Effects of exercise therapy on pain and disability in patients with non-specific neck pain: A systematic review and meta-analysis.

BACKGROUND: Existing systematic reviews and meta-analyses have only focused on patients with chronic non-specific neck pain (NNP), analyzing exercise therapy (ET) only as therapeutic exercise. Therefore, it is necessary to comprehensively review the effects of ET through a meta-analysis comprising a wide range of ETs that are not limited to therapeutic exercise. OBJECTIVES: This study aimed to investigate the effects of ET on pain and disability in patients with NNP. DESIGN: Systematic review and meta-analysis. METHOD: The studies selected for this study were based on the PICO-SD tool as follows: P (patient)-acute, subacute, and chronic NNP patents, I (intervention)-ET, C (comparison)-control and other therapy groups, O (outcome)-pain and disability, and SD (study design)-randomized controlled trial. RESULTS: Twenty-one studies were included. The effects of ET on pain and disability in patients with chronic NNP were significantly different (pain: SMD -1.47, 95% CI: -1.89 to -1.06, I2: 94%; disability: SMD -1.79, 95% CI: -2.31 to -1.27, I2: 94%). The effects of ET on pain (ET vs control: SMD: -1.60, 95% CI: -2.09 to -1.11, I2: 94%; ET vs sham therapy: SMD: -8.75, 95% CI: -10.71 to -6.79) and disability (ET vs control: SMD: -2.16, 95% CI: -2.80 to -1.52, I2: 94%; ET vs sham therapy: SMD: -1.73, 95% CI: -2.42 to -1.05) in NNP patients were significantly different. CONCLUSIONS: This study verified the efficacy of ET in improving pain and disability in patients with chronic NNP. However, evidence supporting the efficacy of ET in patients with acute and subacute NNP is still lacking.

Effects of smart phone use on lower limb joint angle and dynamic balance during gait.

BACKGROUND: Cognitive tasks influence gait by reducing balancing abilities. Diverse studies to date have examined dual-tasking and gait. OBJECTIVE: This study aimed to determine the influences of smart phone use while walking on lower limb joint angle and dynamic balancing ability. METHODS: Thirty healthy subjects were voluntarily recruited from the university population. All subjects were required to perform the tasks under three conditions: not using a smart phone, having a conversation by phone, and playing a smart phone game. Lower limb joint angle and dynamic balance ability related to smart phone use during gait were measured. Motion analysis was used to measure lower limb joint angle changes during gait, while balance measuring equipment was used to measure the dynamic balancing ability. RESULTS: In the stability limit test to measure the changes in dynamic balancing abilities, significant differences were found among the different smart phone use conditions. CONCLUSIONS: Smart phone use during movements that are required for balance requires special attention, and this study provides important basic data for follow-up studies.

Discovery of a Novel Highly Selective Histamine H4 Receptor Antagonist for the Treatment of Atopic Dermatitis.

The histamine H4 receptor (H4R), a member of the G-protein coupled receptor family, has been considered as a potential therapeutic target for treating atopic dermatitis (AD). A large number of H4R antagonists have been disclosed, but no efficient agents controlling both pruritus and inflammation in AD have been developed yet. Here, we have discovered a novel class of orally available H4R antagonists showing strong anti-itching and anti-inflammation activity as well as excellent selectivity against off-targets. A pharmacophore-based virtual screening system constructed in-house successfully identified initial hit compound 9, and the subsequent homology model-guided optimization efficiently led us to discover pyrido[2,3- e]tetrazolo[1,5- a]pyrazine analogue 48 as a novel chemotype of a potent and highly selective H4R antagonist. Importantly, orally administered compound 48 exhibits remarkable efficacy on antipruritus and anti-inflammation with a favorable pharmacokinetic (PK) profile in several mouse models of AD. Thus, these data strongly suggest that our compound 48 is a promising clinical candidate for treatment of AD.

Pseudoxanthomonas putridarboris sp. nov. isolated from rotten tree.

A Gram-staining-negative, rod-shaped, motile bacterium, designated WD12T, was isolated from a rotten tree at Chungbuk National University, South Korea. WD12T grew optimally at 30-37 °C and pH 7.0-7.5 and could assimilate arbutin and potassium-5-ketogluconate. The major cellular fatty acid were iso-C16 : 0, C16 : 0, cyclo C17 : 0, iso-C15 : 0, summed features 3 (comprising C16 : 1ω7c/iso-C15 : 0 2-OH) and anteiso-C15 : 0. The major polar lipids consisted of phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol. The major respiratory quinone was ubiquinone-8 (Q-8). The G+C content of the genomic DNA was 69.1 %. The results of phylogenetic and comparative analysis based on the 16S rRNA gene sequence indicated that WD12T formed a tight phylogenetic lineage with Pseudoxanthomonas mexicana AMX 26BT and Pseudoxanthomonas japonensis 12-3T of the the genus Pseudoxanthomonas in the family Xanthomonadaceae. Sequence similarity to other members of the genus Pseudoxanthomonasranged from 98.6 % (P. mexicana AMX 26BT) to 95.1 % (Pseudoxanthomonas taiwanensis CB-226T). DNA-DNA relatedness between WD12T and eight type strains of species of the genus Pseudoxanthomonasshowing more than 97 % 16S rRNA sequence similarity were 6±0-26±1 %. On the basis of the evidence from this polyphasic study, WD12T represents a novel species of the genus Pseudoxanthomonas, for which the name Pseudoxanthomonas putridarboris sp. nov. is proposed. The type strain is WD12T (=KACC 15045T=LMG 25968T).

Contrast-dependent saturation adjustment for outdoor image enhancement.

Outdoor images captured in bad-weather conditions usually have poor intensity contrast and color saturation since the light arriving at the camera is severely scattered or attenuated. The task of improving image quality in poor conditions remains a challenge. Existing methods of image quality improvement are usually effective for a small group of images but often fail to produce satisfactory results for a broader variety of images. In this paper, we propose an image enhancement method, which makes it applicable to enhance outdoor images by using content-adaptive contrast improvement as well as contrast-dependent saturation adjustment. The main contribution of this work is twofold: (1) we propose the content-adaptive histogram equalization based on the human visual system to improve the intensity contrast; and (2) we introduce a simple yet effective prior for adjusting the color saturation depending on the intensity contrast. The proposed method is tested with different kinds of images, compared with eight state-of-the-art methods: four enhancement methods and four haze removal methods. Experimental results show the proposed method can more effectively improve the visibility and preserve the naturalness of the images, as opposed to the compared methods.

The effects of visual control whole body vibration exercise on balance and gait function of stroke patients.

[Purpose] This study aims to verify the effects of visual control whole body vibration exercise on balance and gait function of stroke patients. [Subjects and Methods] A total of 22 stroke patients were randomly assigned to two groups; 11 to the experimental group and 11 to the control group. Both groups received 30 minutes of Neuro-developmental treatment 5 times per week for 4 weeks. The experimental group additionally performed 10 minutes of visual control whole body vibration exercise 5 times per week during the 4 weeks. Balance was measured using the Functional Reach Test. Gait was measured using the Timed Up and Go Test. [Results] An in-group comparison in the experimental group showed significant differences in the Functional Reach Test and Timed Up and Go Test. In comparing the groups, the Functional Reach Test and Timed Up and Go Test of the experimental group were more significantly different compared to the control group. [Conclusion] These results suggest that visual control whole body vibration exercise has a positive effect on the balance and gait function of stroke patients.

Hyperspectral face recognition using improved inter-channel alignment based on qualitative prediction models.

A fundamental limitation of hyperspectral imaging is the inter-band misalignment correlated with subject motion during data acquisition. One way of resolving this problem is to assess the alignment quality of hyperspectral image cubes derived from the state-of-the-art alignment methods. In this paper, we present an automatic selection framework for the optimal alignment method to improve the performance of face recognition. Specifically, we develop two qualitative prediction models based on: 1) a principal curvature map for evaluating the similarity index between sequential target bands and a reference band in the hyperspectral image cube as a full-reference metric; and 2) the cumulative probability of target colors in the HSV color space for evaluating the alignment index of a single sRGB image rendered using all of the bands of the hyperspectral image cube as a no-reference metric. We verify the efficacy of the proposed metrics on a new large-scale database, demonstrating a higher prediction accuracy in determining improved alignment compared to two full-reference and five no-reference image quality metrics. We also validate the ability of the proposed framework to improve hyperspectral face recognition.

Novel monoclonal antibody against beta 1 integrin enhances cisplatin efficacy in human lung adenocarcinoma cells.

The use of anti-beta 1 integrin monoclonal antibody in lung cancer treatment has proven beneficial. Here, we developed a novel monoclonal antibody (mAb), called P5, by immunizing mice with human peripheral blood mononuclear cells (PBMC). Its anti-tumor effect is now being tested, in a clinical phase III trial, in combinatorial treatments with various chemical drugs. To confirm that P5 indeed binds to beta 1 integrin, cell lysates were immunoprecipitated with commercial anti-beta 1 integrin mAb (TS2/16) and immunoblotted against P5 to reveal a 140 kDa molecular weight band, as expected. Immunoprecipitation with P5 followed by LC/MS protein sequence analysis further verified P5 antigen to be beta 1 integrin. Cisplatin treatment upregulated cell surface expression of beta 1 integrin in A549 cells, while causing inhibition of cell growth. When cells were co-treated with different concentrations of P5 mAb, the cisplatin-mediated inhibitory effect was enhanced in a dose-dependent manner. Our findings show that a combinatorial treatment of P5 mAb and cisplatin in A549 cells resulted in a 30% increase in apoptosis, compared to baseline, and significantly more when compared to either the cisplatin or P5 alone group. The entire peptide sequences in CDR from variable region of Ig heavy and light chain gene for P5 mAb are also disclosed. Together, these results provide evidence of the beneficial effect of P5 mAb in combinatorial treatment of human lung adenocarcinoma.

Effects of mechanical horseback riding velocity on spinal alignment in young adults.

[Purpose] This study aimed to determine if the velocity of mechanical horseback-riding training can improve spinal alignment in young adults. [Subjects and Methods] Thirty-six subjects were enrolled in this study. The subjects were randomly allocated into high-, moderate-, and low-velocity mechanical horseback-riding training groups. All participants completed one 20-minute session per day, 3 days per week, for 6 weeks. The evaluation was performed before and 6 weeks after the training intervention. The spinal alignment was measured by a Formetric III device. The measurement items were kyphotic angle, lordotic angle, trunk inclination, pelvic torsion, pelvic rotation, and lateral deviation. The data were analyzed using analysis of covariance to determine the statistical significance. [Results] The kyphotic angle and trunk inclination were significantly different among the groups. The kyphotic angles of the high- and moderate-velocity groups were significantly lower than that of the low-velocity group after the intervention. The trunk inclination of the high-velocity group was significantly lower than that of the low-velocity group after intervention. [Conclusion] Higher-velocity mechanical horseback-riding training is more effective than lower-velocity mechanical horseback-riding training for improving spinal alignment.

Tensile Characterization of Single-Walled Carbon Nanotubes with Helical Structural Defects.

Recently, evidence was presented that certain single-walled carbon nanotubes (SWNTs) possess helical defective traces, exhibiting distinct cleaved lines, yet their mechanical characterization remains a challenge. On the basis of the spiral growth model of SWNTs, here we present atomic details of helical defects and investigate how the tensile behaviors of SWNTs change with their presence using molecular dynamics simulations. SWNTs have exhibited substantially lower tensile strength and strain than theoretical results obtained from a seamless tubular structure, whose physical origin cannot be explained either by any known SWNT defects so far. We find that this long-lasting puzzle could be explained by assuming helical defects in SWNTs, exhibiting excellent agreement with experimental observation. The mechanism of this tensile process is elucidated by analyzing atomic stress distribution and evolution, and the effects of the chirality and diameter of SWNTs on this phenomenon are examined based on linear elastic fracture mechanics. This work contributes significantly to our understanding of the growth mechanism, defect hierarchies, and mechanical properties of SWNTs.

P-Glycoprotein, not BCRP, Limits the Brain Uptake of [(18)F]Mefway in Rodent Brain.

PURPOSE: The aim of this study was to determine whether the brain uptake of [(18)F]Mefway is influenced by the action of P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) in rodents. PROCEDURES: [(18)F]Mefway was applied to rats pharmacologically inhibited with tariquidar (TQD) and to genetically disrupted mice. RESULTS: Pretreatment of TQD results in 160% higher hippocampal uptake compared with control rats. In genetically disrupted mice, a maximal brain uptake value of 3.2 SUV in the triple knockout mice (tKO, Mdr1a/b((-/-))Bcrp1((-/-))) was comparable to that of the double knockout mice (dKO, Mdr1a/b((-/-))) and 2-fold those of the wild-type and Bcrp1((-/-)) knockout mice. The differences of binding values were statistically insignificant between control and experimental groups. The brain-to-plasma ratios for tKO mice were also two to five times higher than those for other groups. CONCLUSIONS: [(18)F]Mefway is modulated by P-gp, and not by Bcrp in rodents.

Reduced-order spectral data modeling based on local proper orthogonal decomposition.

Spectral imaging typically generates a large amount of high-dimensional data that are acquired in different sub-bands for each spatial location of interest. The high dimensionality of spectral data imposes limitations on numerical analysis. As such, there is an emerging demand for robust data compression techniques with loss of less relevant information to manage real spectral data. In this paper, we describe a reduced-order data modeling technique based on local proper orthogonal decomposition (POD) in order to compute low-dimensional models by projecting high-dimensional clusters onto subspaces spanned by local reduced-order bases. We refer to the proposed method as the local-based approach because POD finds locally optimal solutions on each group split by k-means clustering. Experimental results are reported on three public domain databases and an in-house database. Comparisons with three leading spectral recovery techniques, three decomposition techniques used for hyperspectral imaging, and two baseline techniques show that the proposed method leads to promising improvement on spectral and colorimetric accuracy corresponding to the reconstructed spectral reflectance.

Effect of Nanoscale Ag Film Thickness on the Electrical and Optical Properties of Transparent IZTO/Ag/IZTO Multilayer Films Deposited on Glass Substrates.

The effect of nanoscale Ag film thickness on the electrical and optical properties in transparent conducting oxide films consisting of an IZTO/Ag/IZTO multilayer were investigated. The homoge- neous morphologies of the Ag films sandwiched between the IZTO films affected the optical and electrical properties of the IZTO/Ag/IZTO multilayer films. The transmittance and resistivity of the IZTO/Ag/IZTO multilayer films decreased with increasing Ag film thickness. The resistivities of the IZTO/Ag/IZTO multilayer films grown on glass substrates were decreased by using an Ag thin inter- layer in comparison with that of the IZTO single layer.

Determination of a novel phosphodiesterase4 inhibitor, 3-[1-(3cyclopropylmethoxy-4-difluoromethoxybenzyl)-1H-pyrazol-3-yl]-benzoic acid (PDE-423) in rat plasma using liquid chromatography-tandem mass spectrometry.

A method for determining a novel phosphodiesterase-4 inhibitor, 3-[1-(3cyclopropylmethoxy-4-difluoromethoxybenzyl)-1H-pyrazol-3-yl]-benzoic acid (PDE-423), in rat plasma was developed and validated using liquid chromatography-tandem mass spectrometry for further pharmacokinetic study for development as a novel anti-asthmatic drug. PDE-423 in the concentration range of 0.02-10 µg/mL was linear with a correlation coefficient of >0.99, and the mean intra- and inter-assay precisions of the assay were 7.50 and 3.86%, respectively. The validated method was used successfully for a pharmacokinetic study of PDE-423 in rats.

Characterization of Two Novel mAbs Recognizing Different Epitopes on CD43.

JL1, a specific epitope on CD43, is a potential biomarker for the diagnosis of acute leukemia. Although qualitative assays for detecting leukemia-specific CD43 exist, there is a need to develop quantitative assays for the same. Here, we developed two novel monoclonal antibodies (mAbs), 2C8 and 8E10, recognizing different epitopes on CD43. These clones are capable of pairing with YG5, another mAb against JL1 epitope, because they were selectively obtained using sandwich ELISA. Antigens recognized by 2C8 and 8E10 were confirmed as CD43 by western blotting using the CD43-hFC recombinant protein. When expression on various leukemic cell lines was investigated, 2C8 and 8E10 displayed a disparity in the distribution of the epitope. Enzyme assays revealed that these mAbs recognized a sialic acid-dependent epitope on CD43. Using normal thymus and lymph node paraffin-embedded tissues, we confirmed a difference in the epitopes recognized by the two mAbs that was predicted based on the maturity of the cells in the tissue. In summary, we developed and characterized two mAbs, 2C8 and 8E10, which can be used with YG5 in a sandwich ELISA for detecting leukemia-specific CD43.

Preclinical pharmacokinetic characterization of 2-(4-(4-(5-(2-phenyl-5-(trifluoromethyl)oxazole-4-carboxamido)-1H-benzo[d]imidazol-2-yl)phenyl)cyclohexyl) acetic acid, a novel DGAT-1 inhibitor.

1. A novel diacylglyceride acyltransferase-1 (DGAT-1) inhibitor, 2-(4-(4-(5-(2-phenyl-5-(trifluoromethyl) oxazole-4-carboxamido)-1H-benzo[d]imidazol-2-yl)phenyl)cyclohexyl) acetic acid (KR-69232), was synthesized for a potential therapeutic use against several metabolic disorders, such as obesity, insulin resistance, and type II diabetes, characterized by excessive triglycerides (TGs) in the blood. 2. The half-lives against phase I metabolism were measured as 75.3 ± 20.9 min and over 120 min in rat and human liver microsomes, respectively. In Caco-2 cell monolayers, extremely low permeability (<0.13 × 10⁻6cm/s) was seen in the absorptive direction, predicting limited intestinal absorption of KR-69232. This compound was highly bound to rat and human plasma proteins (>99.8%). 3. With the intravenous administration of KR-69232 in rats (1, 2, and 5 mg/kg), non-linear kinetics were observed at the highest dose, with significantly higher systemic clearance, higher volume of distribution, and lower dose-normalized AUC. Following oral administration, it exhibited low bioavailability (<10%) and was absorbed slowly (T(max), 3.8-5.2 h) over the dose range. We also confirmed that considerable KR-69232 remained in the intestine at T(max), demonstrating its limited absorption into the systemic circulation.

Analysis of balance ability dependent on the angle of the knee joint in females in their 20s.

The aim of this study was to investigate how balance ability according to angle of the knee joint changes in young female adults wearing a knee orthosis. [Methods] This study was conducted with 11 healthy female adults. The subjects used a knee brace that could be set to angles of 0°, 15°, and 30° of knee flexion. The ability to balance was evaluated by balance assessment. A total of four postures were used for measurements: a forward-facing posture with the eyes open on a stable surface (NO), a forward-facing posture with the eyes closed on a stable surface (NC), a forward-facing posture with the eyes open on an unstable surface (PO), and a forward-facing posture with the eyes closed on an unstable surface (PC). [Results] Regarding the weight distribution index and stability index on a stable surface, there was no interaction according to whether there was visual deprivation or not or according to knee flexion angle. Furthermore, the stability index on an unstable surface showed no interaction according to whether there was visual deprivation or not or according to knee flexion angle. But the WDI on a stable surface showed no interaction according to whether there was visual deprivation or not or according to knee flexion angle. [Conclusion] There were significant differences in the knee extension range of motion of normal elderly people and knee osteoarthritis, and the quadriceps femoris played an important role in knee function in individuals with knee osteoarthritis.

Pharmacokinetic characterization of the novel TAZ modulator TM-25659 using a multicompartment kinetic model in rats and a possibility of its drug-drug interactions in humans.

This study evaluated the pharmacokinetics of the novel TAZ modulator TM-25659 in rats following intravenous and oral administration at dose ranges of 0.5-5 mg/kg and 2-10 mg/kg, respectively. Plasma protein binding, plasma stability, liver microsomal stability, CYP inhibition, and transport in Caco-2 cells were also evaluated. After intravenous injection, systemic clearance, steady-state volumes of distribution, and half-life were dose-independent, with values ranging from 0.434-0.890 mL · h(-1) · kg(-1), 2.02-4.22 mL/kg, and 4.60-7.40 h, respectively. Mean absolute oral bioavailability was 50.9% and was not dose dependent. Recovery of TM-25659 was 43.6% in bile and <1% in urine. In pharmacokinetic modeling studies, the three-compartment (3C) model was appropriate for understanding these parameters in rats. TM-25659 was stable in plasma. Plasma protein binding was approximately 99.2%, and was concentration-independent. TM-25659 showed high permeation of Caco-2 cells and did not appear to inhibit CYP450. TM-25659 was metabolized in phase I and II steps in rat liver microsomes. In conclusion, the pharmacokinetics of TM-25659 was characterized for intravenous and oral administration at doses of 0.5-5 and 2-10 mg/kg, respectively. TM-25659 was eliminated primarily by hepatic metabolism and urinary excretion.

Generation of 1E8 Single Chain Fv-Fc Construct Against Human CD59.

BACKGROUND: Therapeutic approaches using monoclonal antibodies (mAbs) against complement regulatory proteins (CRPs:i.e.,CD46,CD55 and CD59) have been reported for adjuvant cancer therapy. In this study, we generated a recombinant 1E8 single-chain anti-CD59 antibody (scFv-Fc) and tested anti-cancer effect.by using complement dependent cytotoxicity (CDC). METHODS: We isolated mRNA from 1E8 hybridoma cells and amplified the variable regions of the heavy chain (VH) and light chain (VL) genes using reverse-transcriptase polymerase chain reaction (RT-PCR). Using a linker, the amplified sequences for the heavy and light chains were each connected to the sequence for a single polypeptide chain that was designed to be expressed. The VL and VH fragments were cloned into the pOptiVEC-TOPO vector that contained the human CH2-CH3 fragment. Then, 293T cells were transfected with the 1E8 single-chain Fv-Fc (scFv-Fc) constructs. CD59 expression was evaluated in the prostate cancer cell lines using flow cytometry. The enhancement of CDC effect by mouse 1E8 and 1E8 scFv-Fc were evaluated using a cytotoxicity assay. RESULTS: The scFv-Fc constructs were expressed by the transfected 293T cells and secreted into the culture medium. The immunoreactivity of the secreted scFv-Fc construct was similar to that of the mouse 1E8 for CCRF-CEM cells. The molecular masses of 1E8 scFv-Fc were about 120 kDa and 55 kDa under reducing and non-reducing conditions, respectively. The DNA sequence of 1E8 scFv-Fc was obtained and presented. CD59 was highly expressed by the prostate cancer cell line. The recombinant 1E8 scFv-Fc mAb revealed significantly enhanced CDC effect similar with mouse 1E8 for prostate cancer cells. CONCLUSION: A 1E8 scFv-Fc construct for adjuvant cancer therapy was developed.

Characterization of Monoclonal Antibodies against Human Leukocyte Common Antigen (CD45).

BACKGROUND: The leukocyte common antigen (CD45) is a transmembrane-type protein tyrosine phosphatase that has five isoforms. METHODS: We generated seven murine mAbs against human CD45 by injecting cells from different origins, such as human thymocytes, PBMCs, and leukemic cell lines. By using various immunological methods including flow cytometry, immunohistochemistry, and immunoprecipitation, we evaluated the reactivity of those mAbs to CD45 of thymus as well as tonsil lysates. Furthermore, we transiently transfected COS-7 cells with each of gene constructs that express five human CD45 isoforms respectively, and examined the specificities of the mAbs against the transfected isoforms. RESULTS: In case of thymocytes, lymphocytes, and monocytes, all the seven mAbs demonstrated positive reactivities whereas none was reactive to erythrocytes and platelets. The majority of immune cells in formalin-fixed paraffin-embedded thymus and tonsil tissues displayed strong membranous immunoreactivity, and the main antigen was detected near 220 kDa in all cases. Among the mAbs, four mAbs (AP4, DN11, SHL-1, and P6) recognized a region commonly present in all the five isoforms. One mAb, YG27, recognized four isoforms (ABC, AB, BC, and O). Two mAbs, P1 and P14, recognized the isoforms that contain exon A encoded regions (ABC and AB). CONCLUSION: In this study, we confirmed that AP4, DN11, SHL-1, YG27 and P6, are mAbs reactive with the CD45 antigen whereas P1 and P14 are reactive with the CD45RA antigen.