Maternal separation in mice leads to anxiety-like/aggressive behavior and increases immunoreactivity for glutamic acid decarboxylase and parvalbumin in the adolescence ventral hippocampus.

It has been reported that stressful events in early life influence behavior in adulthood and are associated with different psychiatric disorders, such as major depression, post-traumatic stress disorder, bipolar disorder, and anxiety disorder. Maternal separation (MS) is a representative animal model for reproducing childhood stress. It is used as an animal model for depression, and has well-known effects, such as increasing anxiety behavior and causing abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis. This study investigated the effect of MS on anxiety or aggression-like behavior and the number of GABAergic neurons in the hippocampus. Mice were separated from their dams for four hours per day for 19 d from postnatal day two. Elevated plus maze (EPM) test, resident-intruder (RI) test, and counted glutamic acid decarboxylase 67 (GAD67) or parvalbumin (PV) positive cells in the hippocampus were executed using immunohistochemistry. The maternal segregation group exhibited increased anxiety and aggression in the EPM test and the RI test. GAD67-positive neurons were increased in the hippocampal regions we observed: dentate gyrus (DG), CA3, CA1, subiculum, presubiculum, and parasubiculum. PV-positive neurons were increased in the DG, CA3, presubiculum, and parasubiculum. Consistent with behavioral changes, corticosterone was increased in the MS group, suggesting that the behavioral changes induced by MS were expressed through the effect on the HPA axis. Altogether, MS alters anxiety and aggression levels, possibly through alteration of cytoarchitecture and output of the ventral hippocampus that induces the dysfunction of the HPA axis.

A new brain-cutting device and ultraviolet resin-mounted human brain slices as a teaching adjunct for neuroanatomy education.

Although the level of neuroscience research is rapidly developing with the introduction of new technologies, the method of neuroanatomy education remains at the traditional level and requires improvement to meet the needs of educators and trainees. We developed a new three-dimensional (3D) printed device (human brain-cutting mold, HBCM) for creating human brain slices; moreover, we demonstrated a simple method for creating semi-permanent ultraviolet (UV) resin-mounted brain slice specimens for neuroanatomy education. We obtained brain slices of uniform thickness (3 mm) through the HBCM; the resultant brain slices were optimal for assessing morphological details of the human brain. Furthermore, we used an agar-embedding method for brain-slicing with the HBCM, which minimized geometrical distortions of the brain slices. Also, we prepared semi-permanent brain serial specimens using an acrylic brain slice frame and UV-curable resin, which was highly compatible with moist bio-specimens. During UV resin curing, neither air bubble formation nor color change occurred. The resultant UV resin-mounted brain slices produced definite coronal sections with high transparency and morphological accuracy. We also performed 3D modeling by stacking brain slice images that differentiated the cortical area and nine subcortical regions via manual segmentation. This method could be a reliable alternative for displaying high-quality human brain slices and would be helpful for students and trainee to understand anatomical orientation from 2D images to 3D structures. Also, this may present an innovative approach for preparing and preserving coronal sections of the normal or pathological human brain.

Aging and direct medical costs of osteoporotic fractures.

INTRODUCTION: This study estimated the direct medical costs of osteoporotic fractures from a large claims database in Korea. MATERIALS AND METHODS: We compared the medical costs of hip, vertebral, and wrist fractures between two age groups (50-64 years vs 65 years and older). We used a generalized linear model to investigate the drivers of osteoporotic fracture medical costs. RESULTS: Hip fractures had the highest costs, regardless of age, followed by vertebral and wrist. The cost of hip fracture was USD 7285 for those aged 65 years and over and USD 6589 for those aged 50-64 years. The length of hospital days was higher in hip fracture patients, regardless of age, followed by vertebral and wrist. As the number of hospitalizations increased, the medical cost increased by 33.0% (p < 0.0001). Patients older than 65 years who were hospitalized for a fracture had a longer total length of hospital stay, compared to patients aged 50-64, regardlessness of the site of the fracture. The cost of treating fractures among those 65 years and older increased by 31.8% compared to those 50-64 years old (p < 0.0001). The direct medical costs increased by 8.6% as the number of fractures increased (p = 0.041). CONCLUSIONS: We identified that osteoporotic fracture-related medical costs and hospitalization days increased with age. Interventions are effective in reducing fracture risk the potential to yield substantial cost savings.

Aurora B confers cancer cell resistance to TRAIL-induced apoptosis via phosphorylation of survivin.

Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) induces apoptosis selectively in cancer cells while sparing normal cells. However, many cancer cells are resistant to TRAIL-induced cell death. In this study, we examined whether Aurora B, which is frequently overexpressed in cancer cells, is associated with TRAIL resistance. The protein levels of Aurora B were higher in TRAIL-resistant cancer cell lines than in TRAIL-sensitive cancer cell lines. Exogenously expressed Aurora B attenuated TRAIL-induced apoptosis in the tested TRAIL-sensitive cancer cell lines, whereas the small interfering RNA-mediated suppression of Aurora B expression stimulated TRAIL-mediated apoptosis in the tested TRAIL-resistant cancer cell lines. Furthermore, combined treatment with TRAIL and ZM447439, a specific inhibitor of Aurora B, synergistically induced apoptosis in various TRAIL-resistant cancer cells, suggesting that this combined regimen may represent an attractive strategy for effectively treating TRAIL-resistant malignant cancers. Mechanistically, the inhibition of Aurora B activity in various cancer cells commonly downregulated survivin protein levels and potentiated the activation of caspase-3. In addition, Aurora B inhibition induced mitotic catastrophe, which also contributed to the sensitization of cells to TRAIL-mediated apoptosis. Interestingly, forced overexpression of Aurora B increased the protein levels of survivin, but not those of a non-phosphorylatable survivin mutant in which threonine 117 was replaced by alanine, indicating that phosphorylation of survivin is required for this effect. Furthermore, TRAIL-induced apoptosis in MDA-MB-435S cells was attenuated by wild-type survivin but not by the non-phosphorylatable survivin mutant. Collectively, our results demonstrate that Aurora B confers TRAIL resistance to cancer cells via phosphorylation of survivin.

In vivo Preclinical Tumor-Specific Imaging of Superparamagnetic Iron Oxide Nanoparticles Using Magnetic Particle Imaging for Cancer Diagnosis.

Purpose: Magnetic particle imaging (MPI) is an emerging radiation-free, non-invasive three-dimensional tomographic technology that can visualize the concentrations of superparamagnetic iron oxide nanoparticles (SPIONs). To verify the applicability of the previously proposed point-of-care testing MPI (PoCT-MPI) in medical diagnosis and therapeutics, we imaged SPIONs in animal tumor models. Methods: CT26 or MC38 mouse colon carcinoma cells (2 × 106 cells) were subcutaneously injected into the right flank of BALB/c mice. SPIONs were either injected directly into the tumor lesions in the intratumoral group or through tail veins in the intravenous group. CT26 and MC38 tumor models were examined both intratumorally and intravenously to confirm the biological availability of SPIONs using PoCT-MPI. Results: Signals were observed in the tumor lesions from day 1 to day 7. This is the first study to successfully image the pathological region and show the biodistribution of SPIONs in CT26 tumor models using the recently developed PoCT-MPI technology. Furthermore, MC38 tumor models were examined, resulting in similar images to those of the CT26 tumor model in both intratumoral and intravenous groups. Conclusion: The present study demonstrates the biological applicability of PoCT-MPI, which promises to be a powerful diagnostic and therapeutic technique in biomedical imaging.

The Utilization of Medical Devices by Traditional Korean Medicine Doctors Investigated through Traditional Korean Medicine Clinical Studies.

OBJECTIVE: The purpose of this study was to investigate the current status of modern medical devices utilized in diagnosis and treatment in traditional Korean medicine (TKM). METHODS: We searched the following six Korean electronic databases to collect TKM clinical studies that were published in a five-year period (January 2012 to December 2016). Clinical studies of TKM when medical devices were used for diagnosis or treatment were investigated. RESULTS: The search generated a total of 3,735 articles, and 1,328 of these were considered to be clinical studies. Of a total of 1,328 clinical studies of TKM, 774 articles (58.3%) used medical devices for diagnosis or treatment, and 554 articles (41.7%) did not use medical devices for diagnosis or treatment. The three most used diagnostic devices were as follows: MRI scanners, which were used in 194 (20.6%) studies; X-ray machines, which were used in 172 studies (18.3%); and CT scanners, which were used in 139 studies (14.8%). The three most used treatment devices were electroacupuncture equipment (20.3%), transcutaneous electrical nerve stimulation (TENS) equipment (18.4%), and interferential current therapy (ICT) equipment (16.4%). CONCLUSIONS: This study suggests that TKM doctors use diagnostic information derived from modern medical devices clinically. It is therefore necessary to institutionalize considering changes to the medical acts of traditional medicine (TM) doctors. Additionally, this information can be utilized as a reference for developing TM policy and education.

Neuroanatomical distribution of galectin-3 in the adult rat brain.

Galectin-3 is a member of the lectin subfamily that enables the specific binding of ß-galactosides. It is expressed in a broad spectrum of species and organs, and is known to have various functions related to cell adhesion, signal transduction, and proinflammatory responses. Although, expression of galectin-3 in some activated neuroglia under neuroinflammation has been well documented in the central nervous system, little is known about the neuronal expression and distribution of galectin-3 in normal brain. To describe the cellular and neuroanatomical expression map of galectin-3, we performed galectin-3 immunohistochemistry on the entire normal rat brain and subsequently analyzed the neuronal distribution. Galectin-3 expression was observed not only in some neuroglia but also in neurons. Neuronal expression of galectin-3 was observed in many functional parts of the cerebral cortex and various other subcortical nuclei in the hypothalamus and brainstem. Neuroanatomical analysis revealed that robust galectin-3 immuno-signals were present in many hypothalamic nuclei related to a variety of physiological functions responsible for mediating anxiety responses, energy balance, and neuroendocrine regulation. In addition, the regions highly connected with these hypothalamic nuclei also showed intense galectin-3 expression. Moreover, multiple key regions involved in regulating autonomic functions exhibited high levels of galectin-3 expression. In contrast, the subcortical nuclei responsible for the control of voluntary motor functions and limbic system exhibited no galectin-3 immunoreactivity. These observations suggest that galectin-3 expression in the rat brain seems to be regulated by developmental cascades, and that functionally and neuroanatomically related brain nuclei constitutively express galectin-3 in adulthood.

EC50 and EC95 of remifentanil to prevent rocuronium-induced withdrawal movements in children.

BACKGROUND: Intravenous administration of rocuronium induces intense pain in most patients (60-100%). This could be harmful during anesthesia induction because of the unintended reflex movement of an unconscious patient in response to the pain. Previous studies have reported that remifentanil effectively reduces rocuronium-induced pain and withdrawal movements. This study was designed to evaluate the EC50 and EC95 of remifentanil to prevent withdrawal movements in children. METHODS: We enrolled a total of 171 pediatric patients scheduled for general anesthesia in this study. Remifentanil was administrated by target-controlled infusion. Effect-site target concentrations ranged from 0.5 to 3.0 ng/ml. At each concentration, experiments were repeated in 10-20 patients. Propofol 2 mg/kg and rocuronium 0.9 mg/kg were administrated after equilibration of plasma and effect-site target remifentanil concentration. The withdrawal movements were graded on a 4-point scale. The EC50 and EC95 of remifentanil to prevent rocuronium-induced withdrawal movements were determined by using a logistic regression model. RESULTS: The logistic regression model showed that the probability of preventing rocuronium-induced withdrawal movement was as follows: exp (-3.49 + 2.07 × remifentanil concentration) / (1 + exp [-3.49 + 2.07 × remifentanil concentration]). EC50 and EC95 were 1.69 ng/ml (95% confidence intervals [CIs], 1.42-1.87) and 3.11 ng/ml (95% CIs, 2.79-3.72), respectively. CONCLUSIONS: Administration of remifentanil at an effect-site target concentration of 3.1 ng/ml could effectively prevent rocuronium-induced withdrawal movements.

Antiemetic effect of propofol administered at the end of surgery in laparoscopic assisted vaginal hysterectomy.

BACKGROUND: Postoperative nausea and vomiting (PONV) commonly occur after general anesthesia, especially in women. In this study, we evaluated the antiemetic efficacy of propofol administered at the end of surgery in highly susceptible patients undergoing a laparoscopy-assisted vaginal hysterectomy. METHODS: A total of 107 women undergoing a laparoscopy-assisted vaginal hysterectomy under general anesthesia were enrolled for this prospective, double-blind, randomized study. Fifteen minutes before the end of surgery, all patients received 50 µg fentanyl and 1 of following 3 doses; 0.5 mg/kg of propofol (propofol 0.5 group), 1 mg/kg of propofol (propofol 1.0 group), and normal saline (control group). All patients received intravenous patient-controlled analgesia (PCA). Emergence time, a visual analog scale for pain and nausea, duration of postanesthesia care unit (PACU) stay, and frequency of antiemetic use were recorded at 0-2, 2-24, and 24-48 hours postoperatively. RESULTS: The incidence of nausea significantly lower in the propofol 0.5 and propofol 1.0 groups than in the control group (12.1 vs 14.7 vs 40%). During the first postoperative 2 hours, antiemetics were less frequently administered in the propofol 0.5 and propofol 1.0 groups than in the control group (3.0 vs 5.9 vs 22.5%). Emergence time was slightly longer in the propofol 0.5 and propofol 1.0 groups than in the control group, but there was no significant difference in PACU stay time was observed between the 3 groups. CONCLUSIONS: The results of this study suggest that low-dose propofol administration at the end of surgery may effectively reduce the incidence of PONV within 2 hours postoperatively in highly susceptible women undergoing a laparoscopiy-assisted vaginal hysterectomy and receiving opioid-based PCA.

Comparison of ramosetron's and ondansetron's preventive anti-emetic effects in highly susceptible patients undergoing abdominal hysterectomy.

BACKGROUND: This study compared the preventive effects of ramosetron and ondansetron on postoperative nausea and vomiting (PONV) in highly susceptible patients undergoing abdominal hysterectomy. METHODS: In a prospective, randomized, double-blinded study, a total of 120 highly susceptible women (nonsmokers, those receiving opioid-based IV patient-controlled analgesia [PCA]) undergoing abdominal hysterectomy were included in the study. Patients were divided into 2 groups and each group received either 0.3 mg of ramosetron or 4 mg of ondansetron, IV. All patients received fentanyl-based IV PCA during the 48 h postoperative periods. The incidences of PONV and side effects of 5-HT(3) antagonists (headache and dizziness) were assessed at 3 intervals (<2 h, 2-24 h and 24-48 h) postoperatively. RESULTS: Patients in the ramosetron group showed a significantly higher ratio of complete response and lower incidence of nausea during the 24-48 h interval after surgery compared with those the ondansetron group. CONCLUSIONS: Ramosetron (0.3 mg) is more effective in preventing delayed PONV in highly susceptible women undergoing abdominal hysterectomy compared with ondansetron (4 mg).

DNA methylation and not allelic variation regulates STAT6 expression in human T cells.

STAT6 transcription factor, which has been implicated in commitment to Th2, is known to be activated by IL-4 and IL-13. Accordingly, STAT6 is primarily responsible for the transcriptional effects of IL-4 and IL-13. STAT6-deficient mice are known to have defective IL-4-mediated functions, such as B cell proliferation, Th2 cell development and IgE secretion; therefore, they primarily contain the Th1 phenotype. However, the mechanism responsible for regulation of STAT6 expression transcriptionally and post-transcriptionally has yet to be elucidated. Here, we characterized the human STAT6 promoter gene and found that the transcriptional regulatory elements CCAAT and ATF were important for the STAT6 promoter activity. Direct sequencing analysis revealed that the 13 GT repeat allelic variation in noncoding exon 1 of the STAT6 gene appeared more frequently in 91 patients with asthma or rheumatoid arthritis than the 15 GT repeat variation, which is the dominant phenotype in healthy controls. However, it appears that this allelic variation did not affect the STAT6 transcriptional activity. Interestingly, treatment with a DNA methyltransferase inhibitor markedly increased the expression of STAT6 mRNA and protein in human primary T cells. In contrast, IFN-gamma treatment significantly repressed the STAT6 transcriptional activity. Therefore, the present study provides insight into the molecular basis of STAT6 expression, and in particular, demonstrates that STAT6 expression is associated with DNA hypermethylation rather than promoter polymorphisms or allelic variations.