Anti-inflammatory and antioxidant properties of Schisandrin C promote mitochondrial biogenesis in human dental pulp cells.

AIM: To examine the properties of Schisandrin C as an anti-inflammatory and antioxidant compound, and whether its characteristics promote mitochondrial biogenesis in human dental pulp cells (HDPCs). METHODOLOGY: HDPCs were extracted from fresh third molars and cultured for experiments. Reactive oxidative stress (ROS) and nitric oxide (NO) formation were analysed by a Muse cell analyser. Western blotting and gelatin zymography were used to identify the presence of antioxidants, as well as anti-inflammatory and mitochondrial biogenesis with specific antibody. An unpaired Student's t-test was used for statistical analysis. RESULTS: Schisandrin C inhibited lipopolysaccharide-stimulated inflammatory molecules; interleukin 1 beta, tumour necrosis factor alpha, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, matrix metalloproteinase-2 and -9, NO production, ROS formation, nuclear factor kappa B translocation (P < 0.05) through the mitogen-activated protein kinase pathway. Schisandrin C increased the expression of superoxide dismutase enzymes as well as haem oxygenase-1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha through the phosphorylated-protein kinase B (p-Akt) and nuclear factor erythroid 2-related factor-2 pathways (P < 0.05). The anti-inflammatory and antioxidant properties of Schisandrin C promoted mitochondrial biogenesis. CONCLUSIONS: Schisandrin C has the potential to reduce inflammation and oxidation and to promote mitochondrial biogenesis. Therefore, Schisandrin C may be considered for use as an anti-inflammatory compound for oral inflammation through mitochondrial biogenesis.

Randomized clinical trial of immersive virtual reality tour of the operating theatre in children before anaesthesia.

BACKGROUND: A virtual reality (VR) tour of the operating theatre before anaesthesia could provide a realistic experience for children. This study was designed to determine whether a preoperative VR tour could reduce preoperative anxiety in children. METHODS: Children scheduled for elective surgery under general anaesthesia were randomized into a control or VR group. The control group received conventional information regarding anaesthesia and surgery. The VR group watched a 4-min video showing Pororo, the famous little penguin, visiting the operating theatre and explaining what is in it. The main outcome was preoperative anxiety, assessed using the modified Yale Preoperative Anxiety Scale (m-YPAS) before entering the operating theatre. Secondary outcomes included induction compliance checklist (ICC) and procedural behaviour rating scale (PBRS) scores during anaesthesia. RESULTS: A total of 69 children were included in the analysis, 35 in the control group and 34 in the VR group. Demographic data and induction time were similar in the two groups. Children in the VR group had a significantly lower m-YPAS score than those in the control group (median 31·7 (i.q.r. 23·3-37·9) and 51·7 (28·3-63·3) respectively; P < 0·001). During anaesthesia, the VR group had lower ICC and PBRS scores than the control group. CONCLUSION: This preoperative VR tour of the operating theatre was effective in alleviating preoperative anxiety and increasing compliance during induction of anaesthesia in children undergoing elective surgery. Registration number: UMIN000025232 (http://www.umin.ac.jp/ctr).

Donepezil 23 mg in Asian patients with moderate-to-severe Alzheimer's disease.

BACKGROUND: Ethnic diversity between different populations may affect treatment safety and efficacy. AIMS AND METHODS: A subanalysis to a global trial (study 326) was carried out to ascertain the safety and efficacy of donepezil 23 mg/day compared with donepezil 10 mg/day in Asian patients with moderate-to-severe Alzheimer's disease. Changes in cognition and global functioning were measured by the Severe Impairment Battery (SIB) and Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), respectively, at week 24. RESULTS: Cognitive improvement measured by SIB score was greater with donepezil 23 mg than with donepezil 10 mg (+1.36 vs -1.56]; difference, 2.92). There was no difference between the groups in global function measured by the CIBIC-Plus (3.94 and 3.95, respectively). Overall, 119 patients (82.1%) receiving donepezil 23 mg and 56 (71.8%) receiving donepezil 10 mg experienced ≥1 treatment emergent adverse events (TEAEs). In the donepezil 23 mg group, the incidence of TEAEs was higher among patients of lower weight (<55 kg) at baseline than in those of higher weight (64 of 75 patients [85.3%] vs 55 of 70 patients [78.5%]). CONCLUSIONS: The benefits and risks associated with donepezil 23 mg in Asian patients are comparable to those of the global study population.

The structural connectivity of the recurrent transient global amnesia.

BACKGROUND: One of recent interesting hypotheses of transient global amnesia (TGA) pathophysiology is the preexisting vulnerability of the memory network in patients with TGA. AIM OF THE STUDY: To verify the hypothesis that patients with recurrent amnestic attacks may have more disrupted structural connectivity than patients of a single TGA event, we compared the brain imaging of patients with repeated episodes of TGA with those who experienced a single attack. METHODS: Seven patients who were having recurrent TGA and 14 age- and sex-matched control subjects who had only a single episode of TGA participated in the study. Diffusion tensor images from both groups were assessed and analyzed using tract-based spatial statistics. RESULTS: The fractional anisotropy and mean diffusivity values were not reduced in any lesion within the memory pathway of recurrent patient group when compared with those of single event group. CONCLUSION: No disruptions in the structural connectivity of the memory pathway were observed in patients with recurrent TGA attacks, refuting the hypothesis that recurrent TGA patients present predisposing weakness of the memory network. The stability of structural connectivity suggests that repeated hippocampal lesions associated with TGA do not affect the microstructure of the brain.

Identification of a novel HLA-A*29 allele, HLA-A*29:01:09, by sequence-based typing in a Korean individual.

HLA-A*29:01:09 differs from A*29:01:01:01 by one nucleotide difference at nucleotide position 414.

Tenofovir-based alternate therapies for chronic hepatitis B patients with partial virological response to entecavir.

Entecavir (ETV) is a first-line antiviral therapy for treating chronic hepatitis B (CHB); however, some patients have suboptimal response to ETV. Currently, there are limited data on how to approach these patients. Therefore, our aim was to compare the effectiveness of two alternate therapies--tenofovir (TDF) monotherapy and combination therapy of ETV+TDF--in CHB patients with ETV partial virological response. We conducted a retrospective study of 68 patients who had partial virological response to ETV, defined as having detectable HBV DNA following at least 12 months of ETV, and were switched to TDF monotherapy (n = 25) or ETV+TDF (n = 43). Patients were seen in seven US liver/community-based clinics and started on ETV between 2005 and 2009. The majority of patients were male; the vast majority were Asian and had positive hepatitis B e antigen (HBeAg). Patients in both groups had similar pretreatment characteristics. Complete viral suppression (CVS) rates with TDF monotherapy and ETV+TDF were similar after 6 months (71% vs 83%, P = 0.23) and 12 months (86% vs 84%, P = 0.85), and there was no statistically significant difference in CVS rates even when only patients with higher HBV DNA levels at switch (>1000 IU/mL) were evaluated. Multivariate analysis indicated that ETV+TDF was not an independent predictor of CVS compared to TDF monotherapy (OR = 1.19, P = 0.63). In conclusion, TDF monotherapy and ETV+TDF are comparable in achieving CVS in CHB patients with partial virological response to ETV. Long-term alternate therapy with one pill (TDF monotherapy) vs two pills (ETV+TDF) could lead to lower nonadherence rates and better treatment outcomes.

Identification of a novel HLA-C*08 allele, HLA-C*08:78, by sequence-based typing in a Korean individual.

HLA-C*08:78 differs from C*08:01:01 by a nonsynonymous mutation at codon 239 (GGA to AGA) in exon 4.

Identification of a novel HLA-A*02 allele, A*02:428, by sequence-based typing.

HLA-A*02:428 differs from A*02:06:01 by a non-synonymous mutation at codon 260 (CAT to GAT) in exon 4.

Sex determination from partial segments and maximum femur lengths in Koreans using computed tomography.

BACKGROUND: The aim of this study was to establish standards for determining sex from fragmentary and complete femurs in a Korean population. MATERIALS AND METHODS: The statistical analysis of 12 variables (6 about breadth and 6 about length) based on 100 Korean femurs (from 50 males and 50 females) showed that all variables have significant sex differences. RESULTS: The most accurate discriminant variable was the condylar breadth parallel with epicondylar breadth (87.6% accuracy). In contrast, the transverse shaft diameter was not a discriminant variable for sex determination (67.0% accuracy). Breadth-related variables were generally more accurate than length-related variables. Three variables (vertical diameter of the neck [VDN], medial epicondylarlength [MCL], and condylar breadth [CB]) were selected from stepwise analysis fordiscriminating sex (93.5% accuracy). The discriminating equation was as follows: 0.171 × VDN + 0.172 × MCL + 0.128 × CB2 - 21.471. CONCLUSIONS: The results of this study are helpful for determining sex, even if a femur is found in a fragmented condition in the field.

Evolutionary and dispersal history of Eurasian house mice Mus musculus clarified by more extensive geographic sampling of mitochondrial DNA.

We examined the sequence variation of mitochondrial DNA control region and cytochrome b gene of the house mouse (Mus musculus sensu lato) drawn from ca. 200 localities, with 286 new samples drawn primarily from previously unsampled portions of their Eurasian distribution and with the objective of further clarifying evolutionary episodes of this species before and after the onset of human-mediated long-distance dispersals. Phylogenetic analysis of the expanded data detected five equally distinct clades, with geographic ranges of northern Eurasia (musculus, MUS), India and Southeast Asia (castaneus, CAS), Nepal (unspecified, NEP), western Europe (domesticus, DOM) and Yemen (gentilulus). Our results confirm previous suggestions of Southwestern Asia as the likely place of origin of M. musculus and the region of Iran, Afghanistan, Pakistan, and northern India, specifically as the ancestral homeland of CAS. The divergence of the subspecies lineages and of internal sublineage differentiation within CAS were estimated to be 0.37-0.47 and 0.14-0.23 million years ago (mya), respectively, assuming a split of M. musculus and Mus spretus at 1.7 mya. Of the four CAS sublineages detected, only one extends to eastern parts of India, Southeast Asia, Indonesia, Philippines, South China, Northeast China, Primorye, Sakhalin and Japan, implying a dramatic range expansion of CAS out of its homeland during an evolutionary short time, perhaps associated with the spread of agricultural practices. Multiple and non-coincident eastward dispersal events of MUS sublineages to distant geographic areas, such as northern China, Russia and Korea, are inferred, with the possibility of several different routes.

Skin cell targeting with self-assembled ligand addressed nanoemulsion droplets.

Dermo-pharmacy and cosmetic industries have utilized nanotechnologies for two decades. Initially proposed as vector systems for encapsulation of actives, they gained interest in increasing cutaneous bioavailability. Here, we assay the benefits of self-assembled nanoemulsions bearing ligands for targeting specific skin cells. Nanoemulsions, small droplets ranging typically from 20 nm to 150 nm, possess key properties for further use in cosmetics: long-term stability, optical transparency, extended range of textures and versatility. We investigated this nanoemulsion system and show ability to encapsulate a range of cosmetic actives with various physicochemical properties. Furthermore, this nanoemulsion presents a low cytotoxicity and is capable of directly targeting skin cells through simple addition of specific ligand in a one-step production protocol. This is of interest for increasing bioavailability of actives encapsulated into nanoemulsion droplets which may have penetrated the skin barrier to specific skin cell. Taken together, these chemical and in vitro observations suggest follow-up with in vivo models.

Excretory-secretory products of Giardia lamblia induce interleukin-8 production in human colonic cells via activation of p38, ERK1/2, NF-κB and AP-1.

Giardia lamblia, a pathogen causing diarrhoeal outbreaks, is interesting how it triggers immune response in the human epithelial cells. This study defined the crucial roles of signalling components involved in G. lamblia-induced cytokine production in human epithelial cells. Incubation of the gastrointestinal cell line HT-29 with G. lamblia GS trophozoites triggered production of interleukin (IL)-1ß, IL-8 and tumour necrosis factor (TNF)-α. IL-8 production was not significantly decreased by physically separating the HT-29 cells and G. lamblia GS trophozoites. Indeed, treatment of HT-29 with G. lamblia excretory-secretory products (ESP) induced IL-8 production. Electrophoretic mobility gel shift and transfection assays using mutagenized IL-8 promoter reporter plasmids indicated that IL-8 production by G. lamblia ESP occurs through activation of two transcriptional factors, nuclear factor kappaB (NF-κB) and activator protein 1 (AP-1) in HT-29 cells. In addition, activation of two mitogen-activated protein kinases (MAPKs), p38 and ERK1/2, was also detected in the HT-29 cells stimulated with G. lamblia ESP. Selective inhibition of these MAPKs resulted in decreased production of ESP-induced IL-8. These results indicate that activation of p38, ERK1/2 MAPK, NF-κB and AP-1 comprises the signalling pathway responsible for IL-8 production by G. lamblia ESP.

Effects of Material Thickness and Pretreatment on the Interfacial Gap of Translucent Zirconia Restorations with Self-adhesive Resin Cement.

PURPOSE: The first objective was to determine if the dual-curing of self-adhesive resin cement (SAC) with reduced light penetrating through zirconia had an effect on interfacial gap of zirconia restorations. The second purpose was to examine whether pretreatment methods for universal adhesive affected interfacial gap. The last aim was to compare the microhardness of SAC polymerized under different zirconia thicknesses. METHODS AND MATERIALS: This study evaluated self-adhesive resin cement (RelyX U200, 3M ESPE) after different pretreatment with universal adhesive (Single Bond Universal, 3M ESPE) under different polymerization conditions. CAD/CAM inlay cavities were prepared on extracted third molars. Translucent zirconia restorations were milled using Katana UTML (Kuraray). The teeth were divided into three groups: Groups I, II, and III in which the restoration thicknesses were 1, 2, and 3 mm. Each Group had three subgroups according to different pretreatment methods. For subgroup-1, no pretreatment was done on the prepared cavity. For subgroup-2, universal adhesive was applied and light-cured before cement placement (precure method). For subgroup-3, universal adhesive was applied; however, light-curing was done after cement placement (cocure method). After thermo-cycling, the interfacial gap at the restoration-tooth interface was investigated using swept-source optical coherence tomography imaging. Finally, microhardness was measured for SAC under different zirconia thicknesses. For statistical analysis, the interfacial gap was analyzed using two-way analysis of variance (ANOVA) to test the effect of cavity depth and pretreatment. In terms of each cavity depth and pretreatment, the interfacial gap was compared using one-way ANOVA and Scheffe's test. One-way ANOVA was also performed for comparison of the Vickers hardness results. RESULTS: Different thicknesses of the restoration resulted in differences in interfacial gaps except between the precure method of Groups I and II (p<0.05). The effect of universal adhesive pretreatment was different depending on the restoration thickness with exceptions in Groups I and III (p<0.05). Vickers hardness number decreased as the low radiant exposure of light was applied (p<0.05). CONCLUSION: Interfacial gap of zirconia restorations can differ depending on the material thickness, pretreatment, and activation mode. Reduced light intensity penetrating through zirconia may lead to higher interfacial gap percentage and lower microhardness of the self-adhesive resin cement. Application of a universal adhesive showed similar or reduced interfacial gaps in the cement space.

Analysis of 2D periodic nanostructures with an oxide overlayer via spectroscopic ellipsometry.

The accurate nondestructive determination of the shapes or critical dimensions of periodic nanostructures is essential to the current integrated-circuits technology. Optical critical dimension (OCD) metrology is fast, nondestructive, and can be used in air, allows higher sampling rates compared to the non-optical methods such as scanning electron microscopy (SEM) or atomic-force microscopy (AFM), and does not damage the sample. The data are typically analyzed via rigorous coupled-wave analysis (RCWA), where the sample is modeled as a series of layers whose dimensional parameters are determined by a least-squares fit. The layers are typically approximated as a combination of core material and ambient. Oxide overlayers and surface roughness are common, however, and call into question two-phase approximation. In this study, a structure that is periodic in two dimensions and that is coated with a thin (3 nm) oxide was studied, and an extension of the RCWA method that allows structural information to be extracted from optical data even in the presence of oxide overlayers or surface roughness was developed.

A new HLA-B*15 allele, HLA-B*9587, identified by sequence-based typing in a Korean individual.

A new HLA-B*9587 showed one nucleotide difference from B*15010101 at nucleotide 127 with substitution G-->C (codon 19 GAG-->CAG) resulting in a coding change from Glu to Gln (E19Q).

Nondestructive analysis of coated periodic nanostructures from optical data.

Optical data are essential for the accurate nondestructive determination of profiles of periodic structures in integrated-circuit technology. In rigorous coupled-wave analysis, the sample is generally modeled as layers consisting of a single material and the ambient. We extend present capabilities to the analysis of structures with overlayers and demonstrate our approach by determining quantitatively the thicknesses of top, sidewall, and bottom oxides of deliberately and naturally oxidized structures.

Effects of magnesium sulphate on intraoperative neuromuscular blocking agent requirements and postoperative analgesia in children with cerebral palsy.

BACKGROUND: In this double-blind, randomized, placebo-controlled study, we evaluated the effects of magnesium sulphate on neuromuscular blocking agent requirements and analgesia in children with cerebral palsy (CP). METHODS: We randomly divided 61 children with CP undergoing orthopaedic surgery into two groups. The magnesium group (Group M) received magnesium sulphate 50 mg kg(-1) i.v. as a bolus and 15 mg kg(-1) h(-1) by continuous infusion during the operation. The control group (Group S) received the same amount of isotonic saline. Rocuronium was administered 0.6 mg kg(-1) before intubation and 0.1 mg kg(-1) additionally when train-of-four counts were 2 or more. I.V. fentanyl and ketorolac were used to control postoperative pain. Total infused analgesic volumes and pain scores were evaluated at postoperative 30 min, and at 6, 24, and 48 h. RESULTS: The rocuronium requirement of Group M was significantly less than that of Group S [0.29 (0.12) vs 0.42 (0.16) mg kg(-1) h(-1), P<0.05]. Cumulative analgesic consumption in Group M was significantly less after operation at 24 and 48 h (P<0.05), and pain scores in Group M were lower than in Group S during the entire postoperative period (P<0.05). Serum magnesium concentrations in Group M were higher until 24 h after operation (P<0.05). The incidence of postoperative nausea and vomiting and rescue drug injections was similar in the two groups. No shivering or adverse effects related to hypermagnesaemia were encountered. CONCLUSIONS: I.V. magnesium sulphate reduces rocuronium requirements and postoperative analgesic consumption in children with CP.

The cardiac biomarker sodium-calcium exchanger (NCX-1) can differentiate between heart failure and renal failure: a comparative study of NCX-1 expression in dogs with chronic mitral valvular insufficiency and azotemia.

BACKGROUND: The sodium-calcium exchanger (NCX-1), an established cardiac biomarker, was postulated previously as differentiating between heart failure (HF) and renal failure (RF) in dogs. The effect of azotemia on NCX-1 expression has not been studied. HYPOTHESIS: In contrast to other cardiac biomarkers (eg, N-terminal-proBNP), we hypothesized that the expression level of NCX-1 is not influenced by either azotemia or decreased renal clearance. ANIMALS: Fifteen client-owned healthy control dogs, 14 dogs with chronic mitral valvular insufficiency (CMVI), classified based on severity of the disease by the established International Small Animal Cardiac Health Council classification system, and 15 dogs with RF, grouped according to the International Renal Interest Society stage classification. METHODS: A comparative study of the expression levels of NCX-1, evaluated in peripheral blood samples from dogs with HF, RF, and healthy controls by quantitative PCR. RESULTS: NCX-1 expression was significantly increased in moderate (2.99±0.61 [fold changes relative to normal group]) to severe (4.35±1.44) CMVI dogs (P<.01). In contrast, NCX-1 expression was not increased in the azotemic dogs. Furthermore, there was also no correlation between increased concentrations of creatinine and urea nitrogen in serum and NCX-1 expression in the RF group. CONCLUSIONS AND CLINICAL IMPORTANCE: Azotemia likely does not affect NCX-1 expression.

Interfacial Evaluation of CAD/CAM Resin Inlays on the Cavity Floor Using Swept-source Optical Coherence Tomography.

CLINICAL RELEVANCE: When a resin nanoceramic inlay is cemented using self-adhesive cement, a universal dentin adhesive can be applied to the prepared cavity. The application of the adhesive before self-adhesive cement placement provides similar or better interfacial adaptation than without the adhesive. SUMMARY: Purpose: The first objective of this study was to determine whether the luting material used for computer-aided design and computer-aided manufacture resin nanoceramic inlays affected interfacial adaptation. The second objective was to investigate whether application of a universal dentin adhesive before cementation affected interfacial adaptation. The final objective was to compare the inlay-side and dentin-side interfaces in the cement space.Methods and Materials: Seventy-four class I cavities were prepared on extracted human third molars. Cavities were optically scanned, and resin nanoceramic inlays were milled using Lava Ultimate blocks (3M ESPE). For the control groups, the fabricated inlays were cemented using Panavia V5 (Kuraray Noritake) or FujiCem 2 (GC). For the experimental groups, the teeth were randomly divided into groups I and II. Group I contained four subgroups using different luting materials; in all subgroups, the inlays were cemented and dual cured without pretreatment. Group II contained six subgroups in which inlays were cemented and dual cured after application of a universal dentin adhesive. After thermocycling, interfacial adaptation was measured using swept-source optical coherence tomography (SS-OCT) imaging and statistically compared among groups.Results: Interfacial adaptation was different depending on the luting material used (p<0.05). After application of a universal adhesive, some subgroups showed improved interfacial adaptation (p<0.05). In the comparison of inlay-side and dentin-side interfaces, no difference was found in interfacial adaptation (p>0.05).Conclusions: Interfacial adaptation for resin nanoceramic inlays differed with luting material. For some self-adhesive cements, application of a universal adhesive before cementation improved interfacial adaptation.

Identification of a novel HLA-Cw*04 allele, HLA-Cw*040106, by sequence-based typing in the Korean population.

A new human leukocyte antigen-Cw*0401 allele showed one nucleotide difference from Cw*04010101 in exon 3 at nucleotide position 561 (codon 163 ACG-->ACT) without a coding change.