[Evaluation of the Effects of Long-Term Indwelling Ureteral Stents on Preserving Renal Parenchyma and Function in Patients with Ureteral Stenosis].

Although ureteral stenting is a common conservative treatment for ureteral stricture, it is unclear whether a long-term indwelling ureteral stent protects the kidney against parenchymal atrophy and functional deterioration. In this study, we evaluated the changes in renal parenchymal thickness (RPT) and estimated the glomerular filtration rates (eGFR) in patients with indwelling ureteral stents for one year or more. As a control, we also evaluated changes in RPT associated with indwelling percutaneous nephrostomy (PNS) for one year or more. Polymer ureteral stents were used and replaced every three months. RPT was measured using computed tomography (CT). Totally, 69 renal units in 55 patients with baseline and follow up CT scans available were enrolled. The median follow-up period was 29 months. The etiologies of ureteral obstruction were malignant and benign disease in 27 and 28, respectively. RPT was reduced obviously in most cases. At 1 year, the median reduction rate of RPT was 17.3% in unilateral cases, which was significantly higher than that in the healthy contralateral kidney. There was a strong correlation between eGFR and total RPT including the contralateral kidney. The reduction rate of RPT in kidneys with ureteral stents including bilateral cases was also significantly higher than that in 39 renal units of 35 patients with PNS. The results of this study suggest that the long-term efficacy of indwelling ureteral stents in preserving renal function is limited. Regular imaging may be essential to evaluate the residual renal function.

Measurement of work-related psychological injury with depressive symptoms.

OBJECTIVE: This study aimed to measure the level of psychological injury caused by work-related stress as well as the severity of depression among workers. METHOD: First, we conducted an online survey and recruited 500 workers diagnosed with depression or adjustment disorder to investigate what type of stress they experienced within six months before onset. Second, we conducted another online survey and recruited 767 participants who experienced some form of work-related stress. All the participants were classified into four groups by whether or not they were diagnosed with depression and whether or not they quit their jobs due to work-related stress. We used the Impact of Event Scale-Revised (IES-R) to measure psychological injury caused by work-related stressful events and the Patient Health Questionnaire (PHQ)-9 to assess the severity of depression. RESULTS: In study 1, 62.4% of workers diagnosed with depression or adjustment disorder experienced work-related stress within six months before onset. In study 2, the IES-R mean scores were 40.7 (SD = 23.1) for Group A (workers with depression and quit their jobs) and 36.67 (SD = 23.4) for Group B (workers with depression but stayed at their jobs), with both exceeding the cut-off point (24/25) of PTSD (Post-Traumatic Stress Disorder), while the mean score of Group C (workers who did not have depression but quit their jobs because of work-related stress) was 20.74 (SD = 21.2), and it was 13.89 (SD = 17.4) for Group D (workers who had work-related stress but stayed at their jobs), with both of them below the cut-off point of PTSD. The total scores of IES-R of Group A and Group B were significantly higher than those of Group C and Group D(p < 0.001). There was a significant positive correlation between the scores of IES-R and PHQ-9 for all four groups (r = 0.708). CONCLUSIONS: This study suggests that it is necessary to measure not only depressive symptoms but also the level of psychological injury resulting from stressful events in the workplace to assess workers with depression.

Pharmacokinetic Study of 14C-Radiolabeled p-Boronophenylalanine (BPA) in Sorbitol Solution and the Treatment Outcome of BPA-Based Boron Neutron Capture Therapy on a Tumor-Bearing Mouse Model.

BACKGROUND AND OBJECTIVE: Boron neutron capture therapy (BNCT) is a binary cancer treatment that combines boron administration and neutron irradiation. The tumor cells take up the boron compound and the subsequent neutron irradiation results in a nuclear fission reaction caused by the neutron capture reaction of the boron nuclei. This produces highly cytocidal heavy particles, leading to the destruction of tumor cells. p-boronophenylalanine (BPA) is widely used in BNCT but is insoluble in water and requires reducing sugar or sugar alcohol as a dissolvent to create an aqueous solution for administration. The purpose of this study was to investigate the pharmacokinetics of 14C-radiolabeled BPA using sorbitol as a dissolvent, which has not been reported before, and confirm whether neutron irradiation with a sorbitol solution of BPA can produce an antitumor effect of BNCT. MATERIALS AND METHODS: In this study, we evaluated the sugar alcohol, sorbitol, as a novel dissolution aid and examined the consequent stability of the BPA for long-term storage. U-87 MG and SAS tumor cell lines were used for in vitro and in vivo experiments. We examined the pharmacokinetics of 14C-radiolabeled BPA in sorbitol solution, administered either intravenously or subcutaneously to a mouse tumor model. Neutron irradiation was performed in conjunction with the administration of BPA in sorbitol solution using the same tumor cell lines both in vitro and in vivo. RESULTS: We found that BPA in sorbitol solution maintains stability for longer than in fructose solution, and can therefore be stored for a longer period. Pharmacokinetic studies with 14C-radiolabeled BPA confirmed that the sorbitol solution of BPA distributed through tumors in much the same way as BPA in fructose. Neutron irradiation was found to produce dose-dependent antitumor effects, both in vitro and in vivo, after the administration of BPA in sorbitol solution. CONCLUSION: In this report, we demonstrate the efficacy of BPA in sorbitol solution as the boron source in BNCT.

ANCA-Associated Vasculitis in a Patient with Chronic Thromboembolic Pulmonary Hypertension.

An 82-year-old woman with a history of chronic thromboembolic pulmonary hypertension (CTEPH) presented with malaise, left facial nerve paralysis and the positive seroconversion of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA). She was diagnosed with ANCA-associated vasculitis (AAV). Administration of corticosteroids significantly improved her symptoms, with a decline in the serum MPOANCA level. Ten months later than the initial presentation, she developed an AAV exacerbation with lung infiltration and pericardial effusion, which improved with high-dose corticosteroid therapy. To date, a limited number of AAV cases concomitant with pulmonary hypertension have been reported. The case report presented herein suggests a potential role for CTEPH in the development of AAV.

COVID-19 vaccine-associated organizing pneumonia.

We report the first case of organizing pneumonia (OP) associated with a new coronavirus disease (COVID-19) vaccination. A 78-year-old woman developed cough and dyspnoea 10 days after receiving BNT162b2. Chest computed tomography (CT) revealed consolidation in the bilateral lower lobes of the lungs. Although antibiotic treatment did not improve her symptoms, she received a second vaccination as scheduled. She was referred to our hospital because of worsening dyspnoea on day 9 after the second vaccination, with reversed halo signs in the bilateral lower pulmonary lobes and new consolidation in the left lingual region on chest CT on day 15. She was diagnosed with OP based on bronchoalveolar lavage and transbronchial lung biopsy findings. Treatment with oral prednisolone 0.5 mg/kg/day immediately improved the symptoms and chest imaging findings. In the absence of other triggering factors, we considered this case as being COVID-19 vaccine-associated following the first and second vaccinations.

Severe Post-COVID-19 Organizing Pneumonia during Cancer Immunochemotherapy.

A 44-year-old man developed coronavirus disease 2019 (COVID-19) pneumonia during immunochemotherapy consisting of carboplatin, paclitaxel, and pembrolizumab for non-small cell lung cancer. Low-grade fever, followed by mild hypoxemia, and febrile neutropenia, were observed, and granulocyte colony-stimulating factor (G-CSF) was administered until the recovery of neutropenia, when he developed a high fever, severe hypoxemia, and hypotension accompanied by consolidation in the bilateral lungs. His conditions promptly improved after treatment including hydrocortisone and the primary and metastatic tumors remained regressed for 10 months without further treatment. Post-COVID-19 organizing pneumonia during cancer immunochemotherapy can be aggravated by immune-checkpoint inhibitors and G-CSF.

Risk scoring tool for forearm skin tears in Japanese older adults: A prospective cohort study.

[Aim] Because painful skin tears frequently occur in older patients, the prevention of skin tears is fundamental to improve their quality of life. However, a risk assessment tool for skin tears has not been established yet in Japan. Therefore, we aimed to propose a risk scoring tool for skin tears in Japanese older adult. [Methods] We conducted a prospective cohort study with 6-month follow-up in two long-term care hospitals in Japan. A total of 257 inpatients were recruited. Patient and skin characteristics were collected at baseline, and the occurrence of forearm skin tears were examined during follow-up. To develop a risk scoring tool, we identified risk factors, and converted their coefficients estimated in the multiple logistic regression analysis into simplified scores. The predictive accuracy of the total score was evaluated. [Results] Of 244 participants, 29 developed forearm skin tears during the follow-up period, a cumulative incidence of 13.5%. Senile purpura, pseudoscar, contracture, and dry skin were identified as risk factors for skin tears. Their weighted scores were 6, 4, 5, and 6, respectively. The area under the receiver operating characteristic curve of the total score was 0.806. At a cut-off score of 12, the sensitivity was 0.86, and the specificity was 0.67. [Conclusion] Our forearm skin tear risk scoring tool showed high accuracy, whereas specificity was low. This tool can contribute to prevent forearm skin tears in Japanese older adults.

A Combination of Cryopreservation and Kneading Maintains the Usability of Mohs Paste.

Mohs paste is useful for controlling exudates from wounds and infections and is used to treat patients with inoperable skin tumors. Unfortunately, Mohs paste is difficult to preserve because its viscosity and stickiness increase dramatically immediately after preparation, resulting in decreased usability. In this study, the combined use of cryopreservation and kneading was shown to improve long-term storage of Mohs paste. At 25°C, Mohs pastes solidified rapidly, and viscosity reached approximately 700 Pa·s 5 h after preparation. In contrast, cryopreservation at -20°C attenuated hardening of Mohs pastes, and kneading also decreased viscosity. The viscosity of Mohs pastes cotreated with cryopreservation and kneading after 7 months of storage was <70 Pa·s. In addition, tissue invasion with these stored pastes was similar to freshly prepared Mohs paste. Results suggest that the combination of cryopreservation and kneading permits Mohs paste to be stored over extended periods, which may increase the utility of the paste for clinical use.

An Atherogenic Paigen-Diet Aggravates Nephropathy in Type 2 Diabetic OLETF Rats.

Diabetic nephropathy develops in association with hyperglycemia, is aggravated by atherogenic factors such as dyslipidemia, and is sometimes initiated before obvious hyperglycemia is seen. However, the precise mechanisms of progression are still unclear. In this study, we investigated the influence of an atherogenic Paigen diet (PD) on the progression of nephropathy in spontaneous type 2 diabetic OLETF rats. Feeding PD to male OLETF rats for 12 weeks caused an extensive increase in excretion of urinary albumin and markers of tubular injury such as KIM-1 and L-FABP, accompanied by mesangial expansion and tubular atrophy. PD significantly increased plasma total cholesterol concentration, which correlates well with increases in urine albumin excretion and mesangial expansion. Conversely, PD did not change plasma glucose and free fatty acid concentrations. PD enhanced renal levels of mRNA for inflammatory molecules such as KIM-1, MCP-1, TLR4 and TNF-α and promoted macrophage infiltration and lipid accumulation in the tubulointerstitium and glomeruli in OLETF rats. Intriguingly, PD had little effect on urine albumin excretion and renal morphology in normal control LETO rats. This model may be useful in studying the complex mechanisms that aggravate diabetic nephropathy in an atherogenic environment.

Dietary cholesterol atherogenic changes in juvenile rabbits.

Atherosclerotic lesion formation starts during fetal development and progresses with age after adolescence. However, atherogenesis during the juvenile period has not been studied thoroughly. In this study, we examined the atherogenic susceptibility of juvenile rabbits to cholesterol feeding. Male New Zealand White rabbits aged 8 (younger group) and 12 (older group) weeks were fed a 0.5% cholesterol-containing diet for 8 weeks, and then their aortic atherosclerotic lesion areas were evaluated. Plasma concentrations of total cholesterol, triglycerides, and phospholipids did not differ between the two groups; however, plasma concentrations of high-density lipoprotein cholesterol were 23% lower in the younger than in the older group. Atherosclerotic lesion areas were significantly larger in the younger group (32±21%). However, only moderate changes were observed in these areas in the older group (3.3±0.3%). Histological examination showed marked intimal thickening and macrophage accumulation in the aortic lesions of rabbits in the younger group. To the best of our knowledge, this is the first study to show that dietary cholesterol-induced atherogenic changes markedly occur during a short period in juvenile rabbits.

Add-on effect of probucol in atherosclerotic, cholesterol-fed rabbits treated with atorvastatin.

OBJECTIVE: Lowering the blood concentration of low-density lipoprotein (LDL) cholesterol is the primary strategy employed in treating atherosclerotic disorders; however, most commonly prescribed statins prevent cardiovascular events in just 30% to 40% of treated patients. Therefore, additional treatment is required for patients in whom statins have been ineffective. In this study of atherosclerosis in rabbits, we examined the effect of probucol, a lipid-lowering drug with potent antioxidative effects, added to treatment with atorvastatin. METHODS AND RESULTS: Atherosclerosis was induced by feeding rabbits chow containing 0.5% cholesterol for 8 weeks. Probucol 0.1%, atorvastatin 0.001%, and atorvastatin 0.003% were administered solely or in combination for 6 weeks, beginning 2 weeks after the start of atherosclerosis induction. Atorvastatin decreased the plasma concentration of non-high-density lipoprotein cholesterol (non-HDLC) dose-dependently; atorvastatin 0.003% decreased the plasma concentration of non-HDLC by 25% and the area of atherosclerotic lesions by 21%. Probucol decreased the plasma concentration of non-HDLC to the same extent as atorvastatin (i.e., by 22%) and the area of atherosclerotic lesions by 41%. Probucol with 0.003% atorvastatin decreased the plasma concentration of non-HDLC by 38% and the area of atherosclerotic lesions by 61%. Co-administration of probucol with atorvastatin did not affect the antioxidative effects of probucol, which were not evident on treatment with atorvastatin alone, such as prevention of in vitro LDL-oxidation, increase in paraoxonase-1 activity of HDL, and decreases in plasma and plaque levels of oxidized-LDL in vivo. CONCLUSIONS: Probucol has significant add-on anti-atherosclerotic effects when combined with atorvastatin treatment; suggesting that this combination might be beneficial for treatment of atherosclerosis.

Time course-changes in phosphatidylcholine profile during oxidative modification of low-density lipoprotein.

BACKGROUND: Oxidized phosphatidylcholines (oxPC) and lysophosphatidylcholine (lysoPC) generated during the formation of oxidized low-density lipoprotein (oxLDL) are involved in atherosclerotic lesion development. We investigated the time course-changes in phosphatidylcholine (PC) molecular species during oxidation of LDL to determine how those atherogenic PCs are produced. METHODS: Human and rabbit LDLs were pretreated with or without a selective platelet-activating factor acetylhydrolase (PAF-AH) inhibitor. LDL was oxidized by incubation with copper sulfate, and PC profiles were analyzed by liquid chromatography-tandem mass spectrometry. RESULTS: When human LDL was oxidized, the peak areas for polyunsaturated fatty acid (PUFA)-containing PC species dramatically decreased after a short lag period, concomitantly lysoPC species increased sharply. Although a variety of oxPC species containing oxidized fatty acyl groups or cleaved acyl chains are formed during LDL oxidation, only a few oxPC products accumulated in oxLDL: 1-palmitoyl-2-(9-oxo-nonanoyl) PC and long-chain oxPC with two double bonds. Pretreatment of LDL with the PAF-AH inhibitor greatly reduced lysoPC production while it had no effect on lipid peroxidation reactions and oxPC profiles. Rabbit LDL, which has a different composition of PC molecular species and needs a longer time to reach achieve full oxidation than human LDL, also accumulated lysoPC during oxidation. The increase in lysoPC in rabbit oxLDL was suppressed by pretreatment with the PAF-AH inhibitor. The major oxPC species formed in rabbit oxLDL were almost the same as human oxLDL. CONCLUSIONS: These results suggest that lysoPC species are the major products and PAF-AH activity is crucial for lysoPC generation during oxidation of LDL. The oxPC species accumulated are limited when LDL is oxidized with copper ion in vitro.

Probucol inhibits the initiation of atherosclerosis in cholesterol-fed rabbits.

BACKGROUND: Probucol and statin are often prescribed for treating atherosclerosis. These two drugs exhibit different mechanisms but it is unknown whether they have the same anti-atherogenic properties. In the current study, we examined whether these two drugs at optimal doses could inhibit the initiation of atherosclerosis in cholesterol-fed rabbits in the same way. METHODS: New Zealand White rabbits were fed a cholesterol-rich diet for 5 weeks to produce the early-stage lesions of atherosclerosis. Drug-treated rabbits were administered either probucol or atorvastatin and serum lipids and aortic atherosclerotic lesions were compared with those in a control group. RESULTS: Atorvastatin treatment significantly reduced serum total cholesterol levels while probucol treatment led to significant reduction of high-density lipoprotein cholesterol levels without changing total cholesterol levels compared with those in the control group. Compared with the control, probucol treatment led to 65% (p < 0.01) reduction while atorvastatin treatment led to 23% (p = 0.426) reduction of the aortic lesion area. Histological and immunohistochemical analyses revealed that the lesions of the probucol-treated group were characterized by remarkable reduction of monocyte adherence to endothelial cells and macrophage accumulation in the intima compared with those of both atorvastatin and control groups. Furthermore, low-density lipoprotein (LDL) isolated from the probucol group exhibited prominent anti-oxidative reaction, which was not present in LDL isolated from either the atorvastatin-treated or the control group. CONCLUSIONS: This study suggests that probucol inhibits the initiation of atherosclerosis by reducing monocyte adherence and infiltration into the subintima. Anti-oxidization of LDL by probucol protects more effectively against early-stage lesion formation than statin-mediated lipid-lowering effects.

Estimate hidden dynamic profiles of siRNA effect on apoptosis.

BACKGROUND: For the representation of RNA interference (RNAi) dynamics, several mathematical models based on systems of ordinary differential equations (ODEs) have been proposed. These models consist of equations for each molecule that are involved in RNAi phenomena. Therefore, many real-value parameters must be optimized to identify the models. They also have many 'hidden variables', which cannot be observed directly through experimentation. Calculation of the values of the hidden variables is generally very difficult, if not impossible in some special cases. Identification of the ODE models is also quite difficult. RESULTS: We show that the simplified logistic Lotka-Volterra model, a well-established ODE model for biological and biochemical phenomena, can represent RNAi dynamics as a predator-prey system. Although a hidden variable exists in the model, its values can be determined and made visible as dynamic profiles of RNA-decomposing effects of siRNAs. Correlation analysis shows that the model parameters correlate highly with the total effect of the siRNA. CONCLUSIONS: The results suggest that analyses using our model are useful to estimate dynamic profiles of siRNA effects on apoptosis and to score siRNA by its effects on apoptosis, namely 'phenotypic scoring'.

Human apolipoprotein A-II protects against diet-induced atherosclerosis in transgenic rabbits.

OBJECTIVE: Apolipoprotein (apo) A-II is the second major apo of high-density lipoproteins, yet its pathophysiological roles in the development of atherosclerosis remain unknown. We aimed to examine whether apo A-II plays any role in atherogenesis and, if so, to elucidate the mechanism involved. METHODS AND RESULTS: We compared the susceptibility of human apo A-II transgenic (Tg) rabbits to cholesterol diet-induced atherosclerosis with non-Tg littermate rabbits. Tg rabbits developed significantly less aortic and coronary atherosclerosis than their non-Tg littermates, while total plasma cholesterol levels were similar. Atherosclerotic lesions of Tg rabbits were characterized by reduced macrophages and smooth muscle cells, and apo A-II immunoreactive proteins were frequently detected in the lesions. Tg rabbits exhibited low levels of plasma C-reactive protein and blood leukocytes compared with non-Tg rabbits, and high-density lipoproteins of Tg rabbit plasma exerted stronger cholesterol efflux activity and inhibitory effects on the inflammatory cytokine expression by macrophages in vitro than high-density lipoproteins isolated from non-Tg rabbits. In addition, ß-very-low-density lipoproteins of Tg rabbits were less sensitive to copper-induced oxidation than ß-very-low-density lipoproteins of non-Tg rabbits. CONCLUSIONS: These results suggest that enrichment of apo A-II in high-density lipoprotein particles has atheroprotective effects and apo A-II may become a target for the treatment of atherosclerosis.

A novel selective stimulus presentation for P300 speller.

The P300 speller is one of the brain-computer interfaces, allowing users to spell letters just by thoughts. Due to the low signal-to-noise ratio of the P300, however, stimuli are repeatedly presented so that EEG signals can be averaged, which improves the accuracy but degrades the speed. The authors have proposed to discontinue the stimulus presentation adaptively to the P300 response and have shown its superiority in the performance over the standard way that presents a prefixed number of stimuli. In addition to this adaptive stimulus termination, this paper proposes to select stimuli to be presented to avoid presenting redundant stimuli. Both off-line and on-line experiments show that the proposed method is more effective than our conventional method.

New methods for reverse transfection with siRNA from a solid surface.

We describe two efficient and inexpensive methods for reverse transfection with siRNA from a solid surface. One method involves localized reverse transfection from spots on a glass slide, which is mainly useful for making "transfection microarrays" (TMAs). The other involves reverse transfection in multiple wells of microtiter plates. Conditions for cell culture, preparation of reagents, and details of reverse transfection have been determined for several lines of cells, but we focus here on experiments with HeLa cells. In particular, we evaluated the efficiency of transfection, the cytotoxic effects of reverse transfection, and the efficiency of gene "knockdown" by transfection. We also performed phenotypic screening for a functional gene, during which cell viability was evaluated in terms of fluorescence from Calcein-AM. Our methods for reverse transfection with siRNA should be powerful tools that are useful for high-throughput analysis of functional genes.

Application of support vector machines to reliability-based automatic repeat request for Brain-Computer Interfaces.

A Brain-Computer Interface (BCI) is a system that could enable patients like those with Amyotrophic Lateral Sclerosis to control some equipment and to communicate with other people, and has been anticipated to be achieved. One of the problems in BCI research is a trade-off between speed and accuracy, and it is practically important to adjust those two performance measures effectively. So far the authors have considered BCIs as communications between users and computers, and have proposed an error control method, Reliability-Based Automatic Repeat reQuest (RB-ARQ). It has been shown that, with Linear Discriminant Analysis (LDA) as a classifier, RB-ARQ is more effective than other error control methods. In this paper, Support Vector Machines (SVMs), one of the most popular classifiers, are applied to RB-ARQ. A quantitative comparison showed that there was no significant difference between LDA and SVM. Also, it was demonstrated that RB-ARQ improved the accuracy from the one acquired by the top ranked methods in the BCI competition to 100 percents, with less loss of the speed.

Transfection microarray and the applications.

Microarray transfection has been extensively studied for high-throughput functional analysis of mammalian cells. However, control of efficiency and reproducibility are the critical issues for practical use. By using solid-phase transfection accelerators and nano-scaffold, we provide a highly efficient and reproducible microarray-transfection device, "transfection microarray". The device would be applied to the limited number of available primary cells and stem cells not only for large-scale functional analysis but also reporter-based time-lapse cellular event analysis.

Phosphorylated H2AX foci in tumor cells have no correlation with their radiation sensitivities.

Ionizing radiation causes DNA double strand breaks (DSBs), which produce a chromosomal change with the modification of chromatin protein. The histone H2AX is phosphorylated, and phosphorylated H2AX makes a focus. The phosphorylated H2AX focus is regarded as recruiting mediators of repair factors of DNA DSBs. Although most of the initial phosphorylated H2AX foci disappear with the repair of DNA DSBs, a few foci remain, and whether these residual DSBs are correlated with radiosensitivity is not clear. Therefore, we examined the correlation between residual DSBs and cellular radiosensitivity after ionizing radiation. We found that half of the non-irradiated normal cells had a few phosphorylated H2AX foci constantly, and most of the cells irradiated with less than 1% of the colony-forming dose had phosphorylated H2AX foci even 5 days after irradiation. Some tumor cell lines had phosphorylated H2AX foci even under non-irradiated conditions. These results indicate that residual phosphorylated H2AX foci may show loss of colony-forming potential after irradiation in normal cell lines. However, results suggested that there was not a close correlation between residual foci and radiosensitivity in some tumor cell lines, which showed high expression of endogenous phosphorylated H2AX foci. Moreover, micronuclei induced by X-ray irradiation had phosphorylated H2AX foci, but phosphorylated ATM, phosphorylated DNA-PKcs, and 53BP1 foci were not co-localized. These results suggest that DNA DSBs may be not a direct cause of micronuclei generation or H2AX phosphorylation. (227 words).