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Adrenalectomy is the gold standard for canine adrenal tumours, but not always recommended due to patient age, underlying conditions and perioperative mortality. Ethanol ablation is an alternative in human medicine for poor surgical candidates. A 13-year-old neutered female toy-poodle with hypercortisolism presented with severe haematuria. Ultrasonography revealed left adrenal and right kidney tumours. Due to high surgical risk, simultaneous laparotomic right nephroureterectomy and ethanol ablation of the left adrenal tumour were performed. Post-ethanol injection complications included transient hypertension and arrhythmia, which resolved spontaneously. The adrenal tumour size decreased within 2.5 months, and cortisol levels normalised within 8 days, remaining stable for 12 months. No hypercortisolism signs were observed without trilostane until death from renal insufficiency. Autopsy showed that the ablated left adrenal gland was an adrenocortical tumour and had shrunk. Ethanol ablation may be a feasible alternative to adrenalectomy for high-risk canine patients., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Characterization and quantification of plasmonic nanoparticles at the single particle level have become increasingly important with the advancements in nanotechnology and their application to various biological analyses including diagnostics, photothermal therapy, and immunoassays. While various nanoparticle detection methodologies have been developed and widely used, simultaneous measurement of light absorption and scattering from individual plasmonic nanoparticles in flow is still challenging. Herein, we describe a novel nanofluidic detection platform that enables simultaneous measurement of absorption and scattering signals from individual nanoparticles within a nanochannel. Our detection platform utilized optical diffraction phenomena by a single nanochannel as both a readout signal for photothermal detection and a reference light for interferometric scattering detection. Through the elucidation of the frequency effect on the detection performance and optimization of experimental conditions, we achieved the classification of gold and silver nanoparticles with a diameter of 20-60 nm at an average accuracy score of 82.6 ± 2.1% by measured data sets of absorption and scattering signals. Furthermore, we demonstrated the concentration determination of plasmonic nanoparticle mixtures using a trained Support vector machine (SVM) classifier. Our simple yet sensitive nanofluidic detection platform will be a valuable tool for the analysis of nanoparticles and their applications to chemical and biological assays.

Aim: An assertive case management intervention program, ACTION-J, proved effective for preventing suicide attempters from reattempting suicide within 6 months. The ACTION-J randomized trial was conducted as part of the "National Strategic Research Projects." The program has been covered by the national medical payment system of Japan since 2016. The aim of the Post-ACTION-J Study (PACS) was to examine the current implementation status of assertive case management in a real-world clinical setting., Methods: PACS was a prospective, multicenter registry cohort study. The participants were suicide attempters admitted to the emergency departments of 10 participating medical facilities from October 2016 to September 2018. The assertive case management intervention developed by the ACTION-J Study was offered to all patients, and the primary outcome was the duration and frequency of use of the intervention at 6 months., Results: A total of 1159 patients were admitted to emergency departments after a suicide attempt during the study period, 144 of whom were included in our analysis. The proportion of participants who received the intervention for 6 months was 72.2% (104/144), and 63.9% (92/144) of the patients completed ≥7 case management interviews within 6 months., Conclusion: The findings of this study indicate successful implementation of an assertive case management intervention program based on the ACTION-J Study in a real-world clinical setting, following its integration with the national medical payment scheme in Japan. The study provided the useful information that could improve the implementation of assertive case management interventions in future., Competing Interests: The authors declare no conflicts of interest., (© 2023 The authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

In nanofluidics, surface control is a critical technology because nanospaces are surface-governed spaces as a consequence of their extremely high surface-to-volume ratio. Various surface patterning methods have been developed, including patterning on an open substrate and patterning using a liquid modifier in microchannels. However, the surface patterning of a closed nanochannel is difficult. In addition, the surface evaluation of closed nanochannels is difficult because of a lack of appropriate experimental tools. In this study, we verified the surface patterning of a closed nanochannel by vacuum ultraviolet (VUV) light and evaluated the surface using streaming-current measurements. First, the C 18 modification of closed nanochannels was confirmed by Laplace pressure measurements. In addition, no streaming-current signal was detected for the C 18 -modified surface, confirming the successful modification of the nanochannel surface with C 18 groups. The C 18 groups were subsequently decomposed by VUV light, and the nanochannel surface became hydrophilic because of the presence of silanol groups. In streaming-current measurements, the current signals increased in amplitude with increasing VUV light irradiation time, indicating the decomposition of the C 18 groups on the closed nanochannel surfaces. Finally, hydrophilic/hydrophobic patterning by VUV light was performed in a nanochannel. Capillary filling experiments confirmed the presence of a hydrophilic/hydrophobic interface. Therefore, VUV patterning in a closed nanochannel was demonstrated, and the surface of a closed nanochannel was successfully evaluated using streaming-current measurements.

Miniaturization of column diameter in liquid chromatography is one of the major trends in separation sciences toward single-cell proteomics and metabolomics. Micro/nanoscale open tubular (OT) capillaries are promising tools for efficient separation analyses of the ultra-small volume of samples. However, highly sensitive and label-free on-column detection is still challenging for such ultra-small capillaries. In this study, we developed a photothermal detector using optical diffraction phenomena by a single nanocapillary. Our detection method realized concentration determination of unlabeled sample solutions in a nanocapillary with 460 nm inner diameter. The calculated limit of detection was 0.12 µM, which corresponds to 16 molecules in a detection volume of 0.23 fL. Furthermore, normal-phase chromatography was performed on a 12 cm long nanocapillary, and femtoliter sample injection, efficient separation, and label-free detection of dye molecules were demonstrated. Our photothermal detector will be widely used as a universal tool for chemical/biological analyses using capillaries with micro/nanoscale diameters., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The progress of nanotechnology has developed nanofluidic devices utilizing nanochannels with a width and/or depth of sub-100 nm (10 1 nm channels), and several experiments have been implemented in ultra-small spaces comparable to DNAs and proteins. However, current experiments utilizing 10 1 nm channels focus on a single function or operation; integration of multiple analytical operations into 10 1 nm channels using nanofluidic circuits and fluidic control has yet to be realized despite the advantage of nanochannels. Herein, we report the establishment of a label-free molecule detection method for 10 1 nm channels and demonstration of sequential analytical processes using integrated nanofluidic devices. Our absorption-based detection method called photothermal optical diffraction (POD) enables non-invasive label-free molecule detection in 10 1 nm channels for the first time, and the limit of detection (LOD) of 1.8 μM is achieved in 70 nm wide and deep nanochannels, which corresponds to 7.5 molecules in the detection volume of 7 aL. As a demonstration of sampling in 10 1 nm channels, aL-fL volumetric sampling is performed using 90 nm deep cross-shaped nanochannels and pressure-driven fluidic control from three directions. Finally, the POD and volumetric sampling are combined with nanochannel chromatography, and separation analysis in 10 1 nm channels is demonstrated. The experimental results reported in this paper will contribute to the advances in 10 1 nm fluidic devices which have the potential to provide a novel platform for chemical/biological analyses.

Nanofluidics have recently attracted significant attention with regard to the development of new functionalities and applications, and producing new functional devices utilizing nanofluidics will require the fabrication of nanochannels. Fused silica nanofluidic devices fabricated by top-down methods are a promising approach to realizing this goal. Our group previously demonstrated the analysis of a living single cell using such a device, incorporating nanochannels having different sizes (10 2 -10 3 nm) and with branched and confluent structures and surface patterning. However, fabrication of geometrically-controlled nanochannels on the 10 1 nm size scale by top-down methods on a fused silica substrate, and the fabrication of micro-nano interfaces on a single substrate, remain challenging. In the present study, the smallest-ever square nanochannels (with a size of 50 nm) were fabricated on fused silica substrates by optimizing the electron beam exposure time, and the absence of channel breaks was confirmed by streaming current measurements. In addition, micro-nano interfaces between 10 3 nm nanochannels and 10 1 μm microchannels were fabricated on a single substrate by controlling the hydrophobicity of the nanochannel surfaces. A micro-nano interface for a single cell analysis device, in which a nanochannel was connected to a 10 1 μm single cell chamber, was also fabricated. These new fabrication procedures are expected to advance the basic technologies employed in the field of nanofluidics.

Nanofluidic devices have become a powerful tool for extremely precise analyses at a single-molecule/nanoparticle level. However, a simple and sensitive molecular detection method is essential for nanofluidic devices because of ultrasmall volume (fL-aL). One such technology is photothermal spectroscopy (PTS), which utilizes light absorption and thermal relaxation by target molecules. Recently, we developed a photothermal optical diffraction (POD) detection method as PTS for nanofluidic devices. However, the detectable concentration range was in the order of μM (10 2 to 10 4 molecules), and further improvement in detection performance is strongly required. Here, we demonstrate solvent-enhanced POD with optimized experimental conditions and show its capability of concentration determination of nonfluorescent molecules in nanochannels at a countable molecular level. A relationship between the POD signal and thermal/optical properties of solvents is elucidated. We estimate the diffraction factor and photothermal factor of the solvent enhancement effect by thermal simulations and theoretical calculations. Experimental results show good agreement with the prediction, and the detection performance of the POD is successfully improved. At the optimized condition, we demonstrate the concentration determination with the limit of detection of 75 nM, which corresponds to an average of 10 molecules in a detection volume of 0.23 fL. Our sensitive nonfluorescent molecule detection method will be applied to a wide range of chemical/biological analyses utilizing nanofluidics.

Column miniaturization of liquid chromatography is a major trend in separation sciences with the advent of single-cell proteomics and metabolomics. Nanochannel chromatography is one of the promising tools for single-cell analyses because it provides ultra-small sample volume and high separation efficiency. However, non-fluorescent molecular detection in such small channels is still quite difficult due to fL-aL sample volume, which hinders further miniaturization of nanochannels. In this study, we overcame the size limitation of nanochannel chromatography by our label-free molecular detection method: photothermal optical diffraction (POD), which utilizes the photothermal effect of analytes and optical diffraction by nanochannel. The combination of the nanochannel chromatography and the POD enables 1.8 fL sample separation and label-free molecule detection in nanochannels with 800 nm width and 300 nm depth at the optimized experimental conditions. The limit of detection is 5.4 zmol (3300 molecules), approximately 50 times lower than the conventional label-free detection method. Furthermore, the theoretical plate number is calculated to be 10 5 plates/m, and the separation performance is discussed. Our label-free detection method will be widely used as a universal detector for nanochannel chromatography., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Detection and characterization of individual nanoparticles less than 100 nm are important for semiconductor manufacturing, environmental monitoring, biomedical diagnostics, and drug delivery. Photothermal spectroscopy is a light absorptiometry and promising method for detection and characterization because of its high sensitivity and selectivity compared with light scattering or electrical detection methods. However, the characterization of individual nanoparticles in liquids is still challenging for conventional photothermal detection methods. Here, we report a method for the ultrasensitive detection and accurate characterization of individual nanoparticles in liquids by photothermal optical diffraction, which utilizes enhancement of optical diffraction by a nanochannel after light absorption and heat generation of individual nanoparticles in the channel. Our method realized individual 20 nm Au nanoparticle detection with almost 100% detection efficiency by utilizing nanochannels, leading to concentration determination without a calibration curve. Furthermore, we measured individual nanoparticle size and discriminated 20 and 40 nm Au nanoparticles from their photothermal signals. Our photothermal-based nanoparticle detection method in nanochannels has a potential for a wide range of applications such as on-site evaluation of synthesized plasmonic nanoparticles and drug delivery particles.

Integrating analytical systems in 10 1 -10 3 nm spaces provides ultrasensitive analytical devices at the single cell and the single molecule levels due to the ultrasmall space, and fundamental technologies for nanofluidics are developed. A simple and ultrasensitive detection method is one of the essential technologies for nanofluidics; however, it is still challenging due to the ultrasmall volume at the attoliter to femtoliter scale. In this study, we report a new photothermal detection method of nonfluorescent molecules for a 10 2 nm space, photothermal optical diffraction (POD), which utilizes light absorption and heat generation by an analyte and optical diffraction by a nanochannel after heat diffusion. Concentration determination of nonfluorescent molecules in a 400 nm channel was successfully demonstrated, and a limit of detection (LOD) of 5.0 μM was achieved, corresponding to 500 molecules (0.84 zmol) in a detection volume of 230 aL. Also, detection in a 200 nm channel was successfully demonstrated without degradation of the LOD. Our method can be widely used for chemical and biological analyses in 10 2 -10 3 nm nanofluidics.

Perfluorooctane sulfonate (PFOS) is a persistent environmental contaminant. Although studies have described PFOS-induced neurotoxicity in animal brains and neuronal cells, the molecular mechanisms of PFOS-induced neurotoxicity based on the distribution properties, especially during developmental periods, have not been clarified. To clarify the mechanisms of PFOS-induced neuronal vulnerability during developmental periods, we examined changes in glutamate receptor 2 (GluR2) expression and related neurotoxicity in PFOS-treated primary cortical neurons and neonatal rat brains. Exposure of cortical neurons to 1 μM PFOS for 9 days resulted in decreased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR2 expression, which subsequently enhanced vulnerability to glutamate by increasing intracellular Ca 2+ concentrations. The brain-plasma ratio of PFOS in pups was approximately five times higher than that in dams, although there were no differences in liver-plasma ratio between dams and pups. GluR2 expression in pup cerebral cortex decreased after exposure to 2.0 mg/kg PFOS, and kainic acid induced histopathological abnormalities in PFOS-exposed pups. Our findings suggest that decreased neuronal GluR2 expression is involved in PFOS-induced neurotoxicity, especially during the fetal and neonatal periods.

In vitro estimating strategies for potential neurotoxicity are required to screen multiple substances. In a previous study, we showed that exposure to low-concentrations of some chemicals, such as organotin, decreased the expression of GluR2 protein, which is a subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors, and led to neuronal vulnerability. This result suggested that GluR2 decreases as an index of neuronal cell sensitivity and vulnerability to various toxic insults. Accordingly, we developed a versatile method that is a large scale determination of GluR2 protein expression in the presence of environmental chemicals by means of AlphaLISA technology. Various analytical conditions were optimized, and then GluR2 protein amount was measured by the method using AlphaLISA. The GluR2 amounts were strongly correlated with that of measured by western blotting, which is currently used to determine GluR2 expression. An ideal standard curve could be written with the authentic GluR2 protein from 0 ng to 100 ng. Subsequently, twenty environmental chemicals were screened and nitenpyram was identified as a chemical which lead to decrease in GluR2 protein expression. This assay may provide a tool for detecting neurotoxic chemicals according to decreases in GluR2 protein expression.

WYK-1 is a dipeptidyl peptidase IV inhibitor produced by Aspergillus oryzae strain AO-1. Because WYK-1 is an isoquinoline derivative consisting of three l-amino acids, we hypothesized that a nonribosomal peptide synthetase was involved in its biosynthesis. We identified 28 nonribosomal peptide synthetase genes in the sequenced genome of A. oryzae RIB40. These genes were also identified in AO-1. Among them, AO090001000009 (wykN) was specifically expressed under WYK-1-producing conditions in AO-1. Therefore, we constructed wykN gene disruptants of AO-1 after nonhomologous recombination was suppressed by RNA interference to promote homologous recombination. Our results demonstrated that the disruptants did not produce WYK-1. Furthermore, the expression patterns of 10 genes downstream of wykN were similar to the expression pattern of wykN under several conditions. Additionally, homology searches revealed that some of these genes were predicted to be involved in WYK-1 biosynthesis. Therefore, we propose that wykN and the 10 genes identified in this study constitute the WYK-1 biosynthetic gene cluster.

We identified a novel fermented substance (FKA) produced by the edible Aspergillus oryzae strain AO-1 that inhibited dipeptidyl peptidase IV (DPP-IV) (IC(50) = 3.41 mg · mL(-1)). HPLC analysis of FKA showed specific one metabolite (WYK-1), which inhibited DPP-IV (IC(50) = 6.98 μM). WYK-1 was identified as a tetrahydroxyisoquinoline derivative. Interestingly, we examined 60 strains of A. oryzae, AO-1 was the only A. oryzae strain that produces WYK-1. This is the first report that an edible A. oryzae strain produces a DPP-IV inhibitor such as WYK-1. This study also suggests that FKA has applications in the development of novel antihyperglycemic therapeutics or functional foods., (Copyright © 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

A retinal specimen from a 68-year-old patient with glaucoma and branch retinal vein occlusion was examined by light and electron microscopy. The venous and arterial lumina were filled with erythrocytes, and many erythrocytes extravasated into the venous wall. We suggest that constant rubbing of endothelial cells of the occluded vein results in damage and erythrocyte extravasation was caused by diapedesis.

Purpose: To correlate the ophthalmoscopic and histological findings on human retinal blood vessels of patients with sclerosis and hypertension, respectively., Methods: Ophthalmoscopy, light microscopy, and transmission and scanning electron microscopy with histochemical staining were performed on eyes obtained from patients with a malignant orbital tumor, with absolute glaucoma, or with hypertensive retinopathy., Results: The retinal arteries in aged patients with ophthalmoscopic sclerotic blood vessels had walls in which the smooth muscle cells had been replaced by collagen fibers, proteoglycan filaments, and ruthenium red-positive materials. The venous blood columns were hidden by numerous swollen nerve fibers and extending Müller cell processes. In a patient with accelerated hypertensive retinopathy, some of the muscle cells in the arteriolar walls were edematous. Focal and generalized narrowing of the retinal arteries appeared to be caused by a true functional constriction of the smooth muscle cells in the walls., Conclusions: The ophthalmoscopic signs, such as reflection of the retinal arterial blood column and crossing phenomena, were supported by sclerotic manifestations clearly visible upon histological examination. There were some organic changes in the retinal arteries in a patient with accelerated hypertensive retinopathy, but the ophthalmoscopic narrowings appeared to result from a functional constriction of the smooth muscle cells in these vessels.

High levels of foreign gene expression in mouse hepatocytes can be achieved by the rapid injection of a large volume of naked plasmid (pDNA) into animals via the tail vein, the so-called hydrodynamics-based procedure. In this study, we evaluated the efficacy of hydrodynamics-based tumor necrosis factor alpha (TNFalpha) transfer for tumor treatment, in which the naked pDNA encoding TNFalpha was administered into the tail vein following an intravenous injection of B16 melanoma cells. The mice treated with TNFalpha-expressing pDNA displayed a profound reduction in lung metastasis. These results suggest that the hydrodynamics-based transfer of naked pDNA is a convenient and efficient method of TNFalpha gene therapy against metastatic tumors.