Intra- and Inter-rater Reliability of the Lumbar-Locked Thoracic Rotation Test in Patients With Neck Pain.

PURPOSE: Neck pain is a common musculoskeletal disorder. Therefore, establishing effective physical therapy for neck pain is one of the most important issues. In addition, in physical therapy for neck pain, it is important to evaluate the thoracic spine, which is an adjacent region of the neck. The lumbar-locked rotation test is designed to evaluate the rotational range of the thoracic spine. However, the reliability of the test when performed on patients with neck pain has not been confirmed. OBJECTIVE: We aimed to determine the intra- and inter-rater reliability of the lumbar-locked rotation test in patients with neck pain. METHODS: In this study involving 43 patients, two separate examiners measured thoracic spine rotation. Both examiners conducted three measurements for each side, before and after a five-minute interval. Reliability was assessed using various intra-class correlation coefficient (ICC) models. RESULTS: The intra-rater reliability showed ICC values of 0.99 for both examiners. The inter-rater reliability showed ICC values of 0.98 for both right and left thoracic rotations. CONCLUSION: The findings strongly suggest that the lumbar-locked rotation test has high within-session intra- and inter-rater reliability for patients with neck pain. This test can be considered a reliable method of measuring the thoracic spine rotational range of motion in patients with neck pain in clinical practice.

Cortical projection to the subventricular zone and its effect on adult neurogenesis in mice.

Various brain regions/nuclei project axons to the subventricular zone (SVZ), a postnatal neurogenic niche. In adults, neurogenesis is controlled by neuronal activity, via neurotransmitters. Glutamate is a major excitatory neurotransmitter, and glutamate receptors are expressed in SVZ cells. Although the cerebral cortex is a major source of glutamate and the medial cortex projects axons to the medial striatum next to the SVZ, it remains unclear whether cortical neurons regulate adult neurogenesis in vivo. First, to analyze axonal projection, plasmid vector expressing DsRed was introduced to the medial cortex by in utero electroporation. At the adult stage, DsRed-labeled axons were detected in the dorsolateral, striatal, and septal areas of the SVZ, and where they were in contact with neuroblasts. Furthermore, maturation of the cortical projection and the SVZ appeared to synchronize during postnatal stages. Next, stab injuries were made in the bilateral medial cortex to interrupt cortical input to the SVZ. At 17 days post-injury, cell proliferation in the SVZ and tangential migration of neuroblasts to the olfactory bulb were not significantly affected. There were clusters of neuroblasts in the striatum close to the SVZ in all experimental groups, but the number and size of neuroblast clusters were significantly larger in the medial cortex-injured group compared with the other experimental groups. These neuroblast clusters had a morphology of tangentially migrating cells to the olfactory bulb. These results suggest that cortical input to the SVZ inhibits the radial migration of neuroblasts to converge with the migration pathway in vivo.

Analysis of cervical and upper thoracic spinal segmental rotation angles during end-range neck rotation: Comparison with and without neck pain.

BACKGROUND: Neck pain is a common manifestation of musculoskeletal disorders of the cervical and thoracic spine. Manual therapy interventions to the thoracic spine are recommended for treating patients with several types of neck pain. However, only a few studies have investigated the thoracic spine mobility associated with neck movement. OBJECTIVES: Compare cervical and upper thoracic rotation angles in subjects with and without neck pain. METHODS: The subjects included nine individuals who experienced neck pain (pain, Group P) and 11 who did not (non-pain, Group N). The rotation angle was measured using MRI. The imaging limb position was at 90% of the maximum neck rotation. The MR images were analyzed using image analysis software to calculate the rotation angle of C1 to Th3. The rotation angle of the segment was then calculated by subtracting the rotation angle corresponding to the lower vertebra from that corresponding to the upper vertebra. The total rotation of each segment was calculated as the sum of the right and left rotation angle. Then, the segmental rotation angles were compared between groups. RESULTS/FINDINGS: The rotation angles of C3-C4, C7-Th1, and Th1-Th2 were significantly smaller in Group P than in Group N, and C5-C6 and C6-C7 were significantly larger in Group P than in Group N. There was no statistical difference in rotational angle at all other spinal levels measured. CONCLUSIONS: The results of this study indicate subjects with neck pain had hypermobility of the lower cervical spine and hypomobility of the cervico-thoracic junction and upper thoracic spine compared with subjects without neck pain. These results add to current understanding of biomechanical factors that may be related to neck pain.

Improvement in Double Staining With Fluoro-Jade C and Fluorescent Immunostaining: FJC Staining Is Not Specific to Degenerating Mature Neurons.

Fluoro-Jade C (FJC) staining has been used to detect degenerating neurons in tissue sections. It is a simple and easy staining procedure and does not depend on the manner of cell death. In some experiments, double staining with FJC and fluorescent immunostaining (FI) is required to identify cell types. However, pretreatment for FJC staining contains some processes that are harsh to fluorophores, and the FI signal is greatly reduced. To overcome this issue, we improved the double staining protocol to acquire clear double-stained images by introducing the labeled streptavidin-biotin system. In addition, several studies indicate that FJC can label non-degenerating glial cells, including resting/reactive astrocytes and activated microglia. Moreover, our previous study indicated that degenerating mesenchymal cells were also labeled by FJC, but it is still unclear whether FJC can label degenerating glial cells. Acute encephalopathy model mice contained damaged astrocytes with clasmatodendrosis, and 6-aminonicotinamide-injected mice contained necrotic astrocytes and oligodendrocytes. Using our improved double staining protocol with FJC and FI, we detected FJC-labeled degenerating astrocytes and oligodendrocytes with pyknotic nuclei. These results indicate that FJC is not specific to degenerating neurons in some experimental conditions.

Relationship between frequency spectrum of heart rate variability and autonomic nervous activities during sleep in newborns.

INTRODUCTION: We analyzed the frequency spectrum of two neonatal sleep stages, namely active sleep and quiet sleep, and the relationship between these sleep stages and autonomic nervous activity in 74 newborns and 16 adults as a comparison. METHOD: Active and quiet sleep were differentiated by electroencephalogram (EEG) patterns, eye movements, and respiratory wave patterns; autonomic activity was analyzed using the RR interval of simultaneously recorded electrocardiogram (ECG) signals. Power values (LFa, absolute low frequency; HFa, absolute high frequency), LFa/HFa ratio, and the values of LFn (normalized low frequency) and HFn (normalized high frequency) were obtained. Synchronicity between the power value of HFa and the LFa/HFa ratio during active and quiet sleep was also examined by a new method of chronological demonstration of the power values of HFa and LFa/HFa. RESULTS: We found that LFa, HFa and the LFa/HFa ratio during active sleep were significantly higher than those during quiet sleep in newborns; in adults, on the other hand, the LFa/HFa ratio during rapid eye movement (REM) sleep, considered as active sleep, was significantly higher than that during non-REM sleep, considered as quiet sleep, and HFa values during REM sleep were significantly lower than those during non-REM sleep. LFn during quiet sleep in newborns was significantly lower than that during active sleep. Conversely, HFn during quiet sleep was significantly higher than that during active sleep. Analysis of the four classes of gestational age groups at birth indicated that autonomic nervous activity in a few preterm newborns did not reach the level seen in full-term newborns. Furthermore, the power value of HFa and the LFa/HFa ratio exhibited reverse synchronicity. CONCLUSION: These results indicate that the autonomic patterns in active and quiet sleep of newborns are different from those in REM and non-REM sleep of adults and may be develop to the autonomic patterns in adults, and that parasympathetic activity is dominant during quiet sleep as compared to active sleep from the results of LFn and HFn in newborns. In addition, in some preterm infants, delayed development of the autonomic nervous system can be determined by classifying the autonomic nervous activity pattern of sleep stages.

ONO-pincer ruthenium complex-bound norvaline for efficient catalytic oxidation of methoxybenzenes with hydrogen peroxide.

The enhanced catalytic activity of ruthenium complex-bound norvaline Boc-l-[Ru]Nva-OMe 1, in which the ONO-pincer ruthenium complex Ru(pydc)(terpy) 2 is tethered to the α-side chain of norvaline, has been demonstrated for the oxidation of methoxybenzenes to p-benzoquinones with a wide scope of substrates and unique chemoselectivity.

A dimer model of human calcitonin13-32 forms an α-helical structure and robustly aggregates in 50% aqueous 2,2,2-trifluoroethanol solution.

Determining the cause of human calcitonin (hCT) aggregation could be of help in the effort to utilize hCT for treatment of hypercalcemia. Here we report that a dimer model of hCT13-32 aggregated to a greater degree than native hCT under aqueous 2,2,2-trifluoroethanol conditions. Analyses using circular dichroism spectroscopy, thioflavine-T binding assays and atomic force microscopy suggest that the α-helical portion of hCT is important for initiation of the aggregation process, which yields long fibrils. Dimerization, which stabilizes the ß-sheet structure of hCT, enhances aggregation potency. Dimerization of hCT stabilizes the α-helix under aqueous TFE conditions, leading to the long fibril formation. Up to now, there have been no reports of using a dimer model to investigate the properties of hCT aggregation. Our findings could potentially serve as the basis for development of novel hCT derivatives that could be utilized for treatment of hypercalcemia, as well as for development of novel therapeutics for other ailments caused by amyloid peptides. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Synthesis and Applications of (ONO†Pincer)Ruthenium-Complex-Bound Norvalines.

Two (ONO pincer)ruthenium-complex-bound norvalines, Boc-[Ru(pydc)(terpy)]Nva-OMe (1; Boc=tert-butyloxycarbonyl, terpy=terpyridyl, Nva=norvaline) and Boc-[Ru(pydc)(tBu-terpy)]Nva-OMe (5), were successfully synthesized and their molecular structures and absolute configurations were unequivocally determined by single-crystal X-ray diffraction. The robustness of the pincer Ru complexes and norvaline scaffolds against acidic/basic, oxidizing, and high-temperature conditions enabled us to perform selective transformations of the N-Boc and C-OMe termini into various functional groups, such as alkyl amide, alkyl urea, and polyether groups, without the loss of the Ru center or enantiomeric purity. The resulting dialkylated Ru-bound norvaline, n-C11 H23 CO-l-[Ru(pydc)(terpy)]Nva-NH-n-C11 H23 (l-4) was found to have excellent self-assembly properties in organic solvents, thereby affording the corresponding supramolecular gels. Ru-bound norvaline l-1 exhibited a higher catalytic activity for the oxidation of alcohols by H2 O2 than parent complex [Ru(pydc)(terpy)] (11 a).

Upregulation of cellular glutathione levels in human ABCB5- and murine Abcb5-transfected cells.

BACKGROUND: Previously, we have demonstrated that human ABCB5 is a full-sized ATP-binding cassette transporter that shares strong homology with ABCB1/P-glycoprotein. ABCB5-transfected cells showed resistance to taxanes and anthracyclines. Herein, we further screened ABCB5 substrates, and explored the mechanism of resistance. METHODS: Sensitivity of the cells to test compounds was evaluated using cell growth inhibition assay. Cellular levels of buthionine sulfoximine (BSO), glutathione and amino acids were measured using HPLC and an enzyme-based assay. Cellular and vesicular transport of glutathione was evaluated by a radiolabeled substrate. Expression levels of glutathione-metabolizing enzymes were assessed by RT-PCR. RESULTS: Human ABCB5-transfected 293/B5-11 cells and murine Abcb5-transfected 293/mb5-8 cells showed 6.5- and 14-fold higher resistance to BSO than the mock-transfected 293/mock cells, respectively. BSO is an inhibitor of gamma-glutamylcysteine ligase (GCL), which is a key enzyme of glutathione synthesis. 293/B5-11 and 293/mb5-8 cells also showed resistance to methionine sulfoximine, another GCL inhibitor. A cellular uptake experiment revealed that BSO accumulation in 293/B5-11 and 293/mb5-8 cells was similar to that in 293/mock cells, suggesting that BSO is not an ABCB5 substrate. The cellular glutathione content in 293/B5-11 and 293/mb5-8 cells was significantly higher than that in 293/mock cells. Evaluation of the BSO effect on the cellular glutathione content showed that compared with 293/mock cells the BSO concentration required for a 50 % reduction in glutathione content in 293/B5-11 and 293/mb5-8 cells was approximately 2- to 3-fold higher. This result suggests that the BSO resistance of the ABCB5- and Abcb5-transfected cells can be attributed to the reduced effect of BSO on the transfectants. Cellular and vesicular transport assays showed that the transport of radiolabeled glutathione in 293/B5-11 cells was similar to that in 293/mock cells. The mRNA expression of genes encoding glutathione-metabolizing enzymes in 293/B5-11 cells was similar to that in 293/mock cells. The cellular content of Glu, a precursor of glutathione, in 293/B5-11 and 293/mb5-8 cells was higher than that in 293/mock cells. CONCLUSIONS: ABCB5/Abcb5-transfected cells showed resistance to BSO, which is not a substrate of ABCB5. Our results suggest that ABCB5/Abcb5 upregulates cellular glutathione levels to protect cells from various poisons.

Catalyst design for iron-promoted reductions: an iron disilyl-dicarbonyl complex bearing weakly coordinating η2-(H-Si) moieties.

Iron disilyl dicarbonyl complex 1, in which two H-Si moieties of the 1,2-bis(dimethylsilyl)benzene ligand were coordinated to the iron center in an η(2)-(H-Si) fashion, was synthesized by the reaction of (η(4)-C6H8)Fe(CO)3 with 2 equiv. of 1,2-bis(dimethylsilyl)benzene under photo-irradiation. Complex 1 demonstrated high catalytic activity toward the hydrogenation of alkenes, the hydrosilylation of alkenes and the reduction of carbonyl compounds.

Synthesis and self-assembly of NCN-pincer Pd-complex-bound norvalines.

The NCN-pincer Pd-complex-bound norvalines Boc-D/L-[PdCl(dpb)]Nva-OMe (1) were synthesized in multigram quantities. The molecular structure and absolute configuration of 1 were unequivocally determined by single-crystal X-ray structure analysis. The robustness of 1 under acidic/basic conditions provides a wide range of N-/C-terminus convertibility based on the related synthetic transformations. Installation of a variety of functional groups into the N-/C-terminus of 1 was readily carried out through N-Boc- or C-methyl ester deprotection and subsequent condensations with carboxylic acids, R(1)COOH, or amines, R(2)NH2 , to give the corresponding N-/C-functionalized norvalines R(1)-D/L-[PdCl(dpb)]Nva-R(2) 2-9. The dipeptide bearing two Pd units 10 was successfully synthesized through the condensation of C-free 1 with N-free 1. The robustness of these Pd-bound norvalines was adequately demonstrated by the preservation of the optical purity and Pd unit during the synthetic transformations. The lipophilic Pd-bound norvalines L-2, Boc-L-[PdCl(dpb)]Nva-NH-n-C11H23, and L-4, n-C4H9CO-L-[PdCl(dpb)]Nva-NH-n-C11H23, self-assembled in aromatic solvents to afford supramolecular gels. The assembled structures in a thermodynamically stable single crystal of L-2 and kinetically stable supramolecular aggregates of L-2 were precisely elucidated by cryo-TEM, WAX, SAXS, UV/Vis, IR analyses, and single-crystal X-ray crystallography. An antiparallel ß-sheet-type aggregate consisting of an infinite one-dimensional hydrogen-bonding network of amide groups and π-stacking of PdCl(dpb) moieties was observed in the supramolecular gel fiber of L-2, even though discrete dimers are assembled through hydrogen bonding in the thermodynamically stable single crystal of L-2. The disparate DSC profiles of the single crystal and xerogel of L-2 indicate different thermodynamics of the molecular assembly process.