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Since complex structure of the human respiratory system leads to the profound effect of the air flow and particle deposition, a realistic and flexible airway model is crucial for predicting in vivo lung deposition of pharmaceutical aerosol. This work presented a CFD study of air and particle flows in a realistic parametrically controlled airway model developed by Kitaoka under different inspiratory conditions. The results were analysed with simulation data obtained in the classic Weibel airway (WA) model and compared with previous experimental and simulation studies. The comparison showed both difference and similarity between two models. The inspiratory airflow was symmetric in the WA model, whereas in the Kitaoka model non-symmetrical airflow was dominated throughout airways. The Kitaoka model, in comparison to the WA model, also showed more complicated particle deposition pattern with larger particle deposition efficiency. The flow rate, however, showed a similar effect to both models; i.e. generally particle deposition efficiency was higher as flowrate was higher. The Kitaoka model was then extended from 7 generations (KG7) to 11 generations (KG11) to study the effect of airway generation. The simulations showed little difference between two structures in terms of inspiratory air velocity and particle deposition efficiency. This suggests that the KG7 model is sufficiently structured to obtain realistic particle deposition pattern. The study demonstrates the Kitaoka model has a great potential in modelling lung deposition of particles under different conditions.

Background This 24-week, multicenter, randomized, exploratory, comparative, open-label, phase-IV study assessed the safety and efficacy of prolonged-release tacrolimus (PR-T) with reduced-dose versus standard-dose corticosteroids in stable kidney transplant recipients in Korea after converting from cyclosporine-based therapy. Methods At baseline, patients were converted from cyclosporine-based to PR-T-based immunosuppression and randomized (1:1) to receive either corticosteroids maintained at prestudy dose (standard-dose group) or tapered from week 4 to 50% of the prestudy dose by week 12 (reduced-dose group). Patients were seen at baseline and weeks 1, 4, 12, and 24. The primary endpoint was change in estimated glomerular filtration rate (Modification-of-Diet-in-Renal-Disease-4) between baseline and week 24. Secondary endpoints included either acute rejection or patient-reported satisfaction with PR-T. Adverse events (AEs) were recorded. Results Overall, 150 patients were randomized into a reduced-dose group (n = 73) and a standard-dose group (n = 77). At week 24, mean ± standard deviation for corticosteroid dose was 2.5 ± 0.9 mg and 5.0 ± 1.3 mg, respectively. Mean change in estimated glomerular filtration rate from baseline to week 24 was +1.5 ± 9.1 mL/min/1.73 m2 (P = .1567) and +3.4 ± 10.6 mL/min/1.73 m2 (P = .0065), respectively, and not significantly different between groups. There were no acute rejection episodes. Most respondents (>70%) considered PR-T more convenient than cyclosporine. AE incidence was similar between groups. The most common AEs experienced by ≥3% of patients in either treatment group were gastrointestinal events (20.8% and 28.6% of patients receiving reduced- and standard-dose corticosteroids, respectively). Most AEs in both treatment groups were mild or moderate in severity. Conclusion Renal function was maintained following conversion from cyclosporine to PR-T, irrespective of corticosteroid regimen; PR-T enables reduced corticosteroid dosage.

Background Combined liver and kidney transplant is a very complex surgery. To date, there has been no report on the intraoperative management of patients with impaired cardiac function undergoing simultaneous ABO-compatible liver and ABO-incompatible kidney transplant from 2 living donors. Case Report A 60-year-old man underwent simultaneous ABO-compatible liver and ABO-incompatible kidney transplant from 2 living donors because of IgA nephropathy and alcoholic liver cirrhosis. The preoperative cardiac findings revealed continuous aggravation, shown by large left atrial enlargement, severe left ventricular hypertrophy, a very prolonged QT interval, and a calcified left anterior descending coronary artery. Severe hypotension with very weak pulsation and severe bradycardia developed, with an irregular junctional rhythm noted immediately after the liver graft was reperfused. Although epinephrine was administered as a rescue drug, hemodynamics did not improve, and central venous pressure and mean pulmonary arterial pressure increased to potentially fatal levels. Emergency phlebotomy via the central line was performed. Thereafter, hypotension and bradycardia recovered gradually as the central venous pressure and mean pulmonary arterial pressure decreased. The irregular junctional rhythm returned to a sinus rhythm, but the QTc interval was slightly more prolonged. Because of poor cardiac capacity, the volume and rate of fluid infusion were increased aggressively to maintain appropriate kidney graft perfusion after confirming vigorous urine production of the graft. Conclusions A heart with impaired function due to both end-stage liver and kidney diseases may be less able to withstand surgical stress. Further study on cardiac dysfunction will be helpful for the management of patients undergoing complex transplant surgery.

Device-associated infection (DAI) is an important issue related to patient safety. It is important to reduce unnecessary device utilization in order to decrease DAI rates.To investigate the time trend of device utilization ratios (DURs) of voluntarily participating hospitals, collected over a 10-year period through the Korean National Healthcare-associated Infections Surveillance System (KONIS).DURs from 2006 to 2015 in 190 intensive care units (ICUs) participating in KONIS were included in this study. DURs were calculated as the ratio of device-days to patient-days. The pooled incidences of DAIs and DURs were calculated for each year of participation, and the year-wise trends were analysed.Year-wise ventilator utilization ratio (V-DUR) increased significantly from 0.40 to 0.41 (F = 6.27, P 0.01), urinary catheter utilization ratio (U-DUR) increased non-significantly from 0.83 to 0.84 (F = 1.66, P = 0.10), and C-line utilization ratio (CL-DUR) decreased non-significantly from 0.55 to 0.51 (F = 1.62, P = 0.11). In the subgroup analysis, 'medical ICU' (F = 2.79, P 0.01) and 'hospital with900 beds' (F = 3.07, P 0.01) were associated with the significant increase in V-DUR.In Korea, V-DUR showed a significant, year-wise increasing trend. The trends for U-DUR and CL-DUR showed no significant decrease. Efforts are required to ensure the reduction of DURs.

We investigated whether low serum C3 level can cross-sectionally estimate severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in immunosuppressive drug-naive patients at diagnosis. We retrospectively reviewed the medical records of 139 patients with AAV, who were first classified as AAV at Severance Hospital. We obtained clinical and laboratory data including serum complement 3 (C3) level and calculated Birmingham vasculitis activity score (BVAS) at diagnosis. We stratified AAV patients into three groups according to the tertile of BVAS and defined the lower limit of the highest tertile as the cutoff for severe AAV (BVAS at diagnosis ≥ 16) at diagnosis. Low serum C3 level was defined as C3

Extension-block pinning represents a simple and reliable surgical technique. Although this procedure is commonly performed successfully, some patients develop postoperative extension loss. To date, the relationship between extension-block Kirschner wire (K-wire) insertion angle and postoperative extension loss in mallet finger fracture remains unclear.We aimed to clarify this relationship and further evaluate how various operative and non-operative factors affect postoperative extension loss after extension-block pinning for mallet finger fracture.A retrospective study was conducted to investigate a relationship between extension block K-wire insertion angle and postoperative extension loss. The inclusion criteria were: (1) a dorsal intra-articular fracture fragment involving 30% of the base of the distal phalanx with or without volar subluxation of the distal phalanx; and (2)3 weeks delay from the injury without treatment. Extension-block K-wire insertion angle and fixation angle of the distal interphalangeal (DIP) joint were assessed using lateral radiograph at immediate postoperative time. Postoperative extension loss was assessed by using lateral radiograph at latest follow-up. Extension-block K-wire insertion angle was defined as the acute angle between extension block K-wire and longitudinal axis of middle phalangeal head. DIP joint fixation angle was defined as the acute angle between the distal phalanx and middle phalanx longitudinal axes.Seventy-five patients were included. The correlation analysis revealed that extension-block K-wire insertion angle had a negative correlation with postoperative extension loss, whereas fracture size and time to operation had a positive correlation (correlation coefficient for extension block K-wire angle: -0.66, facture size: +0.67, time to operation: +0.60). When stratifying patients in terms of negative and positive fixation angle of the DIP joint, the independent t-test showed that mean postoperative extension loss is -3.67° and +4.54° (DIP joint fixation angles of0° and ≥0°, respectively, P=0.024). When stratifying patients in terms of extension-block K-wire insertion angle (30°, 30°-40°,40°), ANOVA showed significantly less postoperative extension loss for higher insertion angles (40°) than for medium insertion angles (30°-40°). Mean postoperative extension loss difference between higher insertion angle (40°) and medium insertion angle (30°-40°) was 11° (P=0.002).Using an insertion angle of the extension-block K-wire of 40°-45° and a slightly hyperextended position of the DIP joint may help reducing postoperative extension loss.Therapeutic level III.

Microalgae – unicellular photosynthetic organisms – have received increasing attention for their ability to biologically convert CO2 into valuable products. The commercial use of microalgae requires screening strains to improve the biomass productivity to achieve a high-throughput. Here, we developed a microfluidic method that uses a magnetic field to separate the microdroplets containing different concentrations of microalgal cells. The separation efficiency is maximized using the following parameters that influence the amount of lateral displacement of the microdroplets: magnetic nanoparticle concentration, flow rate of droplets, x- and y-axis location of the magnet, and diameter of the droplets. Consequently, 91.90% of empty, 87.12% of low-, and 90.66% of high-density droplets could be separated into different outlets through simple manipulation of the magnetic field in the microfluidic device. These results indicate that cell density-based separation of microdroplets using a magnetic force can provide a promising platform to isolate microalgal species with a high growth performance.

This increasing consumption of fossil fuels and emission of greenhouse gases causes climate change. Thus, the development of alternative energy sources such as biofuel is necessary. Microalgae have been spotlighted as renewable energy resources because the potential for producing biofuels from CO2. However, the unit cost for the production of algae-based biofuel must be reduced for commercialization compared to the petroleum. The optimization of culture conditions of microalgal strains is crucial to increase lipid production for economically viable biofuels. We rapidly analyzed the combined effect of various stress conditions (nitrogen starvation, temperature, pH, and salt concentration) on the lipid production in various strains using a multiplex microfluidic system, enabling multiple operations from cell culture to lipid extraction of different strains. We found the lipid productivity was enhanced by 25 to 54% under combinations of two stress condition compared to the single stress condition. However, the combination of more than three stress conditions reduced the lipid productivities of all microalgal strains because of more stressful environment to the cells compared to the combinations of two stress conditions. We further validated the synergistic effect of combined stress conditions in flask culture with the increases in lipid productivities by up to 106% compared to the single stress condition. We also observed that fatty acids composition, which influences the quality of algal biofuels, was changed according to the combination of stress conditions. In particular, C. protothecoides can be good candidate for production of high quality of biodiesel, because it has high CN, IV and low CFPP which is suitable for high quality of biodiesel. These results indicate that combination of multiple stress conditions can be efficient strategy for the optimization of microalgal cultivation to produce algal biofuels with high quality and economic feasibility.

The braking hose in the automotive hydraulic braking system exhibits the complicated anisotropic large deformation while its movable end is moving along the cyclic path according to the steering and bump/rebound motions of vehicle. The complicated large deformation may cause not only the interference with other adjacent automotive parts but also the durability problem resulting in the fatal microcraking. In this regard, the design of highdurable braking hose with the interference-free layout becomes a hot issue in the automotive industry. However, since it has been traditionally relied on the cost-/time-consuming trial and error experiments, the cost- and timeeffective optimum design method that can replace the experiment is highly desirable. Meanwhile, the hose deformed configuration and fatigue life are different for different hose cyclic paths, so that their characteristic investigation becomes an important preliminary research subject. As a preliminary step for developing the optimum design methodology, we in this study investigate the hose deformed configuration and the fatigue life for four representative hose cyclic paths.

Background Cytokine genotypes have previously been studied in patients undergoing solid organ transplantation; certain polymorphisms have been implicated in the development of acute rejection (AR) and graft dysfunction (GD). Allograft outcomes determined, in part, by alloimmune responses is mainly mediated by T-cell responses, activated and driven by cytokines. Interleukin-4 (IL-4) is one such cytokine, which exerts its biological effects through binding to the IL-4 receptor (IL-4R) complex on target cells. In the present study, we investigated whether polymorphisms of the IL-4 and/or IL-4R gene were associated with susceptibility to acute AR and GD after kidney transplantation. Methods We analyzed 2 single nucleotide polymorphism (SNPs) of IL-4 (rs2243250 and rs2070874) and 3 SNPs of IL-4R (rs1801275, rs2107356, and rs1805010) in 344 kidney transplant recipients. These patients included 62 of whom had developed AR and 215 of whom had GD in 1 year after kidney transplantation. Results The AR group included 62 patients (45 men and 17 women). There was a statistically significant difference in the male-to-female ratio and the use of tacrolimus in the AR group. The GD group included 215 patients. Patients who developed GD were more likely to be older and have an underlying cause of end-stage renal disease that was unknown compared with patients who did not have GD, the cause of which was typically known. Among the SNPs examined, 1 of the SNPs in the IL-4R gene (ie, rs1801275) showed a statistical association with AR (co-dominant model, P = .061; dominant model, P = .019; and log-addictive model, P = .029). In addition, 1 of the IL-4R SNPs (ie, rs2107356) was statistically associated with GD (dominant model, P = .034). No significant difference in the IL-4 genotype was observed between the AR/GD and non-AR/non-GD subjects. Conclusions One IL-4R gene polymorphism (rs1801275) was associated with AR. In addition, a separate IL-4R SNP (rs2107356) was statistically associated with GD after kidney transplantation.

As the most feasible solution beyond FinFET technology, a gate-all-around Multi-Bridge-Channel MOSFET (MBCFET) technology is successfully demonstrated including a fully working high density SRAM. MBCFETs are fabricated using 90% or more of FinFET processes with only a few revised masks, allowing easy migration from FinFET process. Not only on-target but also multiple Vt is achieved in challengingly limited vertical spacing between channels. Also, reliability of MBCFETs is shown to be comparable to that of FinFETs. Three representative superior characteristics of MBCFET compared to FinFET have been demonstrated — better gate control with 65 mV/dec sub-threshold swing (SS) at short gate length, higher DC performance with a larger effective channel width (Weff) at reference footprint, and design flexibility with variable nanosheet (NS) widths. The optimization of the standard cell design by using variable NS width is evaluated. The usefulness of MBCFET as a multi-purpose performance provider is proven by the modulation of effective capacitance (Ceff), effective resistance (Reff) and frequency by Weff control. Finally, mass production feasibility with MBCFET is proven through a fully working high density SRAM circuit.

Endoscopic third ventriculostomy (ETV) is a common alternative method for the management of hydrocephalus in selected patients. A retrospective chart review was conducted to review our experience with ETV for patients with a variety of causes for hydrocephalus. A total of 67 children with median age of 10.8 years (range= 8 weeks to 21 years) underwent 76 ETVs from July 1992 to June 2003. Two procedures were abandoned due to anatomical distortion. The medical records, operative reports, and imaging studies, were retrospectively reviewed with regard to outcome, complications and patency rate. Treatment failure was defined as the need to shunt the patient within 4 weeks of performing the ETV. The overall success rate was 83% with a mean follow-up 40.8 months. Nine patients underwent 11 repeat ETVs at an average interval period of 24 months with a patency rate of 90% following the second procedure. Ten of eleven patients who underwent re-ETV were ultimately shunt-independent. The highest success rates were achieved for obstructive hydrocephalus from midbrain/tectal tumor (100%, n = 4), pineal tumor (100%, n = 3), intraventricular tumor or cyst (100%, n = 2), and post-infectious hydrocephalus (100%, n = 1). Lower patency rates were noted in patients with Chiari malformation (0%, n = 1) and posterior fossa tumors (63%, n = 8). Due to the efficacy of ETV, it should be considered as the primary procedure, rather than ventricular peritoneal shunts, in carefully selected children. The reliability rate is dependent upon the age and etiology of hydrocephalus.

This paper proposes an offshore WPP (wind power plant) shutdown algorithm that does not use a braking system and meets the required ramp rate in the grid code in various storm-driven conditions. The proposed algorithm determines the number of WGs (wind generators) to shut down simultaneously to achieve this requirement without using brakes. Based on the storm speed and direction measured at a WM (wind mast) installed several kilometers away from the WPP, the storm-arrival time from the WM to each WG is calculated. Then, an arrival-ordered sequence is generated for the WGs based on these storm-arrival times. The WGs are grouped in a predetermined number to shut down simultaneously. The shutdown start- and end-times of the WGs are determined by considering the storm-arrival time and the shutdown duration time. The algorithm re-calculates the storm-arrival times and the shutdown start- and end-times of the WGs if the storm speed and/or direction change. The various test results demonstrate that the algorithm successfully shuts down the WPP without using a brake by meeting the required ramp rate even when the storm speed and direction change.

AIM: To investigate the role of O-GlcNAcylation of nuclear factor-kappa B (NF-κB) in retinal ganglion cell (RGC) death and analysedthe effect of Aralia elata (AE) on neurodegeneration in diabetic mice. METHODS: C57BL/6mice with streptozotocin-induced diabetes were fed daily with AE extract or control (CTL) diet at the onset of diabetes mellitus (DM). Two months after injection of streptozotocin or saline, the degree of cell death and the expression of O-GlcNAc transferase (OGT), N-acetyl-b-D-glucosaminidase (OGA), O-GlcNAcylated proteins, and O-GlcNAcylation of NF-κB were examined. RESULTS: AE did not affect the metabolic status of diabetic mice. The decrease in the inner retinal thickness (P

For economically viable biofuel production from microalgae, it is necessary to develop efficient analytical platforms for quantitative evaluation of different lipid productivities of numerous microalgal species. Currently, microalgal culture, lipid accumulation, and lipid extraction depend on conventional benchtop methods requiring laborious and time-consuming processes. A poly(dimethylsiloxane) (PDMS)-based integrated microfluidic platform was developed to perform multiple steps in sample preparation on a single device for efficient and quantitative analysis of lipid from various microalgal strains. To achieve this goal, a simple microchannel with a micropillar array was integrated to connect the cell chamber and output reservoir, which act as a filtration unit that enables medium change and solvent extraction by fluid injection using a syringe pump. Multiple processes of cell culture, lipid accumulation, and lipid extraction were successfully accomplished using a single device without time-consuming and labor-intensive steps. Various conditions of solvent volume and temperature were investigated to optimize lipid extraction yield in the microfluidic device. The lipid extraction efficiency in the microfluidic system was higher than that in bulk using the same solvent. The lipid extraction efficiency achieved using less toxic aqueous isopropanol on the integrated device was 113.6% of that obtained with the conventional Bligh-Dyer method. Finally, lipid productivities of different microalgal strains grown in the microfluidic device were analyzed and compared. These results demonstrate that this simple integrated microfluidic platform can be applied as an alternative to conventional benchtop methods for efficient sample preparation in microalgal lipid analysis.

This study evaluated the effects of renal impairment (RI) and haemodialysis (HD) on the pharmacokinetics of gemigliptin, a novel dipeptidyl peptidase-4 (DPP-4) inhibitor. After a 100 mg administration to subjects with normal renal function (n = 23) or RI (n = 24), plasma, urine or dialysate samples were analysed. Control subjects were matched to patients based on age, gender and body mass index. Patients with mild, moderate, severe RI and end-stage renal disease (ESRD) showed 1.20, 2.04, 1.50 and 1.66-fold (1.10, 1.49, 1.22 and 1.21-fold) increase of mean area under the time-plasma concentration curve from 0 to infinity (AUCinf) [maximum plasma concentration (Cmax)] of gemigliptin, respectively. Pharmacokinetics of gemigliptin was comparable between HD and non-HD periods in ESRD patients. Less than 4% of the dose was removed by 4 h HD. RI appeared to have modest effect on the gemigliptin disposition. No dose adjustment in patients with RI is proposed on the basis of exposure-response relationship. Impact of HD on the removal of gemigliptin was negligible.

Purpose A national organ transplant registry is an indispensable organizational requirement for patient care, research, and planning. Even though the Korean Network for Organ Sharing (KONOS) has established a database for a waiting list, organ allocation, and incidence of organ transplantation since 2000, an integrated registry including post-transplantation data is needed for better understanding of organ transplantation. Recently, the Korean Society for Transplantation (KST) and the Korean Center for Disease Control (KCDC) designed a web-based organ transplant registry, named the Korean Organ Transplant Registry (KOTRY). As an initial project of KOTRY, we retrospectively analyzed kidney transplantations (KTs) performed in 2009 and 2010. Methods A total of 2292 KTs (91.9%) from 46 hospitals (80.7%) were collected and analyzed. Ninety-five elements related to KT were selected and analyzed. Results Proportions of male recipients and retransplantations were 58.4% and 7.1%, respectively. Even though glomerulonephritis was the most common cause of end-stage renal disease (ESRD) (28.4%), the number of diabetic nephropathy cases was increasing. The living donor (LD) to deceased donor (DD) ratio was 1.69:1. Because of a serious organ shortage in Korea, DD kidneys with a low initial estimated glomerular filtration rate (eGFR) of 2 (21.2%) and expanded criteria donors (ECDs; 18.3%) are frequently used. Other noticeable findings are the increasing number of wife donors and ABO-incompatible (ABOi) transplants for O + recipients. Conclusions The epidemiological profile of transplantation is different from country to country. The number of organ transplantations in East Asian countries is rapidly growing, however, there are few epidemiological data about this region in the literature. With the establishment of KOTRY, it was possible to present the first nationwide epidemiological data of Korean KTs.

Introduction/Background Plantar fasciitis is very troublesome in clinical fields. Although steroid injection has been a widely used treatment option in musculoskeletal disorders, there have been arguments about the effectiveness in plantar fasciitis. This study is to determine the effectiveness of steroid injection in the treatment of plantar fasciitis. Material and method Meta-analysis was conducted using searching engines such as Google Scholar, PubMed, CINAHL, Embase and manual searching which were searched to December 2017. The following key search terms were used; plantar fasciopathy fasciitis in google scholar, “fasciitis, plantar”[Mesh] with two filter options “Randomized Controlled Trial” and “human” in PubMed, plantar fasciopathy fasciitis in CINAHL, plantar AND fasciopathy AND (“fasciitis” OR “fasciitis”/exp OR fasciitis) in Embase. Two articles were also found using manual searching. Total 35 articles were found and duplicates were removed. Two reviewers reviewed and selected the articles, which has randomized controlled design and eligible data. Four articles were determined to be relevant, meeting inclusion and exclusion criteria. Results We found that the overall standardized mean differences of pain outcome between steroid injection and other treatments or sham was −0.57 (95% confidence interval: −0.83 to −0.30), with low heterogeneity (P = 0.52, I2 = 0%) at 1 month, but −0.33 (95% confidence interval: −0.76 to 0.10, P = 0.13, I2 = 50%) at 3 month. It suggested evidence of the effectiveness of short-term steroid injection, compared with autologous blood injection or other conservative treatment, but limited evidence of long-term effectiveness and functional improvement. Conclusion Although steroid injection in treating plantar fasciitis has been arguing, there is evidence of the effectiveness of steroid injection in relieving pain for 1 month. But further study is needed to determine long-term effectiveness of steroid injection.

Background The phase II trial evaluated the efficacy and safety of low starting dose of afatinib in patients with advanced epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). In primary analysis, progression free survival (PFS) met the primary endpoint. Here, we report updated survival outcomes. Methods This study was a multi-center, single-arm, open-label phase II trial. Treatment-naive patients with common EGFR mutation-positive NSCLC were treated with afatinib starting at a dose of 20 mg/day. If tolerated, the dose is increased by 10- mg increments up to 50mg/day. PFS and overall survival (OS) were re-evaluated at the final data cut-off point (October 2018). Results 46 patients were enrolled. Median age was 73 years (range, 43-86). The median follow-up was 31.9 months. Median PFS of entire population was 15.2 months (95% confident interval (CI), 13.2–21.2), and 2-year PFS rate was 27.7% (95% CI, 17.1-44.7). Median OS was not estimated, and the 2-year overall survival was 76.1% (95% CI, 64.7-89.5). Performance status (PS) and existence of brain metastases at study entry were revealed to have significant impact on the survival with Cox-regression test. Among patients with disease progression on afatinib (n = 36), rebiopsy was performed on 29 patients, and T790M was proved positive on 14 patients. Twelve out of the 14 patients positive for T790M received osimertinib as a second line therapy. Median time from enrollment to progression on the osimertinib (PFS2) was 32.6 months (95%CI: 20.5-NE). Conclusions Low starting dose afatinib therapy demonstrated promising OS outcome. PS and existence of brain metastases were predictive factors of this therapy. Clinical trial identification UMIN 000016444. Legal entity responsible for the study Kyoto Thoracic Oncology Research Group. Funding Has not received any funding. Disclosure T. Yokoyama: Honoraria (self): Boehringer Ingelheim Japan; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Novartis; Honoraria (self): AstraZeneca; Honoraria (self): Ono pharmaceutical; Honoraria (self): MSD. H. Yoshioka: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Eli Lilly Japan; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Novartis; Honoraria (self): Merck Serono; Honoraria (self): Kyowa Kirin; Honoraria (self): AstraZeneca; Honoraria (self): Ono pharmaceutical; Honoraria (self): Daiichi Sankyo; Honoraria (self): MSD. D. Fujimoto: Honoraria (self), Research grant / Funding (self): AstraZeneca KK; Honoraria (self): Ono Pharmaceutical Co Lt; Honoraria (self): Bristol-Myers Squibb Co Ltd; Honoraria (self): Taiho Pharmaceutical Co ; Honoraria (self), Research grant / Funding (self): Chugai Pharmaceutical Co Ltd; Honoraria (self): MSD KK; Honoraria (self): Boehringer Ingelheim Japan Inc; Honoraria (self): Eli Lilly Japan KK. K. Hirano: Honoraria (self): Boehringer Ingelheim Japan. T. Ishida: Honoraria (self): Boehringer Ingelheim Japan. T. Hirai: Research grant / Funding (institution): Boehringer Ingelheim Japan. All other authors have declared no conflicts of interest.

We recently demonstrated that pain-sensing neurons in the trigeminal system can be selectively anesthetized by co-application of QX-314 with the TRPV1 receptor agonist, capsaicin (QX cocktail). Here we examined whether this new anesthetic strategy can block the neuronal changes in the brainstem following molar tooth extraction in the rat. Adult male Sprague-Dawley rats received infiltration injection of anesthetic 10 min prior to lower molar tooth extraction. Neuronal activation was determined by immunohistochemistry for the proto-oncogene protein c-Fos in transverse sections of the trigeminal subnucleus caudalis (Sp5C). After tooth extraction, c-Fos-like immunoreactivity (Fos-LI) detected in the dorsomedial region of bilateral Sp5C was highest at 2 hrs ( p < .01 vs. naïve ipsilateral) and declined to pre-injury levels by 8 hrs. Pre-administration of the QX cocktail significantly reduced to sham levels Fos-LI examined 2 hrs after tooth extraction; reduced Fos-LI was also observed with the conventional local anesthetic lidocaine. Pulpal anesthesia by infiltration injection was confirmed by inhibition of the jaw-opening reflex in response to electrical tooth pulp stimulation. Our results suggest that the QX cocktail anesthetic is effective in reducing neuronal activation following tooth extraction. Thus, a selective pain fiber ‘nociceptive anesthetic’ strategy may provide an effective local anesthetic option for dental patients in the clinic.

10nm logic technology using Si FinFET is developed for low power and high performance applications. Power-speed gain of 27% compared to 14nm technology node was obtained using four key developments: 1) advanced gate stack engineering enabling 4 multi-Vt devices, 2) 3rd generation Fin technology, 3) highly doped source/drain (S/D), and 4) contact resistance optimization. CVD liner for BEOL process was also applied for better metal fill capability. Finally yield of the smallest ever SRAM with 0.04um2 SRAM bit-cell size was demonstrated.

BACKGROUND AND PURPOSE: We reported the MR findings of spinal metastatic lesions after SRS according to the volumetric changes (in press). However, in the case of osteoblastic metastatic lesions, tumor volume usually doesn9t change during remission. In this study, we retrospectively analyzed pre- and post-SRS CT and MR imaging findings of locally controlled osteoblastic spinal metastatic lesions besides volumetric changes MATERIALS AND METHODS: Among 113 spinal metastatic lesions in 72 patients, 10 lesions were osteoblastic. CT and MR images were reviewed to identify 4 parameters: 1) changes in tumor volume, 2) changes in CT attenuation, 3) changes in T2 signal intensities and 4) changes in degrees of contrast enhancement. RESULTS: Tumor volume was unchanged in 9 lesions and increased in 1 lesion. CT attenuation increased in 7 lesions and T2 signal intensities were heterogenous with dark signal foci within the tumor in 3 of 7 lesions and with dark and bright signal foci within the tumor in 4 of 7 lesions. In 3 lesions where CT attenuation decreased, T2 signal intensity became heterogenous with dark and bright foci in 2 of 3 lesions and T2 signal intensity became normalized in 1 lesion. The degree of contrast enhancement decreased in 8 lesions but 2 lesions showed persistent contrast enhancement. CONCLUSIONS: Further progression of sclerotic changes was a more common finding than loss of sclerotic foci. Main MR imaging features of osteoblastic lesions after treatment were development of dark with or without bright signal foci, with decrease in contrast enhancement.

The purpose of the present study was to analyze the lower stiffness over the difference between soft and stiff landings during hopping. Five male subjects performed hopping on two legs at 2.5 Hz. During the experiments, 3D motion capture system was used to obtain the kinematic data and two force plates were synchronized to calculate the kinetic data. We determined lower extremity stiffness of the knee and ankle from kinetic and kinematic data. Leg stiffness was approximately 1.2-times significantly higher in stiff landing than in soft landing_ There was no significant difference in knee joint stiffness between soft and stiff landings. Ankle joint stiffness was approximately 1.34-times significantly higher in stiff landing than in soft landing. These results suggest that humans adjust lower extremity stiffness over the comparison of two different landing methods we evaluated.

The femoral nerve innervates the quadriceps muscles and its dermatome supplies anteromedial thigh and medial foot. Paralysis of the quadriceps muscles due to the injury of the femoral nerve results in disability of the knee joint extension and loss of sensory of the thigh. A child could walk independently even though he had injured his femoral nerve severely due to the penetrating wound in the medial thigh. We measured and analyzed his gait performance in order to find the mechanisms that enabled him to walk independently. The child was eleven-year-old boy and he could not extend his knee voluntarily at all during a month after the injury. His gait analysis was performed five times (GA1~GA5) for sixteen months. His temporal-spatial parameters were not significantly different after the GA2 or GA3 test, and significant asymmetry was not observed except the single support time in GA1 results. The Lower limb joint angles in affected side had large differences in GA1 compared with the normal normative patterns. There were little knee joint flexion and extension motion during the stance phase in GA1 The maximum ankle plantar/dorsi flexion angles and the maximum knee extension angles were different from the normal values in the sound side. Asymmetries of the joint angles were analyzed by using the peak values. Significant asymmetries were found in GA1with seven parameters (ankle: peak planter flexion angle in stance phase, range of motion; ROM, knee: peak flexion angles during both stance and swing phase, ROM, hip: peak extension angle, ROM) while only two parameters (maximum hip extension angle and ROM of hip joint) had significant differences in GA5. The mid-stance valleys were not observed in both right and left sides of vertical ground reaction force (GRF) in the GA1, GA2. The loading response peak was far larger than the terminal stance peak of vertical ground reaction curve in the affected side of the GA3, GA4, GA5. The measured joint moment curves of the GA1, GA2, GA3 had large deviations and all of kinetic results had differences with the normal patterns. EMG signals described an absence of the rectus femoris muscle activity in the GA1 and GA2 (affected side). The EMG signals were detected in the GA3 and GA4 but their patterns were not normal yet, then their normal patterns were detected in the GA5. Through these following gait analysis of a child who had selective injuries on the knee extensor muscles, we could verify the actual functions of the knee extensor muscles during gait, and we also could observe his recovery and asymmetry with quantitative data during his rehabilitation.