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We have earlier established a direct measurement method for assessing stool physical consistency using a texture analyzer (TAXT). The present study aimed to evaluate the stool softening effect of Lacticaseibacillus paracasei strain Shirota (LcS) using TAXT in a double-blind, randomized, placebo-controlled study. Sixty-four healthy participants with a Bristol stool form scale (BSFS) 1/2 ≥ 50% during screening consumed fermented milk containing LcS or a placebo beverage daily for 8 weeks. Stool consistency and water content were determined using TAXT and a lyophilizer, respectively. Participants evaluated their defecation using the BSFS. Stool consistency evaluated by a texture analyzer (TAXT) in the LcS group tended to be softer than that in the placebo group (p = 0.052). Subgroup analyses (TAXT value at baseline ≥ 4.5) showed that stool consistency was significantly softer in the LcS group (p = 0.014). Stool water content was also significantly higher in the LcS group than in the placebo group, but the proportion of normal stools was not statistically significant. We were unable to find evidence for the softening effect of LcS under the present study's conditions. However, its efficacy may be confirmed by targeting participants with physically hard stools and TAXT values ≥ 4.5.
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Defecación , Heces , Lacticaseibacillus paracasei , Probióticos , Humanos , Método Doble Ciego , Heces/química , Heces/microbiología , Masculino , Femenino , Adulto , Probióticos/administración & dosificación , Lacticaseibacillus paracasei/fisiología , Voluntarios Sanos , Persona de Mediana Edad , Adulto Joven , Productos Lácteos CultivadosRESUMEN
Study Design: Retrospective cohort study. Purpose: This study aimed to compare data from patients who received intradiscal condoliase (chondroitin sulfate ABC endolyase) injection for primary lumbar disc herniation (LDH) and recurrent LDH. Overview of Literature: Chemonucleolysis with condoliase for LDH is a treatment with relatively good results and a high safety profile; however, few studies have reported recurrence after LDH surgery. Methods: The study participants were 249 patients who underwent intradiscal condoliase injection for LDH at nine participating institutions, including 241 patients with initial LDH (group C) and eight with recurrent LDH (group R). Patient characteristics including age, sex, body mass index, disease duration, intervertebral LDH level, smoking history, and diabetes history were evaluated. Low back pain/leg pain Numerical Rating Scale (NRS) scores and the Oswestry Disability Index (ODI) were used to evaluate clinical symptoms before treatment and at 6 months and 1 year after treatment. Results: Low back pain NRS scores (before treatment and at 6 months and 1 year after treatment, respectively) in group C (4.9 â 2.6 â 1.8) showed significant improvement until 1 year after treatment. Although a tendency for improvement was observed in group R (3.5 â 2.8 â 2.2), no significant difference was noted. Groups C (6.6 â 2.4 â 1.4) and R (7.0 â 3.1 â 3.2) showed significant improvement in the leg pain NRS scores after treatment. Group C (41.4 â 19.5 â 13.7) demonstrated significant improvement in the ODI up to 1 year after treatment; however, no significant difference was found in group R (35.7 â 31.7 â 26.4). Conclusions: Although intradiscal condoliase injection is less effective for LDH recurrence than for initial cases, it is useful for improving leg pain and can be considered a minimally invasive and safe treatment method.
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BACKGROUND: Although posterior decompression with fusion (PDF) are effective for treating thoracic myelopathy, surgical treatment has a high risk of various complications. There is currently no information available on the perioperative complications in thoracic ossification of the longitudinal ligament (T-OPLL) and thoracic ossification of the ligamentum flavum (T-OLF). We evaluate the perioperative complication rate and cost between T-OPLL and T-OLF for patients underwent PDF. METHODS: Patients undergoing PDF for T-OPLL and T-OLF from 2012 to 2018 were detected in Japanese nationwide inpatient database. One-to-one propensity score matching between T-OPLL and T-OLF was performed based on patient characteristics and preoperative comorbidities. We examined systemic and local complication rate, reoperation rate, length of hospital stays, costs, discharge destination, and mortality after matching. RESULTS: In a total of 2,660 patients, 828 pairs of T-OPLL and T-OLF patients were included after matching. The incidence of systemic complications did not differ significantly between the T-OPLL and OLF groups. However, local complications were more frequently occurred in T-OPLL than in T-OLF groups (11.4% vs. 7.7% P = 0.012). Transfusion rates was also significantly higher in the T-OPLL group (14.1% vs. 9.4%, P = 0.003). T-OPLL group had longer hospital stay (42.2 days vs. 36.2 days, P = 0.004) and higher medical costs (USD 32,805 vs. USD 25,134, P < 0.001). In both T-OPLL and T-OLF, the occurrence of perioperative complications led to longer hospital stay and higher medical costs. While fewer patients in T-OPLL were discharged home (51.6% vs. 65.1%, P < 0.001), patients were transferred to other hospitals more frequently (47.5% vs. 33.5%, P = 0.001). CONCLUSION: This research identified the perioperative complications of T-OPLL and T-OLF in PDF using a large national database, which revealed that the incidence of local complications was higher in the T-OPLL patients. Perioperative complications resulted in longer hospital stays and higher medical costs.
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Bases de Datos Factuales , Descompresión Quirúrgica , Ligamento Amarillo , Osificación del Ligamento Longitudinal Posterior , Complicaciones Posoperatorias , Fusión Vertebral , Vértebras Torácicas , Humanos , Masculino , Femenino , Vértebras Torácicas/cirugía , Ligamento Amarillo/cirugía , Fusión Vertebral/economía , Fusión Vertebral/efectos adversos , Fusión Vertebral/métodos , Persona de Mediana Edad , Descompresión Quirúrgica/economía , Descompresión Quirúrgica/efectos adversos , Descompresión Quirúrgica/métodos , Anciano , Osificación del Ligamento Longitudinal Posterior/cirugía , Osificación del Ligamento Longitudinal Posterior/economía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/economía , Japón/epidemiología , Osificación Heterotópica/cirugía , Osificación Heterotópica/economía , Osificación Heterotópica/epidemiología , Tiempo de Internación/economía , Reoperación/economía , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Pacientes Internos , Resultado del TratamientoRESUMEN
Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, aberrant immune activation, and extensive tissue fibrosis of the skin and internal organs. Because of the complicated nature of its pathogenesis, the underlying mechanisms of SSc remain incompletely understood. Angiogenic factor with a G-patch domain and a Forkhead-associated domain 1 (AGGF1) is a critical factor in angiogenesis expressed on vascular endothelial cells, associated with inflammatory and fibrotic responses. To elucidate the possible implication of AGGF1 in SSc pathogenesis, we investigated the association between serum AGGF1 levels and clinical manifestations in SSc patients. We conducted a cross-sectional analysis of AGGF1 levels in sera from 60 SSc patients and 19 healthy controls with enzyme-linked immunosorbent assay. Serum AGGF1 levels in SSc patients were significantly higher than those in healthy individuals. In particular, diffuse cutaneous SSc patients with shorter disease duration had higher levels compared to those with longer disease duration and limited cutaneous SSc patients. Patients with higher serum AGGF1 levels had a higher incidence of digital ulcers, higher modified Rodnan Skin Scores (mRSS), elevated serum Krebs von den Lungen-6 (KL-6) levels, C-reactive protein levels, and right ventricular systolic pressures (RVSP) on the echocardiogram, whereas they had reduced percentage of vital capacity (%VC) and percentage of diffusing capacity of the lungs for carbon monoxide (%DLCO) in pulmonary functional tests. In line, serum AGGF1 levels were significantly correlated with mRSS, serum KL-6 and surfactant protein D levels, RVSP, and %DLCO. These results uncovered notable correlations between serum AGGF1 levels and key cutaneous and vascular involvements in SSc, suggesting potential roles of AGGF1 in SSc pathogenesis.
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Proteínas Angiogénicas , Mucina-1 , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Adulto , Mucina-1/sangre , Proteínas Angiogénicas/sangre , Esclerodermia Sistémica/sangre , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/inmunología , Estudios de Casos y Controles , Anciano , Proteína C-Reactiva/análisis , Piel/patología , Capacidad Vital , Úlcera Cutánea/sangre , Úlcera Cutánea/etiología , Úlcera Cutánea/diagnóstico , Úlcera Cutánea/patología , Índice de Severidad de la EnfermedadAsunto(s)
Vacunas contra la COVID-19 , Carcinoma de Células Escamosas , Síndrome de Sweet , Humanos , Carcinoma de Células Escamosas/tratamiento farmacológico , COVID-19 , Vacunas contra la COVID-19/efectos adversos , Neoplasias de Cabeza y Cuello , Recurrencia Local de Neoplasia , Nivolumab/uso terapéutico , Síndrome de Sweet/inducido químicamenteRESUMEN
BACKGROUND AND PURPOSE: Mean pulmonary artery pressure (mPAP) is a key index for chronic thromboembolic pulmonary hypertension (CTEPH). Using machine learning, we attempted to construct an accurate prediction model for mPAP in patients with CTEPH. METHODS: A total of 136 patients diagnosed with CTEPH were included, for whom mPAP was measured. The following patient data were used as explanatory variables in the model: basic patient information (age and sex), blood tests (brain natriuretic peptide (BNP)), echocardiography (tricuspid valve pressure gradient (TRPG)), and chest radiography (cardiothoracic ratio (CTR), right second arc ratio, and presence of avascular area). Seven machine learning methods including linear regression were used for the multivariable prediction models. Additionally, prediction models were constructed using the AutoML software. Among the 136 patients, 2/3 and 1/3 were used as training and validation sets, respectively. The average of R squared was obtained from 10 different data splittings of the training and validation sets. RESULTS: The optimal machine learning model was linear regression (averaged R squared, 0.360). The optimal combination of explanatory variables with linear regression was age, BNP level, TRPG level, and CTR (averaged R squared, 0.388). The R squared of the optimal multivariable linear regression model was higher than that of the univariable linear regression model with only TRPG. CONCLUSION: We constructed a more accurate prediction model for mPAP in patients with CTEPH than a model of TRPG only. The prediction performance of our model was improved by selecting the optimal machine learning method and combination of explanatory variables.
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Hipertensión Pulmonar , Embolia Pulmonar , Humanos , Hipertensión Pulmonar/diagnóstico , Presión Arterial , Ecocardiografía/métodos , Válvula Tricúspide , Péptido Natriurético Encefálico , Embolia Pulmonar/complicaciones , Embolia Pulmonar/diagnóstico por imagen , Enfermedad CrónicaRESUMEN
Background: Treatment for pyogenic spondylitis tends to be prolonged; however, few studies have examined the factors associated with the time required for infection control. Therefore, we analyzed a consecutive cohort of patients to identify factors associated with the time required to control infection in pyogenic spondylitis. This study aimed to clarify the factors linked to the duration necessary for achieving infection control in cases of pyogenic spondylitis, using C-reactive protein (CRP) normalization as an indicator. Methods: In this retrospective observational study, we investigated 108 patients diagnosed with pyogenic spondylitis. We evaluated the number of days from the first visit to CRP normalization; for cases wherein CRP did not normalize, the number of days to the date of final blood sampling was evaluated. In the present study, infection control in pyogenic spondylitis was defined as a CRP falling within the normal range (≤0.14 mg/dL). We performed univariate and multivariate Cox regression analyses to identify various factors associated with the time required for CRP normalization in pyogenic spondylitis. Results: The mean time required for CRP normalization was 148 days. Univariate Cox regression analysis showed that the serum creatinine level, estimated glomerular filtration rate (eGFR), lymphocyte percentage, neutrophil percentage, CRP level, CRP-albumin ratio, and neutrophil-to-lymphocyte ratio were significantly associated with the time required to control infection. Multivariate Cox regression analysis showed that a higher neutrophil percentage, diabetes mellitus, and a lower eGFR were the independent factors associated with a longer infection control time. Conclusions: We found that a higher neutrophil percentage, diabetes mellitus, and a lower eGFR were significantly associated with a longer time for CRP normalization in pyogenic spondylitis. These findings may help identify patients with pyogenic spondylitis who are at a high risk for an extended infection control period.
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BACKGROUND: Reoperation, sometimes multiple, is common with progressively worse outcomes in patients with degenerative lumbar spine diseases. Lysophosphatidylcholine (LPC), a precursor of lysophosphatidic acid, in the cerebrospinal fluid (CSF) is a possible biomarker for neuropathic pain and discriminating neuropathic pain caused by lumbar spinal canal stenosis (LSCS) from other etiologies. This study aimed to explore this possible use of LPC species in the CSF. METHODS: Patients with LSCS (n = 137) and persistent spinal pain syndrome (n = 22) were subjected in this multi-site observational study. The CSF was collected by lumbar puncture. Using liquid chromatography-tandem mass spectrometry, we measured 6 LPC species, (16:0), (18:0), (18:1), (18:2), (20:4), and (22:6), in the CSF. We compared the LPC values between the groups and determined the cutoff levels that could efficiently discriminate the groups with high accuracy. RESULTS: The levels of all measured LPC species were significantly higher in the LSCS group than the persistent spinal pain syndrome group. Four LPC species demonstrated more than 0.80 area under the curve obtained from the receiver operating characteristic curve analysis. Although the specificity of cutoff levels for the 6 LPC species was low to moderate, their sensitivity was consistently high. CONCLUSIONS: The existing diagnostic protocols combining physical examinations and morphological imaging studies for lumbar spinal pain have limited sensitivity. Measuring LPC species in the CSF is a promising objective laboratory test and could be suitable for detecting the presence of lumbar spinal stenosis and can help indications for surgery.
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Dolor de la Región Lumbar , Neuralgia , Estenosis Espinal , Humanos , Dolor de la Región Lumbar/complicaciones , Vértebras Lumbares/cirugía , Lisofosfatidilcolinas , Neuralgia/complicaciones , Estenosis Espinal/etiologíaRESUMEN
The renin-angiotensin system in the brain plays a pivotal role in modulating sympathetic nerve activity and contributes to the pathogenesis of hypertension. Angiotensin II (Ang II) type 1 receptor (AT1R)-associated protein (ATRAP) promotes internalization of AT1R while suppressing pathological overactivation of AT1R signaling. However, the pathophysiological function of ATRAP in the brain remains unknown. Therefore, this study aims to investigate whether ATRAP in the paraventricular nucleus (PVN) is involved in neurogenic hypertension pathogenesis in Ang II-infused rats. The ATRAP/AT1R ratio, which serves as an indicator of tissue AT1R hyperactivity, tended to decrease within the PVN in the Ang II group than in the vehicle group. This suggests an Ang II-induced hyperactivation of the AT1R signaling pathway in the PVN. Lentiviral vectors were generated to stimulate ATRAP expression. At 6 weeks of age, rats were microinjected with LV-Venus (Venus-expressing lentivirus) or LV-ATRAP (Venus-ATRAP-expressing lentivirus). The rats were then randomly divided into four groups: (1) Vehicle/LV-Venus, (2) Vehicle/LV-ATRAP, (3) Ang II/LV-Venus, and (4) Ang II/LV-ATRAP. Two weeks after microinjection, vehicle or Ang II was administered systemically for 2 weeks. In the Ang II/LV-ATRAP group, systolic blood pressure at 1 and 2 weeks following administration was significantly lower than that in the Ang II/LV-Venus group. Furthermore, urinary adrenaline levels tended to decrease in the Ang II/LV-ATRAP group than in the Ang II/LV-Venus group. These findings suggest that enhanced ATRAP expression in the PVN suppresses Ang II-induced hypertension, potentially by suppressing hyperactivation of the tissue AT1R signaling pathway and, subsequently, sympathetic nerve activity.
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Angiotensina II , Hipertensión , Animales , Ratas , Angiotensina II/farmacología , Presión Sanguínea , Núcleo Hipotalámico Paraventricular/metabolismo , Receptor de Angiotensina Tipo 1/metabolismoRESUMEN
The growing significance of messenger RNA (mRNA) therapeutics in diverse medical applications, such as cancer, infectious diseases, and genetic disorders, highlighted the need for efficient and safe delivery systems. Lipid nanoparticles (LNPs) have shown great promise for mRNA delivery, but challenges such as toxicity and immunogenicity still remain to be addressed. In this study, we aimed to compare the performance of polyplex nanomicelles, our original cationic polymer-based carrier, and LNPs in various aspects, including delivery efficiency, organ toxicity, muscle damage, immune reaction, and pain. Our results showed that nanomicelles (PEG-PAsp(DET)) and LNPs (SM-102) exhibited distinct characteristics, with the former demonstrating relatively sustained protein production and reduced inflammation, making them suitable for therapeutic purposes. On the other hand, LNPs displayed desirable properties for vaccines, such as rapid mRNA expression and potent immune response. Taken together, these results suggest the different potentials of nanomicelles and LNPs, supporting further optimization of mRNA delivery systems tailored for specific purposes.
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BACKGROUND: Although right ventricular (RV) enlargement may affect RV diastolic dysfunction assessed by end-diastolic forward flow (EDFF) in patients with repaired tetralogy of Fallot (TOF), EDFF may also be modified by left ventricular (LV) hemodynamics. We hypothesized that EDFF is affected by LV hemodynamics, not limited to RV diastolic stiffening.MethodsâandâResults: Among 145 consecutive patients with repaired TOF who underwent catheterization, hemodynamic properties in 47 with consistent EDFF and 75 without EDFF were analyzed. Compared with patients without EDFF, those with EDFF had a large RV volume with a high regurgitant fraction. Although cardiac index and central venous pressure (CVP) were similar, contrast injection augmented CVP and LV end-diastolic pressure (EDP) in patients with vs. those without EDFF, suggesting compromised diastolic reserve. In patients with EDFF, the velocity-time integral (VTI) of EDFF was positively correlated with LVEDP and systemic vascular resistance, in addition to RV EDP. EDFF-VTI was correlated with hepatic venous wedge pressure and markers of hepatic dysfunction. Subanalysis of the older (≥6 years) half of the study cohort revealed that EDFF was associated with bi-atrial enlargement independent of RV volume, highlighting the pronounced role of EDFF on the diastolic property in the aged cohort. CONCLUSIONS: EDFF-VTI in patients with repaired TOF reflects RV diastolic dysfunction, affected by the left heart system. EDFF-VTI indicates blood stagnation, which may be attributed to end-organ damage.
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Tetralogía de Fallot , Disfunción Ventricular Derecha , Humanos , Anciano , Diástole , Hemodinámica , Resistencia Vascular , Disfunción Ventricular Derecha/complicaciones , Función Ventricular DerechaRESUMEN
BACKGROUND: Small cell lung cancer (SCLC) is a neuroendocrine tumor with poor prognosis. Neuroendocrine tumors possess characteristics of both nerve cells and hormone-secreting cells; therefore, targeting the neuronal properties of these tumors may lead to the development of new therapeutic options. Among the endogenous signaling pathways in the nervous system, targeting the glutamate pathway may be a useful strategy for glioblastoma treatment. Perampanel, an antagonist of the synaptic glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR), has been reported to be effective in patients with glioblastoma. In this study, we aimed to investigate the antitumor effects of AMPAR antagonists in human SCLC cell lines. METHODS: We performed to examine the expression of AMPAR using Western blot and immunohistochemical analysis. The antitumor effects of AMPAR antagonists on human SCLC cell lines were investigated in vitro and in vivo. We also analyzed the signaling pathway of AMPAR antagonists in SCLC cell lines. Statistical analysis was performed by the GraphPad Prism 6 software. RESULTS: We first examined the expression of endogenous AMPAR in six human SCLC cell lines, detecting AMPAR proteins in all of them. Next, we tested the anti-proliferative effect of two AMPAR antagonists, talampanel and cyanquixaline, using SCLC cells in vitro and in vivo. Both AMPAR antagonists inhibited cell proliferation and mitogen-activated protein kinase (MAPK) phosphorylation in SCLC cells in vitro. Further, we observed reduced proliferation of implanted cell lines in an in vivo setting, assessed by Ki-67 immunohistochemistry. Additionally, using immunohistochemical analysis we confirmed AMPAR protein expression in human SCLC samples. CONCLUSION: AMPAR may be a potential therapeutic target for SCLC.
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Background: Due to its association with bone metabolic status and muscle strength/mass, vitamin D deficiency has the potential to affect neurological symptom recovery after surgery for degenerative cervical myelopathy (DCM). However, few studies have investigated the effects of vitamin D deficiency (serum 25(OH)D <20 ng/mL) on surgical outcomes in DCM patients. Herein, we investigated the prevalence of vitamin D deficiency in patients with DCM, and determined whether vitamin D deficiency affects surgical outcomes for DCM. Methods: In this retrospective observational study we assessed the recovery rate 1 year after surgery in 91 patients diagnosed with DCM who underwent surgery. First, we analyzed the correlation between vitamin D levels and various background factors. Then, patients were divided into 2 groups according to vitamin D sufficiency, and univariate analysis was performed on vitamin D and surgical outcomes. Finally, Spearman correlation analyses were performed to identify factors correlated with recovery rate after surgery for DCM. Results: The average Japanese Orthopedic Association score for the assessment of cervical myelopathy (C-JOA score) improved postoperatively. Age was positively correlated with vitamin D levels, and parathyroid hormone levels were negatively correlated with vitamin D levels. Among the 91 patients, 79.1% of patients were diagnosed with vitamin D deficiency. No significant differences in recovery rate were found between the vitamin D-deficient and vitamin D-sufficient groups. Finally, the Spearman correlation analysis showed a positive correlation between the preoperative C-JOA motor dysfunction score in the lower extremities and the recovery rate, while age demonstrated a negative correlation with recovery rate. Conclusions: No association was found between vitamin D deficiency and clinical outcomes after surgery for DCM. The results of this study do not support the need to normalize vitamin D levels for achieving neurological improvements in patients with DCM.
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Genomic imprinting at the mouse Igf2/H19 locus is controlled by the H19 ICR, within which paternal allele-specific DNA methylation originating in sperm is maintained throughout development in offspring. We previously found that a 2.9 kb transgenic H19 ICR fragment in mice can be methylated de novo after fertilization only when paternally inherited, despite its unmethylated state in sperm. When the 118 bp sequence responsible for this methylation in transgenic mice was deleted from the endogenous H19 ICR, the methylation level of its paternal allele was significantly reduced after fertilization, suggesting the activity involving this 118 bp sequence is required for methylation maintenance at the endogenous locus. Here, we determined protein binding to the 118 bp sequence using an in vitro binding assay and inferred the binding motif to be RCTG by using a series of mutant competitors. Furthermore, we generated H19 ICR transgenic mice with a 5-bp substitution mutation that disrupts the RCTG motifs within the 118 bp sequence, and observed loss of methylation from the paternally inherited transgene. These results indicate that imprinted methylation of the H19 ICR established de novo during the post-fertilization period involves binding of specific factors to distinct sequence motifs within the 118 bp sequence.
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Impresión Genómica , Animales , Masculino , Ratones , Metilación de ADN/genética , Fertilización , Factor II del Crecimiento Similar a la Insulina/genética , Factor II del Crecimiento Similar a la Insulina/metabolismo , Ratones Endogámicos ICR , Ratones Transgénicos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Semen/metabolismo , Secuencias Reguladoras de Ácidos NucleicosRESUMEN
To investigate the effects of phosphorylation on the function of the human positive cofactor 4 (PC4), an enhanced molecular dynamics (MD) simulation was performed. The simulation system consists of the N-terminal intrinsic disordered region (IDR) of PC4 and a complex that comprises the C-terminal acidic activation domain of a herpes simplex virion protein 16 (VP16ad) and a homodimer of the C-terminal structured core domain of PC4 (PC4ctd). An earlier report of an experimental study reported that the PC4-VP16ad interaction is modulated by incremental phosphorylation of the IDR. That report also proposed a dynamic model where phosphorylated serine residues of a segment (SEAC) in the IDR contact positively charged residues (lysin and arginine) of another segment (K-rich) in the IDR. This contact formation induced by the phosphorylation results in variation of PC4-VP16ad interaction. However, this contact formation has not yet been measured directly because it is transiently formed and because the SEAC and K-rich segments are unstructured with high flexibility. We performed two simulations to mimic the incremental phosphorylation: the IDR was not phosphorylated in one simulation and only partially phosphorylated in the other. Our simulation results indicate that the phosphorylation weakens the IDR-VP16ad contact considerably with the induction of a compact structure in the IDR. This structure was stabilized by electrostatic interactions between the phosphorylated serine residues of a segment and lysine or arginine residues of another segment in the IDR, but the conformational fluctuation of this compact structure was considerably large. Consequently, the present study supports the experimentally proposed dynamic model. Results of this study can be important for computational elucidation of the functional modulation of PC4.
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The excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) contribute to epileptogenesis. Thirty patients with epilepsy and 31 healthy controls are scanned using positron emission tomography with our recently developed radiotracer for AMPARs, [11C]K-2, which measures the density of cell-surface AMPARs. In patients with focal-onset seizures, an increase in AMPAR trafficking augments the amplitude of abnormal gamma activity detected by electroencephalography. In contrast, patients with generalized-onset seizures exhibit a decrease in AMPARs coupled with increased amplitude of abnormal gamma activity. Patients with epilepsy had reduced AMPAR levels compared with healthy controls, and AMPARs are reduced in larger areas of the cortex in patients with generalized-onset seizures compared with those with focal-onset seizures. Thus, epileptic brain function can be regulated by the enhanced trafficking of AMPAR due to Hebbian plasticity with increased simultaneous neuronal firing and compensational downregulation of cell-surface AMPARs by the synaptic scaling.