Development of a New Two-Arm Transurethral Surgical System for En Bloc Resection of Bladder Tumor: A Preclinical Study.

Backgrounds and Objectives: To overcome the piecemeal nature of bladder tumor resection, en bloc resection of bladder tumor (ERBT) has been introduced. ERBT is difficult for surgeons to perform using the currently available system because it has only one arm. Herein, we aimed to develop a new transurethral surgical system to facilitate two-arm ERBT and to report the results of preclinical experiments using tumor phantoms. Methods: Initially, we aimed to develop a brand-new surgical system for ERBT but, after trial and error, we redirected our development to the creation of three elements: the left arm to grasp the tumor; the right arm to cut the tumor; and the system to operate the arms that can be attached to the existing surgical system (UES-40 SurgMaster® [Olympus Co. Ltd., Tokyo, Japan]). The current system was evaluated by performing simulated ERBTs using tumor phantoms made from konjac jelly. Results: Following the assembly of developed arms into the UES-40 SurgMaster, we conducted preliminary ERBTs. After performing several resections, we adopted a basket-shaped forceps as the left arm instead of grasping forceps and an arched electrode as the right arm. The two arms and single endoscope were placed in an equilateral triangle. We performed ERBT for the tumor phantoms that ranged from 0.5 to 2.0 cm without major redo. Conclusion: Herein, we introduced our development for two-arm ERBT. The current concept of "two-hand transurethral surgery" has the potential to be developed in future in vivo and clinical trials.

Improvement of implantation potential in mouse blastocysts derived from IVF by combined treatment with prolactin, epidermal growth factor and 4-hydroxyestradiol.

STUDY QUESTION: Can supplementation of medium with prolactin (PRL), epidermal growth factor (EGF) and 4-hydroxyestradiol (4-OH-E2) prior to embryo transfer improve implantation potential in mouse blastocysts derived from IVF? SUMMARY ANSWER: Combined treatment with PRL, EGF and 4-OH-E2 improves mouse blastocyst implantation rates, while alone, each factor is ineffective. WHAT IS KNOWN ALREADY: Blastocyst dormancy during delayed implantation caused by ovariectomy is maintained by continued progesterone treatment in mice, and estrogen injection rapidly activates blastocysts to implantation-induced status in vivo. While the expression of many proteins is upregulated in implantation-induced blastocysts, selective proteolysis by proteasomes, such as estrogen receptor α (ESR1), occurs in implantation-induced blastocysts to achieve implantation-competent status. It is worth evaluating the proteins expressed during these periods to identify humoral factors that might improve the implantation potential of IVF-derived blastocysts because the poor quality of embryos obtained by IVF is one of the major causes of implantation failure. STUDY DESIGN, SIZE, DURATION: Superovulated oocytes from ICR mice were fertilized with spermatozoa and then cultured in vitro in potassium simplex optimized medium (KSOM) without phenol red (KSOM-P) for 90-96 h. Blastocysts were treated with PRL (10 or 20 mIU/mL), EGF (5 or 10 ng/mL) or 4-OH-E2 (1 or 10 nM) in KSOM-P for 24 h. PARTICIPANTS/MATERIALS, SETTING, METHODS: Levels of breast cancer 1 (BRCA1), EGF receptor (EGFR, also known as ERBB1), ERBB4, tubulointerstitial nephritis antigen-like 1 (TINAGL1) and ESR1 protein were examined with immunohistochemical analysis using immunofluorescence methods and confocal laser scanning microscopy. For embryo transfer, six blastocysts were suspended in HEPES-buffered KSOM-P medium and transferred into the uteri of recipient mice on the morning of Day 4 (0900-1000 h) of pseudopregnancy (Day 1 = vaginal plug). The number of implantation sites was then recorded on Day 6 using the blue dye method. MAIN RESULTS AND THE ROLE OF CHANCE: PRL, EGF and 4-OH-E2 each promoted BRCA1 protein level in the trophectoderm (TE). While PRL treatment resulted in an increase in EGFR, EGF increased both EGFR and ERBB4 in the blastocyst TE. TINAGL1 in the TE was enhanced by 4-OH-E2, which also increased localization of this protein to the basement membrane. Treatment with PRL, EGF or 4-OH-E2 alone did not improve blastocyst implantation rates. Combined treatment with PRL, EGF and 4-OH-E2 resulted in increased levels of EGFR, ERBB4, TINAGL1 and BRCA1 in the TE, whereas ESR1 was not upregulated in the treated blastocysts. Furthermore, combined treatment with PRL, EGF and 4-OH-E2 improved blastocyst implantation rates versus control (P = 0.009). LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: Our studies were carried out in a mouse model, and the conclusions were drawn from limited results obtained from one species. Whether the increase in EGFR, ERBB4 and TINAGL1 protein in the TE improves implantation potential of blastocysts needs to be further studied experimentally by assessing other expressed proteins. The influence of combined supplementation in vitro of PRL, EGF and 4-OH-E2 on implantation also requires further examination and optimization in human blastocysts before it can be considered for clinical use in ART. WIDER IMPLICATIONS OF THE FINDINGS: Enhanced implantation potential by combined treatment with PRL, EGF and 4-OH-E2 appears to result in the upregulation of at least two distinct mechanisms, namely signaling via EGF receptors and basement membrane formation during the peri-implantation period in mice. While PRL, EGF and 4-OH-E2 each promoted BRCA1 protein level in the TE, treatment with each alone did not improve blastocyst implantation. Therefore, BRCA1 protein appears to be unnecessary for the attachment reaction in blastocysts in mice Combined supplementation of PRL, EGF and 4-OH-E2 might also be of relevance for embryo transfer of human IVF-derived blastocysts for ART. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by the JSPS KAKENHI [Grant numbers 22580316 and 25450390 (to H.M.)] and the Joint Research Project of Japan-U.S. Cooperative Science Program (to H.M.). The authors have no conflict of interest to declare.

Efficient terahertz detection in a sheet cavity using a nonlinear optical parametric process.

We designed and simulated a GaP-based sheet cavity structure for room-temperature THz wave detection via a nonlinear optical (NLO) parametric process, using photonic conversion from THz frequencies to the optical domain. The sheet cavity structure consisted of a GaP rectangular waveguide for THz waves. Pump enhancement in the cavity and strong confinement of the THz wave in the waveguide resulted in a high power conversion efficiency of 1% (detection at 5 THz). The noise equivalent power for THz wave detection using an optical single-photon detector was estimated to be in the order of a few fW Hz(-1/2), which was higher than that obtained using room-temperature bolometers, field-effect transistors, and other NLO processes.

Concept of annular vector beam generation at terahertz wavelengths via a nonlinear parametric process.

In this paper, we describe our theoretical investigation and calculations for a terahertz (THz)-wave profile generated by difference frequency mixing (DFM) of focused, cylindrically symmetric, and polarized optical vector beams. Using vector diffraction theory, the second-order nonlinear polarization was estimated from the electric field components of the optical pump beams penetrating uniaxial, birefringent nonlinear optics (NLO) crystals, GaSe and CdSe. The approximate beam patterns of the THz waves were simulated using DFM formulation. The intensity patterns of the THz waves for GaSe and CdSe showed sixfold symmetry and cylindrical symmetry, respectively, based on the nonlinear susceptibility tensor of the crystals. As the phase-matching angle θ(PM) was constant with respect to the c axis of the NLO crystals, an annular vector beam with a narrow width was expected.

Pump enhanced monochromatic terahertz-wave parametric oscillator toward megawatt peak power.

Pump enhanced optical parametric oscillation under a cavity phase matching configuration is an effective way to obtain monochromatic THz waves with high pulse energy. Numerical simulations are conducted for THz wave generations using a GaP sheet cavity. By optimizing the optical pulse duration and cavity configuration, the estimated peak power of THz waves is 4 MW at 3 THz, which corresponds to the photon conversion efficiency of η≈0.81. Our proposed scheme can generate a THz wave with high pulse energy, which is suitable for the nonlinear optical effects in the THz frequency region.

THz-wave generation via difference frequency mixing in strained silicon based waveguide utilizing its second order susceptibility χ((2)).

Terahertz (THz) wave generation via difference frequency mixing (DFM) process in strain silicon membrane waveguides by introducing the straining layer is theoretically investigated. The Si(3)N(4) straining layer induces anisotropic compressive strain in the silicon core and results in the appearance of the bulk second order nonlinear susceptibility χ((2)) by breaking the crystal symmetry. We have proposed waveguide structures for THz wave generation under the DFM process by .using the modal birefringence in the waveguide core. Our simulations show that an output power of up to 0.95 mW can be achieved at 9.09 THz. The strained silicon optical device may open a widow in the field of the silicon-based active THz photonic device applications.

Design of a GaP/Si composite waveguide for CW terahertz wave generation via difference frequency mixing.

We design a GaP/Si composite waveguide to achieve efficient terahertz (THz) wave generation under collinear phase-matched difference frequency mixing (DFM) between near-infrared light sources. This waveguide structure provides a strong mode confinement of both near-infrared sources and THz wave, resulting in an efficient mode overlapping. The numerical results show that the waveguide can produce guided THz wave (5.93 THz) with a power conversion efficiency of 6.6×10(-4) W(-1). This value is larger than previously obtained with the bulk GaP crystal: 0.5×10(-9) W(-1) [J. Lightwave Technol.27, 3057 (2009)]. Our proposed composite waveguide can be achieved by bridging the telecom wavelength and THz frequency region.

Degradation of estrogen receptor α in activated blastocysts is associated with implantation in the delayed implantation mouse model.

Implantation of a blastocyst into a receptive uterus involves a series of highly coordinated cellular and molecular events directed by ovarian estrogen and progesterone. In particular, estrogen is essential for on-time uterine receptivity and blastocyst activation in mice. Although estrogen receptor α (ERα) is expressed in blastocysts, its targeted disruption leaves embryonic development and implantation unaffected. Therefore, the role of ERα in implanting blastocysts remains unclear. Using a delayed implantation model in mice, we showed increased expression of ERα in implantation-induced (activated) blastocysts; however, this ERα expression in activated blastocysts decreased within 6-h culture. In contrast, breast cancer 1 (Brca1) was maintained in the blastocysts during the culture. The treatment of activated blastocysts with the proteasome inhibitor MG132 demonstrated that proteolysis is associated with down-regulation of ERα expression in activated blastocysts. Embryo transfer of MG132-treated activated blastocysts into recipient mice on the morning of Day 4 of pseudopregnancy (Day 1 = vaginal plug) showed a decreased implantation rate, whereas combined treatment with MG132 and the ER antagonist, ICI 182,780, resulted in recovery of the rate of implantation. This study has revealed that down-regulation of ERα in activated blastocyst is associated with completion of blastocyst implantation after embryo transfer on the morning of Day 4 of pseudopregnancy. Our results also suggest that selective protein turnover, such as that of ERα, occurs in activated blastocysts, while expression of other proteins, including Brca1, is maintained at the same stage.

Elliptically polarized THz-wave generation from GaP-THz planar waveguide via collinear phase-matched difference frequency mixing.

We carried out terahertz (THz)-wave generation from the GaP planar waveguides under collinear phase-matched difference-frequency mixing of two near-infrared sources. TE- and TM-mode of THz-waves were generated simultaneously by adjusting the polarization direction of two incident infrared sources. The phase shift between TE- and TM-mode of THz-wave in the waveguide was dependent on the waveguide length and contributed to the generation of the elliptical polarized THz-wave. The ellipticity of generated THz-wave increased as waveguide length increased. We indicated the possibility of control of rotational direction of elliptical polarization of emitted THz wave.

A high-peak-power UV picosecond-pulse light source based on a gain-switched 1.55 microm laser diode and its application to time-resolved spectroscopy of blue-violet materials.

We generated sub-kilowatt peak-power and 6-ps duration 390-nm optical pulses via the fourth harmonic generation of amplified optical output from a gain-switched 1.55-microm laser diode. We obtained a power-conversion-efficiency of 12% from 1.55-microm to 390-nm light, and subsequently applied the ultraviolet pulses to time-resolved spectroscopy of blue-violet luminescent materials, including a Coumarine dye solution and nitride semiconductor materials using single-photon and two-photon excitation schemes.