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The most frequent genetic cause of focal epilepsies is variations in the GAP activity toward RAGs 1 complex genes DEP domain containing 5 (DEPDC5), nitrogen permease regulator 2-like protein (NPRL2) and nitrogen permease regulator 3-like protein (NPRL3). Because these variations are frequent and associated with a broad spectrum of focal epilepsies, a unique pathology categorized as GATORopathy can be conceptualized. Animal models recapitulating the clinical features of patients are essential to decipher GATORopathy. Although several genetically modified animal models recapitulate DEPDC5-related epilepsy, no models have been reported for NPRL2- or NPRL3-related epilepsies. Here, we conditionally deleted Nprl2 and Nprl3 from the dorsal telencephalon in mice [Emx1cre/+; Nprl2f/f (Nprl2-cKO) and Emx1cre/+; Nprl3f/f (Nprl3-cKO)] and compared their phenotypes with Nprl2+/-, Nprl3+/- and Emx1cre/+; Depdc5f/f (Depdc5-cKO) mice. Nprl2-cKO and Nprl3-cKO mice recapitulated the major abnormal features of patients-spontaneous seizures, and dysmorphic enlarged neuronal cells with increased mechanistic target of rapamycin complex 1 signaling-similar to Depdc5-cKO mice. Chronic postnatal rapamycin administration dramatically prolonged the survival period and inhibited seizure occurrence but not enlarged neuronal cells in Nprl2-cKO and Nprl3-cKO mice. However, the benefit of rapamycin after withdrawal was less durable in Nprl2- and Nprl3-cKO mice compared with Depdc5-cKO mice. Further studies using these conditional knockout mice will be useful for understanding GATORopathy and for the identification of novel therapeutic targets.
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Epilepsias Parciales , Epilepsia , Animales , Modelos Animales de Enfermedad , Epilepsias Parciales/genética , Epilepsia/genética , Proteínas Activadoras de GTPasa/genética , Proteínas de Transporte de Membrana/genética , Ratones , Ratones Noqueados , Mutación , Nitrógeno/metabolismo , Convulsiones , Sirolimus , Telencéfalo/metabolismo , Proteínas Supresoras de Tumor/genéticaRESUMEN
Edible basidiomycetes are highly active in the oxidative decomposition and polymerisation of polyphenols, and soybeans contain large amounts of isoflavones, which are polyphenol glycosides. Isoflavone aglycones exhibit weak estrogenic activities. In this study, we investigated the isoflavone content, polyphenol production, antioxidant activity and ergothioneine (EGT) content of soybeans fermented by Pleurotus cornucopiae and Pleurotus ostreatus. Isoflavone glycosides, which were abundant in unfermented soybeans, decreased, and aglycones increased on day 10 of culture in both edible basidiomycete-fermented soybeans. The total maximum polyphenol content in soybeans fermented by both mushrooms were approximately 4 times higher on day 30 to 40 of culture, than that of unfermented soybeans. P. cornucopiae-fermented soybeans showed maximum antioxidant activity on day 20 of culture, and this was approximately 6.1 times higher than that of unfermented soybeans. EGT was not detected in unfermented soybeans, whereas both fermented soybeans showed a maximum EGT content on day 20 of culture, which was especially high in P. cornucopiae-fermented soybeans. The antioxidant activity and EGT of P. cornucopiae-fermented soybeans were higher than those of P. ostreatus, suggesting that EGT was responsible for the increase in the antioxidant activity of P. cornucopiae-fermented soybeans.
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STUDY DESIGN: A retrospective cohort study. OBJECTIVE: The study aimed to investigate the related factors affecting physical activity-related quality of life (QOL) after 2 years of cervical laminoplasty for degenerative cervical myelopathy (DCM), focusing on the degree of preoperative degeneration of the cervical multifidus muscles. SUMMARY OF BACKGROUND DATA: The association between paraspinal muscle degeneration and clinical outcomes after spinal surgery is being investigated. The effect of preoperative degeneration of the cervical multifidus muscles in patients undergoing cervical laminoplasty is ambiguous. METHODS: Patients who underwent laminoplasty for DCM and followed up for more than 2 years were reviewed. To evaluate physical QOL, the physical component summary (PCS) of the 36-Item Short-Form Health Survey (SF-36) was recorded at 2 years postoperatively. The degree of preoperative degeneration in the multifidus muscles at the C4 and C7 levels on axial T2-weighted magnetic resonance imaging (MRI) was categorized according to the Goutallier grading system. The correlation between 2-year postoperative PCS and each preoperative clinical outcome, radiographic parameter, and MRI finding, including Goutallier classification, was analyzed. Variables with a P value <0.10 in univariate analysis were included in multiple linear regression analysis. RESULTS: In total, 106 consecutive patients were included. The 2-year postoperative PCS demonstrated significant correlation with age ( R =-0.358, P =0.002), preoperative JOA score ( R =0.286, P =0.021), preoperative PCS ( R =0.603, P <0.001), C2-C7 lordotic angle ( R =-0.284, P =0.017), stenosis severity ( R =-0.271, P =0.019), and Goutallier classification at the C7 level ( R =-0.268, P =0.021). In multiple linear regression analysis, sex (ß=-0.334, P =0.002), age (ß=-0.299, P =0.013), preoperative PCS (ß=0.356, P =0.009), and Goutallier classification at the C7 level (ß=-0.280, P =0.018) were significantly related to 2-year postoperative PCS. CONCLUSIONS: Increased degeneration of the multifidus muscle at the C7 level negatively affected physical activity-related QOL postoperatively. These results may guide spine surgeons in predicting physical activity-related QOL in patients with DCM after laminoplasty. LEVEL OF EVIDENCE: Level III.
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Vértebras Cervicales , Laminoplastia , Músculos Paraespinales , Calidad de Vida , Enfermedades de la Médula Espinal , Humanos , Masculino , Femenino , Persona de Mediana Edad , Vértebras Cervicales/cirugía , Vértebras Cervicales/diagnóstico por imagen , Músculos Paraespinales/diagnóstico por imagen , Anciano , Enfermedades de la Médula Espinal/cirugía , Enfermedades de la Médula Espinal/diagnóstico por imagen , Actividad Motora , Adulto , Imagen por Resonancia Magnética , Estudios RetrospectivosRESUMEN
STUDY DESIGN: Multicenter, prospective cohort study. OBJECTIVE: The current study aimed to identify the incidence of residual paresthesias after surgery for degenerative cervical myelopathy (DCM), and to demonstrate the impact of these symptoms on clinical outcomes and patient satisfaction. SUMMARY OF BACKGROUND DATA: Surgery for DCM aims to improve and/or prevent further deterioration of physical function and quality-of-life (QOL) in the setting of DCM. However, patients are often not satisfied with their treatment for myelopathy when they have severe residual paresthesias, even when physical function and QOL are improved after surgery. MATERIALS AND METHODS: The authors included 187 patients who underwent laminoplasty for DCM. All patients were divided into two groups based on their visual analog scale score for paresthesia of the upper extremities at one year postoperatively (>40 vs. ≤40 mm). Preoperative factors, changes in clinical scores and radiographic factors, and satisfaction scales at one year postoperatively were compared between groups. The authors used mixed-effect linear and logistic regression modeling to adjust for confounders. RESULTS: Overall, 86 of 187 patients had severe residual paresthesia at one year postoperatively. Preoperative patient-oriented pain scale scores were significantly associated with postoperative residual paresthesia ( P =0.032). A mixed-effect model demonstrated that patients with severe postoperative residual paresthesia showed significantly smaller improvements in QOL ( P =0.046) and myelopathy ( P =0.037) than patients with no/mild residual paresthesia. Logistic regression analysis identified that residual paresthesia was significantly associated with lower treatment satisfaction, independent of improvements in myelopathy and QOL (adjusted odds ratio: 2.5, P =0.010). CONCLUSION: In total, 45% of patients with DCM demonstrated severe residual paresthesia at one year postoperatively. These patients showed significantly worse treatment satisfaction, even after accounting for improvements in myelopathy and QOL. As such, in patients who experience higher preoperative pain, multidisciplinary approaches for residual paresthesia, including medications for neuropathic pain, might lead to greater clinical satisfaction. LEVEL OF EVIDENCE: 3.
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Parestesia , Enfermedades de la Médula Espinal , Humanos , Parestesia/epidemiología , Parestesia/etiología , Estudios Prospectivos , Calidad de Vida , Incidencia , Resultado del Tratamiento , Vértebras Cervicales/cirugía , Enfermedades de la Médula Espinal/epidemiología , Enfermedades de la Médula Espinal/cirugía , DolorRESUMEN
STUDY DESIGN: Level 3 retrospective cohort case-control study. PURPOSE: This study aimed to investigate the risk factors for distal junctional kyphosis (DJK) caused by osteoporotic vertebral fractures following spinal reconstruction surgery, with a focus on the sagittal stable vertebra. OVERVIEW OF LITERATURE: Despite the rarity of reports on DJK in this setting, DJK was reported to reduce when the lower instrumented vertebra (LIV) was extended to the sagittal stable vertebra in the posterior corrective fixation for Scheuermann's disease. METHODS: This study included 46 patients who underwent spinal reconstruction surgery for thoracolumbar osteoporotic vertebral fractures and kyphosis and were followed up for 1 year postoperatively. DJK was defined as an advanced kyphosis angle >10° between the LIV and one lower vertebra. The patients were divided into groups with and without DJK. The risk factors of the two groups, such as patient background, surgery-related factors, radiographic parameters, and clinical outcomes, were analyzed. RESULTS: The DJK and non-DJK groups included 14 and 32 patients, respectively, without significant differences in patient background. Those with instability in the distal adjacent LIV disc had a significantly higher risk of DJK occurrence (28.6% vs. 3.2%, p=0.027). DJK occurrence significantly increased in those with the sagittal stable vertebra not included in the fixation range (57.1% vs. 18.8%, p=0.020). Other preoperative radiographic parameters were not significantly different. Instability in the distal adjacent LIV disc (adjusted odds ratio, 14.50; p=0.029) and the exclusion of the sagittal stable vertebra from the fixation range (adjusted odds ratio, 5.29; p=0.020) were significant risk factors for DJK occurrence. CONCLUSIONS: Regarding spinal reconstruction surgery in patients with osteoporotic vertebral fractures, instability in the distal adjacent LIV disc and the exclusion of the sagittal stable vertebra from the fixation range were risk factors for DJK occurrence in the short term.
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Introduction: Few studies have assessed the minimum clinically important difference (MCID) of each Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) domain. This study assessed MCIDs of JOABPEQ in patients with lumbar spine disease by generation. Methods: We evaluated the JOABPEQ score of 805 consecutive patients with lumbar spine disease undergoing posterior surgery preoperatively and 1 year postoperatively. MCIDs of each JOABPEQ domain were determined using anchor- and distribution-based methods according to age. A question based on the concept of a health transition item was used as the anchor for the MCID decision. Results: Overall, MCIDs of the JOABPEQ were 28.6 and 27.3 points for pain-related disorder and gait disturbance, respectively. The MCID for the lumbar spine dysfunction domain did not reach 0.6 over the area under the curve. Regarding the differences among generations, MCIDs of pain-related disorder and gait disturbance domains differed slightly between the elderly and middle-aged. The psychological disorder domain did not reflect clinically meaningful changes in the elderly. MCIDs of the social life disturbance domain decreased with age. Conclusions: Focusing on achieving the ideal responsiveness of patient-reported outcomes across generations, MCIDs of the pain-related disorder and gait disturbance domains may be valuable for patients, regardless of age, when adopting the JOABPEQ for patients with lumbar spine disease undergoing surgery. This study only evaluated cases that underwent posterior lumbar surgery. Future research will necessitate conducting surveys concerning the outcomes of various treatments for lumbar spine disease.
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BACKGROUND CONTEXT: Implementing machine learning techniques, such as decision trees, known as prediction models that use logical construction diagrams, are rarely used to predict clinical outcomes. PURPOSE: To develop a clinical prediction rule to predict clinical outcomes in patients who undergo minimally invasive lumbar decompression surgery for lumbar spinal stenosis with and without coexisting spondylolisthesis and scoliosis using a decision tree model. STUDY DESIGN/SETTING: A retrospective analysis of prospectively collected data. PATIENT SAMPLE: This study included 331 patients who underwent minimally invasive surgery for lumbar spinal stenosis and were followed up for ≥2 years at 1 institution. OUTCOME MEASURES: Self-report measures: The Japanese Orthopedic Association (JOA) scores and low back pain (LBP)/leg pain/leg numbness visual analog scale (VAS) scores. Physiologic measures: Standing sagittal spinopelvic alignment, computed tomography, and magnetic resonance imaging results. METHODS: Low achievement in clinical outcomes were defined as the postoperative JOA score at the 2-year follow-up <25 points. Univariate and multiple logistic regression analysis and chi-square automatic interaction detection (CHAID) were used for analysis. RESULTS: The CHAID model for JOA score <25 points showed spontaneous numbness/pain as the first decision node. For the presence of spontaneous numbness/pain, sagittal vertical axis ≥70 mm was selected as the second decision node. Then lateral wedging, ≥6° and pelvic incidence minus lumbar lordosis (PI-LL) ≥30° followed as the third decision node. For the absence of spontaneous numbness/pain, sex and lateral olisthesis, ≥3mm and American Society of Anesthesiologists physical status classification system score were selected as the second and third decision nodes. The sensitivity, specificity, and the positive predictive value of this CHAID model was 65.1, 69.8, and 64.7% respectively. CONCLUSIONS: The CHAID model incorporating basic information and functional and radiologic factors is useful for predicting surgical outcomes.
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Escoliosis , Fusión Vertebral , Estenosis Espinal , Espondilolistesis , Animales , Humanos , Escoliosis/cirugía , Estenosis Espinal/complicaciones , Estenosis Espinal/diagnóstico por imagen , Estenosis Espinal/cirugía , Espondilolistesis/complicaciones , Espondilolistesis/diagnóstico por imagen , Espondilolistesis/cirugía , Estudios Retrospectivos , Hipoestesia , Resultado del Tratamiento , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Dolor , Árboles de Decisión , Descompresión , Fusión Vertebral/métodosRESUMEN
Climate change due to global warming is now affecting agricultural production worldwide. In rice, one of the most important crops, water limitation due to irregular rainfall in rainfed lowlands during crop growth limits yield. Dry direct-sowing has been proposed as a water-efficient approach to cope with water stress during rice growth, but poor seedling establishment due to drought during germination and emergence is a problem. Here, we germinated indica rice cultivars Rc348 (drought tolerant) and Rc10 (drought sensitive) under osmotic stress induced by PEG to elucidate mechanisms of germination under drought. Rc348 had higher germination rate and germination index under severe osmotic stress of -1.5 MPa, above those of Rc10. Rc348 showed up-regulated GA biosynthesis, down-regulated ABA catabolism, and up-regulated α-amylase gene expression in imbibed seeds under PEG treatment compared to that of Rc10. During germination, reactive oxygen species (ROS) play important roles in antagonism between gibberellic acid (GA) and abscisic acid (ABA). Embryo of Rc348 treated with PEG had significantly greater expression of NADPH oxidase genes and higher endogenous ROS levels, together with significantly increased endogenous GA1, GA4 and ABA contents compared to that of Rc10. In aleurone layers treated with exogenous GA, expression of α-amylase genes was higher in Rc348 than in Rc10, and expression of NADPH oxidase genes was enhanced with significantly higher ROS content in Rc348, suggesting higher sensitivity of GA to ROS production and starch degradation in aleurone cells of Rc348. These results suggest that the osmotic stress tolerance of Rc348 is due to enhancement of ROS production, GA biosynthesis, and GA sensitivity, resulting in a higher germination rate under osmotic stress.
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STUDY DESIGN: Cross-sectional study. OBJECTIVE: Validate the diagnostic accuracy of a deep-learning algorithm for cervical cord compression due to degenerative canal stenosis on radiography. SUMMARY OF BACKGROUND DATA: The diagnosis of degenerative cervical myelopathy is often delayed, resulting in improper management. Screening tools for suspected degenerative cervical myelopathy would help identify patients who require detailed physical evaluation. MATERIALS AND METHODS: Data from 240 patients (120 with cervical stenosis on magnetic resonance imaging and 120 age and sex-matched controls) were randomly divided into training (n = 198) and test (n = 42) data sets. The deep-learning algorithm, designed to identify the suspected stenosis level on radiography, was constructed using a convolutional neural network model called EfficientNetB2, and radiography and magnetic resonance imaging data from the training data set. The accuracy and area under the curve of the receiver operating characteristic curve were calculated for the independent test data set. Finally, the number of correct diagnoses was compared between the algorithm and 10 physicians using the test cohort. RESULTS: The diagnostic accuracy and area under the curve of the deep-learning algorithm were 0.81 and 0.81, respectively, in the independent test data set. The rate of correct responses in the test data set was significantly higher for the algorithm than for the physician's consensus (81.0% vs . 66.2%; P = 0.034). Furthermore, the accuracy of the algorithm was greater than that of each individual physician. CONCLUSIONS: We developed a deep-learning algorithm capable of suggesting the presence of cervical spinal cord compression on cervical radiography and highlighting the suspected levels on radiographic imaging when cord compression is identified. The diagnostic accuracy of the algorithm was greater than that of spine physicians. LEVEL OF EVIDENCE: Level IV.
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Médula Cervical , Aprendizaje Profundo , Compresión de la Médula Espinal , Enfermedades de la Médula Espinal , Estenosis Espinal , Humanos , Compresión de la Médula Espinal/diagnóstico por imagen , Compresión de la Médula Espinal/etiología , Constricción Patológica , Estenosis Espinal/diagnóstico , Estudios Transversales , Radiografía , Enfermedades de la Médula Espinal/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/patologíaRESUMEN
The antioxidant (AOX) activities of alanyl tyrosine dipeptide-type surfactants with several chain lengths were investigated. The critical micelle concentration decreased exponentially with the carbon number of the hydrophobic chain of the surfactant. The antioxidative property was investigated using the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid ammonium salt) (ABTS) assay and the oxygen radical absorbance capacity (ORAC) assay. The AOX activity was found to be strongly dependent on the chain length in the monomer solution. Therefore, an increase in the molecular size negatively influenced the AOX ability of the tyrosine residue. However, it was almost independent of the chain length of the surfactant in the micellar solution. The micelle particles acted as a catalyst for the reduction of the radicals in the ORAC assay.
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Antioxidantes , Dipéptidos/química , Dipéptidos/farmacología , Interacciones Hidrofóbicas e Hidrofílicas , Tensoactivos/química , Tensoactivos/farmacología , Tirosina/química , Tirosina/farmacología , Carbono/química , Micelas , Soluciones , Relación Estructura-ActividadRESUMEN
The mid-term surgical outcomes of cervical spondylotic myelopathy (CSM), evaluated using the cervical Japanese Orthopedic Association (cJOA) score, are reported to be satisfactory. However, there remains room for improvement in quality-of-life (QOL), especially after short-term follow-up. We aimed to demonstrate changes in mental and physical QOL between short- and mid-term follow-ups and determine the predictive factors for deterioration of QOL. In this retrospective cohort study, 80 consecutive patients underwent laminoplasty for CSM. The outcome measures were Short Form-36 Physical Component Summary (PCS), Mental Component Summary (MCS), and cJOA scores. PCS and MCS scores were compared at the 2- and 5-year postoperative time points. Additionally, a multivariate logistic regression model was used to identify the predictive factors for deterioration. Significant factors in the logistic regression analysis were analyzed using receiver-operating characteristic curves. The results showed that MCS scores did not deteriorate after 2 years postoperatively (p = 0.912). Meanwhile, PCS significantly declined between 2 and 5 years postoperatively (p = 0.008). cJOA scores at 2 years postoperatively were significantly associated with PCS deterioration at 2-year follow-up. In conclusion, only physical QOL might show deterioration after short-term follow-up. Such deterioration is likely in patients with a cJOA score <13.0 at 2 years postoperatively.
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A consistent evaporation model is developed for the conservative Allen-Cahn-based phase-field lattice Boltzmann method that uses an appropriate source term to recover the advection-diffusion equation for the specific humidity. To evaluate the accuracy of the proposed scheme, simulations are conducted of a steady-state one-dimensional Stefan flow for a flat interface and a three-dimensional evaporating sessile droplet on a flat substrate for a curved interface. It is confirmed that the results for the evaporative mass flux of the Stefan flow agree well with those obtained from the analytical solution within a specific humidity range of 0.8 or less at the liquid-gas interface. For the sessile droplet case, the results for the dependence of the contact angle on the evaporative mass flux and its profile show good agreement with those obtained from the model of Hu and Larson [J. Phys. Chem. B 106, 1334 (2002)JPCBFK1520-610610.1021/jp0118322].
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STUDY DESIGN: A retrospective case control study. PURPOSE: The purpose of this study was to compare the surgical outcomes of multilevel lateral lumbar interbody fusion (LIF) and multilevel posterior lumbar interbody fusion (PLIF) in the surgical treatment of adult spinal deformity (ASD) and to evaluate the sagittal plane correction by combining LIF with posterior-column osteotomy (PCO). OVERVIEW OF LITERATURE: The surgical outcomes between multilevel LIF and multilevel PLIF in ASD patients remain unclear. METHODS: We retrospectively reviewed 31 ASD patients who underwent multilevel LIF combined with PCO (LIF group, n=14) or multilevel PLIF (PLIF group, n=17) and with a minimum 2-year follow-up. In the comparison between LIF and PLIF groups, their mean age at surgery was 69.4 vs. 61.8 years while the mean follow-up period was 29.2 vs. 59.3 months. We evaluated the transition of pelvic incidence-lumbar lordosis (PI-LL) and disc angle (DA) in the LIF group, in fulcrum backward bending (FBB), after LIF and after posterior spinal fusion (PSF) with PCO. The spinopelvic radiographic parameters were compared between LIF and PLIF groups. RESULTS: Compared with the PLIF group, the LIF group had less blood loss and comparable surgical outcomes with respect to radiographic data, health-related quality of life scores and surgical time. In the LIF group, the mean DA and PI-LL were unchanged after LIF (DA, 5.8°; PI-LL, 15°) compared with the values using FBB (DA, 4.3°; PI-LL, 15°) and improved significantly after PSF with PCO (DA, 8.1°; PI-LL, 0°). CONCLUSIONS: In the surgical treatment of ASD, multilevel LIF is less invasive than multilevel PLIF and combination of LIF and PCO would be necessary for optimal sagittal correction in patients with rigid deformity.