Investigation of dispersion-managed, polarization-maintaining Er-doped figure-nine ultrashort-pulse fiber laser.

Figure-nine fiber lasers can realize all-polarization-maintaining, self-started, highly stable mode-locked laser sources, and are very attractive for applications such as optical frequency combs, metrology, etc. In this work, we investigated a dispersion-managed, polarization-maintaining, Er-doped, ultrashort-pulse figure-nine fiber laser both experimentally and numerically. Stable, self-started, passive mode-locking operation was achieved in a wide net cavity dispersion region, covering the soliton, stretched pulse, and dissipative soliton mode-locking regimes. A 132 fs ultrashort pulse with spectral width of 46 nm was obtained in the stretched pulse mode-locking regime. The initial mode-locking process and dynamics inside the cavity, in addition to the fundamental characteristics of the output pulses, were examined via numerical analysis. Owing to the asymmetric configuration, the propagation behaviors were different between the two counter-propagation directions. It was found that a large breathing had already started before the passive mode-locking point in stretched pulse mode-locking operation. Intense overshoots were also observed at the beginning of passive mode-locking. Numerical results were almost in agreement with the experimental ones.

The effects of a participatory structured group educational program on the development of CKD: a population-based study.

BACKGROUND: The type of lifestyle guidance that is effective for preventing development of chronic kidney disease (CKD) is unknown. Here, we aim to investigate the effects of a participatory structured group education (SGE) program on the development of CKD in a population-based study. METHODS: We retrospectively analyzed 1060 adult special health check-up examinees with CKD. Examinees with an estimated glomerular filtration rate (eGFR) from 50 to 60 mL/min/1.73 m2 and/or proteinuria 1+ were encouraged to attend an SGE program. The SGE program included participatory small group discussions on the attendees' remaining risk factors. The primary outcome of this study was the change in eGFR per year. RESULTS: The changes in eGFR in examinees who attended the SGE program (n = 209, + 2.9 mL/min/1.73 m2 [95% confidence interval (CI) + 1.9 to + 3.9]) significantly improved compared with control (n = 383, + 1.2 mL/min/1.73 m2 [95% CI + 0.5 to + 1.9], p = 0.006). Attending an SGE program was independently and positively related to the changes in eGFR at 1 year after attendance, after adjusting for classical covariates (ß = 1.55 [95% CI 0.37-2.73], p = 0.01). Attending an SGE program was effective for the examinees with a lower eGFR compared with those with only proteinuria. CONCLUSIONS: Our SGE program showed the beneficial effects of preventing the development of CKD, independent of classical factors. The type of SGE program that is more effective for preventing development of CKD should be investigated in a long-term analysis.

A fast- and positively photoswitchable fluorescent protein for ultralow-laser-power RESOLFT nanoscopy.

Fluorescence nanoscopy has revolutionized our ability to visualize biological structures not resolvable by conventional microscopy. However, photodamage induced by intense light exposure has limited its use in live specimens. Here we describe Kohinoor, a fast-switching, positively photoswitchable fluorescent protein, and show that it has high photostability over many switching repeats. With Kohinoor, we achieved super-resolution imaging of live HeLa cells using biocompatible, ultralow laser intensity (0.004 J/cm(2)) in reversible saturable optical fluorescence transition (RESOLFT) nanoscopy.

[ROBOT-ASSISTED RADICAL PROSTATECTOMY FOR MEN AGE 75 AND OLDER].

(Objectives) Surgical treatment prostate cancer in elderly patients is controversial. However, robot-assisted radical prostatectomy (RARP) is a less invasive procedure than conventional surgery. Therefore, we perform RARP for elderly patients whose general condition is good (Performance status ≤1). The aim of this study is to evaluate surgical, oncological and functional outcomes for RARP in men age 75 and older. (Patients and methods) From July 2013 to April 2016, 300 patients underwent RARP at our institution. They were divided into two groups: an older patient group (≥75 years) and a younger patient group (<75 years). Treatment outcomes for each group, including surgical, oncological and functional outcomes, were compared. (Results) There were no statistically significant differences in surgical outcomes with the exception of nerve sparing rates (older patients: 5.9% vs. younger patients: 17.7%, P=0.0192). Importantly, intra- and postoperative complication rates were similar in both groups (minor complication: 7.4% vs. 3.9%, P=0.322, major complication: 0.0% vs. 2.2%, P=0.592). Regarding oncological outcomes, including positive surgical margin rate and PSA failure (PSA>0.2 ng/ml) at 12 months after surgery, no significant differences existed. Lastly, functional outcomes between the groups, including continence (≤1 pads/day) at 12 months after surgery, had no significant differences. (Conclusions) Our data suggests that RARP can be performed safely for men age 75 and older, and can become a good option for older patients with prostate cancer.

[MICROCYSTIC VARIANT OF UROTHELIAL CARCINOMA IN URINARY BLADDER: A CASE REPORT].

In the present report, we describe a patient with microcystic variant of urothelial carcinoma in urinary bladder. In March 2016, a 71-year-old man presented with bladder tumors found incidentally by ultrasonography. Cystoscopy and contrast-enhanced computed tomography (CT) revealed multiple invasive tumor of posterior wall, with a maximum diameter of 33 mm. Transurethral resection (TUR) of bladder tumors was performed. Pathological diagnosis was urothelial carcinoma, high grade, T2 or more. Invasive urothelial carcinoma was diagnosed and laparoscopic radical cystectomy with orthotopic neobladder was performed accordingly in April 2016. Pathological findings indicated a diagnosis of microcystic variant of urothelial carcinoma. At present, six months after surgery, the patient remains free of recurrence and metastasis. Here we review the characteristics of 4 microcystic variant of urothelial carcinoma cases reported in Japan.

Point spread function analysis with saturable and reverse saturable scattering.

Nonlinear plasmonics has attracted a lot of interests due to its wide applications. Recently, we demonstrated saturation and reverse saturation of scattering from a single plasmonic nanoparticle, which exhibits extremely narrow side lobes and central peaks in scattering images [ACS Photonics 1(1), 32 (2014)]. It is desirable to extract the reversed saturated part to further enhance optical resolution. However, such separation is not possible with conventional confocal microscope. Here we combine reverse saturable scattering and saturated excitation (SAX) microscopy. With quantitative analyses of amplitude and phase of SAX signals, unexpectedly high-order nonlinearities are revealed. Our result provides greatly reduced width in point spread function of scattering-based optical microscopy. It will find applications in not only nonlinear material analysis, but also high-resolution biomedical microscopy.

Measurement of a saturated emission of optical radiation from gold nanoparticles: application to an ultrahigh resolution microscope.

We show that scattering from a single gold nanoparticle is saturable for the first time. Wavelength-dependent study reveals that the saturation behavior is governed by depletion of surface plasmon resonance, not the thermal effect. We observed interesting flattening of the point spread function of scattering from a single nanoparticle due to saturation. By extracting the saturated part of scattering via temporal modulation, we achieve λ/8 point spread function in far-field imaging with unambiguous separation of adjacent particles.

Saturated excitation microscopy with optimized excitation modulation.

Saturated excitation (SAX) microscopy utilizes the nonlinear relation between fluorescence emission and excitation under saturated excitation to improve the spatial resolution of confocal microscopy. In this study, we theoretically and experimentally investigate the saturation of fluorescence excitation under modulated excitation to optimize the excitation conditions for SAX microscopy. Calculation of the relationships between fluorescence and excitation intensity with different modulation frequencies reveals that the lifetime of the triplet state of the fluorescent probe strongly affects the strength of the demodulated fluorescence signals. We also find that photobleaching shows little dependence on the modulation frequency. These investigations allow us to determine the optimum excitation conditions, that is, the conditions providing sufficient fluorescence saturation without strong photobleaching. For a sample stained with ATTO Rho6G phalloidin, we estimate the optimal excitation conditions, which are produced with 50 kHz excitation modulation and a 50 µsec pixel dwell time, and successfully perform three-dimensional imaging with sub-diffraction resolution.

Impact of lymph node dissection on surgical and oncological outcomes in patients undergoing robot-assisted radical cystectomy for bladder cancer: a multicenter retrospective study.

This study was performed to clarify the therapeutic and diagnostic roles of lymph node dissection (LND) by examining the impact of LND and lymph node yield (LNY) on oncological outcomes in patients undergoing robot-assisted radical cystectomy (RARC). Between 2014 and 2021, 216 patients underwent LND during RARC at Tokushima University Hospital and affiliated hospitals. Among the 216 patients, we compared 115 patients with an LNY of ≥ 20 and 101 with an LNY of < 20 to investigate the impact of LNY on surgical and oncological outcomes. Furthermore, we investigated the impact of LNY and the extent of LND on oncological outcomes by dividing the extent of LND into two groups (standard and extended). The 3-year rates of overall survival (OS) (p = 0.256), cancer-specific survival (CSS) (p = 0.791), and recurrence-free survival (RFS) (p = 0.953) did not differ between the two groups divided by the LNY. A higher LNY was associated with a significantly higher lymph node positivity rate (p = 0.020). The incidence of LND-related major complications was not significantly different between the two groups (p = 0.910). The 3-year survival rates did not differ between the two groups divided by the extent of LND: OS (p = 0.366), CSS (p = 0.814), and RFS (p = 0.689). The LNY and extent of LND were not associated with oncological outcomes in patients undergoing LND during RARC, whereas a higher LNY was associated with lymph node positivity. In the era of adjuvant therapy with immune checkpoint inhibitors, LND during RARC has an important diagnostic role in the detection of pathological node positivity.

Virtual cavernoscopy: a novel diagnostic tool for use in the corpus cavernosal lumen in patients with erectile dysfunction.

OBJECTIVE: • To evaluate virtual cavernoscopy as a diagnostic tool in erectile dysfunction. PATIENTS AND METHODS: • Forty patients who visited our hospital for investigation of erectile dysfunction underwent cavernosography using three-dimensional (3D)-computed tomography (CT). • Virtual cavernoscopic images were reconstructed from 3D-CT data. RESULTS: • Virtual cavernoscopic images were obtained from all patients. • Virtual cavernoscopy visualized the corpus cavernosal lumen surrounded by the tunica albuginea, the septum of the cavernosum, the outlets of the veins, and cavernous arteries. • The visualization of each structure depended on the window level (WL). At WL 400, the virtual cavernoscopy visualized only a fibrous structure. At this WL, the internal view of the corpus cavernosum was expressed as a hollow space. At WL 1600, the virtual cavernoscopy visualized the cavernous artery as a filling defect. • Out of 80 lumens in the 40 subjects, arteries in 14 lumens were detected by both virtual cavernoscopy and CT angiography, while arteries in 50 lumens were detected only by virtual cavernoscopy. Arteries in two lumens could not be visualized by either method and those in 14 lumens were visualized only by CT angiography. CONCLUSION: • In visualizing the artery, conventional imaging techniques depend on blood flow, whereas using virtual cavernoscopy an artery can be visualized independently of blood flow. Virtual cavernoscopy is unique in this regard and we therefore believe that this new imaging technology will contribute to better ED practice.

Three-dimensional CT cavernosography: reconsidering venous ligation surgery on the basis of the modern technology.

OBJECTIVE: • To examine the feasibility of three-dimensional (3D) CT cavernosography in the diagnosis of corporal veno-occlusive dysfunction. PATIENTS AND METHODS: • The subjects were 55 patients who had failed to respond to phosphodiesterase type 5 inhibitors. We performed pharmacodynamic infusion cavernosometry and cavernosography, using 60 mg papaverine hydrochloride. • Cavernosography was performed at 90 mmHg intracavernous pressure, using a multi-slice CT scan system. The 3D images were reconstructed using aquarius net station, ver.2 computer software. • For comparison with conventional cavernosography, maximum intensity projection (MIP) images were used. A flow of 20 mL/min or being more capable of maintaining 90 mmHg of intracavernous pressure indicated veno-occlusive dysfunction. RESULTS: • Forty-five of the 55 patients were diagnosed with corporal veno-occlusive dysfunction. 3D-CT cavernosography revealed drainage veins in all 45 cases, including cavernous veins, dorsal veins, crural veins and other emissary veins. • Compared with 3D-CT cavernosography, observing cavernous veins and the proximal part of the deep dorsal veins using MIP imaging was especially difficult because the origins of the penile veins are often behind the pelvic bone or cavernous body. • Of the patients who seemingly had leakage via the deep dorsal vein, 80.6% did not in fact have leakage via this vein, but had other leakages. The image resolution of 3D-CT cavernosography was significantly higher than that of MIP. CONCLUSION: • 3D-CT cavernosography can provide high-resolution images of venous drainage from any angle. We conclude that the images obtained by 3D-CT cavernosography are very helpful for both the diagnosis of corporal veno-occlusive dysfunction and the anatomical study of the human penile venous system.

Changes in Prevalence and Health Checkup Coverage Rate of Chronic Kidney Disease (CKD) after Introduction of Prefecture-Wide CKD Initiative: Results of the Kagawa Association of CKD Initiatives.

The National Health Insurance (NHI) special health checkup system in Japan targets the NHI population aged 40-74 years. Since 2015, the Kagawa NHI special health checkup was initiated in a prefecture-wide chronic kidney disease (CKD) initiative, including renal examination as an essential item in NHI health checkups. Here, we aimed to investigate the effects of the prefecture-wide CKD initiative. We conducted a retrospective cohort survey using the Kagawa National Health Insurance database created by the Kagawa National Health Insurance Organization. Results of the NHI health checkup (2015-2019) and prefecture-wide outcomes (2013-2019) were analyzed. The prevalence of CKD among examinees who underwent the NHI health checkup increased from 17.7% in 2015 to 23.2% in 2019. The percentage of examinees who completed a medical visit was 29.4% in 2015. After initiation of the initiative, the NHI health checkup coverage rate increased significantly, from a mean (standard deviation) of 40.8% (0.4%) to 43.2% (1.1%) (p = 0.04). After the start of the CKD initiative, we found an increase in the prevalence of CKD and the NHI health checkup coverage rate.

High-spatial-resolution deep tissue imaging with spectral-domain optical coherence microscopy in the 1700-nm spectral band.

We present three-dimensional (3-D) high-resolution spectral-domain optical coherence microscopy (SD-OCM) by using a supercontinuum (SC) fiber laser source with 300-nm spectral bandwidth (full-width at half-maximum) in the 1700-nm spectral band. By using low-coherence interferometry with SC light and a confocal detection scheme, we realized lateral and axial resolutions of 3.4 and 3.8 µm in tissue (n = 1.38), respectively. This is, to the best of our knowledge, the highest 3-D spatial resolution reported among those of Fourier-domain optical coherence imaging techniques in the 1700-nm spectral band. In our SD-OCM, to enhance the imaging depth, a full-range method was implemented, which suppressed the formation of a coherent ghost image and allowed us to set the zero-delay position inside the samples. We demonstrated the 3-D high-resolution imaging capability of 1700-nm SD-OCM through the measurement of an interference signal from a mirror surface and imaging of a single 200-nm polystyrene bead and a pig thyroid gland. Deep tissue imaging at a depth of up to 1.8 mm was also demonstrated. This is the first demonstration of 3-D high-resolution SD-OCM in the 1700-nm spectral band.

Signal-to-background ratio and lateral resolution in deep tissue imaging by optical coherence microscopy in the 1700 nm spectral band.

We quantitatively investigated the image quality in deep tissue imaging with optical coherence microscopy (OCM) in the 1700 nm spectral band, in terms of the signal-to-background ratio (SBR) and lateral resolution. In this work, to demonstrate the benefits of using the 1700 nm spectral band for OCM imaging of brain samples, we compared the imaging quality of OCM en-face images obtained at the same position by using a hybrid 1300 nm/1700 nm spectral domain (SD) OCM system with shared sample and reference arms. By observing a reflective resolution test target through a 1.5 mm-thick tissue phantom, which had a similar scattering coefficient to brain cortex tissue, we confirmed that 1700 nm OCM achieved an SBR about 6-times higher than 1300 nm OCM, although the lateral resolution of the both OCMs was similarly degraded with the increase of the imaging depth. Finally, we also demonstrated high-contrast deep tissue imaging of a mouse brain at a depth up to 1.8 mm by using high-resolution 1700 nm SD-OCM.

Excitation of erbium-doped nanoparticles in 1550-nm wavelength region for deep tissue imaging with reduced degradation of spatial resolution.

Rare-earth-doped nanoparticles are one of the emerging probes for bioimaging due to their visible-to-near-infrared (NIR) upconversion emission via sequential single-photon absorption at NIR wavelengths. The NIR-excited upconversion property and high photostability make this probe appealing for deep tissue imaging. So far, upconversion nanoparticles include ytterbium ions (Yb3 + ) codoped with other rare earth ions, such as erbium (Er3 + ) and thulium (Tm3 + ). In these types of upconversion nanoparticles, through energy transfer from Yb3 + excited with continuous wave light at a wavelength of 980 nm, upconversion emission of the other rare earth dopants is induced. We have found that the use of the excitation of Er3 + in the 1550-nm wavelength region allows us to perform deep tissue imaging with reduced degradation of spatial resolution. In this excitation­emission process, three and four photons of 1550-nm light are sequentially absorbed, and Er3 + emits photons in the 550- and 660-nm wavelength regions. We demonstrate that, compared with the case using 980-nm wavelength excitation, the use of 1550-nm light enables us to moderate degradation of spatial resolution in deep tissue imaging due to the lower light scattering coefficient compared with 980-nm light. We also demonstrate that live cell imaging is feasible with this 1550 nm excitation.

Visible-wavelength two-photon excitation microscopy with multifocus scanning for volumetric live-cell imaging.

Two-photon excitation microscopy is one of the key techniques used to observe three-dimensional (3-D) structures in biological samples. We utilized a visible-wavelength laser beam for two-photon excitation in a multifocus confocal scanning system to improve the spatial resolution and image contrast in 3-D live-cell imaging. Experimental and numerical analyses revealed that the axial resolution has improved for a wide range of pinhole sizes used for confocal detection. We observed the 3-D movements of the Golgi bodies in living HeLa cells with an imaging speed of 2 s per volume. We also confirmed that the time-lapse observation up to 8 min did not cause significant cell damage in two-photon excitation experiments using wavelengths in the visible light range. These results demonstrate that multifocus, two-photon excitation microscopy with the use of a visible wavelength can constitute a simple technique for 3-D visualization of living cells with high spatial resolution and image contrast.

Multi-Purpose Nanovoid Array Plasmonic Sensor Produced by Direct Laser Patterning.

We demonstrate a multi-purpose plasmonic sensor based on a nanovoid array fabricated via inexpensive and highly-reproducible direct femtosecond laser patterning of thin glass-supported Au films. The proposed nanovoid array exhibits near-IR surface plasmon (SP) resonances, which can be excited under normal incidence and optimised for specific applications by tailoring the array periodicity, as well as the nanovoid geometric shape. The fabricated SP sensor offers competitive sensitivity of ≈ 1600 nm/RIU at a figure of merit of 12 in bulk refractive index tests, as well as allows for identification of gases and ultra-thin analyte layers, making the sensor particularly useful for common bioassay experiments. Moreover, isolated nanovoids support strong electromagnetic field enhancement at lattice SP resonance wavelength, allowing for label-free molecular identification via surface-enhanced vibration spectroscopy.

Effect of aldosterone on isolated human penile corpus cavernosum tissue.

OBJECTIVE: To clarify the physiological effects of aldosterone on human penile corpus cavernosum (hPCC) tissue, as aldosterone has a wider physiological action than just the maintenance of electrolyte balance, and there are mineralocorticoid receptors, i.e. aldosterone receptors, in hPCC tissue. MATERIALS AND METHODS: Specimens of hPCC were obtained from 10 patients (mean age 38 years, range 21-75), with informed consent and approval by the local ethics committee. One patient had a penectomy because of penile cancer, and nine had a penile biopsy because of erectile dysfunction. Patients with diabetes mellitus, hypertension or ischaemic heart disease were excluded. In a pharmacological study we evaluated the effect of aldosterone on the isolated hPCC tissues. RESULTS: Aldosterone caused no significant change in resting tension and did not affect the nitric oxide-dependent relaxation reaction. However, the dose-response curve of noradrenaline was shifted to the left when the strip preparation was treated with aldosterone (1 x 10(-5)M) for 20 min before administering noradrenaline. Moreover, the shift to the left was completely blocked when spironolactone (anti-aldosterone agent) was added as a pre-treatment. Pre-treatment with aldosterone also significantly extended the mean (SEM) time required to reach 50% relaxation of a noradrenaline-induced contraction, of 9.3 (1.5) min, vs the control, of 5.2 (1.0) min (P = 0.002). CONCLUSION: Aldosterone has no direct contractile action or a relaxant action on human penile cavernous tissue, but acts to significantly enhance the noradrenaline-induced contraction. The effect on the noradrenaline-induced contraction is probably caused by aldosterone enhancing the affinity of the alpha-receptors for noradrenaline in hPCC. We suggest that aldosterone acts to enhance contraction of hPCC tissue, and is one of the restraining factors for human penile erection.

Variations of the internal pudendal artery as a congenital contributing factor to age at onset of erectile dysfunction in Japanese.

OBJECTIVE: To investigate the relationship between variations of the pelvic artery arrangement and the age at erectile dysfunction (ED) onset, as some men develop ED while relatively young, while others maintain erectile function into old age despite having cardiovascular diseases, thus congenital factors might be involved. PATIENTS AND METHODS: We examined 290 units of internal iliac arteries (IIA) in 145 patients showing repeated incomplete erectile response to intracavernosal injections with prostaglandin E(1). Patients with cardiovascular risk factors, neurological disease or pelvic injury were excluded. The pelvic artery arrangement, evaluated by three-dimensional computed tomographic angiography, was classified anatomically into five types: Type 1 (normal or basic type), in which the internal pudendal artery (IPA) originates from the anterior trunk at the level between the linea terminalis and the major ischial notch; Type 2, the IPA originates from the anterior trunk of the IIA at the level of the major ischial notch or more distally; Type 3, the IPA originates directly from the IIA at a level proximal to the linea terminalis; Type 4, the IPA originates together with the superior and inferior gluteal artery within 1 cm of each other; and Type 5, the penile blood supply is dependent on arteries other than the IPA, such as the obturator artery. RESULTS: Among the 290 units, eight could not be classified due to poor image quality. There were no statistically significant differences in blood flow parameters among the types of IIAs, but there was a statistically significant difference in the IPA type at the age of onset of ED. Type 1 (153 units or 53%) anatomy, was more common in patients who developed ED at an advanced age. Types 2, 3 and 4 were more common in patients with onset of ED at an early age (log-rank test P < 0.001, P = 0.044, P < 0.001, respectively). Compared with patients with the common type of IIAs bilaterally, patients with any of the variations bilaterally are at risk of early onset of ED (log-rank test: P = 0.002). CONCLUSION: In these anatomical studies, nearly half of all internal artery units are variations in type. Congenital factors might contribute to the development of ED. If a man has bilateral variation from the common type (Type 1), he might develop ED approximately 10 years earlier than those who are identical in every way except for their IPA (Type 1) arrangements.

Beyond the diffraction-limit biological imaging by saturated excitation microscopy.

We demonstrate high-resolution fluorescence imaging in biological samples by saturated excitation (SAX) microscopy. In this technique, we saturate the population of fluorescence molecules at the excited state with high excitation intensity to induce strong nonlinear fluorescence responses in the center of laser focus, which contributes the improvement of the spatial resolution in three dimensions. Using SAX microscopy, we observed stained microtubules in HeLa cells with improved spatial resolution. We also measured the relation of the fluorescence and excitation intensity with several kinds of fluorescence dyes and, in the results, confirmed that SAX microscopy has the potential to observe any kind of fluorescence samples in current usage.