Experimental model for irradiating a restricted region of the rat brain using heavy-ion beams

Heavy-ion beams have the feature to administer a large radiation dose in the vicinity of the endpoint in the beam range, its irradiation system and biophysical characteristics are different from ordinary irradiation instruments like X-rays or gamma-rays. In order to get clarify characteristic effects of heavy-ion beams on the brain, we have developed an experimental system for irradiating a restricted region of the rat brain using heavy-ion beams. The left cerebral hemispheres of the adult rat brain were irradiated at dose of 50Gy charged carbon particles (290MeV/nucleon 5mmspread-out Bragg peak). After irradiation, the characteristics of the heavy-ion beams and the animal model were studied. Histological examination and measurement showed that extensive necrosis was observed between 2.5mmand7.5mmdepth from the surface of the rat head, suggesting a relatively high dose and uniform dose was delivered among designed depths and the spread-out bragg peak used here successfully and satisfactorily retained its high-dose localization in the defined region. We believe that our experimental model for irradiating a restricted region of the rat brain using heavy-ion beams is a good model for analyzing regional radiation susceptibility of the brain

Prevalence and predictors of direct discharge home following hospitalization of patients with serious adverse events managed by the rapid response system in Japan: a multicenter, retrospective, observational study

Aim: The rapid response system (RRS) is an in-hospital medical safety system. To date, not much is known about patient disposition after RRS activation, especially discharge home. This study aimed to investigate the prevalence, characteristics, and outcomes of patients with adverse events who required RRS activation. Methods: Retrospective data from the In-Hospital Emergency Registry in Japan collected from April 2016 to November 2020 were eligible for our analysis. We divided patients into Home Discharge, Transfer, and Death groups. The primary outcome was the prevalence of direct discharge home, and independently associated factors were determined using multivariable logistic regression. Results: We enrolled 2,043 patients who met the inclusion criteria. The prevalence of discharge home was 45.7%; 934 patients were included in the Home Discharge group. Age (adjusted odds ratio [AOR] 0.96; 95% confidence interval [CI], 0.95-0.97), malignancy (AOR 0.69; 95% CI, 0.48-0.99), oxygen administration before RRS (AOR 0.49; 95% CI, 0.36-0.66), cerebral performance category score on admission (AOR 0.38; 95% CI, 0.26-0.56), do not attempt resuscitation order before RRS (AOR 0.17; 95% CI, 0.10-0.29), RRS call for respiratory failure (AOR 0.50; 95% CI, 0.34-0.72), RRS call for stroke (AOR 0.12; 95% CI, 0.03-0.37), and intubation (AOR 0.20; 95% CI, 0.12-0.34) were independently negative, and RRS call for anaphylaxis (AOR 15.3; 95% CI, 2.72-86.3) was positively associated with discharge home. Conclusion: Less than half of the in-hospital patients under RRS activation could discharge home. Patients' conditions before RRS activation, disorders requiring RRS activation, and intubation were factors that affected direct discharge home

Diverse Cell Populations Involved in Regeneration of Renal Tubular Epithelium following Acute Kidney Injury

Renal tubular epithelium has the capacity to regenerate, repair, and reepithelialize in response to a variety of insults. Previous studies with several kidney injury models demonstrated that various growth factors, transcription factors, and extracellular matrices are involved in this process. Surviving tubular cells actively proliferate, migrate, and differentiate in the kidney regeneration process after injury, and some cells express putative stem cell markers or possess stem cell properties. Using fate mapping techniques, bone marrow-derived cells and endothelial progenitor cells have been shown to transdifferentiate into tubular components in vivo or ex vivo. Similarly, it has been demonstrated that, during tubular cell regeneration, several inflammatory cell populations migrate, assemble around tubular cells, and interact with tubular cells during the repair of tubular epithelium. In this review, we describe recent advances in understanding the regeneration mechanisms of renal tubules, particularly the characteristics of various cell populations contributing to tubular regeneration, and highlight the targets for the development of regenerative medicine for treating kidney diseases in humans

Histological and elemental changes in the rat brain after local irradiation with carbon ion beams

The left cerebral hemispheres of adult Sprague-Dawley rat brains were irradiated at doses of 30, 50, or 100 Gy with changed carbon particles (290 MeV/nucleon; 5 mm spread-out Bragg peak). The spread-out Bragg peak used here successfully and satisfactorily retained its high-dose localization in the defined region. A histological examination showed that necrotic tissue damage, hemorrhage in the thalamus, and vasodilatations around the necrotic region were induced at 8 weeks after 100 Gy irradiation. The regions with tissue damage correlated well with those expected from the radiation-dose distribution, indicating an advantage of charged carbon particles for irradiating restricted brain regions. An X-ray fluorescent analysis demonstrated a decrease in the concentrations of K and P, and an increase in the concentrations of Cl, Fe, Zn in the damaged region at 8 weeks post-irradiation, though no significant changes were observed before 4 weeks of post-irradiation. This may indicate that even the very high radiation doses used here did not induce acute and immediate neuronal cell death, in contrast with ischemic brain injury were acute neuronal cell death occurred and the elemental concentrations changed within a day after the induction of ischemia

Serum Thrombomodulin in Myeloperoxidase-Antineutrophil Cytoplasmic Antibody (MPO-ANCA)-Associated Vasculitis.

Background and Aims : Although serum or plasma thrombomodulin (TM) was reported to be increased in various diseases with vascular injuries, blood TM was also shown to be influenced by renal function. In this study, we determined whether serum TM (sTM) could be a marker of vascular injury in patients with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis, in which kidneys are often affected. Methods : Thirteen patients with MPO-ANCA-associated vasculitis were investigated and 43 patients with chronic glomerulonephritis (CGN) served as a control. sTM was measured by one-step sandwich enzyme immunoassay method. Results : A significant positive correlation was found between sTM and serum creatinine (sCr) (sTM=2.24×sCr+2.16, r=0.91, P<0.001) in patients with CGN. In order to correct sTM for renal function, we calculated corrected sTM according to the following formula : corrected sTM (%)=[measured sTM/expected sTM at the measured sCr]×100=[sTM/(2.24×sCr+2.16)]×100. Patients with MPO-ANCA-associated vasculitis tended to have lower levels of corrected sTM before treatment compared to patients with CGN, but not significantly (86.8±23.2% vs. 98.7±18.3%, ANCA vs. CGN, P=0.12). Corrected sTM was increased significantly within 1 month after the beginning of treatment (145.7±46.9%, P=0.008, vs. before treatment in each patient). In remission, corrected sTM returned to the same levels of CGN (104.5±38.6%, P=0.03, vs. within 1 month in each patient). Conclusions : These results showed that sTM corrected for renal function does not simply reflect disease activity in MPO-ANCA-associated vasculitis