We assessed the risk factors for major amputation of diabetic foot ulcers (DFUs) in patients with diabetic kidney disease (DKD) stages 3b–5. For DFU assessment, in addition to DFU location and presence of infection, ischemia, and neuropathy, vascular calcification was assessed using the medial arterial calcification (MAC) score. Of 210 patients, 26 (12.4%) underwent major amputations. Only the location and extension of DFU, represented by Texas grade differed between the minor and major amputation groups. However, after adjusting for covariates, ulcer location of mid- or hindfoot (vs. forefoot, odds ratio [OR] = 3.27), Texas grades 2 or 3 (vs. grade 0, OR = 5.78), and severe MAC (vs. no MAC, OR = 4.46) was an independent risk factor for major amputation (all P < 0.05). The current use of antiplatelets was a possible protective factor for major amputations (OR = 0.37, P = 0.055). In conclusion, DFU with severe MAC is associated with major amputation in patients with DKD.

The activation of neurotrophic signaling pathways following the upregulation of glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-β family, has a potential neuroprotective effect in the adult brain. Herein, we report that hippocampal transduction of adeno-associated virus serotype 1 (AAV1) with a constitutively active form of ras homolog enriched in brain [Rheb(S16H)], which can stimulate the production of brain-derived neurotrophic factor (BDNF) in hippocampal neurons, induces the increases in expression of GDNF and GDNF family receptor α-1 (GFRα-1), in neurons and astrocytes in the hippocampus of rat brain in vivo . Moreover, upregulation of GDNF and GFRα-1 contributes to neuroprotection against thrombin-induced neurotoxicity in the hippocampus. These results suggest that AAV1-Rheb(S16H) transduction of hippocampal neurons, resulting in neurotrophic interactions between neurons and astrocytes, may be useful for neuroprotection in the adult hippocampus.

Purpose: The purpose of this study was to reveal the clinicopathological characteristics and prognostic implications associated with fibroblast growth factor receptor 1 (FGFR1) amplification in colorectal cancers (CRCs). Materials and Methods: We measured the copy number of FGFR1 by droplet digital polymerase chain reaction (ddPCR), and analyzed the FGFR1 expression by immunohistochemistry, in 764 surgically resected CRCs (SNUH2007 dataset, 384 CRCs; SNUH Folfox dataset, 380 CRCs). Results: CRCs with ≥ 3.3 copies of the FGFR1 gene were classified as FGFR1 amplified. FGFR1 amplification was found in 10 of the 384 CRCs (2.6%) in the SNUH2007 dataset, and in 28 of the 380 CRCs (7.4%) in the SNUH Folfox dataset. In the SNUH2007 dataset, there was no association between the FGFR1 copy number status and sex, gross appearance, stage, or differentiation. High FGFR1 expression was associated with female sex and KRAS mutation. At the molecular level, FGFR1 amplification was mutually exclusive with BRAF mutation, microsatellite instability, and MLH1 methylation, in both SNUH2007 and SNUH Folfox datasets. Survival analysis revealed that FGFR1 amplification was associated with significantly worse clinical outcome compared with no FGFR1 amplification, in both SNUH2007 and SNUH Folfox datasets. Within the SNUH2007 dataset, CRC patients with high FGFR1 expression had an inferior progression-free survival compared with those with low FGFR1 expression. The FGFR inhibitor, PD173074, repressed the proliferation of a CRC cell line overexpressing FGFR1, but not of cells with FGFR1 amplification. Conclusion FGFR1 amplification measured by ddPCR can be a prognostic indicator of poor clinical outcome in patients with CRCs.

OBJECTIVE: To evaluate the association between progression of curvature of scoliosis, and correction for functional component in patients with juvenile idiopathic scoliosis (JIS). METHODS: We retrospectively reviewed medical data of patients prescribed custom molded foot orthosis (FO) to correct inequality of RCSPA (resting calcaneal stance position angle), and chose 52 patients (26 females, 26 males) with Cobb angle ≥10° in radiology and uneven pelvic level at iliac crest by different RCSPA (≥3°) as a factor of functional scoliosis. They had different hump angle ≥5° in forward bending test, for idiopathic scoliosis component. Their mean age and mean period of wearing FO were 79.5±10.6 months and 18.6±0.70 months. RESULTS: Cobb angle was reduced from 22.03°±4.39° initially to 18.86°±7.53° after wearing FO. Pelvis height difference and RCSPA difference, were reduced from 1.07±0.25 cm initially to 0.60±0.36, and from 4.25°±0.71° initially to 1.71°±0.75° (p < 0.01). Cobb angle improved most in 9 months. However, there was no significant improvement for those with more than 25° of Cobb angle initially. Mean Cobb angle improved in all age groups, but patients less than 6 years had clinically significant improvement of more than 5°. CONCLUSION: JIS can have functional components, which should be identified and managed. Foot orthosis is useful in correcting functional factors, in the case of pelvic inequality caused by different RCSPA, for patients with juvenile idiopathic scoliosis.
Female ; Foot Orthoses ; Fungi ; Humans ; Leg Length Inequality ; Pelvis ; Retrospective Studies ; Scoliosis* ; Socioeconomic Factors ; Spine*

PURPOSE: In this study, the retrospective radiographic study is executed to evaluate amount of bone loss of various conditions in patients using customized abutment for 4 years of follow-up. MATERIALS AND METHODS: The subjects of this study were implant fixed dental prosthesis using CAD/CAM customized abutments. CAD/CAM customized abutment and fixed dental prosthesis were manufactured by the Prosthodontics Department of Chosun University Dental Hospital from August 1, 2011 to July 31, 2012. Radiological assessments were performed on the patients who were treated by the fixed prosthodontics. After each treatment, a retrospective study was performed for a total of 4 years at 3 months, 6 months, 1 year, 2 years, 3 years, and 4 years. RESULTS: As a result of the study, the customized abutment using CAD/CAM showed less bone loss than the results of existing research. There was no statistically significant differences at alveolar bone loss between splinting group and non-splinting group (respectively 0.27 mm, 0.5 mm). Also, there were statistically significant differences at alveolar bone loss in mx. anterior, mx. posterior, mn. anterior and mn. posterior part (respectively 1.37 mm, 0.39 mm, 0.00 mm, 0.30 mm). CONCLUSION: The customized abutment using CAD/CAM showed less bone loss than the results of existing research, there were statistically significant differences at alveolar bone loss in implant positions.
Alveolar Bone Loss ; Dental Prosthesis ; Follow-Up Studies ; Humans ; Prosthodontics ; Retrospective Studies ; Splints

The authors found out that this article was omitted “Funding section” for grant support.

Background: Controlled-release oxycodone/naloxone (OXN-CR) maintains the effect of opioid-induced analge-sia through oxycodone while reducing the occurrence rate of opioid-induced constipation through naloxone. The present study was designed to assess the non-inferiority of OXN-CR to controlled-release oxycodone (OX-CR) for the control of cancer-related pain in Korean patients. Methods: In this randomized, open-labeled, parallel-group, phase IV study, we enrolled patients aged 20 years or older with moderate to severe cancer-related pain [numeric rating scale (NRS) pain score≥4] from seven Korean oncology/hematology centers. Patients in the intention-to-treat (ITT) population were randomized (1:1) to OXN-CR or OX-CR groups. OXN-CR was administered starting at 20 mg/10 mg per day and up-titrated to a maximum of 80 mg/40 mg per day for 4 weeks, and OX-CR was administered starting at 20 mg/day and up-titrated to a maximum of 80 mg/day for 4 weeks. The primary efficacy endpoint was the change in NRS pain score from baseline to week 4, with non-inferiority margin of?1.5. Secondary endpoints included analgesic rescue medication intake, patient-reported change in bowel habits, laxative intake, quality of life (QoL), and safety assessments. Results: Of the ITT population comprising 128 patients, 7 with missing primary efficacy data and 4 who violated the eligibility criteria were excluded from the efficacy analysis. At week 4, the mean change in NRS pain scores was not significantly different between the OXN-CR group (n= 58) and the OX-CR group (n= 59) (?1.586 vs.?1.559, P= 0.948). The lower limit of the one-sided 95％ confidence interval (?0.776 to 0.830) for the difference exceeded the non-inferiority margin (P < 0.001). The OXN-CR and OX-CR groups did not differ significantly in terms of analgesic rescue medication intake, change in bowel habits, laxative intake, QoL, and safety assessments. Conclusions: OXN-CR was non-inferior to OX-CR in terms of pain reduction after 4 weeks of treatment and had a similar safety profile. Studies in larger populations of Korean patients with cancer-related pain are needed to further investigate the effectiveness of OXN-CR for long-term pain control and constipation alleviation.

PURPOSE: The aim of this study was to establish an anthropometric reference of the stomach for gastric cancer surgery and a modeling formula to predict stomach length. MATERIALS AND METHODS: Data were retrieved for 851 patients who underwent total gastrectomy at the Seoul National University Hospital between 2008 and 2013. Clinicopathological data and measurements from a formalin-fixed specimen were reviewed. The lengths (cm) of the greater curvature (GC) and lesser curvature (LC) were measured. Anthropometric data of the stomach were compared according to age, body weight, height (cm), and body mass index. To predict stomach length, two multiple regression analyses were performed. RESULTS: The mean lengths of the GC and LC were 22.2±3.1 cm and 16.3±2.6 cm, respectively. The men’s GC length was significantly greater than the women’s (22.4±3.1 cm vs. 21.2±2.9 cm, P=0.003). Patients aged >70 years showed significantly longer LC than those aged <50 years (16.9±2.9 cm vs. 15.9±2.4 cm, P=0.002). Patients with body weights >70 kg showed significantly longer GC than those with body weights <55 kg (23.0±2.9 cm vs. 21.4±3.2cm, P<0.001). In the predicted models, 4.11% of the GC was accounted for by age and weight; and 4.94% of the LC, by age, sex, height, and weight. CONCLUSIONS: Sex, age, height, and body weight were associated with the length of the LC, while sex and body weight were the only factors that were associated with the length of the GC. However, the prediction model was not sufficiently strong.
Body Mass Index ; Body Weight ; Gastrectomy ; Humans ; Organ Size ; Seoul ; Stomach Neoplasms ; Stomach*

Persistently activated JAK/STAT3 signaling pathway plays a pivotal role in various human cancers including major carcinomas and hematologic tumors, and is implicated in cancer cell survival and proliferation. Therefore, inhibition of JAK/STAT3 signaling may be a clinical application in cancer therapy. Here, we report that 2-cyclohexylimino-6-methyl-6,7-dihydro-5H-benzo [1,3]oxathiol-4-one (BOT-4-one), a small molecule inhibitor of JAK/STAT3 signaling, induces apoptosis through inhibition of STAT3 activation. BOT-4-one suppressed cytokine (upd)-induced tyrosine phosphorylation and transcriptional activity of STAT92E, the sole Drosophila STAT homolog. Consequently, BOT-4-one significantly inhibited STAT3 tyrosine phosphorylation and expression of STAT3 downstream target gene SOCS3 in various human cancer cell lines, and its effect was more potent in JAK3-activated Hodgkin's lymphoma cell line than in JAK2-activated breast cancer and prostate cancer cell lines. In addition, BOT-4-one-treated Hodgkin's lymphoma cells showed decreased cell survival and proliferation by inducing apoptosis through down-regulation of STAT3 downstream target anti-apoptotic gene expression. These results suggest that BOT-4-one is a novel small molecule inhibitor of JAK3/STAT3 signaling and may have therapeutic potential in the treatment of human cancers harboring aberrant JAK3/STAT3 signaling, specifically Hodgkin's lymphoma.
Animals ; Antineoplastic Agents/chemistry/*pharmacology ; Apoptosis/drug effects ; Bicyclo Compounds, Heterocyclic/chemistry/*pharmacology ; Cell Line ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Drosophila/enzymology/metabolism ; Drosophila Proteins/antagonists & inhibitors/metabolism ; Enzyme Activation/*drug effects ; Gene Expression Regulation, Neoplastic/*drug effects ; Humans ; Janus Kinase 3/*antagonists & inhibitors/metabolism ; Lymphoma/enzymology/*metabolism ; Phosphorylation/drug effects ; STAT Transcription Factors/antagonists & inhibitors/metabolism ; STAT3 Transcription Factor/*antagonists & inhibitors/metabolism ; Signal Transduction/*drug effects

PURPOSE: Computational flow dynamic (CFD) study has not been widely applied in intracranial artery stenosis due to requirement of high resolution in identifying the small intracranial artery. We described a process in CFD study applied to symptomatic severe intracranial (M1) stenosis before and after stenting. MATERIALS AND METHODS: Reconstructed 3D angiography in STL format was transferred to Magics (Materialise NV, Leuven, Belgium) for smoothing of vessel surface and trimming of branch vessels and to HyperMesh (Altair Engineering Inc., Auckland, New Zealand) for generating tetra volume mesh from triangular surface-meshed 3D angiogram. Computational analysis of blood flow in the blood vessels was performed using the commercial finite element software ADINA Ver 8.5 (ADINA R & D, Inc., Lebanon, MA). The distribution of wall shear stress (WSS), peak velocity and pressure in a patient was analyzed before and after intracranial stenting. RESULTS: Computer simulation of wall shear stress, flow velocity and wall pressure before and after stenting could be demonstrated three dimensionally by video mode according to flow vs. time dimension. Such flow model was well correlated with angiographic finding related to maximum degree of stenosis. Change of WSS, peak velocity and pressure at the severe stenosis was demonstrated before and after stenting. There was no WSS after stenting in case without residual stenosis. CONCLUSION: Our study revealed that CFD analysis before and after intracranial stenting was feasible despite of limited vessel wall dimension and could reveal change of WSS as well as flow velocity and wall pressure.
Angiography ; Arteries ; Atherosclerosis ; Blood Vessels ; Cerebral Arteries ; Characidae ; Computer Simulation ; Constriction, Pathologic ; Glycosaminoglycans ; Humans ; Lebanon ; Magic ; Stents