorraquídeo , Polimorfismo de Nucleótido Simple , Adulto , Lesiones Traumáticas del Encéfalo/genética , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad , Inconsciente en PsicologíaRESUMEN
BACKGROUND: Accurate outcome prediction can serve to approach, quantify and categorize severe traumatic brain injury (TBI) coma patients for right median electrical stimulation (RMNS) treatment, which can support rehabilitation plans. As a proof of concept for individual risk prediction, we created a novel nomogram model combining amplitude-integrated electroencephalography (AEEG) and clinically relevant parameters. METHODS: This study retrospective collected and analyzed a total of 228 coma patients after severe TBI in two medical centers. According to the extended Glasgow Outcome Scale (GOSE), patients were divided into a good outcome (GOSE 3-8) or a poor outcome (GOSE 1-2) group. Their clinical and biochemical indicators, together with EEG features, were explored retrospectively. The risk factors connected to the outcome of coma patients receiving RMNS treatment were identified using Cox proportional hazards regression. The discriminative capability and calibration of the model to forecast outcome were assessed by C statistics, calibration plots, and Kaplan-Meier curves on a personalized nomogram forecasting model. RESULTS: The study included 228 patients who received RMNS treatment for long-term coma after a severe TBI. The median age was 40 years, and 57.8% (132 of 228) of the patients were male. 67.0% (77 of 115) of coma patients in the high-risk group experienced a poor outcome after one year and the comparative data merely was 30.1% (34 of 113) in low-risk group patients. The following variables were integrated into the forecasting of outcome using the backward stepwise selection of Akaike information criterion: age, Glasgow Coma Scale (GCS) at admission, EEG reactivity (normal, absence, or the stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs)), and AEEG background pattern (A mode, B mode, or C mode). The C statistics revealed that the nomograms' discriminative potential and calibration demonstrated good predictive ability (0.71). CONCLUSION: Our findings show that the nomogram model using AEEG parameters has the potential to predict outcomes in severe TBI coma patients receiving RMNS treatment. The model could classify patients into prognostic groups and worked well in internal validation.
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Gastrointestinal dysfunction is a common peripheral organ complication after traumatic brain injury (TBI), yet the underlying mechanism remains unknown. TBI has been demonstrated to cause gut microbiota dysbiosis in animal models, although the impacts of gut microbiota dysbiosis on gastrointestinal dysfunction were not examined. Bile acids are key metabolites between gut microbiota and host interactions. Therefore, the aim of this study was to investigate the mechanistic links between them by detecting the alterations of gut microbiota and bile acid profile after TBI. For that, we established TBI in mice using a lateral fluid percussion injury model. Gut microbiota was examined by 16S rRNA sequencing, and bile acids were profiled by ultra-performance liquid chromatography-tandem mass spectrometry. Our results showed that TBI caused intestinal inflammation and gut barrier impairment. Alterations of gut microbiota and bile acid profile were observed. The diversity of gut microbiota experienced a time dependent change from 1 h to 7 days post-injury. Levels of bile acids in feces and plasma were decreased after TBI, and the decrease was more significant in secondary bile acids, which may contribute to intestinal inflammation. Specific bacterial taxa such as Staphylococcus and Lachnospiraceae that may contribute to the bile acid metabolic changes were identifed. In conclusion, our study suggested that TBI-induced gut microbiota dysbiosis may contribute to gastrointestinal dysfunction via altering bile acid profile. Gut microbiota may be a potential treatment target for TBI-induced gastrointestinal dysfunction.
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Lesiones Traumáticas del Encéfalo , Microbioma Gastrointestinal , Animales , Ácidos y Sales Biliares/efectos adversos , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/microbiología , Disbiosis , Ratones , ARN Ribosómico 16S/genéticaRESUMEN
Objective: To evaluate the value of the correlation coefficient between the ICP wave amplitude and the mean ICP level (RAP) and the resistance to CSF outflow (Rout) in predicting the outcome of patients with post-traumatic hydrocephalus (PTH) selected for shunting. Materials and Methods: As a training set, a total of 191 patients with PTH treated with VP shunting were retrospectively analyzed to evaluate the potential predictive value of Rout, collected from pre-therapeutic CSF infusion test, for a desirable recovery level (dRL), standing for the modified rankin scale (mRS) of 0-2. Eventually, there were 70 patients with PTH prospectively included as a validation set to evaluate the value of Rout-combined RAP as a predictor of dRL. We calculated Rout from a CSF infusion test and collected RAP during continuous external lumbar drainage (ELD). Maximum RAP (RAPmax) and its changes relative to the baseline (ΔRAPmax%) served as specific parameters of evaluation. Results: In the training set, Rout was proved to be a significant predictor of dRL to shunting, with the area under the curve (AUC) of 0.686 (p < 0.001) in receiver-operating characteristic (ROC) analysis. In the validation set, Rout alone did not present a significant value in the prediction of desirable recovery level (dRL). ΔRAPmax% after 1st or 2nd day of ELD both showed significance in predicting of dRL to shunting with the AUC of 0.773 (p < 0.001) and 0.786 (p < 0.001), respectively. Significantly, Rout increased the value of ΔRAPmax% in the prediction of dRL with the AUC of 0.879 (p < 0.001), combining with ΔRAPmax% after the 1st and 2nd days of ELD. RAPmax after the 1st and 2nd days of ELD showed a remarkable predictive value for non-dRL (Levels 3-6 in Modified Rankin Scale) with the AUC of 0.891 (p < 0.001) and 0.746 (p < 0.001). Conclusion: Both RAP and Rout can predict desirable recovery level (dRL) to shunting in patients with PTH in the early phases of treatment. A RAP-combined Rout is a better dRL predictor for a good outcome to shunting. These findings help the neurosurgeon predict the probability of dRL and facilitate the optimization of the individual treatment plan in the event of ineffective or unessential shunting.
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Exosomes derived from bone marrow mesenchymal stem cells can inhibit neuroinflammation through regulating microglial phenotypes and promoting nerve injury repair. However, the underlying molecular mechanism remains unclear. In this study, we investigated the mechanism by which exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation. Our in vitro co-culture experiments showed that bone marrow mesenchymal stem cells and their exosomes promoted the polarization of activated BV2 microglia to their anti-inflammatory phenotype, inhibited the expression of proinflammatory cytokines, and increased the expression of anti-inflammatory cytokines. Our in vivo experiments showed that tail vein injection of exosomes reduced cell apoptosis in cortical tissue of mouse models of traumatic brain injury, inhibited neuroinflammation, and promoted the transformation of microglia to the anti-inflammatory phenotype. We screened some microRNAs related to neuroinflammation using microRNA sequencing and found that microRNA-181b seemed to be actively involved in the process. Finally, we regulated the expression of miR181b in the brain tissue of mouse models of traumatic brain injury using lentiviral transfection. We found that miR181b overexpression effectively reduced apoptosis and neuroinflamatory response after traumatic brain injury and promoted the transformation of microglia to the anti-inflammatory phenotype. The interleukin 10/STAT3 pathway was activated during this process. These findings suggest that the inhibitory effects of exosomes derived from bone marrow mesenchymal stem cells on neuroinflamation after traumatic brain injury may be realized by the action of miR181b on the interleukin 10/STAT3 pathway.
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Alternative splicing of Drosophila Dscam1 into 38,016 isoforms provides neurons with a unique molecular code for self-recognition and self-avoidance. A canonical model suggests that the homophilic binding of identical Dscam1 isoforms on the sister branches of mushroom body (MB) axons supports segregation with high fidelity, even when only a single isoform is expressed. Here, we generated a series of mutant flies with a single exon 4, 6, or 9 variant, encoding 1,584, 396, or 576 potential isoforms, respectively. Surprisingly, most of the mutants in the latter two groups exhibited obvious defects in the growth, branching, and segregation of MB axonal sister branches. This demonstrates that the repertoires of 396 and 576 Dscam1 isoforms were not sufficient for the normal patterning of axonal branches. Moreover, reducing Dscam1 levels largely reversed the defects caused by reduced isoform diversity, suggesting a functional link between Dscam1 expression levels and isoform diversity. Taken together, these results indicate that canonical self-avoidance alone does not explain the function of Dscam1 in MB axonal wiring.
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Proteínas de Drosophila , Cuerpos Pedunculados , Animales , Axones/metabolismo , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Cuerpos Pedunculados/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismoRESUMEN
Drosophila melanogaster Dscam1 encodes 38,016 isoforms via mutually exclusive splicing; however, the regulatory mechanism behind this is not fully understood. Here, we found a set of hidden RNA secondary structures that balance the stochastic choice of Dscam1 splice variants (designated balancer RNA secondary structures). In vivo mutational analyses revealed the dual function of these balancer interactions in driving the stochastic choice of splice variants, through enhancement of the inclusion of distal exon 6s by cooperating with docking site-selector pairing to form a stronger multidomain pre-mRNA structure and through simultaneous repression of the inclusion of proximal exon 6s by antagonizing their docking site-selector pairings. Thus, we provide an elegant molecular model based on competition and cooperation between two sets of docking site-selector and balancer pairings, which counteracts the "first-come, first-served" principle. Our findings provide conceptual and mechanistic insight into the dynamics and functions of long-range RNA secondary structures.
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ABSTRACT: BACKGROUND: External ventricular drains (EVDs) are commonly used in neurosurgery. Preventing EVD-related infections is important, and nursing plays a significant role in infection control. However, because of the limited number of neurosurgical nurses and heavy workload in developing countries, well-trained patient care technicians (PCTs) might be able to assist nurses under this circumstance. METHODS: This study retrospectively screened patients who underwent EVD procedures in our medical center from January 2012 to June 2018. Clinical characteristics including EVD-related infection rates of patients with or without PCTs were compared. RESULTS: We analyzed 234 patients in total. There were 26 EVD infection cases, and the overall infection rate was 11.1%. There were 122 patients who were given additional care by PCTs. They were elder (58.1 ± 13.1 vs 49.9 ± 17.0 years old, P < .001) and had lower level preoperational Glasgow Coma Scale (7.04 ± 3.66 vs 13.5 ± 2.53, P < .001) and higher intubation rate (28.7% vs 3.6%, P < .001) than those without PCTs. They also had a longer drainage duration (10.3 ± 4.97 vs 8.01 ± 4.35, P < .001) as well as more cerebrospinal fluid sampling times (2.45 ± 2.00 vs 1.75 ± 1.83, P = .006) and were kept at artificial airway status for a longer duration (10.1 ± 18.7 vs 1.93 ± 7.86, P < .001). External ventricular drain-related infection rates were similar between 2 groups (11.5% vs 10.7%, P = .853). CONCLUSION: Patient care technicians with proper training are beneficial to the prevention of EVD-related infection as a measure of improving staffing adequacy.
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Drenaje , Ventriculostomía , Adolescente , Anciano , Humanos , Control de Infecciones , Atención al Paciente , Estudios RetrospectivosRESUMEN
Interleukin-33 (IL-33), a member of the IL-1 cytokine family, is involved in various diseases. IL-33 exerts its effects via its heterodimeric receptor complex, which comprises suppression of tumorigenicity 2 (ST2) and the IL-1 receptor accessory protein (IL-1RAP). Increasing evidence has demonstrated that IL-33/ST2 signaling plays diverse but crucial roles in the homeostasis of the central nervous system (CNS) and the pathogenesis of CNS diseases, including neurodegenerative diseases, cerebrovascular diseases, infection, trauma, and ischemic stroke. In the current review, we focus on the functional roles and cellular signaling mechanisms of IL-33 in the CNS and evaluate the potential for diagnostic and therapeutic applications.
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Enfermedades del Sistema Nervioso Central/etiología , Enfermedades del Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/metabolismo , Interleucina-33/metabolismo , Animales , Biomarcadores , Enfermedades del Sistema Nervioso Central/diagnóstico , Enfermedades del Sistema Nervioso Central/terapia , Citocinas/metabolismo , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Humanos , Proteína 1 Similar al Receptor de Interleucina-1/metabolismo , Interleucina-33/genética , Transducción de SeñalRESUMEN
Traumatic brain injury (TBI) can cause damage to peripheral organ systems, such as digestive organ system, and alterations of gut microbiota in addition to brain injury. Our previous study found that TBI induced gastrointestinal dysfunction accompanied by alterations of bile acid metabolism. Bile acid and its receptors have been reported to play important roles in various neurological diseases. To further examine the changes of bile acid metabolism in TBI patients, we performed a retrospective clinical analysis. In this study, 177 patients were included, and the results showed that TBI patients had more frequent antibiotic use compared with a control group. Regression analysis identified TBI as an independent factor for reduction of serum bile acid level (B = -1.762, p = 0.006), even with antibiotic use taken into a regression model. Sub-group regression analysis of TBI patients showed that antibiotic use was negatively associated with bile acid level, while creatinine and triglyceride were positively associated with bile acid level. In conclusion, these data indicated that TBI could greatly reduce serum bile acid. This study provided preliminary but novel clinical evidence of TBI interfering with bile acid metabolism, and further studies with large sample sizes are needed to validate these findings in the future.