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Background@#Fusobacterium nucleatum has been identified to promote tumor progression in colorectal cancer (CRC). However, association between F. nucleatum and prognostic or clinicopathological features has been diverse among studies, which could be affected by type of biospecimen (formalin-fixed paraffin-embedded or fresh frozen [FF]). @*Methods@#Articles were systemically reviewed for studies that included the correlation between F. nucleatum and prognosis or clinicopathological features in CRC. @*Results@#Ten articles, eight studies with survival-related features involving 3,199 patients and nine studies with clinical features involving 2,655 patients, were eligible for the meta-analysis. Overall survival, disease-free survival, and cancer-specific survival were all associated with worse prognosis in F. nucleatum–high patients (p<.05). In subgroup analysis, only studies with FF tissues retained prognostic significance with F. nucleatum. In meta-analysis of clinicopathological variables, F. nucleatum level was associated with location within colon, pT category, MLH1 hypermethylation, microsatellite instability status, and BRAF mutation regardless of type of biospecimen. However, lymph node metastasis and KRAS mutation was only associated with F. nucleatum level in FF-based studies. @*Conclusions@#In conclusion, type of biospecimen could affect the role of F. nucleatum as a biomarker associated with clinicopathological features and prognosis.
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Apolipoprotein E (apoE) plays a role in various physiological functions including lipid transport, synaptic plasticity, and immune modulation.Epidemiological studies suggest that the apoE4 allele increases the risk of post-traumatic sequelae. This study was performed to investigate regionspecific effects of the apoE4 isoform on post-traumatic neurodegeneration. Two focal brain injuries were introduced separately in the motor cortex and hippocampus of apoE4 knock-in, apoE3 knock-in, apoE knockout, and wild-type (WT) mice. Western blotting showed that the expression levels of pre-synaptic and post-synaptic markers at the recovery stage were lower in the hippocampal injury core in apoE4 mice, compared with apoE3 and WT mice. Fast glial activation (determined by immunohistochemistry with glial fibrillary acidic protein, ionized calcium binding adaptor molecule 1, and cluster of differentiation 45 antibodies) was characteristic of apoE4 mice with hippocampal injury penumbra. apoE4-specific changes were not observed after cortical injury. The intensity of microglial activation in the hippocampus was inversely correlated with the volume of injury reduction on sequential magnetic resonance imaging examinations, when validated using matched samples. These findings indicate that the effects of the interaction between apoE4 and focal brain damage are specific to the hippocampus. Manipulation of inflammatory cell responses could be beneficial for reducing post-traumatic hippocampal neurodegeneration in apoE4 carriers.
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Apolipoprotein E (apoE) plays a role in various physiological functions including lipid transport, synaptic plasticity, and immune modulation.Epidemiological studies suggest that the apoE4 allele increases the risk of post-traumatic sequelae. This study was performed to investigate regionspecific effects of the apoE4 isoform on post-traumatic neurodegeneration. Two focal brain injuries were introduced separately in the motor cortex and hippocampus of apoE4 knock-in, apoE3 knock-in, apoE knockout, and wild-type (WT) mice. Western blotting showed that the expression levels of pre-synaptic and post-synaptic markers at the recovery stage were lower in the hippocampal injury core in apoE4 mice, compared with apoE3 and WT mice. Fast glial activation (determined by immunohistochemistry with glial fibrillary acidic protein, ionized calcium binding adaptor molecule 1, and cluster of differentiation 45 antibodies) was characteristic of apoE4 mice with hippocampal injury penumbra. apoE4-specific changes were not observed after cortical injury. The intensity of microglial activation in the hippocampus was inversely correlated with the volume of injury reduction on sequential magnetic resonance imaging examinations, when validated using matched samples. These findings indicate that the effects of the interaction between apoE4 and focal brain damage are specific to the hippocampus. Manipulation of inflammatory cell responses could be beneficial for reducing post-traumatic hippocampal neurodegeneration in apoE4 carriers.
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Background@#The prognostic potential of Crohn-like lymphoid reaction (CLR) in colorectal carcinoma (CRC) has been investigated through the assessment of different criteria. @*Methods@#The prognostic impact of CLR was investigated in 636 CRC patients to compare methods from previously published articles. These methods included CLR measured by number of lymphoid aggregates (LAs) (CLR count), LA size greater than or equal to 1 mm (CLR size), CLR density with a cutoff value of 0.38, and subjective criteria as defined by intense CLR. @*Results@#In univariate survival analysis, CLR-positive CRC as defined by the four aforementioned methods was associated with better overall survival (OS) (hazard ratio [HR], 0.463; 95% confidence interval [CI], 0.305 to 0.702; p <.001; HR, 0.656; 95% CI, 0.411 to 1.046; p=.077; HR, 0.363; 95% CI, 0.197 to 0.669; p=.001; and HR, 0.433; 95% CI, 0.271 to 0.690; p<.001, respectively) and disease-free survival (DFS) (HR, 0.411; 95% CI, 0.304 to 0.639; p<.001; HR, 0.528; 95% CI, 0.340 to 0.821; p=.004; HR, 0.382; 95% CI, 0.226 to 0.645, p=.004; and HR, 0.501; 95% CI, 0.339 to 0.741; p<.001, respectively) than CLR-negative CRC, regardless of criteria with the exception of OS for CLR density. In multivariate analysis, two objective criteria (CLR count and CLR density) and one subjective criterion (intense CLR) for defining CLR were considered independent prognostic factors of OS and DFS in CRC patients. @*Conclusions@#CLR has similar traits regardless of criteria, but CLR-positivity should be defined by objective criteria for better reproducibility and prognostic value.
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Background and Objectives@#The efficacy of radiofrequency catheter ablation (RFCA) in atrial fibrillation (AF) is well established. The standard approach to RFCA in AF is pulmonary vein isolation (PVI). However, a large proportion of patients experiences recurrence of atrial tachyarrhythmia. The purpose of this study is to find out whether the AI model can assess AF recurrence in patients who underwent PVI. @*Materials and methods@#This study was a retrospective cohort study that enrolled consecutive patients who under‑ went catheter ablation for symptomatic, drug-refractory AF and PVI. We developed an AI algorithm to predict recur‑ rence of AF after PVI using patient demographics and three-dimensional (3D) reconstructed left atrium (LA) images. @*Results@#We included 527 consecutive patients in the study. The overall mean LA diameter was 42.0 ± 6.8 mm, and the mean LA volume calculated using 3D reconstructed images was 151.1 ± 46.7 ml. During the follow-up period, atrial tachyarrhythmia recurred in 158 patients. The area under the curve (AUC) of the AI model based on a convolu‑ tional neural network (including 3D reconstruction images) was 0.61 (95% confidence interval [CI] 0.53–0.74) using the test dataset. The total test accuracy was 66.3% (57.0–75.6), and the sensitivity was 53.3% (34.8–71.9). The specificity was 73.2% (51.8–75.0), and the F1 score was 52.5% 34.5–66.7). @*Conclusion@#In this study, we developed an AI algorithm to predict recurrence of AF after catheter ablation of PVI using individual reconstructed LA images. This AI model was unable to predict recurrence of AF overwhelmingly;therefore, further large-scale study is needed.
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Background and Objectives@#The efficacy of radiofrequency catheter ablation (RFCA) in atrial fibrillation (AF) is well established. The standard approach to RFCA in AF is pulmonary vein isolation (PVI). However, a large proportion of patients experiences recurrence of atrial tachyarrhythmia. The purpose of this study is to find out whether the AI model can assess AF recurrence in patients who underwent PVI. @*Materials and methods@#This study was a retrospective cohort study that enrolled consecutive patients who under‑ went catheter ablation for symptomatic, drug-refractory AF and PVI. We developed an AI algorithm to predict recur‑ rence of AF after PVI using patient demographics and three-dimensional (3D) reconstructed left atrium (LA) images. @*Results@#We included 527 consecutive patients in the study. The overall mean LA diameter was 42.0 ± 6.8 mm, and the mean LA volume calculated using 3D reconstructed images was 151.1 ± 46.7 ml. During the follow-up period, atrial tachyarrhythmia recurred in 158 patients. The area under the curve (AUC) of the AI model based on a convolu‑ tional neural network (including 3D reconstruction images) was 0.61 (95% confidence interval [CI] 0.53–0.74) using the test dataset. The total test accuracy was 66.3% (57.0–75.6), and the sensitivity was 53.3% (34.8–71.9). The specificity was 73.2% (51.8–75.0), and the F1 score was 52.5% 34.5–66.7). @*Conclusion@#In this study, we developed an AI algorithm to predict recurrence of AF after catheter ablation of PVI using individual reconstructed LA images. This AI model was unable to predict recurrence of AF overwhelmingly;therefore, further large-scale study is needed.
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A popular approach for the study of estrogen receptor α inhibition is to investigate the protein-protein interaction between the estrogen receptor (ER) and the coactivator surface. In our study, we investigated phytochemicals from Rubus coreanus that were able to disrupt ERα and coactivator interaction with an ERα antagonist. The E-screen assay and molecular docking analysis were performed to evaluate the effects of the estrogenic activity of R. coreanus extract and its constituents on the MCF-7 human breast cancer cell line. At 100 µg/mL, R. coreanus extract significantly stimulated cell proliferation (574.57 ± 8.56%). Sanguiin H6, which was isolated from R. coreanus, demonstrated the strongest affinity for the ERα coactivator-binding site in molecular docking analysis, with a binding energy of
Subject(s)
Humans , Breast Neoplasms , Cell Line , Cell Proliferation , Estrogens , Molecular Docking Simulation , Phytochemicals , RubusABSTRACT
PURPOSE: Lapatinib is a candidate drug for treatment of trastuzumab-resistant, human epidermal growth factor receptor 2 (HER2)–positive gastric cancer (GC). Unfortunately, lapatinib resistance renders this drug ineffective. The present study investigated the implication of forkhead box O1 (FOXO1) signaling in the acquired lapatinib resistance in HER2-positive GC cells. MATERIALS AND METHODS: Lapatinib-resistant GC cell lines (SNU-216 LR2-8) were generated in vitro by chronic exposure of lapatinib-sensitive, HER2-positive SNU-216 cells to lapatinib. SNU-216 LR cells with FOXO1 overexpression were generated by stable transfection of a constitutively active FOXO1 mutant (FOXO1A3). HER2 and MET in SNU-216 LR cells were downregulated using RNA interference. The sensitivity of GC cells to lapatinib and/or cisplatin was determined by crystal violet assay. In addition, Western blot analysis, luciferase reporter assay and reverse transcription–polymerase chain reaction were performed. RESULTS: SNU-216 LR cells showed upregulations of HER2 and MET, but downregulation of FOXO1 compared to parental SNU-216 cells. FOXO1 overexpression in SNU-216 LR cells significantly suppressed resistance to lapatinib and/or cisplatin. In addition, FOXO1 negatively controlled HER2 and MET at the transcriptional level and was negatively controlled by these molecules at the post-transcriptional level. A positive crosstalk was shown between HER2 and MET, each of which increased resistance to lapatinib and/or cisplatin. CONCLUSION: FOXO1 serves as an important linker between HER2 and MET signaling pathways through negative crosstalks and is a key regulator of the acquired lapatinib resistance in HER2-positive GC cells. These findings provide a rationale for establishing a novel treatment strategy to overcome lapatinib resistance in a subtype of GC patients.
Subject(s)
Humans , Blotting, Western , Cell Line , Cisplatin , Down-Regulation , Drug Resistance , Gentian Violet , In Vitro Techniques , Luciferases , Parents , ErbB Receptors , Receptor, ErbB-2 , RNA Interference , Stomach Neoplasms , Transfection , Up-RegulationABSTRACT
Epstein-Barr virus (EBV), a common pathogen in humans, is suspected as the cause of multiple pregnancy-related pathologies including depression, preeclampsia, and stillbirth. Moreover, transmission of EBV through the placenta has been reported. However, the focus of EBV infection within the placenta has remained unknown to date. In this study, we proved the expression of latent EBV genes in the endometrial glandular epithelial cells of the placenta and investigated the cytological characteristics of these cells. Sixty-eight placentas were obtained from pregnant women. Tissue microarray was constructed. EBV latent genes including EBV-encoding RNA-1 (EBER1), Epstein-Barr virus nuclear antigen 1 (EBNA1), late membrane antigen (LMP1), and RPMS1 were detected with silver in situ hybridization and/or mRNA in situ hybridization. Nuclear features of EBV-positive cells in EBV-infected placenta were compared with those of EBV-negative cells via image analysis. Sixteen placentas (23.5%) showed positive expression of all 4 EBV latent genes; only the glandular epithelial cells of the decidua showed EBV gene expression. EBV infection status was not significantly correlated with maternal, fetal, or placental factors. The nuclei of EBV-positive cells were significantly larger, longer, and round-shaped than those of EBV-negative cells regardless of EBV-infection status of the placenta. For the first time, evidence of EBV gene expression has been shown in placental tissues. Furthermore, we have characterized its cytological features, allowing screening of EBV infection through microscopic examination.
Subject(s)
Female , Humans , Decidua , Depression , Epithelial Cells , Epstein-Barr Virus Infections , Gene Expression , Herpesvirus 4, Human , Image Cytometry , In Situ Hybridization , Mass Screening , Membranes , Pathology , Placenta , Pre-Eclampsia , Pregnant Women , RNA, Messenger , Silver , Stillbirth , Virus LatencyABSTRACT
BACKGROUND/OBJECTIVES: Oligonol, mainly found in lychee fruit, is an antioxidant polyphenolic compound which has been shown to have anti-inflammatory and anti-cancer properties. The detailed mechanisms by which oligonol may act as an anti-aging molecule have not been determined. MATERIALS/METHODS: In this study, we evaluated the ability of oligonol to modulate sirtuin (SIRT) expression in human lung epithelial (A549) cells. Oligonol was added to A549 cells and reactive oxygen species production, mitochondrial superoxide formation, and p21 protein levels were measured. Signaling pathways activated upon oligonol treatment were also determined by western blotting. Furthermore, the anti-aging effect of oligonol was evaluated ex vivo in mouse splenocytes and in vivo in Caenorhabditis elegans. RESULTS: Oligonol specifically induced the expression of SIRT1, whose activity is linked to gene expression, metabolic control, and healthy aging. In response to influenza virus infection of A549 cells, oligonol treatment significantly up-regulated SIRT1 expression and down-regulated viral hemagglutinin expression. Oligonol treatment also resulted in the activation of autophagy pathways and the phosphorylation of AMP-activated protein kinase (AMPK). Furthermore, oligonol-treated spleen lymphocytes from old mice showed increased cell proliferation, and mRNA levels of SIRT1 in the lungs of old mice were significantly lower than those in the lungs of young mice. Additionally, in vivo lethality assay revealed that oligonol extended the lifespan of C. elegans infected with lethal Vibrio cholerae. CONCLUSIONS: These data demonstrated that oligonol may act as an anti-aging molecule by modulating SIRT1/autophagy/AMPK pathways.
Subject(s)
Animals , Humans , Mice , Aging , AMP-Activated Protein Kinases , Autophagy , Blotting, Western , Caenorhabditis elegans , Cell Proliferation , Fruit , Gene Expression , Hemagglutinins, Viral , Litchi , Lung , Lymphocytes , Orthomyxoviridae , Phosphorylation , Reactive Oxygen Species , RNA, Messenger , Spleen , Superoxides , Vibrio choleraeABSTRACT
PURPOSE: We previously reported that forkhead transcription factors of the O class 1 (FOXO1) expression in gastric cancer (GC) was associated with angiogenesis-related molecules. However, there is little experimental evidence for the direct role of FOXO1 in GC. In the present study, we investigated the effect of FOXO1 on the tumorigenesis and angiogenesis in GC and its relationship with SIRT1. MATERIALS AND METHODS: Stable GC cell lines (SNU-638 and SNU-601) infected with a lentivirus containing FOXO1 shRNA were established for animal studies as well as cell culture experiments. We used xenograft tumors in nude mice to evaluate the effect of FOXO1 silencing on tumor growth and angiogenesis. In addition, we examined the association between FOXO1 and SIRT1 by immunohistochemical tissue array analysis of 471 human GC specimens and Western blot analysis of xenografted tumor tissues. RESULTS: In cell culture, FOXO1 silencing enhanced hypoxia inducible factor-1alpha (HIF-1alpha) expression and GC cell growth under hypoxic conditions, but not under normoxic conditions. The xenograft study showed that FOXO1 downregulation enhanced tumor growth, microvessel areas, HIF-1alpha activation and vascular endothelial growth factor (VEGF) expression. In addition, inactivated FOXO1 expression was associated with SIRT1 expression in human GC tissues and xenograft tumor tissues. CONCLUSION: Our results indicate that FOXO1 inhibits GC growth and angiogenesis under hypoxic conditions via inactivation of the HIF-1alpha-VEGF pathway, possibly in association with SIRT1. Thus, development of treatment modalities aiming at this pathway might be useful for treating GC.
Subject(s)
Animals , Humans , Mice , Angiogenesis Modulating Agents , Hypoxia , Blotting, Western , Carcinogenesis , Cell Culture Techniques , Cell Line , Down-Regulation , Forkhead Transcription Factors , Heterografts , Lentivirus , Mice, Nude , Microvessels , RNA, Small Interfering , Stomach Neoplasms , Tissue Array Analysis , Transcription Factors , Vascular Endothelial Growth Factor AABSTRACT
We report on a first case of bone marrow metastasis by dedifferentiated liposarcoma. A 39-year-old male diagnosed with retroperitoneal dedifferentiated liposarcoma underwent surgery and postoperative radiotherapy. In spite of radiotherapy, his whole-body positron emission tomography showed high uptake in multiple bone metastasis. With thrombocytopenia, bone scan suggested bone marrow involvement. After bone marrow biopsy, bone marrow metastasis by dedifferentiated liposarcoma was finally confirmed. He was administered with systemic chemotherapy with doxorubicin. But he died 3 months after chemotherapy due to disease progression. This case revealed that in a patient of unexplained cytopenia with dedifferentiated liposarcoma, bone marrow metastasis should be in consideration.
Subject(s)
Adult , Humans , Male , Biopsy , Bone Marrow , Disease Progression , Doxorubicin , Drug Therapy , Liposarcoma , Neoplasm Metastasis , Positron-Emission Tomography , Radiotherapy , ThrombocytopeniaABSTRACT
BACKGROUND: Recent studies have revealed that a small subset of Lynch syndrome-associated colorectal carcinomas (CRCs) is caused by a germline EPCAM deletion-induced MSH2 epimutation. Based on the finding of this genetic alteration, we investigated the implications of EPCAM expression changes in microsatellite instability-high (MSI-H) CRCs. METHODS: Expression of EPCAM and DNA mismatch repair proteins was assessed by immunohistochemistry in 168 MSI-H CRCs. Using DNA samples of these tumors, MLH1 promoter methylation status was also determined by methylation-specific real-time polymerase chain reaction method (MethyLight). RESULTS: Among 168 MSI-H CRCs, complete loss (CL) and focal loss (FL) of EPCAM expression was observed in two (1.2%) and 22 (13.1%) cases, respectively. Both of the EPCAM-CL cases were found in MSH2-negative tumors without MLH1 promoter methylation. However, only nine of the 22 EPCAM-FL tumors had MSH2 deficiency. Of the 22 EPCAM-FL tumors, 13 showed MLH1 loss, and among them, nine cases were determined to have MLH1 methylation. EPCAM-FL was significantly associated with advanced stage (p=.043), distant metastasis (p=.003), poor differentiation (p=.001), and signet ring cell component (p=.004). CONCLUSIONS: Loss of EPCAM expression is differentially associated with clinicopathological and molecular features, depending on the completeness of the loss, in MSI-H CRCs.
Subject(s)
Cellular Structures , Colorectal Neoplasms , DNA , DNA Mismatch Repair , Immunohistochemistry , Methylation , Microsatellite Instability , Microsatellite Repeats , Neoplasm Metastasis , Real-Time Polymerase Chain ReactionABSTRACT
OBJECTIVE: To investigate the relationship between removable dentures and swallowing and describe risks. METHODS: Twenty-four patients with removable dentures who were referred for videofluoroscopic swallowing study (VFSS) were enrolled. We evaluated the change of swallowing function using VFSS before and after the removal of the removable denture. The masticatory performance by Kazunori's method, sensation of oral cavity by Christian's method, underlying disease, and National Institutes of Health Stroke Scale for level of consciousness were collected. Functional dysphagia scales, including the oral transit time (OTT), pharyngeal transit time (PTT), percentage of oral residue, percentage of pharyngeal residue, oropharyngeal swallow efficiency (OPSE), and presence of aspiration were measured. RESULTS: Four patients dropped out and 20 patients were analyzed (stroke, 13 patients; pneumonia, 3 patients; and others, 4 patients). The mean age was 73.3+/-11.4 years. There were significant differences before and after the removal of the denture for the OTT. OTT was significantly less after the removal of the denture (8.87 vs. 4.38 seconds, p=0.01). OPSE increased remarkably after the removal of the denture, but without significance (18.24%/sec vs. 25.26%/sec, p=0.05). The OTT and OPSE, while donning a removable denture, were correlated with the masticatory performance (OTT, p=0.04; OPSE, p=0.003) and sensation of oral cavity (OTT, p=0.006; OPSE, p=0.007). CONCLUSION: A removable denture may have negative effects on swallowing, especially OTT and OPSE. These affects may be caused by impaired sensation of the oral cavity or masticatory performance induced by the removable denture.
Subject(s)
Humans , Consciousness , Deglutition , Deglutition Disorders , Denture, Partial, Removable , Dentures , Hypesthesia , Mouth , Pneumonia , Sensation , Stroke , Weights and MeasuresABSTRACT
Astrocytes are reported to have critical functions in ischemic brain injury including protective effects against ischemia-induced neuronal dysfunction. Na-K ATPase maintains ionic gradients in astrocytes and is suggested as an indicator of ischemic injury in glial cells. Here, we examined the role of the Na-K ATPase in the pathologic process of ischemic injury of primary cultured astrocytes. Chemical ischemia was induced by sodium azide and glucose deprivation. Lactate dehydrogenase assays showed that the cytotoxic effect of chemical ischemia on astrocytes began to appear at 2 h of ischemia. The expression of Na-K ATPase alpha1 subunit protein was increased at 2 h of chemical ischemia and was decreased at 6 h of ischemia, whereas the expression of alpha1 subunit mRNA was not changed by chemical ischemia. Na-K ATPase activity was time-dependently decreased at 1, 3, and 6 h of chemical ischemia, whereas the enzyme activity was temporarily recovered to the control value at 2 h of chemical ischemia. Cytotoxicity at 2 h of chemical ischemia was significantly blocked by reoxygenation for 24 h following ischemia. Reoxygenation following chemical ischemia for 1 h significantly increased the activity of the Na-K ATPase, while reoxygenation following ischemia for 2 h slightly decreased the enzyme activity. These results suggest that the critical time for ischemia-induced cytotoxicity of astrocytes might be 2 h after the initiation of ischemic insult and that the increase in the expression and activity of the Na-K ATPase might play a protective role during ischemic injury of astrocytes.
Subject(s)
Adenosine Triphosphatases , Astrocytes , Brain Injuries , Glucose , Ischemia , L-Lactate Dehydrogenase , Neuroglia , Neurons , RNA, Messenger , Sodium AzideABSTRACT
Inverted papilloma (Schneiderian-type papilloma) involving the middle ear is extremely rare. Most of cases originate from the mucosa of the lateral nasal wall, extending into the paranasal sinuses and orbits. Inverted papilloma involving the middle ear has a high recurrence rate and a possibility of malignant change. We experienced a case of inverted papilloma of the middle ear secondary to congenital cholesteatoma surgery. A nine-year old male who was diagnosed with congenital cholesteatoma was treated with intact canal wall tympanomastoidectomy. Nine months later, he underwent a second look operation. In the second surgery, a 3 mm round pinkish mass which was located at the tympanic orifice of Eustachian tube was identified as inverted papilloma. There was no recurrence of cholesteatoma or inverted papilloma four months after the 2nd operation.
Subject(s)
Humans , Male , Cholesteatoma , Ear, Middle , Eustachian Tube , Mucous Membrane , Orbit , Papilloma, Inverted , Paranasal Sinuses , RecurrenceABSTRACT
Vegetative electrode infection after implantation of permanent pacemaker or defibrillator is an uncommon but a serious complication. Diagnosis of the lead infection is particularly important since surgical manipulation is usually required for its treatment. We present 3 cases of electrodes related infective endocarditis among the 154 patients who implanted pacemaker or defibrillator between 2001 and 2004 in Korea university hospital. These complications were difficult to diagnose because of ambiguous clinical manifestations and indeterminate transthoracic echocardiographic (TTE) findings and were finally confirmed by transesophageal echocardiography (TEE).