Preparation of boron nitride-coated carbon fibers and synergistic improvement of thermal conductivity in their polypropylene-matrix composites

The purpose of this study is to prepare boron nitride (BN)-coated carbon fibers (CF) and to investigate the properties of as-prepared fibers as well as the effect of coating on their respective polymer-matrix composites. A sequence of solution dipping and heat treatment was performed to blanket the CFs with a BN microlayer. The CFs were first dipped in a boric acid solution and then annealed in an ammonia-nitrogen mixed gas atmosphere for nitriding. The presence of BN on the CF surface was confirmed using FTIR, XPS, and SEM analyses. Polypropylene was reinforced with BN-CFs as the first filler and graphite flake as the secondary filler. The composite characterization indicates approximately 60% improvement in through-plane thermal conductivity and about 700% increase in the electrical resistivity of samples containing BN-CFs at 20 phr. An increase of two orders of magnitude in the electrical resistivity of BN-CF monofilaments was also observed

Dissociation of Progressive Dopaminergic Neuronal Death and Behavioral Impairments by Bax Deletion in a Mouse Model of Parkinson's Diseases

Parkinson's disease (PD) is a common, late-onset movement disorder with selective degeneration of dopaminergic (DA) neurons in the substantia nigra (SN). Although the neurotoxin 6-hydroxydopamine (6-OHDA) has been used to induce progressive degeneration of DA neurons in various animal models of PD, the precise molecular pathway and the impact of anti-apoptotic treatment on this neurodegeneration are less understood. Following a striatal injection of 6-OHDA, we observed atrophy and progressive death of DA neurons in wild-type mice. These degenerating DA neurons never exhibited signs of apoptosis (i.e., caspase-3 activation and cytoplasmic release of cytochrome C), but rather show nuclear translocation of apoptosis-inducing factor (AIF), a hallmark of regulated necrosis. However, mice with genetic deletion of the proapoptotic gene Bax (Bax-KO) exhibited a complete absence of 6-OHDA-induced DA neuron death and nuclear translocation of AIF, indicating that 6-OHDA-induced DA neuronal death is mediated by Bax-dependent AIF activation. On the other hand, DA neurons that survived in Bax-KO mice exhibited marked neuronal atrophy, without significant improvement of PD-related behavioral deficits. These findings suggest that anti-apoptotic therapy may not be sufficient for PD treatment, and the prevention of Bax-independent neuronal atrophy may be an important therapeutic target

Prevention of mitochondrial impairment by inhibition of protein phosphatase 1 activity in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by progressive loss of motor neurons (MNs) and subsequent muscle weakness. These pathological features are associated with numerous cellular changes, including alteration in mitochondrial morphology and function. However, the molecular mechanisms associating mitochondrial structure with ALS pathology are poorly understood. In this study, we found that Dynamin-related protein 1 (Drp1) was dephosphorylated in several ALS models, including those with SOD1 and TDP-43 mutations, and the dephosphorylation was mediated by the pathological induction of protein phosphatase 1 (PP1) activity in these models. Suppression of the PP1-Drp1 cascade effectively prevented ALS-related symptoms, including mitochondrial fragmentation, mitochondrial complex I impairment, axonal degeneration, and cell death, in primary neuronal culture models, iPSC-derived human MNs, and zebrafish models in vivo. These results suggest that modulation of PP1-Drp1 activity may be a therapeutic target for multiple pathological features of ALS

Serial Assessment of Myocardial Properties Using Cyclic Variation of Integrated Backscatter in an Adriamycin-Induced Cardiomyopathy Rat Model

Although adriamycin (Doxorubicin) is one of the most effective and useful antineoplastic agents for the treatment of a variety of malignancies, its repeated administration can induce irreversible myocardial damage and resultant heart failure. Currently, no marker to detect early cardiac damage is available. The purpose of this study was to investigate whether an assessment of the acoustic properties of the myocardium could enable the earlier detection of myocardial damage after adriamycin chemotherapy. Forty Wistar rats were treated with adriamycin (2 mg/kg, i.v.) once a week for 2, 4, 6 or 8 weeks consecutively. Left ventricular ejection fraction (LVEF) was calculated using M-mode echocardiography data. The magnitude of cardiac cycle dependent variation of integrated backscatter (CVIB) of the myocardium was measured in the mid segment of the septum and in the posterior wall of the left ventricle, using a real time two dimensional integrated backscatter imaging system. LVEF was significantly lower in the adriamycin-treated 8-week group than in the controls (75 ± 9 vs 57 ± 8%, p < 0.05). Myocyte damage was only seen in the 8-week adriamycin-treated group. However, no significant changes of CVIB were observed between baseline or during follow-up in the ADR or control group. In conclusion, serial assessment of the acoustic properties of the myocardium may not be an optimal tool for the early detection of myocardial damage after doxorubicin chemotherapy in a rat model

E2-25K/Hip-2 regulates caspase-12 in ER stress–mediated Aβ neurotoxicity

Amyloid-β (Aβ) neurotoxicity is believed to contribute to the pathogenesis of Alzheimer's disease (AD). Previously we found that E2-25K/Hip-2, an E2 ubiquitin-conjugating enzyme, mediates Aβ neurotoxicity. Here, we report that E2-25K/Hip-2 modulates caspase-12 activity via the ubiquitin/proteasome system. Levels of endoplasmic reticulum (ER)–resident caspase-12 are strongly up-regulated in the brains of AD model mice, where the enzyme colocalizes with E2-25K/Hip-2. Aβ increases expression of E2-25K/Hip-2, which then stabilizes caspase-12 protein by inhibiting proteasome activity. This increase in E2-25K/Hip-2 also induces proteolytic activation of caspase-12 through its ability to induce calpainlike activity. Knockdown of E2-25K/Hip-2 expression suppresses neuronal cell death triggered by ER stress, and thus caspase-12 is required for the E2-25K/Hip-2–mediated cell death. Finally, we find that E2-25K/Hip-2–deficient cortical neurons are resistant to Aβ toxicity and to the induction of ER stress and caspase-12 expression by Aβ. E2-25K/Hip-2 is thus an essential upstream regulator of the expression and activation of caspase-12 in ER stress–mediated Aβ neurotoxicity

Is it possible to reduce intra-hospital transport time for computed tomography evaluation in critically ill cases using the Easy Tube Arrange Device?

Objective Patients are often transported within the hospital, especially in cases of critical illness for which computed tomography (CT) is performed. Since increased transport time increases the risks of complications, reducing transport time is important for patient safety. This study aimed to evaluate the ability of our newly invented device, the Easy Tube Arrange Device (ETAD), to reduce transport time for CT evaluation in cases of critical illness. Methods This prospective randomized control study included 60 volunteers. Each participant arranged five or six intravenous fluid lines, monitoring lines (noninvasive blood pressure, electrocardiography, central venous pressure, arterial catheter), and therapeutic equipment (O2 supply device, Foley catheter) on a Resusci Anne mannequin. We measured transport time for the CT evaluation by using conventional and ETAD method. Results The median transport time for CT evaluation was 488.50 seconds (95% confidence interval [CI], 462.75 to 514.75) and, 503.50 seconds (95% CI, 489.50 to 526.75) with 5 and 6 fluid lines using the conventional method and 364.50 seconds (95% CI, 335.00 to 388.75), and 363.50 seconds (95% CI, 331.75 to 377.75) with ETAD (all P<0.001). The time differences were 131.50 (95% CI, 89.25 to 174.50) and 148.00 (95% CI, 116.00 to 177.75) (all P<0.001). Conclusion The transport time for CT evaluation was reduced using the ETAD, which would be expected to reduce the complications that may occur during transport in cases of critical illness

Efficacy of Tandem High-Dose Chemotherapy and Autologous Stem Cell Rescue in Patients Over 1 Year of Age with Stage 4 Neuroblastoma: The Korean Society of Pediatric Hematology-Oncology Experience Over 6 Years (2000-2005)

The efficacy of tandem high-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR) was investigated in patients with high-risk neuroblastoma. Patients over 1 yr of age who were newly diagnosed with stage 4 neuroblastoma from January 2000 to December 2005 were enrolled in The Korean Society of Pediatric Hematology-Oncology registry. All patients who were assigned to receive HDCT/ASCR at diagnosis were retrospectively analyzed to investigate the efficacy of single or tandem HDCT/ASCR. Seventy and 71 patients were assigned to receive single or tandem HDCT/ASCR at diagnosis. Fifty-seven and 59 patients in the single or tandem HDCT group underwent single or tandem HDCT/ASCR as scheduled. Twenty-four and 38 patients in the single or tandem HDCT group remained event free with a median follow-up of 56 (24-88) months. When the survival rate was analyzed according to intent-to-treat at diagnosis, the probability of the 5-yr event-free survival±95% confidence intervals was higher in the tandem HDCT group than in the single HDCT group (51.2±12.4% vs. 31.3±11.5%, P=0.030). The results of the present study demonstrate that the tandem HDCT/ASCR strategy is significantly better than the single HDCT/ASCR strategy for improved survival in the treatment of high-risk neuroblastoma patients

Short Term Effects of Topical Cyclosporine and Viscoelastic on the Ocular Surfaces in Patients with Dry Eye

PURPOSE: To compare the short term effects of topical 0.05% cyclosporine (CsA) and a mixture of 0.08% chondroitin sulfate and 0.06% sodium hyaluronate (CS-HA) on dry eye ocular surfaces. METHODS: 36 patients with moderate to severe dry eye (5 mm/5 min or less with Schirmer's test or tear break up time (BUT) less than 6 seconds), were treated with topical application of CS-HA on one eye and CsA on the other 4 times a day for 6-8 weeks. BUT, Schirmer's test without anesthesia, and conjunctival impression cytology (CIC; goblet cell density, nucleus to cytoplasmic ratio, and epithelial cell morphology) were evaluated and compared between eyes before and after treatment (repeated measurement of ANOVA). RESULTS: After treatment, BUT and tear wettings were significantly prolonged in each group. Topical CsA treated eyes had greater increase in BUT (p=0.026); there was no significant difference in tear wetting (p=0.132). While the 3 parameters of CIC improved in both groups, goblet cell density was significantly higher in eyes treated with CsA (p=0.033). CONCLUSIONS: While both CS-HA and 0.05% CsA eyedrops improve ocular surfaces, topical CsA may have a better effect on enhancing tear film stability and goblet cell density

Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyte

Background Current diagnostic tests for hereditary spherocytosis (HS) focus on the detection of hemolysis or indirectly assessing defects of membrane protein, whereas direct methods to detect protein defects are complicated and difficult to implement. In the present study, we investigated the patterns of genetic variation associated with HS among patients clinically diagnosed with HS. Methods Multi-gene targeted sequencing of 43 genes (17 RBC membrane protein-encoding genes, 20 RBC enzyme-encoding genes, and six additional genes for the differential diagnosis) was performed using the Illumina HiSeq platform. Results Among 59 patients with HS, 50 (84.7%) had one or more significant variants in a RBC membrane protein-encoding genes. A total of 54 significant variants including 46 novel mutations were detected in six RBC membrane protein-encoding genes, with the highest number of variants found in SPTB (n = 28), and followed by ANK1 (n = 19), SLC4A1 (n = 3), SPTA1 (n = 2), EPB41 (n = 1), and EPB42 (n = 1). Concurrent mutations of genes encoding RBC enzymes (ALDOB, GAPDH, and GSR) were detected in three patients. UGT1A1 mutations were present in 24 patients (40.7%). Positive rate of osmotic fragility test was 86.8% among patients harboring HS-related gene mutations. Conclusions This constitutes the first large-scaled genetic study of Korean patients with HS. We demonstrated that multi-gene target sequencing is sensitive and feasible that can be used as a powerful tool for diagnosing HS. Considering the discrepancies of clinical and molecular diagnoses of HS, our findings suggest that molecular genetic analysis is required for accurate diagnosis of HS.Support was provided by: the National Research Foundation of Korea (NRF) grant funded by the Korea government(MSIT) (NRF-2017R1A2A1A17069780) http://www.nrf.re.kr/