Dimensional changes over time in stereolithographic models fabricated with a 3D printer.

This study aimed to ascertain the effects of the shape of stereolithographic models fabricated with a three-dimensional (3D) printer and the use of different types of liquid resin on the dimensional changes of these models over time, to obtain valuable information for determining the period for which such models can be used following fabrication. Stereolithography models with the shape of a large truncated cone or a small truncated cone were fabricated using liquid resin as surgical guides (Group G) or master casts (Group M). (four groups in total, each n = 11). The shapes of all experimental specimens were measured immediately after fabrication and 1 day, 1 week, 2 weeks, 3 weeks, 4 weeks, 2 months, 3 months, 6 months, 1 year, and 1.5 years later. The shape data collected immediately after fabrication were taken as baseline data, and the dimensional changes over time at each timepoint were calculated. No significant change from 1 day to 1 year after fabrication was observed in any of the groups, but the change after 1.5 years was significantly larger than the changes at the other timepoints (p < 0.001). Significantly larger changes were evident in Group M than in Group G at all timepoints (p < 0.001). These results suggested that, from the viewpoint of dimensional stability over time, stereolithographic models should be used within 1 year of fabrication, and that the type of liquid resin used for stereolithographic model fabrication may affect how its dimensions change over time.

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.

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.

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.

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.

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.

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.

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.

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.

New 2-aryl-1,4-naphthoquinone-1-oxime methyl ether compound induces microtubule depolymerization and subsequent apoptosis.

In this study, we describe the antitumor activity of QO-1, one of the new 2-aryl-1,4-naphthoquinone-1-oxime methyl ether derivatives. QO-1 is a derivative of macarpine, a natural occurring product from Rutaceae plant. It could potently inhibit cell growth when tested on 19 cancer cell lines. To investigate its mechanism, two cell lines (HeLa and MCF-7) sensitive to QO-1 were selected. Based on flow cytometry, it was found to induce G(2)/M-phase arrest. Moreover, it could cause microtubule depolymerization both in vitro and in vivo. On the other hand, QO-1 activated spindle assembly checkpoint (SAC) proteins. Expression of Bub1, one of the SAC, was gradually increased, reaching a peak after 16 - 20 h, and then gradually decreased. Instead, QO-1 increased the sub-G(1) population, which suggested a cell death population. Actually, expression of Bcl-2 family proteins and activation of caspase-3/7 were evidences of apoptosis. Consistent with these results, cells with DNA fragmentation and multinucleated cells were increased time-dependently after QO-1 exposure. In conclusion, QO-1 has promising antitumor effects via microtubule depolymerization.

[Analysis of risk factors of drug-induced lung injury in patients receiving gemcitabine treatment].

Gemcitabine hydrochloride is a very safe medicine that even outpatients can be administered, and the bone marrow depression that is the dose limiting factor remains moderate and does not need special treatment, although it is confirmed in most cases. Meanwhile, caution is required because there is a possibility of drug-induced lung injury and death due to high frequency, compared with the appearance rate described in the packaging insertion. We investigated the clinical background of a patient in whom drug-induced lung injury appeared, and clarified the risk factor by administering gemcitabine hydrochloride. Males, people aged 65 or over, those with a smoking history and those undergoing first-line chemotherapy treatment are at risk of drug-induced lung injury. Attention must be paid to the occurrence of drug-induced lung injury, to examining the clinical course, the chest image, and the blood test, and to do earlier detection, the offending medicine discontinuance, and beginning of the treatment.

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.

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.

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.

Clinical assessment of the relationship between the third molar and the inferior alveolar canal using panoramic images and computed tomography.

PURPOSE: To predict the relationship between lower third molars and the inferior alveolar canal (IAC) from panoramic radiographs, and to establish criteria for using computed tomography (CT). MATERIALS AND METHODS: A retrospective cohort study was performed involving 443 patients (695 teeth). Predictor variables were the distance between the third molar and the IAC, and findings according to the Rood's criteria. Outcome variables were the absence of cortication between the third molar and the IAC on the CT image, and injury of the inferior alveolar nerve (IAN). Statistical analysis was performed to assess the relationship between predictor and outcome variables. RESULTS: All patients had preoperative panoramic radiographs, and 71 patients (119 teeth) also had CT images. On CT examination, 48 teeth (40.3%) showed absence of cortication. Injury of the IAN was reported in 7 cases (1.0%), 5 of which exhibited absence of cortication; the remaining 2 did not have CT scans. Five of the 48 cases showing absence of cortication exhibited IAN injury, and none of the cases with cortication exhibited IAN injury. On the panoramic images, the following signs were strongly correlated with absence of cortication: a superimposed relationship between the third molar and the IAC; darkness of the root; and diversion and narrowing of the IAC. CONCLUSION: Presence of Rood's criteria was a predictor for a contact relationship between the third molar and the IAC, and an indication for CT examination. However, a superimposed relationship and the absence of Rood's criteria did not necessarily signify a separate relationship between third molar and the IAC.

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.

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.

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.