Accuracy of the Contour® Next Link 2.4 blood glucose monitoring system in Japanese individuals: a single-center study.

Aims: Self-monitoring of blood glucose is a useful method for monitoring blood glucose. It is often a key role of a management plan to reduce glycemic variability and diabetic complications. Wireless monitoring systems to connect blood glucose and insulin pumps can facilitate glycemic control. In this study, we evaluated the accuracy of Contour® Next Link 2.4, a blood glucose monitoring system that cooperates wirelessly with most insulin pumps, in Japanese individuals. Methods: In this study, finger-stick samples from 59 individuals were collected at the Tokyo Saiseikai Central Hospital. Blood glucose concentrations were measured with the monitoring systems against an available reference. We evaluated the accuracy of the system based on the ISO 15197:2013 Section 6.3 accuracy criteria. Results: In the present study, 100% of the results fulfilled the ISO 15197:2013 Section 6.3 accuracy criteria (95% within ± 15 mg/dL or ± 15% of reference for glucose < 100 and ≥ 100 mg/dL, respectively). The Parkes-Consensus Error Grid analysis showed that 100% of the results fulfilled within Zone A. Conclusions: The Contour® Next Link 2.4 blood glucose monitoring system fulfilled the ISO 15197:2013 accuracy criteria limit and the consensus error grid criterion. Therefore, this monitoring system for observing blood glucose levels is accurate for Japanese individuals.

ß-Carotene enhances the expression of inflammation-related genes and histone H3 K9 acetylation, K4 dimethylation, and K36 trimethylation around these genes in juvenile macrophage-like THP-1 cells.

ß-Carotene is converted into vitamin A in the body and can remove reactive oxygen species. However, it is still unclear whether ß-carotene alters the expression levels of inflammation-related genes in macrophages and how this is regulated. In the present study, we investigated whether the administration of ß-carotene under hyperglycemic conditions altered the expression level of inflammation-related genes and whether any observed differences were associated with changes in histone modifications in juvenile macrophage-like THP-1 cells. THP-1 cells (from a human monocytic leukemia cell line) were cultured in low glucose (5 mM), high glucose (25 mM), or high glucose (25 mM) + ß-carotene (5 µM) media for 1 day, and mRNA expression levels of genes related to oxidative stress and inflammation, and histone modifications were determined by mRNA microarray and qRT-PCR analyses, and chromatin immunoprecipitation assays, respectively. The expression of inflammation-related genes, such as IL31RA, CD38, and NCF1B, and inflammation-associated signaling pathway genes, such as ITGAL, PRAM1, and CSF3R, were upregulated by ß-carotene under high-glucose conditions. Under these conditions, histone H3 lysine 4 (K4) demethylation, H3K36 trimethylation, and H3K9 acetylation around the CD38, NCF1B, and ITGAL genes were higher in ß-carotene-treated cells than in untreated cells. Treatment of juvenile macrophage-like THP-1 cells with ß-carotene under these high glucose conditions induced the expression of inflammation-related genes, K9 acetylation, and K4 di- and K36 trimethylation of histone H3 around these genes.

Elevational changes in productivity of saplings relate to distribution of two congeneric tree species.

Elevational changes in vegetation are associated with changes in environmental factors, an example of which is provided by the shade-tolerant Abies mariesii and less shade-tolerant Abies veitchii, which dominate forests at high and low elevations, respectively, in subalpine zones of central Japan. In this study, we sought to establish the factors underlying the differential elevational dominance of these two species from the perspective of sapling growth and survival. It is assumed that the growth and survival of saplings is greater at higher rates of surplus production (the value obtained by subtracting the minimum net production to maintain the current sapling leaf mass from the total net production), as sapling leaf mass gradually declines with time if saplings cannot maintain the current sapling leaf mass, thereby increasing the risk of premature mortality. In this regard, we aimed to verify the following two hypotheses: (1) at low elevations, the surplus production rate of A. veitchii is greater than that of A. mariesii in canopy gaps, and vice versa in the forest understory; and (2) at high elevation, the surplus production rate of A. mariesii is greater than that of A. veitchii in both forest understory and canopy gaps. The results obtained in this study were consistent with our two stated hypotheses. In addition, at the low elevation site, the rate of the growth in height of A. veitchii in canopy gaps was greater than that of A. mariesii, indicating that A. veitchii can dominate after disturbance at low elevations. The findings of this study indicate that the differential elevational distribution of the two Abies species can be attributed to interspecific differences in surplus production rates. We believe that these findings will be useful for predicting changes in the distribution of vegetation in response to climate change.

Validity of transcranial Doppler ultrasonography-determined dynamic cerebral autoregulation estimated using transfer function analysis.

Transcranial Doppler ultrasonography (TCD) is used widely to evaluate dynamic cerebral autoregulation (dCA). However, the validity of TCD-determined dCA remains unknown because TCD is only capable of measuring blood velocity and thus only provides an index as opposed to true blood flow. To test the validity of TCD-determined dCA, in nine healthy subjects, dCA was evaluated by transfer function analysis (TFA) using cerebral blood flow (CBF) or TCD-measured cerebral blood velocity during a perturbation that induces reductions in TCD-determined dCA, lower body negative pressure (LBNP) at two different stages: LBNP - 15 mmHg and - 50 mmHg. Internal carotid artery blood flow (ICA Q) was assessed as an index of CBF using duplex Doppler ultrasound. The TFA low frequency (LF) normalized gain (ngain) calculated using ICA Q increased during LBNP at - 50 mmHg (LBNP50) from rest (P = 0.005) and LBNP at - 15 mmHg (LBNP15) (P = 0.015), indicating an impaired dCA. These responses were the same as those obtained using TCD-measured cerebral blood velocity (from rest and LBNP15; P = 0.001 and P = 0.015). In addition, the ICA Q-determined TFA LF ngain from rest to LBNP50 was significantly correlated with TCD-determined TFA LF ngain (r = 0.460, P = 0.016) despite a low intraclass correlation coefficient. Moreover, in the Bland-Altman analysis, the difference in the TFA LF ngains determined by blood flow and velocity was within the margin of error, indicating that the two measurement methods can be interpreted as equivalent. These findings suggest that TCD-determined dCA can be representative of actual dCA evaluated with CBF.

In vitro study on the partitioning of red blood cells using a microchannel network.

To investigate the partitioning properties of red blood cells (RBCs) in the bifurcating capillary vessels, an in vitro experiment was performed to perfuse human RBC suspensions into the microfluidic channels with a width of <10 µm. Two types of microchannel geometries were established. One is a single model comprising one parent and two daughter channels with different widths, and the other is a network model that had a symmetric geometry with four consecutive divergences and convergences. In addition to the fractional RBC flux at each bifurcation, changes in hematocrit levels and flow velocity before and after the bifurcation were investigated. In the single model, non-uniform partitioning of RBCs was observed, and this result was in good agreement with that of the empirical model. Furthermore, in the network model, the RBC distribution in the cross-section before the bifurcation significantly affected RBC partitioning in the two channels after the bifurcation. Hence, there was a large RBC heterogeneity in the capillary network. The hematocrit levels between the channels differed for more than one order of magnitude. Therefore, the findings of the current research could facilitate a better understanding of RBC partitioning properties in the microcirculatory system.

Pivotal Role of Heart for Orthostasis: Left Ventricular Untwisting Mechanics and Physical Fitness.

Augmentation of left ventricular (LV) untwisting due to central hypovolemia is likely to be a compensatory mechanism for maintaining stroke volume, which is reduced by a decrease in cardiac filling during orthostatic stress. Orthostatic intolerance observed in both high and low fitness levels may be explained by the impaired response of LV untwisting due to central hypovolemia.

Evaluation of Antibacterial Activity Expression of the Hinokitiol/Cyclodextrin Complex Against Bacteria.

The purpose of this study was to assess the antimicrobial activity of a solid dispersion prepared by mixing and grinding hinokitiol (HT) with α-cyclodextrin (αCD), ß-cyclodextrin (ßCD), or γ-cyclodextrin (γCD). Antimicrobial activity was evaluated by calculating the minimum inhibitory concentration (MIC) and evaluating the change in the number of bacteria over time. The test microbes used were two Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus), two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and two fungi (Candida albicans and Aspergillus brasiliensis). Calculation of the MIC value of HT using the agar dilution method revealed that the MIC of HT/CD inclusion complexes was lower than that of HT alone. HT irreversibly inhibited the growth of microorganisms in a short amount of time. HT/CD complexes retained the antimicrobial activity of HT as a result of including HT in a CD complex. These results suggest that inclusion of HT, an antimicrobial component, using CDs could lead to appropriate control of the drug release rate and efficient display of antimicrobial activity.

Suction-fixing surgical device for assisting liver manipulation with laparoscopic forceps.

PURPOSE: Noninvasiveness and stability are significant issues in laparoscopic liver resection. Inappropriate grasping force can cause damage or serious bleeding to the liver. In addition, instability of grasping can result unsafe operations or wavered cutting. We propose a surgical device to improve stability of liver manipulation. METHODS: A proposed device adheres to the liver surface with suction fixation, then tunes its stiffness to being hard and shapes like as a bulge on the liver surface to be grasped with laparoscopic forceps. It consists of two soft beams, a chamber sponge, membrane covering the device upper, suburb extrusion wing membrane, a vacuuming tube and to-be-grasped bars. The beams are designed as being non-stretchable and easy to bend. The device is connected to a medical vacuuming pump to vacuum air in the device and then gets hard to transfer forceps operation well. This stiffness tuning mechanism by pneumatic control features the device for achieving good liver shape followability and forceps operation propagation less invasively. The proposed device was tested with rubber phantoms and porcine livers on shape followability, stiffness transition, liver invasiveness and operational usability in the experiments. RESULTS: Performance of the proposed device was assessed in experiments. The device showed good object-shape followability. It held the liver with 2.43-N force for vertical lifting and 4.90-N shear force with - 80 kPa vacuuming pressure. Invasiveness was reduced to acceptable level of liver damage. In usability test, the device grasped the liver stably and transferred surgical forceps operations to the liver surface well. CONCLUSION: The proposed device showed effective performance to improve laparoscopic liver manipulation. It held the liver stably and less invasively and transferred forceps operation force to the liver surface well.

Context-Dependent Modulation of Corticomuscular Coherence in a Series of Motor Initiation and Maintenance of Voluntary Contractions.

For our precise motor control, we should consider "motor context," which involves the flow from feedforward to feedback control. The present study focused on corticomuscular coherence (CMC) to physiologically evaluate how the sensorimotor integration is modulated in a series of movements depending on the motor context. We evaluated CMC between electroencephalograms over the sensorimotor cortex and rectified electromyograms from the tibialis anterior muscle during intermittent contractions with 2 contraction intensities in 4 experiments. Although sustained contractions with weak-to-moderate intensities led to no difference in CMC between intensities, intermittent ballistic-and-hold contractions with 2 intensities (10% and 15% or 25% of the maximal voluntary contraction, MVC) presented in a randomized order resulted in greater magnitude of CMC for the weaker intensity. Moreover, the relative amount of initial error was larger for trials with 10% of MVC, which indicated that initial motor output was inaccurate during weaker contractions. However, this significant difference in CMC vanished in the absence of trial randomization or the application of intermittent ramp-and-hold contractions with slower torque developments. Overall, CMC appears to be modulated context-dependently and is especially enhanced when active sensorimotor integration is required in feedback control periods because of the complexity and inaccuracy of preceding motor control.

A Candidate for Multitopic Probes for Ligand Discovery in Dynamic Combinatorial Chemistry.

Multifunctionalized materials are expected to be versatile probes to find specific interactions between a ligand and a target biomaterial. Thus, efficient methods to prepare possible combinations of the functionalities is desired. The concept of dynamic combinatorial chemistry (DCC) is ideal for the generation of any possible combination, as well as screening for target biomaterials. Here, we propose a new molecular design of multitopic probes for ligand discovery in DCC. We synthesized a new Gable Porphyrin, GP1, having prop-2-yne groups as a scaffold to introduce various functional groups. GP1 is a bis(imidazolylporphyrinatozinc) compound connected through a 1,3-phenylene moiety, and it gives macrocycles spontaneously and quantitatively by strong imidazole-to-zinc complementary coordination. Some different types of functional groups were introduced into GP1 in high yields. Formation of heterogeneous macrocycles composed of GP1 derivatives having different types of substituents was accomplished under equilibrium conditions. These results promise that enormous numbers of macrocycles having various functional groups can be provided when the kinds of GP components increase. These features are desirable for DCC, and the present system using GP1 is a potential candidate to provide a dynamic combinatorial library of multitopic probes to discover specific interactions between a ligand and a biomaterial.

Treatment of bimaxillary protrusion with temporary anchorage devices.

For treatment of severe bimaxillary protrusion in adults, a condition known to be among the most difficult to manage, both the maxillary and mandibular anterior teeth must be fully retracted using all the extraction space available. This article reports the treatment of an adult with severe high-angle bimaxillary protrusion. To correct the protrusion of the anterior teeth, orthodontic anchor screws (OASs) were used to provide absolute anchorage during anterior retraction. Acceptable occlusion, facial profile, and balance were achieved. OASs appear to be very useful for treatment of severe bimaxillary protrusion in adults.

Sodium butyrate enhances the growth inhibitory effect of sunitinib in human renal cell carcinoma cells.

Sunitinib (SU) is a small molecule that inhibits the receptor tyrosine kinase (RTK) signaling pathway, and has been clinically used to treat advanced renal cell carcinoma (RCC). However, SU is not always effective as RCC is a highly chemoresistant type of cancer. One of the factors that confer chemoresistance to RCC is a hypoxic condition. Lack of oxygen activates hypoxia-inducible factor (HIF) protein, which is followed by the upregulation of growth factors, including vascular endothelial growth factor and activation of the RTK signaling pathway. In this context, histone deacetylase inhibitors (HDACIs) are considered prominent combined agents for SU as they downregulate the expression of HIFs. Therefore, the present study aimed to investigate the effectiveness of combined treatment with SU and sodium butyrate (NaBu), an HDACI. Long-term exposure to these agents exerted a stronger growth inhibitory effect in RCC cell lines compared with single treatment groups. Furthermore, combined treatment suppressed HIF-2α protein, which was induced under hypoxic conditions. In addition, this combination sustained the activity of the RTK signaling pathway to the level of intact cells, although a single treatment with SU or NaBu was demonstrated to increase this activity. Overall, it is suggested that the combination of SU and NaBu is effective for overcoming drug resistance in RCC.

Molecular interactions of the inclusion complexes of hinokitiol and various cyclodextrins.

The aim of this study was to prepare inclusion complexes of hinokitiol (HT)/α-cyclodextrin (α-CD) and HT/ß-cyclodextrin (ß-CD) by cogrinding and to evaluate the differences in their formation. The physical properties of the preparation were evaluated by Job's plot, phase solubility studies, differential scanning calorimetry, powder X-ray diffraction, solid fluorescence spectra, and infrared absorption spectra. Intermolecular interaction in the solid state was confirmed to be in the ratios HT/α-CD = 1/2 and HT/ß-CD = 1/1. Results indicated that the dissolution property of HT was improved by inclusion in the complexes HT/α-CD and HT/ß-CD compared with HT crystals. The 1H-1H ROESY NMR spectrum of HT/α-CD showed that part of the seven-membered ring of HT and the isopropyl group of HT was linked to the wider edges of the two α-CDs. In HT/ß-CD, the seven-membered ring of HT interacted with the narrower edge of ß-CD and the isopropyl group of HT interacted with the wider edges. This structure of inclusion complexes was attributed to the difference in the cavity diameter of the CD and was thought to influence the dissolution properties.

Relationship between Self-Reported Dietary Nutrient Intake and Self-Reported Sleep Duration among Japanese Adults.

Several studies have reported that short sleep duration is a risk factor for obesity and metabolic disease. Moreover, both sleep duration and sleep timing might independently be associated with dietary nutrient intake. In this study, we investigated the associations between self-reported sleep duration and dietary nutrient intake, with and without adjustments for variations in sleep timing (i.e., the midpoint of sleep). We conducted a questionnaire survey, comprising a validated brief self-administered diet history questionnaire (BDHQ) and the Japanese version of the Pittsburgh Sleep Quality Index (PSQI) among 1902 healthy Japanese adults and found that the dietary intakes of several nutrients correlated with sleep duration among men regardless of adjustment for the midpoint of sleep. Particularly, (1) small but significant correlations were observed between sleep duration and the percentage of energy from protein, regardless of adjustment for the midpoint of sleep; (2) energy-adjusted intakes of sodium, vitamin D, and vitamin B12 also significantly correlated with sleep duration; and (3) intakes of bread, pulses, and fish and shellfish correlated with sleep duration. In contrast, no significant correlations were observed between sleep duration and dietary intakes among women. This study revealed that after controlling for the midpoint of sleep, sleep duration correlated significantly with the dietary intake of specific nutrients and foods in a population of Japanese men.

Cell autonomous sanctions in legumes target ineffective rhizobia in nodules with mixed infections.

PREMISE OF THE STUDY: To maximize benefits from symbiosis, legumes must limit physiological inputs into ineffective rhizobia that nodulate hosts without fixing nitrogen. The capacity of legumes to decrease the relative fitness of ineffective rhizobia-known as sanctions-has been demonstrated in several legume species, but its mechanisms remain unclear. Sanctions are predicted to work at the whole-nodule level. However, whole-nodule sanctions would make the host vulnerable to mixed-nodule infections, which have been demonstrated in the laboratory and observed in natural settings. Here, we present and test a cell-autonomous model of legume sanctions that can resolve this dilemma. METHODS: We analyzed histological and ultrastructural evidence of sanctions in two legume species, Acmispon strigosus and Lotus japonicus. For the former, we inoculated seedlings with rhizobia that naturally vary in their abilities to fix nitrogen. In the latter, we inoculated seedlings with near-isogenic strains that differ only in the ability to fix nitrogen. KEY RESULTS: In both hosts, plants inoculated with ineffective rhizobia exhibited evidence for a cell autonomous and accelerated program of senescence within nodules. In plants that received mixed inoculations, only the plant cells harboring ineffective rhizobia exhibited features consistent with programmed cell death, including collapsed vacuoles, ruptured symbiosomes, and bacteroids that are released into the cytosol. These features were consistently linked with ultrastructural evidence of reduced survival of ineffective rhizobia in planta. CONCLUSIONS: Our data suggest an elegant cell autonomous mechanism by which legumes can detect and defend against ineffective rhizobia even when nodules harbor a mix of effective and ineffective rhizobial genotypes.

Zinc-rich oysters as well as zinc-yeast- and astaxanthin-enriched food improved sleep efficiency and sleep onset in a randomized controlled trial of healthy individuals.

SCOPE: Zinc is an essential mineral that plays an important role in the body. We previously reported that orally feeding zinc-enriched yeast to mice induces nonrapid-eye-movement sleep. In addition, astaxanthin, an antioxidant abundant in seafood such as salmon and krill, is able to chelate minerals and may promote zinc absorption, which in return may also improve sleep. The purpose of our study was to examine the effect of zinc-rich and astaxanthin-containing food on sleep in humans. METHODS AND RESULTS: We conducted a randomized, double-blinded, placebo-controlled parallel group trial of 120 healthy subjects and recorded their night activity by actigraphy for 12 weeks. These subjects were divided into four groups: placebo, zinc-rich food, zinc-, and astaxanthin-rich food, and placebo supplemented with zinc-enriched yeast and astaxanthin oil. Compared with the placebo group, the zinc-rich food group efficiently decreased the time necessary to fall asleep and improved sleep efficiency, whereas the group that ingested zinc-enriched yeast and astaxanthin oil significantly improved the sleep onset latency. CONCLUSION: Actigraphic sleep monitoring demonstrated that eating zinc-rich food improved sleep onset latency as well as improved the sleep efficiency in healthy individuals.

Changes in the Physicochemical Properties of Piperine/ß-Cyclodextrin due to the Formation of Inclusion Complexes.

Piperine (PP) is a pungent component in black pepper that possesses useful biological activities; however it is practically insoluble in water. The aim of the current study was to prepare a coground mixture (GM) of PP and ß-cyclodextrin (ßCD) (molar ratio of PP/ßCD = 1/1) and subsequently evaluate the solubility of PP and physicochemical properties of the GM. DSC thermal behavior of the GM showed the absence of melting peak of piperine. PXRD profile of the GM exhibited halo pattern and no characteristic peaks due to PP and ßCD were observed. Based on Job's plot, the PP/ßCD complex in solution had a stoichiometric ratio of 1/1. Raman spectrum of the GM revealed scattering peaks assigned for the benzene ring (C=C), the methylene groups (CH2), and ether groups (C-O-C) of PP that were broaden and shifted to lower frequencies. SEM micrographs showed that particles in the GM were agglomerated and had rough surface, unlike pure PP and pure ßCD particles. At 15 min of dissolution testing, the amount dissolved of PP in the GM was dramatically increased (about 16 times) compared to that of pure PP. Moreover the interaction between PP and ßCD cavity was detected by (1)H-(1)H NMR nuclear Overhauser effect spectroscopy NMR spectroscopy.

Maxillary sinus perforation by orthodontic anchor screws.

To facilitate safe placement of orthodontic anchor screws (miniscrews), we investigated the frequency of maxillary sinus perforation after screw placement and the effect of sinus perforation on screw stability. Maxillary sinus perforations involving 82 miniscrews (diameter, 1.6 mm; length, 8 mm) were evaluated using cone-beam computed tomography. All miniscrews were placed in maxillary alveolar bone between the second premolar and first molar for anchorage for anterior retraction in patients undergoing first premolar extraction. The placement torque and screw mobility of each implant were determined using a torque tester and a Periotest device, and variability in these values in relation to sinus perforation was evaluated. Eight of the 82 miniscrews perforated the maxillary sinus. There was no case of sinusitis in patients with miniscrew perforation and no significant difference in screw mobility or placement torque between perforating and non-perforating miniscrews. The sinus floor was significantly thinner in perforated cases than in non-perforated cases. A sinus floor thickness of 6.0 mm or more is recommended in order to avoid miniscrew perforation of the maxillary sinus.

Synthesis and LC-MS/MS analysis of desmosine-CH2, a potential internal standard for the degraded elastin biomarker desmosine.

Desmosine-CH2, an analog of the elastic tissue degradation biomarker desmosine, can be regarded as a potential internal standard for precise quantification of desmosines by LC-MS/MS. In this study, the chemical synthesis of desmosine-CH2 was completed in 22% overall yield in five steps. The LC-MS/MS analysis of desmosine-CH2 was also achieved.

Brevisulcatic acids, marine ladder-frame polyethers from the red tide dinoflagellate Karenia brevisulcata in New Zealand.

The isolation and structural determination of new marine ladder-frame polyethers, brevisulcatic acids-1 (1) and -4 (2) are reported. Brevisulcatic acids were isolated from the dinoflagellate Karenia brevisulcata, which was identified as the causative species of a major red tide event in New Zealand in 1998. The ether ring composition and a ß-hydroxy, γ-methylene valeric acid side chain of 1 and 2 are common, but 2 has a γ-lactone as the 5-membered A-ring while 1 is the seco acid analogue. Compound 2 has structural and bioactivity similarities to brevetoxin A.