Present experiment of BASJE group at Mt. Chacaltaya

A compact air shower array to observe primary cosmic rays above a few TeV has been installed at Mt. Chacaltaya in Bolivia since 1996. This array is available to observe the air showers above 6 TeV and the longitudinal development curves above 50 TeV. The purpose of the observations is to study the chemical composition and the energy spectrum of cosmic rays in the energy region including the “knee” of the energy spectrum. First, the consistency between direct measurements (balloon-borne experiments) and air shower observations in the energy region from 50 TeV to 80 TeV is examined and confirmed. Next, the chemical composition and the energy spectrum are derived from the air shower observations. In the study, the longitudinal developments of shower particles are calculated by Monte Carlo simulations, assuming different chemical compositions above 80 TeV. The characteristics of the present air shower array and the comparison of the preliminary observed results with that of the simulations are presented

Measurement of cosmic ray chemical composition at Mt. Chacaltaya

BASJE grouphas measured the chemical composition of primary cosmic rays with energies around the “knee” with several methods. These measurements show that the averaged mass number of cosmic ray particles increases with energy upto the knee. In order to measure the chemical composition in much wider energy range, we have started a new experiment at Mt. Chacaltaya in 2000

Galactic-disk enhancement of cosmic rays at E > 1012eV

We observed an enhancement of cosmic rays from the Vela region with SAS array at Mt. Chacaltaya in Bolivia. It is not possible to conclude that this enhancement is caused by primary gamma-rays, since the observed events not limited with the less muons in the air showers show the same enhancement. In order to confirm this result with improved statistics and to investigate the energy dependence of this enhancement, we have installed a new array, called MAS array. All the data with much higher statistics show the enhancement along the Whole galactic disk

Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson's Disease

Parkinson's disease (PD) is characterized by severe motor symptoms, and currently there is no treatment that retards disease progression or reverses damage prior to the time of clinical diagnosis. Tauroursodeoxycholic acid (TUDCA) is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD; however, its effect in PD motor symptoms has never been addressed. In the present work, an extensive behavior analysis was performed to better characterize the MPTP model of PD and to evaluate the effects of TUDCA in the prevention/improvement of mice phenotype. MPTP induced significant alterations in general motor performance paradigms, including increased latency in the motor swimming, adhesive removal and pole tests, as well as altered gait, foot dragging, and tremors. TUDCA administration, either before or after MPTP, significantly reduced the swimming latency, improved gait quality, and decreased foot dragging. Importantly, TUDCA was also effective in the prevention of typical parkinsonian symptoms such as spontaneous activity, ability to initiate movement and tremors. Accordingly, TUDCA prevented MPTP-induced decrease of dopaminergic fibers and ATP levels, mitochondrial dysfunction and neuroinflammation. Overall, MPTP-injected mice presented motor symptoms that are aggravated throughout time, resembling human parkinsonism, whereas PD motor symptoms were absent or mild in TUDCA-treated animals, and no aggravation was observed in any parameter. The thorough demonstration of improvement of PD symptoms together with the demonstration of the pathways triggered by TUDCA supports a subsequent clinical trial in humans and future validation of the application of this bile acid in PD.National funds, through the Foundation for Science and Technology (Portugal) (FCT), under the scope of the projects PTDC/NEU-NMC/0248/2012, UID/DTP/04138/2013 and POCI-01-0145-FEDER-007038, and post-doctoral grants SFRH/BPD72891/2010 (to A.I.R.), SFRH/BPD/95855/2013 (to M.J.N.), SFRH/BPD/98023/2013 (to A.N.C.), SFRH/BPD/91562/2012 (to A.S.F.) and UMINHO/BI/248/2016 (to S.D.S.). This work has also been developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Program (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and by FEDER funds, through the Competitiveness Factors Operational Program (COMPETE)info:eu-repo/semantics/publishedVersio

Colony-stimulating factors detected in tumor cells and voided urine are potential prognostic markers for patients with muscle-invasive bladder cancer undergoing radical cystectomy

Yosuke Morizawa,1 Makito Miyake,1 Keiji Shimada,2 Shunta Hori,1 Yoshihiro Tatsumi,1 Yasushi Nakai,1 Nobumichi Tanaka,1 Tomomi Fujii,3 Kiyohide Fujimoto1 1Department of Urology, Nara Medical University, Nara, Japan; 2Department of Pathology, Nara City Hospital, Nara, Japan; 3Department of Diagnostic Pathology, Nara Medical University, Nara, Japan Background: The clinical use of macrophage colony-stimulating factor, granulocyte colony-stimulating factor (G-CSF), and granulocyte macrophage colony-stimulating factor (GM-CSF) has improved the safety of cytotoxic chemotherapy. However, the overexpression of these CSFs in cancers has been reported to be associated with a poor prognosis in various malignancies. We evaluated the potential of CSF expression as a predictor of clinical outcome in patients with muscle-invasive bladder cancer (MIBC).Methods: Consecutive patients (n=58) with MIBC who underwent radical cystectomy (RC) were included in this retrospective study. Treatment-naïve tumor specimens obtained by initial transurethral resection of bladder tumors prior to RC were immunostained with antibodies against macrophage colony-stimulating factor, G-CSF, and GM-CSF. We compared the clinicopathological variables and survival between these groups. Baseline levels of CSFs in the serum and voided urine were quantified using an enzyme-linked immunosorbent assay and compared with the expression of CSFs in the tumor lesions.Results: Low expression of GM-CSF in the tumor cells was significantly correlated with a pathological T4 category (vs T2–3; P=0.02). In univariate survival analysis, high G-CSF and low GM-CSF expression in the tumor lesion were associated with poor outcomes. Furthermore, Cox proportional regression analysis revealed that high G-CSF and low GM-CSF expression in the tumor were independent predictors of shorter recurrence-free survival, cancer-specific survival, and overall survival. The levels of CSFs in voided urine were associated with the expression of CSFs in the tumor lesions.Conclusion: GM-CSF and G-CSF expression in the tumor lesions obtained by initial transurethral resection are independent predictors of poor outcome in MIBC after RC. Levels of G-CSF and GM-CSF in urine before treatment could be useful in prognostication. Keywords: colony-stimulating factor, M-CSF, G-CSF, GM-CSF, muscle-invasive bladder cancer, radical cystectom

Atypical small acinar proliferation and two or more cores of high-grade intraepithelial neoplasia on a previous prostate biopsy are significant predictors of cancer during a transperineal template-guided saturation biopsy aimed at sampling one core for each 1 mL of prostate volume

Yasushi Nakai,1 Nobumichi Tanaka,1 Makito Miyake,1 Shunta Hori,1 Yoshihiro Tatsumi,1,2 Yosuke Morizawa,1 Tomomi Fujii,2 Noboru Konishi,2 Kiyohide Fujimoto1 1Department of Urology, Nara Medical University, 2Department of Pathology, Nara Medical University, Kashihara-shi, Nara, Japan Objective: The objective of this study was to evaluate whether high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP) predict prostate cancer (PCa) during repeat transperineal template saturation biopsy with a high number of cores per prostate volume in patients with persistent clinical suspicion of PCa who underwent at least one previous negative transrectal ultrasound (TRUS)-guided biopsy. Methods: We retrospectively evaluated 135 consecutive patients with persistent clinical suspicion of PCa, despite a set of negative TRUS-guided biopsies and increasing prostate-specific antigen levels; abnormal findings on digital rectal examination, TRUS, or magnetic resonance imaging; previous biopsy showing HGPIN; and previous biopsy showing atypical glands. Transperineal template saturation biopsy (TTSB) was performed at 5mm intervals to sample one core for each 1 mL of prostate volume.  Results: The median rate of biopsy cores per prostate volume was 1.00 (range: 0.75–1.39). The PCa detection rates in patients who were diagnosed with HGPIN, or had two or more cores of HGPIN or ASAP, were 53% (9/17), 89% (8/9), and 83% (10/12), respectively. Two or more HGPIN cores and ASAP were positive predictors of PCa on TTSB. The high-grade cancer rates (Gleason score [GS] ≥7) in patients with ASAP and two or more cores of HGPIN were 20% and 80%, respectively. The cancer detection rate represented by a GS score ≥8 in patients with ASAP or two or more cores of HGPIN at a previous TRUS-guided biopsy was 5.5% (1/18). Conclusion: ASAP or two or more cores of HGPIN at a previous TRUS-guided biopsy strongly indicated the presence of PCa on TTSB. Keywords: atypical small acinar proliferation, high-grade intraepithelial neoplasia, transperineal template-guided saturation biopsy, prostate cancer, repeat biops

Comparison of cancer detection rates by transrectal prostate biopsy for prostate cancer using two different nomograms based on patient’s age and prostate volume

Shunta Hori,1 Nobumichi Tanaka,1 Yasushi Nakai,1 Yosuke Morizawa,1 Yoshihiro Tatsumi,1 Makito Miyake,1 Satoshi Anai,1 Tomomi Fujii,2 Noboru Konishi,2 Yoshinori Nakagawa,3 Syuya Hirao,4 Kiyohide Fujimoto1 1Department of Urology, Nara Medical University, Kashihara, Nara 634-8522, Japan; 2Department of Pathology, Nara Medical University, Kashihara, Nara 634-8522, Japan; 3Department of Urology, Yamatotakada Municipal Hospital, Yamatotakada, Nara 635-8501, Japan; 4Department of Urology, Medical Corporation Katsurakai HIRAO Hospital, Kashihara, Nara 634-0076, Japan Background: The aim of this study is to evaluate the efficacy of two different Nara Urological Research and Treatment Group (NURTG) nomograms allocating 6–12 biopsy cores based on age and prostate volume. Materials and methods: From April 2006 to July 2014, a total of 1,605 patients who underwent initial prostate biopsy were enrolled. Based on a nomogram taking the patient’s age and prostate volume into consideration, 6–12 biopsy cores were allocated. Two types of nomogram were used, for the former group (before March 2009) and latter group (March 2009 onward). Cancer detection rates in all patients and those with prostate-specific antigen values in the gray zone (4.0–10 ng/mL) were compared. Predictive parameters for detection of prostate cancer in gray-zone patients were also investigated. Results: The cancer detection rates in all patients and those in the gray zone were 48% and 38% in the former group and 54% and 41% in the latter group, respectively. The cancer detection rate in all patients was significantly higher in the latter group compared with the former group, but detection in gray-zone patients did not show a significant difference between the two groups (P=0.011 and P=0.37, respectively). Multivariate analysis indicated that age, digital rectal examination, prostate volume, transrectal ultrasonography findings, and volume/biopsy ratio were significant predictive parameters in gray-zone patients. The clinically insignificant cancer detection rate was significantly lower in the latter group compared with the former group (P=0.0008). Conclusion: The latter nomogram provided more acceptable detection rates of clinically significant and insignificant cancer than the former one, and we consider that an initial maximum 12-core transrectal ultrasound-guided needle biopsy may be sufficient for prostate cancer diagnosis. Keywords: age, cancer detection rate, nomogram, prostate cancer, prostate volume, transrectal prostate biops

Quality of life worsened the most severely in patients immediately after intensity-modulated radiation therapy for prostate cancer

Yasushi Nakai,1 Nobumichi Tanaka,1 Satoshi Anai,1 Makito Miyake,1 Isao Asakawa,2 Yosuke Morizawa,1 Shunta Hori,1 Kazumasa Torimoto,1 Tomomi Fujii,3 Masatoshi Hasegawa,2 Kiyohide Fujimoto1 1Department of Urology, Nara Medical University, Nara, Japan; 2Department of Radiation Oncology, Nara Medical University, Nara, Japan; 3Department of Pathology, Nara Medical University, Nara, Japan Purpose: The aim of this study was to evaluate the chronological changes in lower urinary tract symptoms (LUTSs), disease-related quality of life (QOL), and health-related QOL (HR-QOL) of patients who received intensity-modulated radiotherapy (IMRT).Patients and methods: In 121 patients who had received IMRT and were followed up for >2 years, the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), Expanded Prostate Cancer Index Composite (EPIC), and 8-Item Short-Form Health Survey (SF-8) were used before IMRT, at the halfway point in IMRT, immediately after IMRT, and 1–24 months after the completion of IMRT.Results: The IPSS and OABSS and the urinary and bowel domains of the EPIC indicated that QOL worsened at the halfway point in IMRT, further worsened more severely immediately after IMRT, and then improved. The sexual domain of the EPIC significantly decreased at the halfway point in IMRT, which significantly lowered until 24 months. The scores of physical functioning, role physical, bodily pain, vitality, social functioning, and role emotional domains in the SF-8 significantly decreased and reached their lowest points immediately after IMRT.Conclusion: QOL worsened the most severely in patients immediately after IMRT for prostate cancer. This knowledge can influence treatment recommendations and enable patients to make better informed decisions. Keywords: chronological changes, intensity-modulated radiotherapy, prostate cancer, quality of life, radiotherap