Particle radiotherapy for prostate cancer.

Recent advances in external beam radiotherapy have allowed us to deliver higher doses to the tumors while decreasing doses to the surrounding tissues. Dose escalation using high-precision radiotherapy has improved the treatment outcomes of prostate cancer. Intensity-modulated radiation therapy has been widely used throughout the world as the most advanced form of photon radiotherapy. In contrast, particle radiotherapy has also been under development, and has been used as an effective and non-invasive radiation modality for prostate and other cancers. Among the particles used in such treatments, protons and carbon ions have the physical advantage that the dose can be focused on the tumor with only minimal exposure of the surrounding normal tissues. Furthermore, carbon ions also have radiobiological advantages that include higher killing effects on intrinsic radio-resistant tumors, hypoxic tumor cells and tumor cells in the G0 or S phase. However, the degree of clinical benefit derived from these theoretical advantages in the treatment of prostate cancer has not been adequately determined. The present article reviews the available literature on the use of particle radiotherapy for prostate cancer as well as the literature on the physical and radiobiological properties of this treatment, and discusses the role and the relative merits of particle radiotherapy compared with current photon-based radiotherapy, with a focus on proton beam therapy and carbon ion radiotherapy

Treatment with Ligilactobacillus murinus lowers blood pressure and intestinal permeability in spontaneously hypertensive rats

Abstract One feature of hypertension is a microbial imbalance with increased intestinal permeability. In this study, we examined whether an alteration in the microbiota affects blood pressure and intestinal permeability in spontaneously hypertensive rats (SHRs). We performed a 16S metagenome analysis of feces from 10- to 15-week-old SHRs using a synthetic long-read sequencing approach, and found a candidate for the microbiome treatment, Ligilactobacillus murinus (L. murinus), that was robustly decreased. Oral administration of L. murinus to SHRs for 2 weeks significantly inhibited blood pressure elevation and improved endothelium-dependent vasodilation but did not attenuate enhanced vascular contraction in SHR mesenteric arteries. The proximal colon of SHRs exhibited increased intestinal permeability with decreased levels of the tight junction protein claudin 4, morphological changes such as decreased intestinal crypts and elevated TNF-α levels, which was reversed by treatment with L. murinus. Consistent with these intestinal phenotypes, plasma lipopolysaccharides levels were elevated in SHR but decreased following L. murinus administration. We concluded that oral administration of L. murinus to SHRs exerts protective effects on intestinal permeability via restoration of claudin 4 expression and reversal of morphologic disorder, which may improve low-grade endotoxemia and thus reduce development of hypertension via recovery of endothelial vasodilating functions

Immobilization of Target-Bound Aptamer on Field Effect Transistor Biosensor to Improve Sensitivity for Detection of Uncharged Cortisol

Field effect transistor (FET) biosensors are capable of detecting various biomolecules, although challenges remain in the detection of uncharged molecules. In this study, the detection of uncharged cortisol was demonstrated by interfacial design using a technique to immobilize target-bound aptamers. The target-bound aptamers, which formed a higher-order structure than target-unbound aptamers, expanded the distance between adjacent aptamers and reduced the steric hindrance to the conformational change. The density-controlled aptamers efficiently induced their conformational changes with the cortisol binding, which resulted in the improvement of the sensitivity of FET biosensors

Neutron energy spectrum measurement using CLYC7-based compact neutron emission spectrometer in the Large Helical Device

angential compact neutron emission spectrometer (CNES) based on the Cs2LiYCl6:Ce with 7Li-enrichment (CLYC7) scintillator is newly installed in the Large Helical Device (LHD). Measurement of neutron energy spectrum was performed using CNES in tangential neutral beam (NB) heated deuterium plasma discharges. The Doppler shift of neutron energy according to the direction of tangential NB injection has been obtained. When the fast ions moving away from the CNES, lower shifted neutron energy is obtained, whereas the upper shifted neutron energy is obtained when the fast ions moving toward the CNES. The obtained neutron energy is almost consistent with the virgin deuterium-deuterium neutron energy evaluated by the simple two-body kinematic calculation

Characterization of Liquid Scintillator-Based CNES for Deuterium–Deuterium Neutron Emission Spectroscopy in the LHD

ORCID　0000-0002-0160-0468The compact neutron emission spectrometers (CNESs) based on conventional liquid (EJ-301) scintillation detectors were characterized in this work. The CNESs were employed for deuterium–deuterium neutron emission spectroscopy in the Large Helical Device (LHD). Prior to the installation, the EJ-301 scintillation detectors were characterized at the Fast Neutron Laboratory (FNL) of Tohoku University. In order to discriminate the neutron and γ -ray signals, the charge comparison method was used. The neutron energy spectrum was successfully unfolded from the measured recoil proton energy spectrum of the EJ-301 scintillation detector using the derivative unfolding technique. The detector’s energy resolution was examined. In the LHD, EJ-301-based CNESs with both tangential and perpendicular line-of-sight were employed for characterization. Furthermore, the characterization of the CNES was performed in the deuterium–deuterium experiment campaign. The operational capabilities of CNESs in the LHD were examined. Deuterium–deuterium neutron emission spectroscopy in various approaches of neutral beam (NB)-heated plasmas was conducted using CNES. Because of the high energy of the injected fast ions from tangential NB injection, an investigation of the Doppler effect on deuterium–deuterium neutron energy was conducted. The upper and lower shifted deuterium–deuterium neutron energies were observed when the fast ions moved toward and away from the tangential CNES, respectively. As expected, no notable energy shift was observed from fast ions injected by the perpendicular NB injection. Additionally, the 5-D orbit following code DELTA5D, which takes into account Larmor motion effects and the detector’s energy resolution, was utilized to compute the expected deuterium–deuterium neutron energy spectrum that would be measured by the CNES. There was a concurrence between the calculations and experimental results

Effects of d-alanine Intake on Amino Acid Metabolism and Kidney Function in Healthy Adults: A Multicenter, Randomized Pilot Study

Background: d-alanine administration prevented kidney damage in a murine acute kidney injury model. Further data are needed on the influence of d-alanine on kidney function in humans. Objective: This study investigated the effects of d-alanine intake on amino acid metabolism and kidney function in healthy volunteers. Methods: This multicenter pilot study randomly assigned individuals from the general Japanese population to receive 3 g or 6 g of d-alanine intake per day for 7 d in a 1:1 ratio. The primary endpoint was the mean change in plasma and urine d-alanine levels from baseline to 7 d after intake. The secondary endpoints were mean changes in kidney function and other clinical factors. Safety was assessed by evaluating adverse events and clinical parameters. Results: We randomly assigned 24 participants to the 3-g (n = 12) and 6-g d-alanine (n = 12) groups. The mean baseline estimated glomerular filtration rate (eGFR) was 73 mL/min/1.73 m2. The mean plasma d-alanine concentration increased from baseline by 77.5 ± 34.3 and 192.1 ± 80.9 nmol/mL in the 3-g and 6-g d-alanine groups (both p < 0.0001), respectively, in a dose-dependent manner (between-group difference: 114.6 nmol/mL; 95% CI: 62.1–167.2; P = 0.0002). A similar increase was observed for the urine d-alanine to creatinine ratio. The mean eGFR was elevated by 5.7 ± 8.8 mL/min/1.73 m2 in the 6-g d-alanine group (P = 0.045) but did not significantly change in the 3-g d-alanine group. Nonserious adverse events were reported in 11 participants. Conclusions: d-alanine intake increased plasma and urine d-alanine levels and was well tolerated in participants with normal kidney function. These results will be useful in future trials investigating the effects of d-alanine intake on kidney disease progression in patients with chronic kidney disease.This trial was registered at the UMIN Clinical Trials Registry as UMIN000051466