Similarities and differences among Internet gaming disorder, gambling disorder and alcohol use disorder: A focus on impulsivity and compulsivity

Background and aims: The aim of the present study was to test the impulsivities and compulsivities of behavioral addictions, including Internet gaming disorder (IGD) and gambling disorder (GD), by directly comparing them with alcohol use disorder (AUD) and a healthy control (HC) group. Methods: We enrolled male patients who were diagnosed with IGD, GD or AUD, with 15 patients per group, as well as 15 HCs. Trait impulsivity was measured using the Barratt Impulsiveness Scale version 11 (BIS-11). The stop-signal test (SST) from the Cambridge Neuro-psychological Test Automated Battery (CANTAB) was used to assess the patients’ abilities to inhibit prepotent responses. Compulsivity was measured using the intra–extra dimensional set shift (IED) test from the CANTAB. The Trail Making Test (TMT) was also used in this study. Results: The IGD and AUD groups scored significantly higher on the BIS-11 as a whole than did the HC group (p = 0.001 and p = 0.001, respectively). The IGD and AUD groups also scored significantly higher on the BIS-11 as a whole than did the GD group (p = 0.006 and p = 0.001, respectively). In addition, the GD group made significantly more errors (p = 0.017 and p = 0.022, respectively) and more individuals failed to achieve criterion on the IED test compared with the IGD and HC groups (p = 0.018 and p = 0.017, respectively). Discussion: These findings may aid in the understanding of not only the differences in categorical aspects between individuals with IGD and GD but also in impulsivity–compulsivity dimensional domains. Conclusion: Additional studies are needed to elucidate the neurocognitive characteristics of behavioral addictive disorders in terms of impulsivity and compulsivity

Multiple Unilateral Zosteriform Connective Tissue Nevi on the Trunk

Connective tissue nevus is not a true tumor, but rather a hamartoma involving various components of connective tissue. It presents as a slow-growing, painless, flesh-colored, or pink nodule or plaque that is evident from childhood. While any region of the body may be affected, there is a predilection for the trunk and extremities. A 20-month-old girl presented with three ipsilateral confluent popular plaques with zosteriform distribution that had formed over the previous 17 months on the left chest and abdomen. The patient remained asymptomatic. Unlike all previously reported cases demonstrating a single lesion, we report a connective tissue nevi in a child who presented with multiple unilateral zosteriform lesions, an unusual pattern of distribution without evidence of tuberous sclerosis complex

FBXW7-mediated ERK3 degradation regulates the proliferation of lung cancer cells

Extracellular signal-regulated kinase 3 (ERK3) is an atypical member of the mitogen-activated protein kinase (MAPK) family, members of which play essential roles in diverse cellular processes during carcinogenesis, including cell proliferation, differentiation, migration, and invasion. Unlike other MAPKs, ERK3 is an unstable protein with a short half-life. Although deubiquitination of ERK3 has been suggested to regulate the activity, its ubiquitination has not been described in the literature. Here, we report that FBXW7 (F-box and WD repeat domain-containing 7) acts as a ubiquitination E3 ligase for ERK3. Mammalian two-hybrid assay and immunoprecipitation results demonstrated that ERK3 is a novel binding partner of FBXW7. Furthermore, complex formation between ERK3 and the S-phase kinase-associated protein 1 (SKP1)-cullin 1-F-box protein (SCF) E3 ligase resulted in the destabilization of ERK3 via a ubiquitination-mediated proteasomal degradation pathway, and FBXW7 depletion restored ERK3 protein levels by inhibiting this ubiquitination. The interaction between ERK3 and FBXW7 was driven by binding between the C34D of ERK3, especially at Thr417 and Thr421, and the WD40 domain of FBXW7. A double mutant of ERK3 (Thr417 and Thr421 to alanine) abrogated FBXW7-mediated ubiquitination. Importantly, ERK3 knockdown inhibited the proliferation of lung cancer cells by regulating the G1/S-phase transition of the cell cycle. These results show that FBXW7-mediated ERK3 destabilization suppresses lung cancer cell proliferation in vitro

Topical administration of EGF suppresses immune response and protects skin barrier in DNCB-induced atopic dermatitis in NC/Nga mice

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by a complex, heterogeneous pathogenesis including skin barrier dysfunction, immunology, and pruritus. Although epidermal growth factor (EGF) is essential for epithelial homeostasis and wound healing, the effect of EGF on AD remains to be explored. To develop a new therapy for AD, the anti-AD potential of EGF was investigated by inducing AD-like skin lesions in NC/Nga mice using 2,4-dinitrochlorobenzene (DNCB). EGF was administrated to NC/Nga mice to evaluate its therapeutic effect on DNCB-induced AD. EGF treatment improved dermatitis score, ear thickness, epidermal hyperplasia, serum total immunoglobulin E level, and transepidermal water loss in NC/Nga mice with DNCB-induced AD. In addition, levels of skin barrier-related proteins such as filaggrin, involucrin, loricrin, occludin, and zonula occludens-1 (ZO-1) were increased by EGF treatment. These beneficial effects of EGF on AD may be mediated by EGF regulation of Th1/Th2-mediated cytokines, mast cell hyperplasia, and protease activated receptor-2 (PAR-2) and thymic stromal lymphopoietin (TSLP), which are triggers of AD. Taken together, our findings suggest that EGF may potentially protect against AD lesional skin via regulation of skin barrier function and immune response

MMP9 Processing of HSPB1 Regulates Tumor Progression

Matrix metalloproteinases regulate pathophysiological events by processing matrix proteins and secreted proteins. Previously, we demonstrated that soluble heat shock protein B1 (HSPB1) is released primarily from endothelial cells (ECs) and regulates angiogenesis via direct interaction with vascular endothelial growth factor (VEGF). Here we report that MMP9 can cleave HSPB1 and release anti-angiogenic fragments, which play a key role in tumorprogression. We mapped the cleavage sites and explored their physiological relevance during these processing events. HSPB1 cleavage by MMP9 inhibited VEGF-induced ECs activation and the C-terminal HSPB1 fragment exhibited more interaction with VEGF than did full-length HSPB1. HSPB1 cleavage occurs during B16F10 lung progression in wild-type mice. Also, intact HSPB1 was more detected on tumor endothelium of MMP9 null mice than wild type mice. Finally, we confirmed that secretion of C-terminal HSPB1 fragment was significantly inhibited lung and liver tumor progression of B16F10 melanoma cells and lung tumor progression of CT26 colon carcinoma cells, compared to full-length HSPB1. These data suggest that in vivo MMP9-mediated processing of HSPB1 acts to regulate VEGF-induced ECs activation for tumor progression, releasing anti-angiogenic HSPB1 fragments. Moreover, these findings potentially explain an anti-target effect for the failure of MMP inhibitors in clinical trials, suggesting that MMP inhibitors may have pro-tumorigenic effects by reducing HSPB1 fragmentation

An artificial neural-network approach to identify motor hotspot for upper-limb based on electroencephalography: a proof-of-concept study

Abstract Background To apply transcranial electrical stimulation (tES) to the motor cortex, motor hotspots are generally identified using motor evoked potentials by transcranial magnetic stimulation (TMS). The objective of this study is to validate the feasibility of a novel electroencephalography (EEG)-based motor-hotspot-identification approach using a machine learning technique as a potential alternative to TMS. Methods EEG data were measured using 63 channels from thirty subjects as they performed a simple finger tapping task. Power spectral densities of the EEG data were extracted from six frequency bands (delta, theta, alpha, beta, gamma, and full) and were independently used to train and test an artificial neural network for motor hotspot identification. The 3D coordinate information of individual motor hotspots identified by TMS were quantitatively compared with those estimated by our EEG-based motor-hotspot-identification approach to assess its feasibility. Results The minimum mean error distance between the motor hotspot locations identified by TMS and our proposed motor-hotspot-identification approach was 0.22 ± 0.03cm, demonstrating the proof-of-concept of our proposed EEG-based approach. A mean error distance of 1.32 ± 0.15cm was measured when using only nine channels attached to the middle of the motor cortex, showing the possibility of practically using the proposed motor-hotspot-identification approach based on a relatively small number of EEG channels. Conclusion We demonstrated the feasibility of our novel EEG-based motor-hotspot-identification method. It is expected that our approach can be used as an alternative to TMS for motor hotspot identification. In particular, its usability would significantly increase when using a recently developed portable tES device integrated with an EEG device

Pap smear screening for small cell carcinoma of the uterine cervix: a case series and review of the literature

OBJECTIVE: Small cell carcinoma of the uterine cervix (SMCC) is extremely rare, and an aggressive disease that proliferates rapidly. It was often reported that the diagnostic accuracy of cytologic smears in diagnosing SMCC was low. This is a report of the Severance Hospital experience with the patients suffering from SMCC. METHODS: Twenty-seven patients with small cell carcinoma of the uterine cervix were diagnosed and treated at the Severance Hospital from November 1991 to January 2010. The data were analyzed retrospectively, based on the available charts and pathology reports. Various fields, such as chief complaints and symptoms present at first clinic visit, age, International Federation of Obstetrics and Gynecology (FIGO) clinical stage, treatment modality, the 5-year overall survival rate, and recurrence rate were investigated. RESULTS: Among the 27 patients diagnosed with small cell carcinoma of the uterine cervix, 18 of them (66.7%) presented with symptoms, including vaginal bleeding, at the first clinic visit, and the remaining 9 patients (33.3%) showed abnormal Pap smear screening in the process of their routine health check-up. The median age of the patients was 54 years (range, 24 to 77 years). FIGO stage IIB was the most common stage (11 of 27 patients). The 5-year overall survival rate of 21 patients, who could be followed up, was 57.2%. Six patients showed recurrence after remission, and the mean disease free interval of them was 9.2 months (range, 6 to 11 months). Abnormal Pap smear screening results of 9 patients was investigated, and the diagnostic accuracy of the cytologic findings was 22.2%. CONCLUSION: Our study was consistent with the concept that Pap smear screening might not be helpful in early diagnosis of SMCC considering its low diagnostic accuracy. Further large-scale multicenter prospective studies are definitely needed in order to produce abundant information about optimal therapy and diagnosis.ope