Altered excitatory-inhibitory balance within somatosensory cortex is associated with enhanced plasticity and pain sensitivity in a mouse model of multiple sclerosis

S1 IHC in pre-symptomatic and clinical-onset EAE: PV+ cell counts, PNN counts, and Iba-1+ microglia counts. A) Representative fluorescence photomicrographs of PV+ staining (low-mag) in S1 from control (CFA) and EAE animals at the pre-symptomatic stage (7–9 dpi PRE) or clinical onset (ONS). B) Group mean (±S.E.) total PV+ cell counts from S1HL of CFA (n = 8), PRE (n = 4), and ONS (n = 4) EAE animals. No significant differences were observed between groups (one-way ANOVA N.S.). C) Representative fluorescence photomicrographs of WFA+ staining (PNNs) in S1 from control (CFA) and EAE animals at the pre-symptomatic stage (7–9 dpi PRE) or clinical onset (ONS). D) Group mean (±S.E.) total PNN counts from S1HL of CFA (n = 11), PRE (n = 4), and ONS (n = 8) EAE animals. EAE animals exhibited significantly reduced PNN-counts vs. CFA-controls at clinical onset (one-way ANOVA, p = 0.007, post hoc comparisons vs. CFA-controls by Dunnett’s method). E) Representative fluorescence photomicrographs of Iba-1+ staining (PNNs) in S1 from control (CFA) and EAE animals at the pre-symptomatic stage (7–9 dpi PRE) or clinical onset (ONS). F) Group mean (±S.E.) total Iba-1+ counts from S1HL of CFA (n = 13), PRE (n = 4), and ONS (n = 8) EAE animals. EAE animals exhibited significantly increased numbers of Iba-1+ cells (microglial activation) in S1HL vs. CFA-controls at all time points (one-way ANOVA, p = 0.012, post hoc comparisons vs. CFA-controls by Dunnett’s method). (PDF 6418 kb

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Impact of extended-criteria donor lungs according to preoperative recipient status and age in lung transplantation

Background : Organ donor shortage remains as one of the limiting factors for lung transplantation. Given the increase in waiting time, preoperative condition has worsened and affects surgical outcomes. This study aimed to evaluate the immediate postoperative and long-term outcomes of lung transplantation in extended-criteria donor (ECD) lungs compared with standard-criteria donor (SCD) lungs. Methods : A total of 246 patients who had undergone double-lung transplantation during the study period were enrolled. SCD was defined based on the following characteristics: age 300 mmHg. Organ donors who do not fulfill these criteria were classified as ECD. Pre- and postoperative data for outcomes and survival data were analyzed. Results : ECD showed significant association with extracorporeal membrane oxygenation weaning in the operating room (hazard ratio [HR], 0.531; 95% confidence interval [CI], 0.291–0.970; P=0.039) considering recipient’s age and status at operation. The ECD group showed comparable survival rate with the SCD group (HR, 1.413; 95% CI, 0.885– 2.255; P=0.148), with adjustment of other factors. However, when the recipient had Korean Network for Organ Sharing (KONOS) status 0 at the time of transplantation (HR, 1.662; 95% CI, 1.025–2.568; P=0.039), G3 primary graft dysfunction at 72 hours after surgery (HR, 2.508; 95% CI, 1.416–4.440; P=0.002) was a risk factor that decreased survival. Conclusions: The outcome of ECD is not inferior to that of SCD. Therefore, ECD lung should be considered a potential donor organ following active donor management rather than a contraindication of transplantation in highly selected recipients

Clinicopathologic evaluation of myofibroblastoma: A study in two hospitals

Objective To report various anatomic locations and clinical characteristics of pathologically proven myofibroblastoma in Koran patients. Methods Pathologic reports of patients who underwent surgeries at two centers between April 2003 and March 2016 were retrieved from the electronic medical record system of the hospital. Pathologic reports were included after performing a search using the keyword myofibroblastoma. Results The cohort consisted of 11 subjects and included eight female and three male individuals. The patients' ages ranged from 9 to 66 years. Tumors were located in the vagina in three patients and presented in the breast in seven patients. One case presented with an abdominal mass. The tumors ranged in mean size from 4.0 to 53.0 mm. Despite a relatively long-term follow-up, no case had evidence of tumor recurrence. Conclusion We evaluated the various anatomic locations of pathologically proven myofibroblastoma in Korean patients. As an extremely rare tumor, physicians should pay special attention to differential diagnosis. Surgical resection is the preferred method for a cure, and the recurrence rate is extremely low. © 2017 Korean Society of Obstetrics and Gynecology.Y

Negative Feedback Regulation of Aurora-A via Phosphorylation of Fas-associated Factor-1

This study reports that Aurora-A (Aur-A) phosphorylates Fas-associated factor-1 (FAF1) at Ser-289 and Ser-291. Forced expression of a FAF1 mutant mimicking phosphorylation at Ser-289 and Ser-291 (FAF1 DD), but not phosphorylation-deficient FAF1 (FAF1 AA), reduced Aur-A expression. However, transfection of FAF1 DD failed to reduce Aur-A expression in the presence of MG132 and MG115, indicating that this decrease is proteasome-mediated. Additionally, transfection of FAF1 DD suppressed the expression of Aur-A in ts20-BALB cells lacking E1 ubiquitin (Ub) activating enzyme activity at restrictive temperatures and also reduced the expression of Aur-A S51D, a mutant resistant to Ub-dependent degradation. Our data indicate that phosphorylated FAF1 mediates the ubiquitin-independent, proteasome-dependent degradation of Aur-A. Overexpression of FAF1 DD blocked Aur-A-induced centrosome amplification and accumulated cells in G(2)/M phase, representing cellular phenotypes consistent with the anticipated loss of Aur-A. Collectively, our findings support the negative feedback regulation of Aur-A via phosphorylation of the death-promoting protein, FAF1, and disclose the presence of molecular cross-talk between constituents of the cell cycle and cell death machinery.This work was supported by FG08-21-02 of the 21C Frontier Functional Human Genome Project from the Ministry of Education, Science, and Technology in Korea and the Brain Korea 21 Project Fellowship

In vitro fertilization outcomes in women with surgery induced diminished ovarian reserve after endometrioma operation: Comparison with diminished ovarian reserve without ovarian surgery

Objective To compare the in vitro fertilization (IVF) outcomes between women with diminished ovarian reserve (DOR) after endometrioma operation and women with DOR without ovarian surgery. Methods This retrospective case-control study included 124 women aged under 40 and had DOR (serum anti-Müllerian hormone level < 1.1 ng/mL or antral follicle count =6). They participated in fresh first and/or second IVF cycles between March in 2010 and December in 2015. Basal characteristics and IVF outcomes were compared between 47 cycles (32 women) with surgeryinduced DOR and 119 cycles (92 women) with DOR without ovarian surgery. Results Basal characteristics were similar in both groups except that the median ages were lower in the surgery-induced DOR group compared to the DOR group without ovarian surgery. The data regarding the controlled ovarian stimulation and IVF cycle outcomes showed similar result in both groups. Also, clinical pregnancy and live birth rate were not different significantly between two groups. Conclusion In the same condition of DOR, clinical pregnancy and live birth rate were not different significantly between two groups regarding etiology of DOR. © 2017 Korean Society of Obstetrics and Gynecology.Y

15-Deoxy-Delta(12,14)-prostaglandin J(2) stabilizes hypoxia inducible factor-1 alpha through induction of heme oxygenase-1 and direct modification ofprolyl-4-hydroxylase 2

15-Deoxy-(12,14)-prostaglandin J(2) (15d-PGJ(2)), a representative J-series cyclopentenone prostaglandin, has biphasic roles in cell proliferation and apoptosis. Hypoxia inducible factor-1 (HIF-1) regulates expression of various genes involved in tumor growth and angiogenesis. In the present study, treatment of human breast cancer (MCF-7) cells with 15d-PGJ(2) resulted in the accumulation of the -subunit of HIF-1. Pretreatment with zinc protoporphyrin IX, a pharmacological inhibitor of heme oxygenase-1 (HO-1), as well as siRNA knockdown of HO-1 gene in MCF-7 cells attenuated 15d-PGJ(2)-mediated HIF-1 accumulation. 15d-PGJ(2) treatment increased intracellular production of reactive oxygen species (ROS), which was mediated by HO-1 induction. Preincubation of MCF-7 cells with trolox, a water-soluble form of vitamin E, attenuated 15d-PGJ(2)-induced HIF-1 expression although HO-1 expression was unchanged. This finding suggests that ROS accumulated as a consequence of HO-1 up-regulation can enhance HIF-1 expression in MCF-7 cells treated with 15d-PGJ(2). Alternatively, 15d-PGJ(2) was found to covalently bind to HIF-1 prolyl-4-hydroxylase 2 (PHD2) in MCF-7 cells, which hampers the proline hydroxylation of HIF-1, thereby disrupting ubiquitin-dependent proteasomal degradation of this transcription factor. Pretreatment with thiol reducing agents blunted 15d-PGJ(2)-induced HIF-1 stabilization, indicative of a cysteine residue as a direct target of 15d-PGJ(2). Molecular docking analysis suggests that 15d-PGJ(2) preferentially binds to PHD2 in the vicinity of the Cys(201) residue based on binding energies and carbon-sulfur distances. In summary, 15d-PGJ(2) stabilizes HIF-1 in MCF-7 cells through HO-1 induction with subsequent ROS generation and also through direct modification of PHD2