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OBJECTIVE: This study examined prescription trends for benign prostatic hyperplasia (BPH) drug therapy in Japan over the past decade, focusing on drugs rated as grade A according to Japanese clinical guidelines. METHODS: Using the National Database Open Data, this study analyzed prescription data from the fiscal years of 2014 to 2021, tracking α1-blockers, 5α-reductase inhibitors, and phosphodiesterase type 5 inhibitors. We adjusted for demographics and calculated medication costs to determine prescribing patterns and changes in drug utilization. RESULTS: Prescriptions for α1-blockers increased from 9898 per 1000 males in 2014 to 12 613 in 2021. Prescriptions for 5α-reductase inhibitors rose from 1441 per 1000 males in 2014 to 2310 in 2021. Tadalafil prescriptions saw a significant increase, from 900 in 2015 to 2520 in 2021. Despite these increases, the overall market size for BPH drugs decreased from 664 million dollars in 2014 to 279 million dollars in 2021, indicating a shift toward generic medications driven by healthcare policies. CONCLUSIONS: Although BPH medication prescriptions are increasing, driven by Japan's aging population and clinical guidelines, market dynamics are shifting owing to generic and government price adjustments. This analysis underscores the changing BPH treatment landscape in Japan, highlighting the importance of continuous evaluation of treatment efficacy and cost-effectiveness in evolving healthcare policies and demographics.
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Experimental characterization of the nanostructure of metastable functional materials has attracted significant attention with recent advances in computational materials discovery. However, since metastable glass-ceramics are easily damaged by irradiation, damage-free nanoimaging has not been realized thus far. Herein, we propose novel high-contrast coherent diffractive imaging that quantitatively analyzes the intact internal nanostructure of metastable glass-ceramics using femtosecond X-ray pulses. The immersion of sample particles in a solvent helps enhance the reconstructed image contrast and allows us to distinguish an â¼7% electron density difference between an amorphous form and crystals. Furthermore, morphological operations with a band-pass filter quantitatively elucidate the depth information. The evaluated volume ratio of the amorphous to crystalline phases is â¼2.5:1 for the measured metastable (Li2S)70-(P2S5)30 glass-ceramic particle. Sulfide glass-ceramics are used as electrolytes for all-solid-state batteries, which are indispensable for reducing the carbon footprint. Our results will facilitate structural studies on fragile metastable materials with important scientific and industrial implications.
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X-ray free-electron lasers (XFELs) opened up a possibility for molecular-scale single particle imaging (SPI) without the need for crystallization. In SPI experiments, the orientation of each particle has to be determined from the measured diffraction pattern. Preparing unidirectionally-aligned particles can facilitate the determination of the sample orientation. Here, we show the design principles of a liquid cell for three-dimensional imaging of unidirectionally-aligned particles in solution with XFELs. The liquid cell was designed so that neither incident X-rays nor diffracted X-rays are blocked by the substrate of the liquid cell even at high tilt angles. As a feasibility evaluation, we performed coherent diffraction measurements using the cells with a 1 µm focused XFEL beam. We successfully measured coherent diffraction patterns of a nano-fabricated metal pattern at 70° tilt angle and obtained the reconstructed image by applying iterative phase retrieval. The liquid cell will be usefully applied to molecular-scale SPI by using more tightly focused XFELs. In particular, imaging of membrane proteins embedded in lipid membranes is expected to have an enormous impact on life science and medicine.
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Imagenología Tridimensional/métodos , Rayos Láser , Electrones , Diseño de Equipo , Oro/química , Imagenología Tridimensional/instrumentaciónRESUMEN
INTRODUCTION AND HYPOTHESIS: The steep Trendelenburg position, high pneumoperitoneum pressure, and longer surgical time may lead to significantly increased intraocular pressure (IOP), which could result in unexpected eye disease complications, including perioperative visual loss (POVL). We monitored IOP to induce early laparoscopic sacral colpopexy (LSC) safely. METHODS: This prospective study enrolled 39 patients with pelvic organ prolapse (POP), including 10 with eye diseases (6 with normal tension glaucoma and 4 with a narrow anterior chamber and normal range IOP). Enrolled patients underwent LSC under the same surgical settings involving a pneumoperitoneum of 10 mmHg and a Trendelenburg position of 15°. We measured IOP at seven time points during surgery and estimated IOP changes with time in patients with or without eye diseases. RESULTS: All patients, with or without eye diseases, experienced significantly elevated IOP during LSC. There were no significant differences between these groups. The average maximal IOP reached 20 mmHg at the end of surgery, and recovered to baseline values with the patient in the supine position at the end of anesthesia. No patient had an IOP of >40 mmHg as a critical threshold during surgery, and no substantial clinical eye symptoms were seen after LSC. CONCLUSIONS: Laparoscopic sacral colpopexy using an pneumoperitoneum of 10 mmHg and a Trendelenburg position of 15° during a 3-h surgical period could be performed within a safe range of IOP.
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Presión Intraocular/fisiología , Laparoscopía , Glaucoma de Baja Tensión/fisiopatología , Monitoreo Intraoperatorio , Prolapso de Órgano Pélvico/fisiopatología , Prolapso de Órgano Pélvico/cirugía , Vagina/cirugía , Anciano , Femenino , Procedimientos Quirúrgicos Ginecológicos/métodos , Humanos , Glaucoma de Baja Tensión/complicaciones , Persona de Mediana Edad , Prolapso de Órgano Pélvico/complicaciones , Estudios Prospectivos , SacroRESUMEN
X-ray science has greatly benefited from the progress in X-ray optics. Advances in the design and the manufacturing techniques of X-ray optics are key to the success of various microscopic and spectroscopic techniques practiced today. Here the generation of apodized X-ray illumination using a two-stage deformable Kirkpatrick-Baez mirror system is presented. Such apodized illumination is marked by the suppression of the side-lobe intensities of the focused beam. Thus generated apodized illumination was employed to improve the image quality in scanning X-ray fluorescence microscopy. Imaging of a non-isolated object by coherent X-ray diffractive imaging with apodized illumination in a non-scanning mode is also presented.
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To examine the efficacy and safety of tadalafil in the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia with chronic pelvic pain syndrome, we treated 23 Japanese men with tadalafil 5 mg once daily for 4 weeks. The mean age of the participantswas58.7 yearsand the prostate volume was25. 2 ml. Significant improvementsin total International Prostatic Symptom Score, International Prostatic Symptom Score Quality of Life Index, total National Institutes of Health Chronic Prostatitis Symptom Index score, pain subscore, urinary symptom subscore, and quality of life impact subscore, were observed for tadalafil versus before treatment. These findings confirm that tadalafil is a valuable new treatment option for patients with benign prostatic hyperplasia complicated by chronic pelvic pain syndrome.
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Dolor Pélvico/etiología , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Hiperplasia Prostática/tratamiento farmacológico , Tadalafilo/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Hiperplasia Prostática/complicaciones , Resultado del TratamientoRESUMEN
We demonstrate that binary mixtures of small and large gold nanoparticles (GNPs) (5/15, 5/30, 10/30, and 15/30 nm in diameter) in the presence of a glucose-terminated fluorinated oligo(ethylene glycol) ligand can spontaneously form size-segregated assemblies. The outermost layer of the assembly is composed of a single layer of small-sized GNPs, while the larger-sized GNPs are located in the interior, forming what is referred to as a yolk/shell assembly. Time course study reveals that small and large GNPs aggregate together, and these kinetically trapped aggregations were transformed into a size-segregated structure by repeating fusions. A yolk/shell structure was directly visualized in solution by X-ray laser diffraction imaging, indicating that the structure was truly formed in solution, but not through a drying process.
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How a long strand of genomic DNA is compacted into a mitotic chromosome remains one of the basic questions in biology. The nucleosome fibre, in which DNA is wrapped around core histones, has long been assumed to be folded into a 30-nm chromatin fibre and further hierarchical regular structures to form mitotic chromosomes, although the actual existence of these regular structures is controversial. Here, we show that human mitotic HeLa chromosomes are mainly composed of irregularly folded nucleosome fibres rather than 30-nm chromatin fibres. Our comprehensive and quantitative study using cryo-electron microscopy and synchrotron X-ray scattering resolved the long-standing contradictions regarding the existence of 30-nm chromatin structures and detected no regular structure >11 nm. Our finding suggests that the mitotic chromosome consists of irregularly arranged nucleosome fibres, with a fractal nature, which permits a more dynamic and flexible genome organization than would be allowed by static regular structures.
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Cromosomas Humanos/química , Mitosis , Nucleosomas/química , Cromatina/química , Cromatina/ultraestructura , Cromosomas Humanos/ultraestructura , Microscopía por Crioelectrón , Células HeLa , Humanos , Nucleosomas/ultraestructura , Pliegue de Proteína , Dispersión del Ángulo Pequeño , Difracción de Rayos XRESUMEN
Coherent diffraction imaging (CDI) is an established lensless imaging method widely used at the x-ray regime applicable to the imaging of non-periodic materials. Conventional CDI can practically image isolated objects only, which hinders the broader application of the method. We present the imaging of non-isolated objects by employing recently proposed "non-scanning" apodized-illumination CDI at an optical wavelength. We realized isolated apodized illumination with a specially designed optical configuration and succeeded in imaging phase objects as well as amplitude objects. The non-scanning nature of the method is important particularly in imaging live cells and tissues, where fast imaging is required for non-isolated objects, and is an advantage over ptychography. We believe that our result of phase contrast imaging at an optical wavelength can be extended to the quantitative phase imaging of cells and tissues. The method also provides the feasibility of the lensless single-shot imaging of extended objects with x-ray free-electron lasers.
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This study aims at the synthesis of Janus gold nanoparticles (Janus GNPs) with hydrophilic/hydrophobic faces by a simple ligand exchange reaction in an homogeneous system and at the elucidation of the self-assembled structures of the Janus GNPs in water. As hydrophilic surface ligands, we synthesized hexaethylene glycol (E6)-terminated thiolate ligands with C3, C7, or C11 alkyl chains, referred to as E6C3, E6C7, and E6C11, respectively. As a hydrophobic ligand, a butyl-headed thiolate ligand C4-E6C11, in which a C4 alkyl was introduced on the E6C11 terminus, was synthesized. The degree of segregation between the two ligands on the GNPs (5 nm in diameter) was examined by matrix-assisted laser desorption/ionization time-of fright mass spectrometry (MALDI-TOF MS) analysis. We found that the choice of immobilization methods, one-step or two-step addition of the two ligands to the GNP solution, crucially affects the degree of segregation. The two-step addition of a hydrophilic ligand (E6C3) followed by a hydrophobic ligand (C4-E6C11) produced a large degree of segregation on the GNPs, providing Janus-like GNPs. When dispersed in water, these Janus-like GNPs formed assemblies of â¼160 nm in diameter, whereas Domain GNPs, in which the two ligands formed partial domains on the surface, were precipitated even when the molar ratio of the hydrophilic ligand and the hydrophobic ligand on the surface of the NPs was almost 1:1. The assembled structure of the Janus-like GNPs in water was directly observed by pulsed coherent X-ray solution scattering using an X-ray free-electron laser, revealing irregular spherical structures with uneven surfaces.
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Oro/química , Interacciones Hidrofóbicas e Hidrofílicas , Nanopartículas del Metal/química , Nanotecnología , Agua/química , Ligandos , Propiedades de SuperficieRESUMEN
The continuing effort to utilize the unique properties present in a number of strongly correlated transition metal oxides for novel device applications has led to intense study of their transitional phase state behavior. Here we report on time-resolved coherent X-ray diffraction measurements on a single vanadium dioxide nanocrystal undergoing a solid-solid phase transition, using the SACLA X-ray Free Electron Laser (XFEL) facility. We observe an ultrafast transition from monoclinic to tetragonal crystal structure in a single vanadium dioxide nanocrystal. Our findings demonstrate that the structural change occurs in a number of distinct stages attributed to differing expansion modes of vanadium atom pairs.
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We propose a coherent x-ray zoom condenser lens composed of two-stage deformable Kirkpatrick-Baez mirrors. The lens delivers coherent x-rays with a controllable beam size, from one micrometer to a few tens of nanometers, at a fixed focal position. The lens is suitable for diffractive and scanning microscopy. We also propose non-scanning coherent diffraction microscopy for extended objects by using an apodized focused beam produced by the lens with a spatial filter. The proposed apodized-illumination method will be useful in highly efficient imaging with ultimate storage ring sources, and will also open the way to single-shot coherent diffraction microscopy of extended objects with x-ray free-electron lasers.
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Aumento de la Imagen/instrumentación , Lentes , Difracción de Rayos X/instrumentación , Microtomografía por Rayos X/instrumentación , Diseño de Equipo , Análisis de Falla de EquipoRESUMEN
Thermus thermophilus is reportedly polyploid and carries four to five identical genome copies per cell, based on molecular biological experiments. To directly detect polyploidy in this bacterium, we performed live cell imaging by X-ray free-electron laser (XFEL) diffraction and observed its internal structures. The use of femtosecond XFEL pulses enables snapshots of live, undamaged cells. For successful XFEL imaging, we developed a bacterial culture method using a starch- and casein-rich medium that produces a predominance of rod-shaped cells shorter than the focused XFEL beam size, which is slightly smaller than 2 µm. When cultured in the developed medium, the length of T. thermophilus cells, which is typically ~4 µm, was less than half its usual length. We placed living cells in a micro-liquid enclosure array and successively exposed each enclosure to a single XFEL pulse. A cell image was successfully obtained by the coherent diffractive imaging technique with iterative phase retrieval calculations. The reconstructed cell image revealed five peaks, which are most likely to be nucleoids, arranged in a row in the polyploid cell without gaps. This study demonstrates that XFELs offer a novel approach for visualizing the internal nanostructures of living, micrometer-sized, polyploid bacterial cells.
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Rayos Láser , Thermus thermophilus , Humanos , Thermus thermophilus/genética , Rayos X , Difracción de Rayos X , PoliploidíaRESUMEN
The aims of this study were to determine the prevalence and predictors of nocturnal polyuria (NP) in Japanese patients. This multicentral, observational study enrolled patients with the chief complaint of nocturia at 17 Japanese institutions between January 2018 and December 2022. The frequency of daily voiding and volume of urination were evaluated using bladder diaries. NP was diagnosed in patients with an NP index of > 33%. The primary endpoint was NP prevalence in patients with nocturia. The secondary endpoints were the prevalence of NP according to sex and age and the identification of factors predicting NP. This study analyzed 875 eligible patients. NP was present in 590 (67.4%) patients, with prevalence rates of 66.6% and 70.0% in men and women, respectively. Age ≥ 78 years, body mass index (BMI) < 23.0 kg/m2, and patients with ischemic heart or cerebrovascular disease were significant predictors of NP (P < 0.001, P < 0.001, P = 0.014, P = 0.016, respectively). This is the first large multicenter study to investigate the prevalence of NP in Japanese patients with nocturia. NP has a prevalence of 67.4%. Significant predictors of NP include age, BMI, and cardiovascular disease.
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Nocturia , Masculino , Humanos , Femenino , Anciano , Nocturia/epidemiología , Nocturia/diagnóstico , Poliuria/complicaciones , Poliuria/epidemiología , Poliuria/diagnóstico , Estudios Retrospectivos , Prevalencia , Pueblos del Este de AsiaRESUMEN
With the emergence of X-ray free-electron lasers (XFELs), coherent diffractive imaging (CDI) has acquired a capability for single-particle imaging (SPI) of non-crystalline objects under non-cryogenic conditions. However, the single-shot spatial resolution is limited to ~5 nanometres primarily because of insufficient fluence. Here, we present a CDI technique whereby high resolution is achieved with very-high-fluence X-ray focusing using multilayer mirrors with nanometre precision. The optics can focus 4-keV XFEL down to 60 nm × 110 nm and realize a fluence of >3 × 105 J cm-2 pulse-1 or >4 × 1012 photons µm-2 pulse-1 with a tenfold increase in the total gain compared to conventional optics due to the high demagnification. Further, the imaging of fixed-target metallic nanoparticles in solution attained an unprecedented 2-nm resolution in single-XFEL-pulse exposure. These findings can further expand the capabilities of SPI to explore the relationships between dynamic structures and functions of native biomolecular complexes.
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Since the first demonstration of coherent diffraction microscopy in 1999, this lensless imaging technique has been experimentally refined by continued developments. Here, instrumentation and experimental procedures for measuring oversampled diffraction patterns from non-crystalline specimens using an undulator beamline (BL29XUL) at SPring-8 are presented. In addition, detailed post-experimental data analysis is provided that yields high-quality image reconstructions. As the acquisition of high-quality diffraction patterns is at least as important as the phase-retrieval procedure to guarantee successful image reconstructions, this work will be of interest for those who want to apply this imaging technique to materials science and biological samples.
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Microscopía/instrumentación , Animales , Huesos/ultraestructura , Peces , Herpesviridae/ultraestructura , Procesamiento de Imagen Asistido por Computador/instrumentación , Virión/ultraestructura , Difracción de Rayos XRESUMEN
Coherent diffraction microscopy using highly focused hard X-ray beams allows us to three-dimensionally observe thick objects with a high spatial resolution, also providing us with unique structural information, i.e., electron density distribution, not obtained by X-ray tomography with lenses, atom probe microscopy, or electron tomography. We measured high-contrast coherent X-ray diffraction patterns of a shape-controlled Au/Ag nanoparticle and successfully reconstructed a projection and a three-dimensional image of the nanoparticle with a single pixel (or a voxel) size of 4.2 nm in each dimension. The small pits on the surface and a hollow interior were clearly visible. The Au-rich regions were identified based on the electron density distribution, which provided insight into the formation of Au/Ag nanoboxes.
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Imagenología Tridimensional/métodos , Microscopía Electrónica/métodos , Nanoestructuras/ultraestructura , Difracción de Rayos X/métodos , Sustancias Macromoleculares/química , Ensayo de Materiales , Conformación Molecular , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
We developed micro-liquid enclosure arrays (MLEAs) for holding solution samples in coherent diffractive imaging (CDI) using x-ray free-electron lasers (XFELs). Hundreds of fully isolated micro-liquid enclosures are arranged in a single MLEA chip for efficient measurement, where each enclosure is destroyed after exposure to a single XFEL pulse. A semi-automated MLEA assembling system was also developed to enclose solution samples into MLEAs efficiently at high precision. We performed XFEL-based CDI experiments using MLEAs and imaged in-solution structures of self-assembled gold nanoparticles. The sample hit rate can be optimized by adjusting solution concentration, and we achieved a single-particle hit rate of 31%, which is not far from the theoretical upper limit of 37% derived from the Poisson statistics. MELAs allow us to perform CDI measurement under controlled solution conditions and will help reveal the nanostructures and dynamics of particles in solution.
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A valence critical end point existing near the absolute zero provides a unique case for the study of a quantum version of the strong density fluctuation at the Widom line in the supercritical fluids. Although singular charge and orbital dynamics are suggested theoretically to alter the electronic structure significantly, breaking down the standard quasi-particle picture, this has never been confirmed experimentally to date. We provide the first empirical evidence that the proximity to quantum valence criticality leads to a clear breakdown of Fermi liquid behavior. Our detailed study of the mixed valence compound α-YbAlB4 reveals that a small chemical substitution induces a sharp valence crossover, accompanied by a pronounced non-Fermi liquid behavior characterized by a divergent effective mass and unusual T/B scaling in the magnetization.
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Minerals are important for cellular functions, such as transcription and enzyme activity, and are also involved in the metabolism of anticancer chemotherapeutic compounds. Profiling of intracellular elements in individual cells could help in understanding the mechanism of drug resistance in tumors and possibly provide a new strategy of anticancer chemotherapy. Using a recently developed technique of scanning X-ray fluorescence microscopy (SXFM), we analyzed intracellular elements after treatment with cis-diamminedichloro-platinum(II) (CDDP), a platinum-based anticancer agent. The images obtained by SXFM (element array) revealed that the average Pt content of CDDP-resistant cells was 2.6 times less than that of sensitive cells, and the zinc content was inversely correlated with the intracellular Pt content. Data suggested that Zn-related detoxification is responsible for resistance to CDDP. Of Zn-related excretion factors, glutathione was highly correlated with the amount of Zn. The combined treatment of CDDP and a Zn(II) chelator resulted in the incorporation of thrice more Pt with the concomitant down-regulation of glutathione. We propose that the generation of an element array by SXFM opens up new avenues in cancer biology and treatment.