The molecular mechanism underlying the initiation of somatic cell reprogramming into induced pluripotent stem cells (iPSCs) has not been well described. Thus, we generated single-cell-derived clones by using a combination of drug-inducible vectors encoding transcription factors (Oct4, Sox2, Klf4 and Myc) and a single-cell expansion strategy. This system achieved a high reprogramming efficiency after metabolic and epigenetic remodeling. Functional analyses of the cloned cells revealed that extracellular signal-regulated kinase (ERK) signaling was downregulated at an early stage of reprogramming and that its inhibition was a driving force for iPSC formation. Among the reprogramming factors, Myc predominantly induced ERK suppression. ERK inhibition upregulated the conversion of somatic cells into iPSCs through concomitant suppression of serum response factor (SRF). Conversely, SRF activation suppressed the reprogramming induced by ERK inhibition and negatively regulated embryonic pluripotency by inducing differentiation via upregulation of immediate early genes, such as c-Jun, c-Fos and EGR1. These data reveal that suppression of the ERK-SRF axis is an initial molecular event that facilitates iPSC formation and may be a useful surrogate marker for cellular reprogramming.

PURPOSE: Genexol-PM is a Cremophor EL–free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol). MATERIALS AND METHODS: Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m² or Genexol 175 mg/m² intravenously every 3 weeks. The primary outcome was the objective response rate (ORR). RESULTS: The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m² (95.0%), and that of Genexol was 168.3±10.6 mg/m² (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (p(non-inferiority)=0.021, p(superiority)=0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments. CONCLUSION: Compared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.
Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Incidence ; Neutropenia ; Paclitaxel* ; Peripheral Nervous System Diseases ; Polymers* ; Treatment Outcome

PURPOSE: To compare the macular choroidal thickness, ganglion cell complex thickness, peripapillary choroidal thickness and retinal nerve fiber layer thickness among normal, primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) patients using RTVue (Fourier-domain optical coherence tomography; Optovue, Fremont, CA, USA). METHODS: A retrospective analysis of 32 normal controls, 32 POAG and 52 NTG patients was performed. Choroidal thickness, ganglion cell complex thickness and retinal nerve fiber layer thickness were compared among normal controls, POAG and NTG subjects. Additionally, the factors influencing choroidal thickness (age, axial length, spherical equivalent, central corneal thickness, mean deviation, nocturnal dip, blood pressure variability) were analyzed. RESULTS: A total of 32 normal controls, 32 POAG and 52 NTG patients were enrolled in this study. Macular and peripapillary choroidal thicknesses were significantly thinner in the NTG patients. In NTG subjects, the significant influencing factors associated with macular and peripapillary choroidal thicknesses were age, axial length, nocturnal dip (diastolic blood pressure), diastolic blood pressure variability and ganglion cell complex thickness. In POAG patients, significant influencing factors associated with macular and peripapillary choroidal thicknesses were age and axial length. CONCLUSIONS: Choroidal thickness was significantly thinner in NTG patients compared with normal controls and POAG patients. Factors influencing choroidal thickness in NTG patients were age, axial length, nocturnal dip (diastolic blood pressure), diastolic blood pressure variability and ganglion cell complex thickness. In POAG patients, significant factors influencing choroidal thickness were age and axial length.
Blood Pressure ; Choroid* ; Ganglion Cysts ; Glaucoma, Open-Angle* ; Humans ; Low Tension Glaucoma ; Nerve Fibers ; Retinaldehyde ; Retrospective Studies ; Tomography, Optical Coherence

PURPOSE: To compare the macular choroidal thickness, ganglion cell complex thickness, peripapillary choroidal thickness and retinal nerve fiber layer thickness among normal, primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) patients using RTVue (Fourier-domain optical coherence tomography; Optovue, Fremont, CA, USA). METHODS: A retrospective analysis of 32 normal controls, 32 POAG and 52 NTG patients was performed. Choroidal thickness, ganglion cell complex thickness and retinal nerve fiber layer thickness were compared among normal controls, POAG and NTG subjects. Additionally, the factors influencing choroidal thickness (age, axial length, spherical equivalent, central corneal thickness, mean deviation, nocturnal dip, blood pressure variability) were analyzed. RESULTS: A total of 32 normal controls, 32 POAG and 52 NTG patients were enrolled in this study. Macular and peripapillary choroidal thicknesses were significantly thinner in the NTG patients. In NTG subjects, the significant influencing factors associated with macular and peripapillary choroidal thicknesses were age, axial length, nocturnal dip (diastolic blood pressure), diastolic blood pressure variability and ganglion cell complex thickness. In POAG patients, significant influencing factors associated with macular and peripapillary choroidal thicknesses were age and axial length. CONCLUSIONS: Choroidal thickness was significantly thinner in NTG patients compared with normal controls and POAG patients. Factors influencing choroidal thickness in NTG patients were age, axial length, nocturnal dip (diastolic blood pressure), diastolic blood pressure variability and ganglion cell complex thickness. In POAG patients, significant factors influencing choroidal thickness were age and axial length.
Blood Pressure ; Choroid* ; Ganglion Cysts ; Glaucoma, Open-Angle* ; Humans ; Low Tension Glaucoma ; Nerve Fibers ; Retinaldehyde ; Retrospective Studies ; Tomography, Optical Coherence

PURPOSE: To investigate the effects of a delay in finger temperature recovery rate on the hand cold provocation test (HCPT) and a nocturnal dip greater than 10% (dipper) on the progression of glaucomatous visual field (VF) defects in open-angle glaucoma patients when the intraocular pressure (IOP) was well controlled lower than the target pressure. METHODS: 30 patients (58 eyes) with normal tension glaucoma (NTG) and 13 patients (24 eyes) with primary open angle glaucoma, and 12 normal controls (24 eyes) were retrospectively enrolled in this study. We performed HCPT, 24 hour ambulatory blood pressure monitoring (24-hr ABPM), Goldmann applanation tonometer measurements, and VF tests on all subjects. The delay in finger temperature recovery rate was defined as a delay longer than 15% of the mean finger temperature of normal controls over 2 intervals among 5, 10, 15, and 20 minutes after the immersion of cold water. We examined the relationships among the delay in finger temperature recovery rate, dipper, and the progression of glaucomatous VF defects. RESULTS: The finger temperature recovery rate in NTG patients was significantly delayed more than that of normal controls at 5, 10, and 15 minutes after the immersion. The delay in finger temperature recovery rate significantly correlated with dipper in NTG patients. Glaucomatous VF defects were significantly progressed in the presence of dipper in NTG patients. Delay in finger temperature recovery rate was significantly related to the progression of glaucomatous VF defects in NTG patients. In the binary logistic regression test, delay in finger temperature recovery rate was the only factor that was strongly related to the progression of glaucomatous visual field in NTG patients. CONCLUSIONS: When glaucomatous VF defects progressed despite the IOP being well controlled, 24-hr ABPM and HCPT for detecting vascular dysregulation might be helpful for diagnosis and treatment of glaucoma.
Blood Pressure Monitoring, Ambulatory ; Diagnosis ; Fingers* ; Glaucoma* ; Glaucoma, Open-Angle ; Hand ; Humans ; Immersion ; Intraocular Pressure ; Logistic Models ; Low Tension Glaucoma ; Retrospective Studies ; Visual Fields ; Water

PURPOSE: To investigate the influence of water-shed zone (WSZ) and nocturnal dip (ND) on the progression of the glaucomatous visual field (V/F) defects in open-angle glaucoma (OAG) patients when the intraocular pressure (IOP) was maintained under the target pressure. METHODS: We performed fluorescence angiography (FAG), 24-hour ambulatory blood pressure monitoring (24-hr ABPM), and V/F tests. We examined the relationships among WSZ in early-FAG, ND over 10% (dip), and the progression of the glaucomatous V/F defects using chi-square, Fisher's exact, and multivariate logistic regression tests. A p-value < 0.05 was considered statistically significant. RESULTS: When considering the correlation between WSZ and dip, statistical significance was found in OAG (p = 0.024, odds ratio (OR) = 3.308) and normal tension glaucoma (NTG) (p = 0.029, OR = 4.364) patients. In patients with dip, glaucomatous V/F defects significantly progressed (OAG: p = 0.003, OR = 5.938, NTG: p = 0.005, OR = 13.929). In patients with WSZ, the glaucomatous V/F defects progressed in all groups (OAG: p = 0.002, OR = 5.156, NTG: p = 0.024, OR = 4.750, primary open angle glaucoma (POAG): p = 0.021, OR = 8.750). In the patients with WSZ involving optic nerve head, the glaucomatous V/F defects had progressed in OAG (p = 0.004, OR = 5.958) and NTG (p = 0.009, OR = 8.333) groups. Based on binary logistic regression analysis, dip (p = 0.010, OR = 6.227) significantly affected V/F progression only in OAG patients. CONCLUSIONS: In the OAG and NTG groups, ND over 10% influenced the progression of the glaucomatous V/F defects. The patients with WSZ tended to have ND over 10% in OAG and NTG groups and glaucomatous V/F defects progressed in all patients. Therefore, performing early FAG and 24-hr ambulatory blood pressure monitoring may be helpful for glaucoma patients with progressing glaucomatous V/F defects even when the IOP was maintained under the target pressure.
Blood Pressure Monitoring, Ambulatory ; Fluorescein Angiography ; Glaucoma ; Glaucoma, Open-Angle* ; Humans ; Intraocular Pressure ; Logistic Models ; Low Tension Glaucoma ; Odds Ratio ; Optic Disk ; Visual Fields*

We aimed to compare the recommendations of the Korean Medication Algorithm Project for Depressive Disorder 2012 (KMAP-DD 2012) with other recently published treatment guidelines for depressive disorder. We reviewed a total of five recently published global treatment guidelines and compared each treatment recommendation of the KMAP-DD 2012 with those in other guidelines. For initial treatment recommendations, there were no significant major differences across guidelines. However, in the case of nonresponse or incomplete response to initial treatment, the second recommended treatment step varied across guidelines. For maintenance therapy, medication dose and duration differed among treatment guidelines. Further, there were several discrepancies in the recommendations for each subtype of depressive disorder across guidelines. For treatment in special populations, there were no significant differences in overall recommendations. This comparison identifies that, by and large, the treatment recommendations of the KMAP-DD 2012 are similar to those of other treatment guidelines and reflect current changes in prescription pattern for depression based on accumulated research data. Further studies will be needed to address several issues identified in our review.
Depression ; Depressive Disorder* ; Drug Therapy ; Prescriptions

PURPOSE: To investigate the effect of nocturnal dip, carotid artery blood flow, and brain ischemic change on the progression of glaucomatous visual field defect in open-angle glaucoma (OAG) when IOP is less than the target pressure. METHODS: We classified OAG patients (74 patients, 148 eyes) who maintained IOP less than the target pressure as normal tension glaucoma (NTG; 52 patients, 104 eyes) or primary OAG (POAG; 22 patients, 44 eyes). Additionally, we performed 24-hr ambulatory blood pressure monitoring (24-hr ABPM), carotid artery color Doppler U/S (CAD), brain MRI, and visual field (V/F) tests on the patients. Nocturnal dips less than 10% were classified as non-dippers, and dips greater than 10% as dippers. The relationships among nocturnal dip, carotid artery blood flow, brain ischemic change, and progression of glaucomatous V/F defect were examined. RESULTS: In the case of dippers, glaucomatous V/F defects were aggravated, with a relative risk of approximately 1.74 (NTG) and 2.91 (POAG) times that of non-dippers. In NTG, decreased carotid artery blood flow and brain ischemic change furthered glaucomatous V/F defects, with a relative risk of approximately 2.40 and 2.54 times that of normal carotid artery blood flow and brain MRI findings, respectively. However, in POAG, decreased carotid artery blood flow and brain ischemic change were not influenced by the progression of glaucomatous V/F defects. CONCLUSIONS: In dippers, decreased carotid artery blood flow and brain ischemic change caused a progression of glaucomatous V/F defects in NTG and POAG patients. Thus, performing 24-hr ABPM, CAD, and brain MRI should be helpful for glaucoma patients with progression of glaucomatous V/F defects even when the IOP is less than the target pressure. In addition, this analysis provides useful information regarding glaucoma diagnosis and treatment.
Blood Pressure Monitoring, Ambulatory ; Brain ; Brain Ischemia ; Carotid Arteries ; Glaucoma ; Glaucoma, Open-Angle ; Humans ; Low Tension Glaucoma ; Salicylates ; Visual Fields

PURPOSE: We evaluated the thickness of RNFL and optic nerve head parameters with age in normal eyes using Spectral-Domain Optical Coherence Tomography (SD-OCT). METHODS: A total of 128 normal Korean volunteers in different age groups were recruited (age range, 20-70 years). RESULTS: A significant negative correlation in average RNFL thickness with increasing age was found. The inferior areas (130.31 +/- 3.33 micrometer) were significantly thicker than other areas (superior area 119.05 +/- 2.12 micrometer, nasal area 71.80 +/- 0.57 micrometer, temporal area 77.72 +/- 0.16 micrometer). The average C/D ratios (mean 0.38 +/- 0.14) and vertical C/D ratios (mean 0.35 +/- 0.11) both showed significant increases with age, and the vertical C/D ratio correlation coefficient was higher (average C/D ratio r = 0.249, vertical C/D ratio r = 0.537). However, rim area, disc area, and cup volume were not correlated with age. CONCLUSIONS: From these findings, we conclude that, in normal Koreans, the mean RNFL thickness decreases and the C/D ratio increases with age, with the increase in the vertical C/D ratio being greater.
Eye ; Humans ; Optic Disk ; Tomography, Optical Coherence

OBJECTIVE: Since the introduction of selective serotonin reuptake inhibitor in 1980s, there have been many changes in the treatment strategies for depressive disorders. To be of help for clinicians to select appropriate treatment strategies, Korean Medication Algorithm Project for Major Depressive Disorder was developed in 2002 and revised in 2006. To reflect changes in treatment pattern for depressive disorders since 2006, we revised the previous algorithm and developed Korean Medication Algorithm Project for Depressive Disorder 2012 (KMAP-DD 2012). METHODS: 123 psychiatrists who have vast clinical experiences in treating depressive disorders are primarily selected, and the survey was sent to them via mails. Among them, 67 psychiatrists answered the survey. This survey was composed of 44 questionnaires of which the contents covered from overall treatment strategies to treatment strategies under the specific circumstances. Based on 95% confidence interval and overall scores, each treatment of option was classified into three categories of recommendation; first-line, second-line, and third-line treatment option. RESULTS: In child and adolescent, antidepressant monotherapy was selected as first-line treatment option for mild, moderate, and severe episode without psychotic features. The combination of antidepressant and atypical antipsychotics was advocated as first-line treatment option for severe episode with psychotic features. In geriatric depression, antidepressant monotherapy was advocated as treatment of choice for mild to moderate episode. For severe episode without psychotic features, antidepressant monotherapy was selected as first-line treatment option. For severe episode with psychotic features, combination of antidepressant and atypical antipsychotics was selected as treatment of choice. In premenstrual dysphoric disorder, antidepressant monotherapy was advocated as first-line treatment option. In postpartum depression, antidepressant monotherapy was selected as first-line treatment option for mild to moderate episode. For severe episode without psychotic features, both antidepressant monotherapy and combination of antidepressant and atypical antipsychotics were selected as first-line treatment option. For severe episode with psychotic features, both combination of antidepressant and atypical antipsychotics and combination of mood stabilizer and atypical antipsychotics were advocated as first-line treatment option. CONCLUSION: In KMAP-DD 2012, the recommendations for treatment options in Child and Adolescent Depressive Disorder and Geriatric Depression were newly introduced. In aspects of treatment options for Female Depression, KMAP-DD 2006 and KMAP-DD 2012 had some similarities. But there were some changes of the treatment strategies in KMAP-DD 2012 which seemed to reflect recent study results.
Adolescent ; Aged ; Antipsychotic Agents ; Child ; Depression ; Depression, Postpartum ; Depressive Disorder ; Depressive Disorder, Major ; Female ; Humans ; Postal Service ; Psychiatry ; Surveys and Questionnaires ; Serotonin