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Abstract We investigated whether aspartate transaminase (AST)-to-alanine aminotransferase (ALT) ratio and its change during the course of treatment in castration-resistant prostate cancer (CRPC) patients is associated with tumor condition and lethality. Clinical data from 130 CRPC patients were retrospectively evaluated. AST/ALT ratios at the time of prostate cancer (PC) diagnosis, androgen deprivation therapy (ADT), CRPC diagnosis, and the final follow-up examination after CRPC treatment were calculated for each. The prognostic capabilities of the AST/ALT ratio for overall survival (OS) were analyzed by use of the Kaplan–Meier method and Cox hazard models. The median AST/ALT ratio at PC diagnosis was 1.517 and the optimal value predicting lethality defined by the receiver operating curve was 1.467. The AST/ALT ratio decreased once during ADT and then elevated in a stepwise manner with cancer progression. In surviving patients, the median AST/ALT ratio at the time of PC diagnosis was 1.423, which did not change longitudinally, whereas that in patients later deceased was significantly higher (1.620) and further elevated after CRPC diagnosis. Kaplan–Meier curves indicated significantly worse OS in patients with an AST/ALT ratio ≥ 1.467, which was confirmed by multivariate analysis. These findings indicate AST/ALT ratio as a prognostic biomarker for CRPC with longitudinal changes reflecting tumor progression.

ObjectiveThis study aimed to identify the prediction accuracy of the combination of C-reactive protein (CRP) albumin ratio (CAR) and time to castration resistance (TTCR) for overall survival (OS) following development of metastatic castration-resistant prostate cancer (mCRPC).MethodsClinical data from 98 mCRPC patients treated at our institution from 2009 to 2021 were retrospectively evaluated. Optimal cutoff values for CAR and TTCR to predict lethality were generated by use of a receiver operating curve and Youden’s index. The Kaplan–Meier method and Cox proportional hazard regression models for OS were used to analyze the prognostic capabilities of CAR and TTCR. Multiple multivariate Cox models were then constructed based on univariate analysis and their accuracy was validated using the concordance index.ResultsThe optimal cutoff values for CAR at the time of mCRPC diagnosis and TTCR were 0.48 and 12 months, respectively. Kaplan–Meier curves indicated that patients with CAR >0.48 or TTCR

This study aimed to validate the usefulness of parent artery complex coil protection for the treatment of wide-neck, side-branched, and ruptured aneurysms. A microcatheter was first introduced into the aneurysmal sac, and another microcatheter was introduced into the parent artery or near the orifice of the branch artery. A framing coil was deployed partially from the first microcatheter, and a protection coil was deployed from the second microcatheter to prevent protrusion of the first framing coil to the parent artery and side branches. After the first framing coil insertion, the protection coil was withdrawn to confirm the stability of the framing coil and blood flow. The procedures with this technique were successful for 3 patients. Parent artery complex coil protection can be an effective and safe coil embolization technique for the preservation of parent and side branch arteries and an alternative method for emergent ruptured cases.

Abstract Bovine-derived cultured cells, including Madin-Darby bovine kidney cells, are used worldwide; however, lipofection tend to result in low transfection efficiency, which has impeded the progress of veterinary research. We performed experiments to confirm the lipofection efficiency of bovine-derived cultured cells, to identify cells that suitable for lipofection. Several bovine tissues (endometrium, testis, ear tissue and foetal muscle) were collected, and primary cultured cells were prepared. Lipofection assay showed that only bovine endometrium (BE)-derived cells could be transfected efficiently (50‒70%). BE cells can be divided into at least two types of cell populations (BE-1 and BE-2). The BE-1 cells, which were suitable for lipofection, were obtained by passages at short intervals and were negative for cytokeratin- and positive for vimentin-expression; the BE-2 cells did not have these characteristics and were not suitable for lipofection. Furthermore, the BE-1 cells and artificially immortalised cells of BE-1, iBE-1 cells, were utilised in a reporter assay requiring the introduction of multiple DNAs. Endometrial tissues can be collected from living cows, and BE-1 cells can be obtained easily by controlling passaging timing. The production of BE-1 cells and sharing the methods required to prepare them will contribute to the development of veterinary research.

Introduction Basal cell carcinoma of the prostate is a rare prostate malignancy. Its diagnosis and treatment have not been well established yet. Case presentation An 80‐year‐old man was referred to our hospital for undergoing holmium laser enucleation of the prostate with persistent lower urinary tract symptoms. Ultrasonography showed enlarged prostate (41.3 cc) with mid‐lobe hypertrophy. His prostate‐specific antigen and testosterone levels were 0.437 ng/mL and 873 ng/dL, respectively. Histological examination of the enucleated tissue confirmed basal cell carcinoma. The cells were positive for bcl‐2, 34βE12, p63, and cytokeratin 5/6. Ki‐67 labeling index was 5%. Subsequent staging computed tomography scan and bone scintigram showed neither lymph node nor distant metastasis. Currently, the patient is under close follow‐up with imaging, endoscopy, and urodynamic study. Conclusion It is difficult for physicians to detect prostate basal cell carcinoma before benign prostatic hyperplasia surgery. In case of organ‐confined disease, age and Ki‐67 labeling index could be suggestive of subsequent treatment decision‐making.

Introduction. A metastatic testicular tumor is uncommon. We report here a case of testicular metastasis associated with recurrent colorectal cancer. Case Presentation. A 75-year-old male was presented with right scrotum pain one year after undergoing a right hemicolectomy combined with resection of the small intestine and omentum for ascending colon cancer (pT4N0M0). Magnetic resonance imaging of the pelvis showed a 7.3×5.4×4.5 cm mass consisting of a cystic solid tumor. A right inguinal orchiectomy was performed and right testicular pain improved after surgery. Pathology results showed that the tumor was a metastatic adenocarcinoma. The patient subsequently died two months later due to progression of the colon cancer. Conclusion. Although colorectal cancer metastasis to the testis is very uncommon, it should be kept in mind in clinical situations, especially for older males with a testicular mass or discomfort.

Abstract Objectives The effect of rupatadine, a novel H1 antihistamine with platelet‐activating factor antagonist activity, had been demonstrated for itching in Japanese patients with chronic spontaneous urticaria, dermatitis, or pruritus in a 12‐month, open‐label clinical trial (JapicCTI‐152787). However, patients could have received an updose at various timings due to distinct reasons in the study; timing of updose was not evaluated. This study aimed to elucidate the relationship between performance of rupatadine and timing of updose. Methods For 206 enrolled patients was evaluated the total pruritus score (TPS) to Week 2 with 10 mg rupatadine. From Week 3 to Week 52, rupatadine was updosed to 20 mg accordingly. Subpopulation was categorized by absence/presence of updosing and timing of updose (Week 3 or ≥Week 5). Results Reduction of TPS from baseline to Week 2 in patients updosed at Week 3 was significantly lower than those given an updose at ≥Week 5 and fixed dose. However, significant improvement in the change in mean TPS from 1 week pre‐updose to the second week post‐updose was achieved regardless of updose timing, scoring −0.903 for Week 3 and −0.983 for ≥Week 5 (P

Background: Rupatadine is a novel non-sedating second-generation H1-antihistamine with antiplatelet-activating factor activity, first marketed in Spain in 2003. It is used for treating allergic rhinitis in more than 80 countries. This study investigated its efficacy and safety in Japanese patients with seasonal allergic rhinitis (SAR). Methods: This was a randomized, placebo-controlled, double-blind study conducted at 4 medical institutions in Japan (JapicCTI-152785). Adolescent and adult SAR outpatients aged 12–64 years entered a 1-week placebo run-in period. After eligibility was confirmed, patients orally received placebo, rupatadine 10 mg, or 20 mg once daily for 2 weeks. The primary endpoint was a change from baseline to second week of treatment in total 4 nasal symptom score (T4NSS). Results: Nine hundred patients were randomly assigned to placebo, rupatadine 10 mg, or rupatadine 20 mg (302, 298, and 300 patients, respectively). The least squares mean difference in the primary endpoint between rupatadine and placebo was −1.085 for 10 mg, and −1.415 for 20 mg (analysis of covariance, both P

Background: Rupatadine, a novel nonsedating second-generation H1-antihistamine with antiplatelet-activating factor activity, has been used in the treatment of allergic rhinitis and urticaria in European countries since 2003. However, its efficacy and safety in Japanese patients with chronic spontaneous urticaria (CSU) are unknown. Methods: We conducted a prospective, multicenter, randomized, placebo-controlled, double-blind study in adolescent and adult CSU outpatients aged 12 to

Microplastics are increasingly suspected of having serious negative effects on ecological systems and living organisms. These effects are different based on the materials of the microplastics, leading to the importance of the determination of the materials. For material determination, spectral fingerprints based on FT-IR and Raman microspectroscopy are previously and commonly used, though they require patience and special skills. In this study, we have developed a novel technique for microscopic observation of single microplastic particles stained with fluorescent dyes to enable fluorescence-based determination of materials of these particles as a first screening of material determination. Commercially available and popular microplastic particles and fluorescent dyes were used. Fluorescence microscopy was carried out to observe the degree of fluorescent intensity for various combinations of microplastics and dyes based on the difference in fluorescent intensity of microplastics before and after staining with the dyes. We have found a dependence of the fluorescent intensity on the combination of the microplastics and the dye. Fluorescein gave the highest increase in intensity for PS (polystyrene), showing a statistically significant difference between fluorescent intensity for PS and that for PP (polypropylene) or PE (polyethylene). The use of Fluorescein thus enables specific detection of PS. On the other hand, Nile Red gave the highest increase in fluorescence for PP, indicating that the combination of Nile Red and PP gives a significantly greater interaction than with other combinations. The use of Nile Red thus enables the specific detection of PP. These results indicate the possibility of the material determination of microplastics by using fluorescent dyes. This is the first demonstration of the differential determination of the materials of single-particle microplastics based on a material-specific increase in fluorescent intensity by staining microplastics with fluorescent dyes.

A 74-year-old male underwent laparoscopic radical cystectomy for invasive bladder cancer with open surgery for lymph node dissection and urinary diversion (ileal conduit). During the surgery, intestinal malrotation was diagnosed and Ladd procedure was performed. Ileal conduit was performed on the left side after considering the course of mesentery. Although a final diagnosis was reached during the surgery in this case, the presence of intestinal malrotation can be suspected based on the findings of contrast-enhanced computed tomography images obtained before the surgery. Images should be carefully inspected to detect intestinal malrotation when planning urinary diversion involving the intestinal tract. Keywords: Intestinal malrotation, Radical cystectomy, Urinary diversion

To study the genetic diversity of enterovirus G (EV-G) among Japanese pigs, metagenomics sequencing was performed on fecal samples from pigs with or without diarrhea, collected between 2014 and 2016. Fifty-nine EV-G sequences, which were >5,000 nucleotides long, were obtained. By complete VP1 sequence analysis, Japanese EV-G isolates were classified into G1 (17 strains), G2 (four strains), G3 (22 strains), G4 (two strains), G6 (two strains), G9 (six strains), G10 (five strains), and a new genotype (one strain). Remarkably, 16 G1 and one G2 strain identified in diarrheic (23.5%; four strains) or normal (76.5%; 13 strains) fecal samples possessed a papain-like cysteine protease (PL-CP) sequence, which was recently found in the USA and Belgium in the EV-G genome, at the 2C-3A junction site. This paper presents the first report of the high prevalence of viruses carrying PL-CP in the EV-G population. Furthermore, possible inter- and intragenotype recombination events were found among EV-G strains, including G1-PL-CP strains. Our findings may advance the understanding of the molecular epidemiology and genetic evolution of EV-Gs.

We present a case of a 45-year-old female who experienced rupture of a right calyceal diverticulum caused by ureteroscopy. Fifteen hours after the operation, she had severe right flank pain and a high fever (38.9°C). Computed tomography revealed perinephric extravasation of urine and bleeding inside the diverticulum. We diagnosed rupture of a calyceal diverticulum; therefore, we continued antibiotic administration and pain relief medication. She became afebrile on postoperative day 4 and was discharged from the hospital on postoperative day 7. Owing to renal cortex thinning in the diverticula, ureteroscopy is associated with a risk of rupture of calyceal diverticula.

We report a histologically pure stage 1 seminoma with an elevated human chorionic gonadotropin (hCG). A 38 year-old man was referred for the evaluation of the left testicular swelling. He showed an elevated serum hCG level of 25,265 mIU/ml with normal a fetoprotein and lactate dehydrogenase. Imaging showed heterogeneous tumor without any metastatic lesions. We conducted 4 courses of chemotherapy before detecting hCG nadir. The final pathological report showed pure seminoma with syncytiotrophoblastic cells but no choriocarcinoma components. The patient remains disease free until present time. The case raised several questions regarding diagnosis and treatment strategy for bulky testicular seminoma.

Amphipathic α-helices of exchangeable apolipoproteins have shown to play crucial roles in the formation of infectious hepatitis C virus (HCV) particles through the interaction with viral particles. Among the Flaviviridae members, pestivirus and flavivirus possess a viral structural protein Erns or a non-structural protein 1 (NS1) as secretory glycoproteins, respectively, while Hepacivirus including HCV has no secretory glycoprotein. In case of pestivirus replication, the C-terminal long amphipathic α-helices of Erns are important for anchoring to viral membrane. Here we show that host-derived apolipoproteins play functional roles similar to those of virally encoded Erns and NS1 in the formation of infectious particles. We examined whether Erns and NS1 could compensate for the role of apolipoproteins in particle formation of HCV in apolipoprotein B (ApoB) and ApoE double-knockout Huh7 (BE-KO), and non-hepatic 293T cells. We found that exogenous expression of either Erns or NS1 rescued infectious particle formation of HCV in the BE-KO and 293T cells. In addition, expression of apolipoproteins or NS1 partially rescued the production of infectious pestivirus particles in cells upon electroporation with an Erns-deleted non-infectious RNA. As with exchangeable apolipoproteins, the C-terminal amphipathic α-helices of Erns play the functional roles in the formation of infectious HCV or pestivirus particles. These results strongly suggest that the host- and virus-derived secretory glycoproteins have overlapping roles in the viral life cycle of Flaviviridae, especially in the maturation of infectious particles, while Erns and NS1 also participate in replication complex formation and viral entry, respectively. Considering the abundant hepatic expression and liver-specific propagation of these apolipoproteins, HCV might have evolved to utilize them in the formation of infectious particles through deletion of a secretory viral glycoprotein gene.

Although it is not yet possible to replace in vivo animal testing completely, the need for a more efficient method for toxicity testing, such as an in vitro cell-based assay, has been widely acknowledged. Previous studies have focused on mRNAs as biomarkers; however, recent studies have revealed that non-coding RNAs (ncRNAs) are also efficient novel biomarkers for toxicity testing. Here, we used deep sequencing analysis (RNA-seq) to identify novel RNA biomarkers, including ncRNAs, that exhibited a substantial response to general chemical toxicity from nine chemicals, and to benzene toxicity specifically. The nine chemicals are listed in the Japan Pollutant Release and Transfer Register as class I designated chemical substances. We used undifferentiated mouse embryonic stem cells (mESCs) as a simplified cell-based toxicity assay. RNA-seq revealed that many mRNAs and ncRNAs responded substantially to the chemical compounds in mESCs. This finding indicates that ncRNAs can be used as novel RNA biomarkers for chemical safety screening.

We demonstrate that the copolymers containing boronic acid and pyrene units can be utilized for the fluorometric sensing of hydrogen peroxide (H2O2) in aqueous solutions. The copolymer exists in a relatively extended conformation in the absence of H2O2, whereas the polymer chain is contracted by the reaction of boronic acid moieties with H2O2 to form phenol groups. This conformational change induces aggregation of the originally isolated pyrene groups. As a result, relative intensity of excimer emission with respect to monomer emission increases with H2O2 concentration. Accordingly, the present methodology enables us to measure H2O2 by means of ratiometric fluorescence change in the range of 0–30 μM.

Optical colonoscopy is the most common approach to diagnosing bowel diseases through direct colon and rectum inspections. Periodic optical colonoscopy examinations are particularly important for detecting cancers at early stages while still treatable. However, diagnostic accuracy is highly dependent on both the experience and knowledge of the medical doctor. Moreover, it is extremely difficult, even for specialist doctors, to detect the early stages of cancer when obscured by inflammations of the colonic mucosa due to intractable inflammatory bowel diseases, such as ulcerative colitis. Thus, to assist the UC diagnosis, it is necessary to develop a new technology that can retrieve similar cases of diagnostic target image from cases in the past that stored the diagnosed images with various symptoms of colonic mucosa. In order to assist diagnoses with optical colonoscopy, this paper proposes a retrieval method for colonoscopy images that can cope with multiscale objects. The proposed method can retrieve similar colonoscopy images despite varying visible sizes of the target objects. Through three experiments conducted with real clinical colonoscopy images, we demonstrate that the method is able to retrieve objects of any visible size and any location at a high level of accuracy.

Peptide nucleic acid (PNA) has outstanding affinity over DNA for complementary nucleic acid sequences by forming a PNA-DNA heterodimer upon hybridization via Watson-Crick base-pairing. To verify whether PNA probes on an electrode surface enhance sensitivity for potentiometric DNA detection or not, we conducted a comparative study on the hybridization of PNA and DNA probes on the surface of a 10-channel gold electrodes microarray. Changes in the charge density as a result of hybridization at the solution/electrode interface on the self-assembled monolayer (SAM)-formed microelectrodes were directly transformed into potentiometric signals using a high input impedance electrometer. The charge readout allows label-free, reagent-less, and multi-parallel detection of target oligonucleotides without any optical assistance. The differences in the probe lengths between 15- to 22-mer dramatically influenced on the sensitivity of the PNA and DNA sensors. Molecular type of the capturing probe did not affect the degree of potential shift. Theoretical model for charged rod-like duplex using the Gouy-Chapman equation indicates the dominant effect of electrostatic attractive forces between anionic DNA and underlying electrode at the electrolyte/electrode interface in the potentiometry.

IntroductionInternational norms and ethical standards have suggested that compensation for research-related injury should be provided to injured research volunteers. However, statistical data of incidence of compensation claims and the rate of awarding them have been rarely reported.MethodQuestionnaire surveys were sent to pharmaceutical companies and medical institutions, focusing on industry-initiated clinical trials aiming at new drug applications (NDAs) on patient volunteers in Japan.ResultsWith the answers from pharmaceutical companies, the incidence of compensation was 0.8%, including 0.06% of monetary compensation. Of the cases of compensation claims, 99% were awarded. In turn, with the answers from medical institutions, the incidence of compensation was 0.6%, including 0.4% of serious but not death cases, and 0.04% of death cases. Furthermore, most claims for compensation were initiated by medical institutions, rather than by the patients. On the other hand, with the answers from clinical trial volunteers, 3% of respondents received compensations. These compensated cases were 25% of the injuries which cannot be ruled out from the scope of compensation.ConclusionOur study results demonstrated that Japanese pharmaceutical companies have provided a high rate of compensation for clinical trial-related injuries despite the possibility of overestimation. In the era of global clinical development, our study indicates the importance of further surveys to find each country's compensation policy by determining how it is being implemented based on a survey of the actual status of compensation coming from statistical data.

MicroRNAs (miRNAs) are potentially useful biomarkers for the evaluation of cancers and chemical toxicity. However, simply and easily operated detection techniques are increasingly needed to enable their use in the biomedical and environmental fields. In this study, we investigated sequence-specific miRNA detections by surface plasmon resonance (SPR) and electrochemical (EC) imaging measurements on SPR-EC chips possessing a Au electrode array modified with probe DNAs and by employing a miRNA-detection-selective signal amplification method. MiRNAs were sequence-specifically detected by SPR and EC imaging measurements on a single chip. SPR signals were enhanced by a combination process employing the sequencespecific hybridization of miRNAs with the probe DNA, the extension reaction of polyadenine [poly(A)] tails on the 3’ end of the miRNAs by poly(A) polymerase, the binding of T30-Au nanoparticles (AuNPs) to the poly(A) tails, and the reduction reaction of Ag+ catalyzed on the AuNPs, depositing a gray precipitate on the surface. The oxidation reaction of the accumulated Ag precipitation additionally provides EC signal amplification. This process considerably and sequence-specifically amplifies the SPR and EC signals. This setup constitutes a simple and feasible signal amplification method for the on-site detection of miRNA biomarkers. [ABSTRACT FROM AUTHOR]