Exploring the roles of multidimensional versus unidimensional construct of destination social responsibility in explaining destination trust and relationship continuity

Funding: This study was supported by 2021 Research Grant from Kangwon National University.Peer reviewedPublisher PD

Minocycline markedly reduces acute visceral nociception via inhibiting neuronal ERK phosphorylation

<p>Abstract</p> <p>Background</p> <p>Minocycline prevents the development of neuropathic and inflammatory pain by inhibiting microglial activation and postsynaptic currents. But, how minocycline obviates acute visceral pain is unclear. The present study investigated whether minocycline had an any antinociceptive effect on acetic acid-induced acute abdominal pain after intraperitoneal (i.p.) administration of saline or minocycline 1 hour before acetic acid injection (1.0%, 250 μl, i.p.).</p> <p>Results</p> <p>Minocycline (4, 10, or 40 mg/kg) significantly decreased acetic acid-induced nociception (0-60 minutes post-injection) and the enhancement in the number of c-Fos positive cells in the T5-L2 spinal cord induced by acetic acid injection. Also, the expression of spinal phosphorylated extracellular signal-regulated kinase (p-ERK) induced by acetic acid was reduced by minocycline pre-administration. Interestingly, intrathecal introduction of PD98059, an ERK upstream kinase inhibitor, markedly blocked the acetic acid-stimulated pain responses.</p> <p>Conclusions</p> <p>These results demonstrate that minocycline effectively inhibits acetic acid-induced acute abdominal nociception via the inhibition of neuronal p-ERK expression in the spinal cord, and that minocycline may have therapeutic potential in suppressing acute abdominal pain.</p

Directed evolution of CRISPR-Cas9 to increase its specificity

The use of CRISPR-Cas9 as a therapeutic reagent is hampered by its off-target effects. Although rationally designed S. pyogenes Cas9 (SpCas9) variants that display higher specificities than the wild-type SpCas9 protein are available, these attenuated Cas9 variants are often poorly efficient in human cells. Here, we develop a directed evolution approach in E. coli to obtain Sniper-Cas9, which shows high specificities without killing on-target activities in human cells. Unlike other engineered Cas9 variants, Sniper-Cas9 shows WT-level on-target activities with extended or truncated sgRNAs with further reduced off-target activities and works well in a preassembled ribonucleoprotein (RNP) format to allow DNA-free genome editing.

Experimental Study on Flow Control Characteristics of Synthetic Jets over a Blended Wing Body Configuration

Nov. 20-22, 2013, Sunport Hall Takamatsu, Takamatsu, JAPANThis paper presents experimental investigations on the characteristics of synthetic jets over blended wing body configuration. Flow control experiments were performed by using piezoelectrically driven synthetic jet under various flow conditions. In the first step, baseline characteristics of blended wing body configuration were analyzed when synthetic jet was off. Pressure distribution and separated-flow region on the wing surface were examined by changing the angle of attack. Flow control experiments were carried out by synthetic jet to demonstrate the flow control performance in the post-stall regime. Comparative studies were also conducted for a stalled condition. Aerodynamic coefficient was examined by changing synthetic jet operating condition, such as jet oscillation frequency and jet module locations. Based on various comparisons, it was observed that synthetic jet operating conditions have significantly influence on the development of leading-edge vorticies, that is to say, flow control performance of synthetic jet.This research was supported by Defense Acquisition Program Administration and Agency for Defense Development (UC100031JD).OAIID:oai:osos.snu.ac.kr:snu2013-01/104/0000004648/20SEQ:20PERF_CD:SNU2013-01EVAL_ITEM_CD:104USER_ID:0000004648ADJUST_YN:NEMP_ID:A001138DEPT_CD:446CITE_RATE:0FILENAME:api280_bhl_130913.pdfDEPT_NM:기계항공공학부EMAIL:[email protected]:

Operation of national coordinating service for interhospital transfer from emergency departments: experience and implications from Korea

Background Since 2014, Korea has been operating the National Emergency Medical Situation Room (NEMSR) to provide regional emergency departments (EDs) with coordination services for the interhospital transfer of critically ill patients. The present study aimed to describe the NEMSRs experience and interhospital transfer pattern from EDs nationwide, and investigate the factors related to delayed transfers or transfers that could not be arranged by the NEMSR. Methods This study was a retrospective cross-sectional analysis of the NEMSRs coordination registry from 2017 to 2019. The demographic and hospital characteristics related to emergency transfers were analyzed with hierarchical logistic models. Results The NEMSR received a total of 14,003 requests for the arrangement of the interhospital transfers of critically ill patients from 2017 to 2019. Of 10,222 requests included in the analysis, 8297 (81.17%) successful transfers were coordinated by the NEMSR. Transfers were requested mainly due to a shortage of medical staff (59.79%) and ICU beds (30.80%). Delayed transfers were significantly associated with insufficient hospital resources. The larger the bed capacity of the sending hospital, the more difficult it was to coordinate the transfer (odds ratio [OR] for transfer not arranged = 2.04; 95% confidence interval [CI]: 1.48–2.82, ≥ 1000 beds vs. < 300 beds) and the longer the transfer was delayed (OR for delays of more than 44 minutes = 2.08; 95% CI: 1.57–2.76, ≥ 1000 beds vs. < 300 beds). Conclusions The operation of the NEMSR has clinical importance in that it could efficiently coordinate interhospital transfers through a protocolized process and resource information system. The coordination role is significant as information technology in emergency care develops while regional gaps in the distribution of medical resources widen

S6 kinase 1 plays a key role in mitochondrial morphology and cellular energy flow

Mitochondrial morphology, which is associated with changes in metabolism, cell cycle, cell development and cell death, is tightly regulated by the balance between fusion and fission. In this study, we found that S6 kinase 1 (S6K1) contributes to mitochondrial dynamics, homeostasis and function. Mouse embryo fibroblasts lacking S6K1 (S6K1 KO MEFs) exhibited more fragmented mitochondria and a higher level of Dynamin related protein 1 (Drp1) and active Drp1 (pS616) in both whole cell extracts and mitochondria' fraction. In addition, there was no evidence for autophagy and mitophagy induction in S6K1 depleted cells. Glycolysis and mitochondrial respiratory activity was higher in S6K1-KO MEFs, whereas OxPhos ATP production was not altered. However, inhibition of Drp1 by Mdivi1 (Drp1 inhibitor) resulted in higher OxPhos ATP production and lower mitochondrial membrane potential. Taken together the depletion of S6K1 increased Drpl-mediated fission, leading to the enhancement of glycolysis. The fission form of mitochondria resulted in lower yield for OxPhos ATP production as well as in higher mitochondrial membrane potential. Thus, these results have suggested a potential role of S6K1 in energy metabolism by modulating mitochondrial respiratory capacity and mitochondrial morphology.

Dietary fat increases solid tumor growth and metastasis of 4T1 murine mammary carcinoma cells and mortality in obesity-resistant BALB/c mice

Introduction High-fat diets (HFDs) are known to cause obesity and are associated with breast cancer progression and metastasis. Because obesity is associated with breast cancer progression, it is important to determine whether dietary fat per se stimulates breast cancer progression in the absence of obesity. This study investigated whether an HFD increases breast cancer growth and metastasis, as well as mortality, in obesity-resistant BALB/c mice. Methods The 4-week-old, female BALB/c mice were fed HFD (60% kcal fat) or control diet (CD, 10% kcal fat) for 16 weeks. Subsequently, 4T1 mammary carcinoma cells were injected into the inguinal mammary fat pads of mice fed continuously on their respective diets. Cell-cycle progression, angiogenesis, and immune cells in tumor tissues, proteases and adhesion molecules in the lungs, and serum cytokine levels were analyzed with immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay (ELISA). In vitro studies were also conducted to evaluate the effects of cytokines on 4T1 cell viability, migration, and adhesion. Results Spleen and gonadal fat-pad weights, tumor weight, the number and volume of tumor nodules in the lung and liver, and tumor-associated mortality were increased in the HFD group, with only slight increases in energy intake and body weight. HF feeding increased macrophage infiltration into adipose tissues, the number of lipid vacuoles and the expression of cyclin-dependent kinase (CDK)2, cyclin D1, cyclin A, Ki67, CD31, CD45, and CD68 in the tumor tissues, and elevated serum levels of complement fragment 5a (C5a), interleukin (IL)-16, macrophage colony-stimulating factor (M-CSF), soluble intercellular adhesion molecule (sICAM)-1, tissue inhibitors of metalloproteinase (TIMP)-1, leptin, and triggering receptor expressed on myeloid cells (TREM)-1. Protein levels of the urokinase-type plasminogen activator, ICAM-1, and vascular cell adhesion molecule-1 were increased, but plasminogen activator inhibitor-1 levels were decreased in the lungs of the HFD group. In vitro assays using 4T1 cells showed that sICAM-1 increased viability; TREM-1, TIMP-1, M-CSF, and sICAM-1 increased migration; and C5a, sICAM-1, IL-16, M-CSF, TIMP-1, and TREM-1 increased adhesion. Conclusions Dietary fat increases mammary tumor growth and metastasis, thereby increasing mortality in obesity-resistant mice

Evaluation of Foveal and Parafoveal Microvascular Changes Using Optical Coherence Tomography Angiography in Type 2 Diabetes Patients without Clinical Diabetic Retinopathy in South Korea

The aim of this study was to investigate foveal and parafoveal microvascular changes in retinal vascular plexuses in patients with type 2 diabetes mellitus (DM) without clinical diabetic retinopathy (NDR) using optical coherence tomography angiography (OCTA) in South Korea. We included 64 patients in the NDR group and included 48 healthy control subjects for comparison. All subjects underwent ocular examination with visual acuity and wide-field fundus photos. Foveal and parafoveal vessel density and foveal avascular zone (FAZ) area (mm2) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were analyzed. Foveal vessel densities in both the SCP and DCP were decreased in the NDR group compared to the controls (p=0.034 and 0.001, respectively). Vessel densities in the superior and inferior parafoveae in the DCP were decreased in the NDR group compared to the controls (p=0.006 and 0.034, respectively). The FAZs of the SCP and DCP were significantly different between the NDR group and the controls (p=0.003 and 0.001, respectively). The average vessel densities of the SCP and DCP were not correlated with HbA1c, serum creatinine, or the duration of DM in the NDR group. We demonstrated that OCTA can identify early-stage DR before the manifestation of clinically apparent retinopathy in diabetic eyes. Diabetic patients without clinical DR have microvascular alterations (foveal vessel density, parts of the parafovea, and enlarged FAZ) in the SCP and DCP. Our results suggest that OCTA might be a promising tool for early detection of eyes with DR