Timing of re-dosing based on population pharmacokinetic-pharmacodynamics target attainment analysis of cefmetazole in subjects undergoing lower gastrointestinal surgery.

INTRODUCTION: This study was conducted to evaluate the population pharmacokinetics of prophylactic cefmetazole sodium (CMZ) based on the serum concentrations and establish a pharmacodynamics target concentration exceeding the minimum inhibitory concentration (MIC) to design the re-dosing interval. METHODS: Serum (n = 362) samples from 107 individuals were analyzed using a nonlinear mixed-effects model. The pharmacodynamics index obtained was regarded as the probability of maintaining CMZ serum trough exceeding the minimal inhibitory concentration (MIC) of 2 mg/L. This MIC was chosen to account for methicillin-susceptible Staphylococcus aureus (MSSA), E. coli, and Klebsiella pneumoniae RESULTS: The final population pharmacokinetic model was a two-compartment model with linear elimination. Creatinine clearance and body weight were identified as significant covariates influencing the central clearance and volume of distribution in the central compartment. The probability of achieving serum concentrations exceeding the MIC90 for MSSA, E. coli, and Klebsiella pneumoniae for a 1 g dose with a 10 min intravenous infusion was above 90% except for good renal function (CLcr â‰§ 95 mL/min) at 2 h after the initial dose. For patients with good renal function (CLcr â‰§ 95 mL/min), a CMZ of 2 g re-dosing interval seemed necessary to meet the achievement probability. In patients with impaired renal function (CLcr ≤20 mL/min), the probability of achievement exceeded 90% even when the dosing interval was extended to 8 h. CONCLUSIONS: We evaluated re-dosing intervals based on the population pharmacokinetics. Re-dosing intervals should be determined based on renal function.

Reflection-type vapor cell for micro atomic clocks using local anodic bonding of 45° mirrors.

This Letter reports the design, fabrication, and evaluation of reflection-type planar vapor cells for chip-scale atomic clocks. The cell with 2-8 mm cavity length contains two 45° Bragg reflector mirrors assembled using a local anodic bonding. Coherent population trapping resonance of Rb atoms is observed, realizing an atomic clock operation. Allan deviations at an averaging time of 1 s are ${2.2} \times {{1}}{{{0}}^{- 10}}$ and ${9.5} \times {{1}}{{{0}}^{- 11}}$ for 2 mm long and 6 mm long vapor cells, respectively. These results show that planar vapor cells compatible with a system-in-package are feasible without degradation of clock stabilities compared to conventional vertically stacked cells.

Effect of Deep-Defects Excitation on Mechanical Energy Dissipation of Single-Crystal Diamond.

The ultrawide band gap of diamond distinguishes it from other semiconductors, in that all known defects have deep energy levels that are less active at room temperature. Here, we present the effect of deep defects on the mechanical energy dissipation of single-crystal diamond experimentally and theoretically up to 973 K. Energy dissipation is found to increase with temperature and exhibits local maxima due to the interaction between phonons and deep defects activated at specific temperatures. A two-level model with deep energies is proposed to explain well the energy dissipation at elevated temperatures. It is evident that the removal of boron impurities can substantially increase the quality factor of room-temperature diamond mechanical resonators. The deep energy nature of the defects bestows single-crystal diamond with outstanding low intrinsic energy dissipation in mechanical resonators at room temperature or above.

Ion transport by gating voltage to nanopores produced via metal-assisted chemical etching method.

In this work, we report a simple and low-cost way to create nanopores that can be employed for various applications in nanofluidics. Nano sized Ag particles in the range from 1 to 20 nm are formed on a silicon substrate with a de-wetting method. Then the silicon nanopores with an approximate 15 nm average diameter and 200 µm height are successfully produced by the metal-assisted chemical etching method. In addition, electrically driven ion transport in the nanopores is demonstrated for nanofluidic applications. Ion transport through the nanopores is observed and could be controlled by an application of a gating voltage to the nanopores.

Thermal Characterization of Dynamic Silicon Cantilever Array Sensors by Digital Holographic Microscopy.

In this paper, we apply a digital holographic microscope (DHM) in conjunction with stroboscopic acquisition synchronization. Here, the temperature-dependent decrease of the first resonance frequency (S1(T)) and Young's elastic modulus (E1(T)) of silicon micromechanical cantilever sensors (MCSs) are measured. To perform these measurements, the MCSs are uniformly heated from T0 = 298 K to T = 450 K while being externally actuated with a piezo-actuator in a certain frequency range close to their first resonance frequencies. At each temperature, the DHM records the time-sequence of the 3D topographies for the given frequency range. Such holographic data allow for the extracting of the out-of-plane vibrations at any relevant area of the MCSs. Next, the Bode and Nyquist diagrams are used to determine the resonant frequencies with a precision of 0.1 Hz. Our results show that the decrease of resonance frequency is a direct consequence of the reduction of the silicon elastic modulus upon heating. The measured temperature dependence of the Young's modulus is in very good accordance with the previously-reported values, validating the reliability and applicability of this method for micromechanical sensing applications.

Microstructuring of carbon nanotubes-nickel nanocomposite.

In this paper, we develop a novel electroplating method for the synthesis of carbon nanotubes (CNTs)-nickel (Ni) nanocomposite, and present the fabrication of a silicon micromirror with the CNTs-Ni nanocomposite beams to evaluate the mechanical stability of the micromirror in terms of resonant frequency. CNTs are pretreated to have positive charges on their surface and added into a Ni electroplating solution to form a CNTs-Ni nanocomposite electroplating suspension. The weight fraction of the CNTs in the electroplated nanocomposite is 2.4 wt%, and the ultramicroindentation hardness is 18.6 GPa. The mechanical strengthening phenomenon is found in the nanocomposite in comparison with a Ni film. Moreover, the addition of CNTs in the nanocomposite beams effectively increases the shear modulus compared with the pure Ni. The maximum variation of the resonant frequency of the micromirror during a long-term stability test is approximately 0.25%, and its scanning angle is approximately 20°. It shows the potential suitability of the CNTs-Ni nanocomposite with proper design for micromechanical element applications.

Temperature changes in brown adipocytes detected with a bimaterial microcantilever.

Mammalian cells must produce heat to maintain body temperature and support other biological activities. Methods to measure a cell's thermogenic ability by inserting a thermometer into the cell or measuring the rate of oxygen consumption in a closed vessel can disturb its natural state. Here, we developed a noninvasive system for measuring a cell's heat production with a bimaterial microcantilever. This method is suitable for investigating the heat-generating properties of cells in their native state, because changes in cell temperature can be measured from the bending of the microcantilever, without damaging the cell and restricting its supply of dissolved oxygen. Thus, we were able to measure increases in cell temperature of <1 K in a small number of murine brown adipocytes (n = 4-7 cells) stimulated with norepinephrine, and observed a slow increase in temperature over several hours. This long-term heat production suggests that, in addition to converting fatty acids into heat energy, brown adipocytes may also adjust protein expression to raise their own temperature, to generate more heat. We expect this bimaterial microcantilever system to prove useful for determining a cell's state by measuring thermal characteristics.

Advanced treatment of swine wastewater using an agent synthesized from amorphous silica and hydrated lime.

Advanced treatment using an agent synthesized from amorphous silica and hydrated lime (M-CSH-lime) was developed and applied to swine wastewater treatment. Biologically treated wastewater and M-CSH-lime (approximately 6 w/v% slurry) were fed continuously into a column-shaped reactor from its bottom. Accumulated M-CSH-lime gradually formed a bed layer. The influent permeated this layer and contacted the M-CSH-lime, and the treatment reaction progressed. Treated liquid overflowing from the top of the reactor was neutralized with CO2gas bubbling. The colour removal rate approximately exceeded 50% with M-CSH-lime addition rates of > 0.15 w/v%. The removal rate of PO(3⁻)(4) exceeded 80% with the addition of>0.03 w/v% of M-CSH-lime. The removal rates of coliform bacteria and Escherichia coli exceeded 99.9% with > 0.1 w/v%. Accumulated M-CSH-lime in the reactor was periodically withdrawn from the upper part of the bed layer. The content of citric-acid-soluble P2O5 in the recovered matter was>15% when the weight ratio of influent PO(3⁻)(4) -P to added M-CSH-lime was > 0.15. This content was comparable with commercial phosphorus fertilizer. The inhibitory effect of recovered M-CSH-lime on germination and growth of leafy vegetable komatsuna (Brassica rapa var. perviridis) was evaluated by an experiment using the Neubauer's pot. The recovered M-CSH-lime had no negative effect on germination and growth. These results suggest that advanced water treatment with M-CSH-lime was effective for simultaneous removal of colour, [Formula: see text] and coliform bacteria at an addition rate of 0.03-0.15 w/v%, and that the recovered M-CSH-lime would be suitable as phosphorus fertilizer.

[Case report of re-expansion pulmonary edema in a patient with anorexia nervosa after removal of a huge ovarian tumor].

We described a case of 19-year-old female who developed re-expansion pulmonary edema (RPE) after removal of a huge ovarian tumor. Altered lung volume after the surgery was observed by chest X-ray. Preoperatively, the lung was highly compressed by the tumor. Patient was intubated under general anesthesia and was ventilated by pressure controlled mode with only 5 cmH2O of positive end-expiratory pressure (PEEP). P/F ratio was changed from 163 to 444 after removal of the tumor. At the end of the surgery, P/F ratio decreased to 263 with yellow frothy sputum in the endotracheal tube and we diagnosed re-expansion pulmonary edema based on appearing yellow frothy sputum and chest X-ray. No recruitment procedure was carried out through the course except positive pressure ventilation with 5 cmH2O of PEEP in the intensive care unit after surgery. Twelve hours after the surgery, we could not confirm the recovery of lung volume on chest X-ray; however the patient was extubated because of P/F ratio increasing to 507. After 8 days of the surgery, the chest X-ray showed recovery of the lung volume to almost normal size. In this case, the compressed lung needed almost 1 week to recover the lung volume. This change in chest X-ray might indicate inadequate recovery of lung volume by recruitment maneuver and this should be avoided in order not to allow development of unfavorable clinical course of RPE.

[Prominent elevation of liver enzymes after Fontan operation].

It is known that acute liver dysfunction is one of the complications after Fontan operation. We tend to overlook it because their laboratory abnormalities are typically mild and hepatic dysfunction is an uncommon complication in children after cardiac surgery. However, this complication is likely to be an important indicator of poor prognosis. We report a patient who showed a prominent elevation of liver enzymes after Fontan operation. A year and 5 month old boy was scheduled for Fontan operation due to hypoplastic left heart syndrome. We used arterial pressure, central venous pressure and rSO2 probes (INVOS 5100, Somanetics Corp., USA) attaching on his head, abdomen and leg for circulatory management. The operation was performed with the heart beating. The blood removal tubes were inserted to the superior vena cava and inferior vena cava and the blood sending tube was inserted to the innominate artery when Norwood stage 1 was performed. After making an extracardiac conduit and a fenestration, we tried to take off the oxygenator with dopamine 5 microg x kg(-1) x min(-1), dobutamine 3 microg x kg(-1) x min(-1), isosorbide 2.5 microg x kg(-1) x min(-1). The central venous pressure was increased to 22-25 mmHg and systematic arterial pressure was unstable around 50 mmHg. We suggested the surgeons to expand the fenestration because the low flow through it was found on TEE examination, and introduced 15 ppm of nitric monoxide (NO) to decrease pulmonary vascular resistance and to control the central venous pressure at the same time. rSO2 was decreased to 50 temporarily when the oxygenator was taken off, however it was returned to 70 just after expanding the fenestration. On the first postoperative day, the patient showed marked elevations in GOT 17,305 U x l(-1), GPT 8,110 U x l(-1), gradually peaking out to GOT 105 U x l(-1), GPT 1,348 U x l(-1) by the seventh postoperative day. Hepatic dysfunction is related mainly to hemodynamic disturbances and is also related to the abdominal rSO2 and the high central venous pressure.

Metal-Multilayered Nanomechanical Cantilever Sensor for Detection of Molecular Adsorption.

A metal-multilayered nanomechanical cantilever sensor was proposed to reduce the temperature effect for highly sensitive gas molecular detection. The multilayer structure of the sensor reduces the bimetallic effect, allowing for the detection of differences in molecular adsorption properties on various metal surfaces with higher sensitivity. Our results indicate that the sensor exhibits higher sensitivity to molecules with greater polarity under mixed conditions with nitrogen gas. We demonstrate that stress changes caused by differences in molecular adsorption on different metal surfaces can be detected and that this approach could be used to develop a gas sensor with selectivity for specific gas species.

Demonstration of Heterogeneous Structure for Fabricating a Comb-Drive Actuator for Cryogenic Applications.

This study presents an experimental demonstration of the motion characteristics of a comb-drive actuator fabricated from heterogeneous structure and applied for cryogenic environments. Here, a silicon wafer is anodically bonded onto a glass substrate, which is considered to be a conventional heterogeneous structure and is commonly adopted for fabricating comb-drive actuators owing to the low-cost fabrication. The displacement sensor, also with comb-finger configuration, is utilized to monitor the motion characteristics in real time at low temperatures. The irregular motions, including displacement fluctuation and lateral sticking, are observed at specific low temperatures. This can be attributed to the different thermal expansion coefficients of two materials in the heterogeneous structure, further leading to structural deformation at low temperatures. The support spring in a comb-drive actuator is apt to be deformed because of suspended flexible structures, which affect the stiffness of the support spring and generate irregular yield behavior. The irregular yield behavior at low temperatures can be constrained by enhancing the stiffness of the support spring. Finally, we reveal that there are limited applications of the heterogeneous-structure-based comb-drive actuator in cryogenic environments, and simultaneously point out that the material substrate of silicon on the insulator is replaceable based on the homogeneous structure with a thin SiO2 layer.

Association of serum and fat tissue antibiotic concentrations with surgical site infections in lower gastrointestinal surgery.

BACKGROUND: During surgery, the effectiveness of perioperative prophylactic antibiotic administration against surgical site infections is inferred from serum concentrations and not from tissues where local infections occur. This study aimed to measure the serum and tissue concentrations of cefmetazole in colorectal surgery cases to clarify whether there is an association between the incidence of surgical site infections and antibiotic concentrations. METHODS: This prospective cohort study was performed at a single tertiary care center. The data of 105 patients who underwent colorectal surgery between October 2017 and September 2019 were evaluated. The primary outcome was the incidence of surgical site infections. Univariate analysis was performed to investigate the association between surgical site infections, perioperative factors, and the serum and tissue concentrations of cefmetazole. RESULTS: The incidence of surgical site infections was 13/105 (12.4%). Cefmetazole concentrations were measured at initial incision (serum; 101 vs 93.1 mg/L, P = .75, subcutaneous fat tissue; 2.8 vs 3.7 mg/g, P = .15), intestinal resection (serum; 35.1 vs 36.7 mg/L, P = .63, mesenteric adipose tissue; 1.3 vs 1.7 mg/g, P = .55), and at skin closure (serum; 34.5 vs 44.8 mg/L, P = .18, subcutaneous fat tissue; 1.0 vs 2.2 mg/g, P = .09). In univariate analysis with P ≤ .10, cefmetazole concentration in subcutaneous fat tissue at skin closure was found to be a significant risk factor for surgical site infections. Age, additional intraoperative administration of cefmetazole, and creatinine clearance were also significant risk factors for the occurrence of surgical site infections. CONCLUSION: Low subcutaneous fat cefmetazole concentrations at skin closure during gastrointestinal operations may also be involved in the occurrence of surgical site infections.

Neuronal system-dependent facilitation of tumor angiogenesis and tumor growth by calcitonin gene-related peptide.

A neuropeptide, calcitonin gene-related peptide (CGRP), is widely distributed in neuronal systems and exhibits numerous biological activities. Using CGRP-knockout mice (CGRP(-/-)), we examined whether or not endogenous CGRP facilitates angiogenesis indispensable to tumor growth. CGRP increased tube formation by endothelial cells in vitro and enhanced sponge-induced angiogenesis in vivo. Tumor growth and tumor-associated angiogenesis in CGRP(-/-) implanted with Lewis lung carcinoma (LLC) cells were significantly reduced compared with those in wild-type (WT) mice. A CGRP antagonist, CGRP8-37 or denervation of sciatic nerves (L(1-5)) suppressed LLC growth in the sites of denervation compared with vehicle infusion or sham operation. CGRP precursor mRNA levels in the dorsal root ganglion in LLC-bearing WT were increased compared with those in non-LLC-bearing mice. This increase was abolished by denervation. The expression of VEGF in tumor stroma was down-regulated in CGRP(-/-). These results indicate that endogenous CGRP facilitates tumor-associated angiogenesis and tumor growth and suggest that relevant CGRP may be derived from neuronal systems including primary sensory neurons and may become a therapeutic target for cancers.

Three-dimensional imaging of electron spin resonance-magnetic resonance force microscopy at room temperature.

In this study, we demonstrated the three-dimensional (3D) imaging by magnetic resonance force microscopy (MRFM) based on electron spin resonance (ESR) measurements at room temperature. For a microsample containing radicals, the 3D force distribution was obtained using a custom-made Si nanowire and a permanent magnetic particle. Calculation using precise values of the magnetic field distribution is required to define an accurate response function for the 3D deconvolution processing of the spin density distribution. A symmetric resonance magnetic field produces good periodic force maps using a spherical micromagnet, which simplifies the deconvolution processing with resonant slice systems. In addition, the 3D imaging method was processed in the wavenumber space by a Fourier transform that used a simple convolution with noise parameters in the response function. After the reconstruction of the distribution of electron spins (radicals), the shape of the sample agreed with that of the optical image; thus, the accuracy of the internal density structure was verified. We believe that the combination of a Si nanowire and a spherical magnetic particle used for magnetic resonance detection is a good candidate for Fourier transform 3D deconvolution in multiple MRFM applications.

Aluminum doped zinc oxide deposited by atomic layer deposition and its applications to micro/nano devices.

This work reports investigation on the deposition and evaluation of an aluminum-doped zinc oxide (AZO) thin film and its novel applications to micro- and nano-devices. The AZO thin film is deposited successfully by atomic layer deposition (ALD). 50 nm-thick AZO film with high uniformity is checked by scanning electron microscopy. The element composition of the deposited film with various aluminum dopant concentration is analyzed by energy-dispersive X-ray spectroscopy. In addition, a polycrystalline feature of the deposited film is confirmed by selected area electron diffraction and high-resolution transmission electron microscopy. The lowest sheet resistance of the deposited AZO film is found at 0.7 kΩ/□ with the aluminum dopant concentration at 5 at.%. A novel method employed the ALD in combination with the sacrificial silicon structures is proposed which opens the way to create the ultra-high aspect ratio AZO structures. Moreover, based on this finding, three kinds of micro- and nano-devices employing the deposited AZO thin film have been proposed and demonstrated. Firstly, nanowalled micro-hollows with an aspect ratio of 300 and a height of 15 µm are successfully produced . Secondly, micro- and nano-fluidics, including a hollow fluidic channel with a nanowall structure as a resonator and a fluidic capillary window as an optical modulator is proposed and demonstrated. Lastly, nanomechanical resonators consisting of a bridged nanobeam structure and a vertical nanomechanical capacitive resonator are fabricated and evaluated.

Hermetically Packaged Microsensor for Quality Factor-Enhanced Photoacoustic Biosensing.

The use of photoacoustics (PA) being a convenient non-invasive analysis tool is widespread in various biomedical fields. Despite significant advances in traditional PA cell systems, detection platforms capable of providing high signal-to-noise ratios and steady operation are yet to be developed for practical micro/nano biosensing applications. Microfabricated transducers offer orders of magnitude higher quality factors and greatly enhanced performance in extremely miniature dimensions that is unattainable with large-scale PA cells. In this work we exploit these attractive attributes of microfabrication technology and describe the first implementation of a vacuum-packaged microscale resonator in photoacoustic biosensing. Steady operation of this functional approach is demonstrated by detecting the minuscule PA signals from the variations of trace amounts of glucose in gelatin-based synthetic tissues. These results demonstrate the potential of the novel approach to broad photoacoustic applications, spanning from micro-biosensing modules to the analysis of solid and liquid analytes of interest in condense mediums.

Magnetostrictive Performance of Electrodeposited TbxDy(1-x)Fey Thin Film with Microcantilever Structures.

The microfabrication with a magnetostrictive TbxDy(1-x)Fey thin film for magnetic microactuators is developed, and the magnetic and magnetostrictive actuation performances of the deposited thin film are evaluated. The magnetostrictive thin film of TbxDy(1-x)Fey is deposited on a metal seed layer by electrodeposition using a potentiostat in an aqueous solution. Bi-material cantilever structures with the Tb0.36Dy0.64Fe1.9 thin-film are fabricated using microfabrication, and the magnetic actuation performances are evaluated under the application of a magnetic field. The actuators show large magnetostriction coefficients of approximately 1250 ppm at a magnetic field of 11000 Oe.

Enhancing Delta E Effect at High Temperatures of Galfenol/Ti/Single-Crystal Diamond Resonators for Magnetic Sensing.

A conventional wisdom is that the sensing properties of magnetic sensors at high temperatures will be degraded due to the materials' deterioration. Here, the concept of high-temperature enhancing magnetic sensing is proposed based on the hybrid structure of SCD MEMS resonator functionalized with a high thermal-stable ferromagnetic galfenol (FeGa) film. The delta E effect of the magnetostrictive FeGa thin film on Ti/SCD cantilevers is investigated by varying the operating temperature from 300 to 773 K upon external magnetic fields. The multilayer structure magnetic sensor presents a high sensitivity of 71.1 Hz/mT and a low noise level of 10 nT/√Hz at 773 K for frequencies higher than 7.5 kHz. The high-temperature magnetic sensing performance exceeds those of the reported magnetic sensors. Furthermore, an anomalous behavior is observed on the delta E effect, which exhibits a positive temperature dependence with the law of Tn. Based on the resonance frequency shift of the FeGa/Ti/SCD cantilever, the strain coupling in the multilayers of the FeGa/Ti/SCD structure under a magnetic field is strengthened with increasing temperature. The delta E effect shows a strong relationship with the azimuthal angle, θ, as a sine function at 300 and 773 K. This work provides a strategy to develop magnetic sensors for high-temperature applications with performance superior to that of the present ones.

Roles of calcitonin gene-related peptide in facilitation of wound healing and angiogenesis.

Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide produced by tissue-specific alternative splicing of the primary transcript of the calcitonin/CGRP gene. CGRP is widely distributed in the central and peripheral neuronal systems and exhibits numerous biological activities in mammals. We examined in the present study whether or not endogenous CGRP released from neuronal systems facilitates neovascularization indispensable to wound healing. In CGRP knockout mice (CGRP-/-), wound-induced angiogenesis and wound closure were significantly suppressed compared with those in wild-type mice. The suppressed healing in CGRP-/- was accompanied by reduction in expressions of vascular endothelial growth factor (VEGF) in the wound granulation tissues. A CGRP antagonist, CGRP8-37 when infused with mini-osmotic pumps subcutaneously blocked the wound healing processes and reduced the expressions of CD31 and VEGF expression in the wound granulation tissues. Wound healing process was significantly delayed in neuropeptide-depleted mice pretreated with capsaicin, compared with vehicle-treated mice. These results indicate that CGRP derived from neuronal systems may facilitate wound healing and angiogenesis. Targeting of CGRP may be promising in controlling angiogenesis related to pathophysiological conditions.