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1.
Pain Physician ; 24(8): E1191-E1198, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34793639

RESUMO

BACKGROUND: Regional anesthesia has been used to reduce acute postsurgical pain and to  prevent chronic pain. The best technique, however, remains controversial. OBJECTIVES: The aim of this study was to assess the short- and long-term postoperative analgesic efficacy of ultrasound-guided quadratus lumborum block (QLB) in open gastrointestinal surgery. STUDY DESIGN: A randomized, double-blinded, controlled trial. SETTING: Operating room; postoperative recovery room and ward. METHODS: One hundred eighteen patients underwent elective gastrointestinal surgery randomly assigned into 2 groups (QLB group or control group). Before anesthetic induction, QLB was performed bilaterally under ultrasound guidance using 20 mL of 0.375% ropivacaine or saline solution at each abdominal wall. The primary outcome was cumulative oxycodone consumption within 24 h after surgery. The secondary outcomes were acute pain intensity, incidence of chronic pain, and incidence of postoperative nausea or vomiting (PONV), dizziness, and pruritus. RESULTS: The cumulative oxycodone consumption was significantly lower in the QLB group during the first 6, 6-24, 24, and 48 h postoperatively when compared to the control group. At rest or during coughing, the numeric rating scale scores were significantly lower at 1, 3, 6, and 12 h postoperatively in the QLB group compared to the control group. There were no significant differences between the 2 groups regarding the incidence of chronic postoperative pain at 3 or 6 months after surgery. Significant differences were found in the incidence of PONV between the two groups, but other complications, such as dizziness and pruritus, did not differ significantly. LIMITATIONS: We did not confirm the QLB effectiveness with sensory level testing after local anesthetic injection. Cumulative oxycodone consumption could have been affected by the patients' use of oxycodone for nonsurgical pain. CONCLUSIONS: Ultrasound-guided QLB provided superior short-term analgesia and reduced oxycodone consumption and the incidence of PONV after gastrointestinal surgery. However, the incidence of chronic pain was not significantly affected by this anesthetic technique.

2.
Front Med (Lausanne) ; 8: 655686, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34409047

RESUMO

Objective: Investigate whether machine learning can predict pulmonary complications (PPCs) after emergency gastrointestinal surgery in patients with acute diffuse peritonitis. Methods: This is a secondary data analysis study. We use five machine learning algorithms (Logistic regression, DecisionTree, GradientBoosting, Xgbc, and gbm) to predict postoperative pulmonary complications. Results: Nine hundred and twenty-six cases were included in this study; 187 cases (20.19%) had PPCs. The five most important variables for the postoperative weight were preoperative albumin, cholesterol on the 3rd day after surgery, albumin on the day of surgery, platelet count on the 1st day after surgery and cholesterol count on the 1st day after surgery for pulmonary complications. In the test group: the logistic regression model shows AUC = 0.808, accuracy = 0.824 and precision = 0.621; Decision tree shows AUC = 0.702, accuracy = 0.795 and precision = 0.486; The GradientBoosting model shows AUC = 0.788, accuracy = 0.827 and precision = 1.000; The Xgbc model shows AUC = 0.784, accuracy = 0.806 and precision = 0.583. The Gbm model shows AUC = 0.814, accuracy = 0.806 and precision = 0.750. Conclusion: Machine learning algorithms can predict patients' PPCs with acute diffuse peritonitis. Moreover, the results of the importance matrix for the Gbdt algorithm model show that albumin, cholesterol, age, and platelets are the main variables that account for the highest pulmonary complication weights.

6.
Research (Wash D C) ; 2021: 9851609, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34036265

RESUMO

Photonic crystal (PC) barcodes are a new type of spectrum-encoding microcarriers used in multiplex high-throughput bioassays, such as broad analysis of biomarkers for clinical diagnosis, gene expression, and cell culture. Unfortunately, most of these existing PC barcodes suffered from undesired features, including difficult spectrum-signal acquisition, weak mechanical strength, and high ontology fluorescence, which limited their development to real applications. To address these limitations, we report a new type of structural color-encoded PC barcodes. The barcodes are fabricated by the assembly of monodisperse polydopamine- (PDA-) coated silica (PDA@SiO2) nanoparticles using a droplet-based microfluidic technique and followed by pyrolysis of PDA@SiO2 (C@SiO2) barcodes. Because of the templated carbonization of adhesive PDA, the prepared C@SiO2 PC beads were endowed with simultaneous easy-to-identify structural color, high mechanical strength, and ultralow ontology fluorescence. We demonstrated that the structural colored C@SiO2 barcodes not only maintained a high structural stability and good biocompatibility during the coculturing with fibroblasts and tumor cells capture but also achieved an enhanced fluorescent-reading signal-to-noise ratio in the fluorescence-reading detection. These features make the C@SiO2 PC barcodes versatile for expansive application in fluorescence-reading-based multibioassays.

7.
J Alzheimers Dis ; 81(4): 1685-1699, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33967044

RESUMO

BACKGROUND: Accumulating evidence has demonstrated that aging is associated with an exaggerated response to surgical trauma together with cognitive impairments. This has significant implications for the development of clinical phenotype such as perioperative neurocognitive disorders (PND), which is a common complication following surgery, especially for the elderly. However, the mechanism by which aging brain is vulnerable to surgical trauma remains to be elucidated. OBJECTIVE: To test whether age-related alterations in hippocampal network activities contribute to increased risk of PND following surgery. METHODS: Thirty-two adult and seventy-two aged male C57BL/6 mice undergone sevoflurane anesthesia and exploratory laparotomy were used to mimic human abdominal surgery. For the interventional study, mice were treated with minocycline. Behavioral tests were performed post-surgery with open field, novel object recognition and fear conditioning tests, respectively. The brain tissues were then harvested and subjected to biochemistry studies. Local field potential (LFP) recording was performed in another separate experiment. RESULTS: Aged mice displayed signs of neuroinflammation, as reflected by significantly increased proinflammatory mediators in the hippocampus. Also, aged mice displayed persistently decreased oscillation activities under different conditions, both before and after surgery. Further correlation analysis suggested that theta power was positively associated with time with novel object, while γ oscillation activity was positively associated with freezing time to context. Of note, downregulation of neuroinflammation by microglia inhibitor minocycline reversed some of these abnormities. CONCLUSION: Our study highlights that age-related hippocampal oscillation dysregulation increases the risk of PND incidence, which might provide diagnostic/prognostic biomarkers for PND and possible other neurodegenerative diseases.


Assuntos
Hipocampo/fisiopatologia , Laparotomia/efeitos adversos , Complicações Cognitivas Pós-Operatórias/etiologia , Reconhecimento Psicológico/fisiologia , Envelhecimento , Animais , Comportamento Animal/fisiologia , Condicionamento Psicológico/fisiologia , Medo , Masculino , Camundongos , Complicações Cognitivas Pós-Operatórias/fisiopatologia
8.
Clin Med Insights Oncol ; 15: 11795549211000017, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33854400

RESUMO

Objective: Over 1 million new cases of hepatocellular carcinoma (HCC) are diagnosed worldwide every year. Its prognosis remains poor, and the 5-year survival rate in all disease stages is estimated to be between 10% and 20%. Radiofrequency ablation (RFA) has become an important local treatment for liver cancer, and machine learning (ML) can provide many shortcuts for liver cancer medical research. Therefore, we explore the role of ML in predicting the total mortality of liver cancer patients undergoing RFA. Methods: This study is a secondary analysis of public database data from 578 liver cancer patients. We used Python for ML to establish the prognosis model. Results: The results showed that the 5 most important factors were platelet count (PLT), Alpha-fetoprotein (AFP), age, tumor size, and total bilirubin, respectively. Results of the total death model for liver cancer patients in test group: among the 5 algorithm models, the highest accuracy rate was that of gbm (0.681), followed by the Logistic algorithm (0.672); among the 5 algorithms, area under the curve (AUC) values, from high to low, were Logistic (0.738), DecisionTree (0.723), gbm (0.717), GradientBoosting (0.714), and Forest (0.693); Among the 5 algorithms, gbm had the highest precision rate (0.721), followed by the Logistic algorithm (0.714). Among the 5 algorithms, DecisionTree had the highest recall rate (0.642), followed by the GradientBoosting algorithm (0.571). Conclusion: Machine learning can predict total death after RFA in liver cancer patients. Therefore, ML research has great potential for both personalized treatment and prognosis of liver cancer.

11.
Brain Res Bull ; 171: 172-182, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33753210

RESUMO

Both environmental stress and immune challenge can induce abnormal neurobehavior. However, the impact of chronic stress on immune challenge-related neurobehavioral abnormalities is still controversial. Hence, we aimed to investigate the effects of chronic stress on immune challenge-related neurobehavioral abnormalities and explore the possible underlying mechanisms. During the first set of experiments, mice were reared under normal condition (NC) or chronic stress (CS) for 4 consecutive weeks. They were allocated to the following four groups: NC + normal saline (NS) group, CS + NS group, NC + lipopolysaccharide (LPS) group, and CS + LPS group. Open field, elevated plus maze, fear conditioning, novel object recognition, and forced swimming tests were performed, and their tissues were harvested. During the second set of experiments, after rearing the mice under the above conditions for 3 weeks, microelectrodes were implanted into the CA1 of the hippocampus. After recovery for 1 week under the respective environmental conditions, the mice were allocated to four groups, as in the first experiments. The basal (home cage) and task (fear conditioning)-related local field potential (LFP) were recorded. In the present study, LPS significantly induced a decrease in the freezing to context and discrimination ratio. However, only the freezing to context was further reduced by prior chronic stress. This suggested that chronic stress worsened fear memory impairment induced by acute LPS challenge. Consistent with the change in fear memory, LPS significantly decreased the expression of PV in the CA1, which was further downregulated by prior chronic stress. On the other hand, LPS inhibited the power of both basal and task-related θ oscillations in the CA1. Only the task-related θ power was further decreased by chronic stress. In conclusion, our study showed that the phenotypic loss of PV interneurons and the decrease in the power of the θ oscillation in the CA1 aggravated by chronic stress may mediate, at least in part, the deterioration of fear memory impairment induced by LPS.

12.
Pain Res Manag ; 2021: 6668152, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33574975

RESUMO

Background: Several predictors have been shown to be independently associated with chronic postsurgical pain for gastrointestinal surgery, but few studies have investigated the factors associated with acute postsurgical pain (APSP). The aim of this study was to identify the predictors of APSP intensity and severity through investigating demographic, psychological, and clinical variables. Methods: We performed a prospective cohort study of 282 patients undergoing gastrointestinal surgery to analyze the predictors of APSP. Psychological questionnaires were assessed 1 day before surgery. Meanwhile, demographic characteristics and perioperative data were collected. The primary outcomes are APSP intensity assessed by numeric rating scale (NRS) and APSP severity defined as a clinically meaningful pain when NRS ≥4. The predictors for APSP intensity and severity were determined using multiple linear regression and multivariate logistic regression, respectively. Results: 112 patients (39.7%) reported a clinically meaningful pain during the first 24 hours postoperatively. Oral morphine milligram equivalent (MME) consumption (ß 0.05, 95% CI 0.03-0.07, p < 0.001), preoperative anxiety (ß 0.12, 95% CI 0.08-0.15, p < 0.001), and expected postsurgical pain intensity (ß 0.12, 95% CI 0.06-0.18, p < 0.001) were positively associated with APSP intensity. Furthermore, MME consumption (OR 1.15, 95% CI 1.10-1.21, p < 0.001), preoperative anxiety (OR 1.33, 95% CI 1.21-1.46, p < 0.001), and expected postsurgical pain intensity (OR 1.36, 95% CI 1.17-1.57, p < 0.001) were independently associated with APSP severity. Conclusion: These results suggested that the predictors for APSP intensity following gastrointestinal surgery included analgesic consumption, preoperative anxiety, and expected postsurgical pain, which were also the risk factors for APSP severity.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Medição da Dor/métodos , Dor Pós-Operatória/etiologia , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco
13.
Aging (Albany NY) ; 13(5): 7190-7198, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33638946

RESUMO

Frailty is associated with perioperative adverse outcomes, especially for the elderly. This study aimed to assess whether frailty was an independent risk factor of one-year mortality in frail patients after elective orthopedic surgery. In this prospective study, three hundred and thirteen patients aged ≥ 65 years, undergoing elective orthopedic surgery were finally included. Frailty assessed by the Clinical Frailty Score (CFS) before the surgery was present in 29.7% (93/313). Among them, 7.7% of patients (24/313) died at one year after surgery. In multivariate logistic analysis, higher CFS (OR = 2.271, 95% CI= 1.472-3.504) was found to be an independent risk factor of one-year mortality after surgery in elderly orthopedic patients. The area under the receiver operating characteristic curve of the model was 0.897 (95% CI 0.834-0.959). In addition, we found higher Charlson comorbidity index (OR= 1.498, 95% CI = 1.082-2.073) was also a significant risk factor. In conclusion, frailty is associated with increased one-year mortality in elderly patients after elective orthopedic surgery, which should be considered as a routine assessment tool in preoperative practice.


Assuntos
Fragilidade/mortalidade , Procedimentos Ortopédicos/mortalidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Estudos Prospectivos , Fatores de Risco
14.
Aging (Albany NY) ; 13(6): 8706-8719, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33619234

RESUMO

Lung adenocarcinoma is the most common subtype of non-small cell lung cancer, and platelet receptor-related genes are related to its occurrence and progression. A new prognostic indicator based on platelet receptor-related genes was developed with multivariate COX analysis. Prognostic markers based on platelet-related risk score perform moderately in prognosis prediction. The functional annotation of this risk model in high-risk patients shows that the pathways related to cell cycle, glycolysis and platelet-derived related factors are rich. It is worth noting that somatic mutation analysis shows that TTN and MUC16 have higher mutation burdens in high-risk patients. Moreover, the differential genes of high- and low-risk groups are regulated by copy number variation and miRNA. And we provide a free online nomogram web tool based on clinical factors and the risk score (https://wsxzaq.shinyapps.io/wsxzaq_nomogram/). The score has been verified among three independent external cohorts (GSE13213, GSE68465 and GSE72094), and is still an independent risk factor for lung adenocarcinoma. In addition, among the other 6 cancers, the OS prognosis of high and low-risk groups of PRS is different (P < 0.05). Our research results have screened multiple platelet differential genes with clinical significance and constructed a meaningful prognostic risk score (PRS).


Assuntos
Adenocarcinoma de Pulmão/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Mutação , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Variações do Número de Cópias de DNA , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Nomogramas , Prognóstico , Medição de Risco , Taxa de Sobrevida
15.
Curr Med Res Opin ; 37(4): 629-634, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33539249

RESUMO

OBJECTIVE: To investigate the effect of 5 machine learning algorithms in predicting total hepatocellular carcinoma (HCC) postoperative death outcomes. METHODS: This study was a secondary analysis. A prognosis model was established using machine learning with python. RESULTS: The results from the machine learning gbm algorithm showed that the most important factors, ranked from first to fifth, were: preoperative aspartate aminotransferase (GOT), preoperative AFP, preoperative cereal third transaminase (GPT), preoperative total bilirubin, and LC3. Postoperative death model results for liver cancer patients in the test group: of the 5 algorithm models, the highest accuracy rate was that of forest (0.739), followed by the gbm algorithm (0.714); of the 5 algorithms, the AUC values, from high to low, were forest (0.803), GradientBoosting (0.746), gbm (0.724), Logistic (0.660) and DecisionTree (0.578). CONCLUSION: Machine learning can predict total hepatocellular carcinoma postoperative death outcomes.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Algoritmos , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia , Aprendizado de Máquina , Prognóstico
16.
Sci Rep ; 11(1): 1300, 2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446730

RESUMO

To construct a machine learning algorithm model of lymph node metastasis (LNM) in patients with poorly differentiated-type intramucosal gastric cancer. 1169 patients with postoperative gastric cancer were divided into a training group and a test group at a ratio of 7:3. The model for lymph node metastasis was established with python machine learning. The Gbdt algorithm in the machine learning results finds that number of resected nodes, lymphovascular invasion and tumor size are the primary 3 factors that account for the weight of LNM. Effect of the LNM model of PDC gastric cancer patients in the training group: Among the 7 algorithm models, the highest accuracy rate was that of GBDT (0.955); The AUC values for the 7 algorithms were, from high to low, XGB (0.881), RF (0.802), GBDT (0.798), LR (0.778), XGB + LR (0.739), RF + LR (0.691) and GBDT + LR (0.626). Results of the LNM model of PDC gastric cancer patients in test group : Among the 7 algorithmic models, XGB had the highest accuracy rate (0.952); Among the 7 algorithms, the AUC values, from high to low, were GBDT (0.788), RF (0.765), XGB (0.762), LR (0.750), RF + LR (0.678), GBDT + LR (0.650) and XGB + LR (0.619). Single machine learning algorithm can predict LNM in poorly differentiated-type intramucosal gastric cancer, but fusion algorithm can not improve the effect of machine learning in predicting LNM.


Assuntos
Bases de Dados Factuais , Aprendizado de Máquina , Modelos Biológicos , Neoplasias Gástricas , Adulto , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
17.
Sci Rep ; 11(1): 1571, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452440

RESUMO

To explore the predictive performance of machine learning on the recurrence of patients with gastric cancer after the operation. The available data is divided into two parts. In particular, the first part is used as a training set (such as 80% of the original data), and the second part is used as a test set (the remaining 20% of the data). And we use fivefold cross-validation. The weight of recurrence factors shows the top four factors are BMI, Operation time, WGT and age in order. In training group:among the 5 machine learning models, the accuracy of gbm was 0.891, followed by gbm algorithm was 0.876; The AUC values of the five machine learning algorithms are from high to low as forest (0.962), gbm (0.922), GradientBoosting (0.898), DecisionTree (0.790) and Logistic (0.748). And the precision of the forest is the highest 0.957, followed by the GradientBoosting algorithm (0.878). At the same time, in the test group is as follows: the highest accuracy of Logistic was 0.801, followed by forest algorithm and gbm; the AUC values of the five algorithms are forest (0.795), GradientBoosting (0.774), DecisionTree (0.773), Logistic (0.771) and gbm (0.771), from high to low. Among the five machine learning algorithms, the highest precision rate of Logistic is 1.000, followed by the gbm (0.487). Machine learning can predict the recurrence of gastric cancer patients after an operation. Besides, the first four factors affecting postoperative recurrence of gastric cancer were BMI, Operation time, WGT and age.


Assuntos
Previsões/métodos , Recidiva Local de Neoplasia/fisiopatologia , Neoplasias Gástricas/fisiopatologia , Idoso , Algoritmos , China , Feminino , Humanos , Modelos Logísticos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Estudos Retrospectivos , Medição de Risco/métodos , Neoplasias Gástricas/cirurgia
18.
CNS Neurosci Ther ; 27(2): 174-185, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32961023

RESUMO

INTRODUCTION: Presenilin enhancer2 (Pen-2) is an essential subunit of γ-secretase, which is a key protease responsible for the cleavage of amyloid precursor protein (APP) and Notch. Mutations on Pen-2 cause familial Alzheimer disease (AD). However, it remains unknown whether Pen-2 regulates neuronal survival and neuroinflammation in the adult brain. METHODS: Forebrain neuron-specific Pen-2 conditional knockout (Pen-2 cKO) mice were generated for this study. Pen-2 cKO mice expressing Notch1 intracellular domain (NICD) conditionally in cortical neurons were also generated. RESULTS: Loss of Pen-2 causes astrogliosis followed by age-dependent cortical atrophy and neuronal loss. Loss of Pen-2 results in microgliosis and enhanced inflammatory responses in the cortex. Expression of NICD in Pen-2 cKO cortices ameliorates neither neurodegeneration nor neuroinflammation. CONCLUSIONS: Pen-2 is required for neuronal survival in the adult cerebral cortex. The Notch signaling may not be involved in neurodegeneration caused by loss of Pen-2.

19.
Inflammation ; 44(1): 307-320, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32918665

RESUMO

Sepsis-associated encephalopathy (SAE) is a clinical syndrome of brain dysfunction secondary to sepsis, which is characterized by long-term neurocognitive deficits such as memory, attention, and executive dysfunction. However, the mechanisms underlying SAE remain unclear. By using transcriptome sequencing approach, we showed that hippocampal S100A9 was significantly increased in sepsis induced by cecal ligation and puncture (CLP) or lipopolysaccharide (LPS) challenge. Thus, we used S100A9 inhibitor Paquinimod to study the role of S100A9 in cognitive impairments in CLP-induced and LPS-induced mice models of SAE. Sepsis survivor mice underwent behavioral tests or the hippocampal tissues subjected to Western blotting, real-time quantitative PCR, and immunohistochemistry. Our results showed that CLP-induced and LPS-induced memory impairments were accompanied with increased expressions of hippocampal microglia Iba1 and CD86 (M1 markers), but reduced expression of Arg1 (M2 marker). Notably, S100A9 inhibition significantly improved the survival rate and learning and memory impairments in sepsis survivors, with a shift from M1 to M2 phenotype. Taken together, our study suggests that S100A9 upregulation might contribute to learning and memory impairments by promoting microglia M1 polarization in sepsis survivors, whereas S100A9 inhibition might provide a potential therapeutic target for SAE.


Assuntos
Calgranulina B/biossíntese , Polaridade Celular/fisiologia , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/metabolismo , Microglia/metabolismo , Sepse/metabolismo , Animais , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/psicologia , Camundongos , Camundongos Endogâmicos C57BL , Sepse/complicações , Sepse/psicologia , Regulação para Cima/fisiologia
20.
Neurobiol Dis ; 148: 105212, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33276084

RESUMO

PDK1 (3-Phosphoinositide dependent protein kinase-1) is a member in the PI3K (phosphatidylinositol 3 kinase) pathway and is implicated in neurodevelopmental disease with microcephaly. Although the role of PDK1 in neurogenesis has been broadly studied, it remains unknown how PDK1 may regulate oligogenesis in the central nervous system (CNS). To address this question, we generated oligodendrocyte (OL) lineage cells specific PDK1 conditional knockout (cKO) mice. We find that PDK1 cKOs display abnormal white matter (WM), massive loss of mature OLs and severe defect in myelination in the CNS. In contrast, these mutants exhibit normal neuronal development and unchanged apoptosis in the CNS. We demonstrate that deletion of PDK1 severely impairs OL differentiation. We show that genetic or pharmacological inhibition of PDK1 causes deficit in the mammalian target of rapamycin (mTor) signaling and down-regulation of Sox10. Together, these results highlight a critical role of PDK1 in OL differentiation during postnatal CNS development.

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