Aggregation of magnetic nanoparticles in biological solvents evaluated by HTS-SQUID magnetic immunoassay system

Magnetic nanoparticles (MNPs) have been studied for various medical applications by taking advantage of their unique magnetic properties. Magnetic immunoassay (MIA) is a technique for the rapid detection of target biomarkers by antigen-antibody reaction between antibody-modified MNPs and the target biomarker. In this study, we aim to improve the accuracy of the MIA, we evaluated the AC magnetic properties of MNPs in the biological solvents. To measure the magnetic signal of MNPs, we used the developed HTS-SQUID magnetic immunoassay system. First, we evaluated the instability of the HTS-SQUID magnetic immunoassay system using pellets of manganese (II) fluoride. The results show that the device instability due to operating time does not affect the measurement of magnetic signal changes in MNPs due to biological solvents. Since the magnetic properties of MNPs depend on particle size and viscosity, we measured the time evolution of the magnetic signal of Resovist in glycerin, human serum, sheep whole blood, and NaCl. It was found that the magnetic signal of Resovist decreased exponentially with ions contained in the solvent. The results are fitted as the exponential double function, suggesting that the magnetic signal of MNPs in biological solvents is affected by the aggregation of MNPs in the blood and that there are at least two steps in the mechanism of the aggregation

Plasma S100A12 Levels and Peripheral Arterial Disease in End-Stage Renal Disease

Background: S100A12 is an endogenous ligand of the receptor for advanced glycation end products (RAGE). Plasma S100A12 levels are high in end-stage renal disease (ESRD) patients undergoing maintenance hemodialysis (HD). Peripheral arterial disease (PAD) is common in HD patients and is associated with increased cardiovascular morbidity and mortality rates in this population. To date, however, no study has specifically assessed the relationship between plasma S100A12 and PAD in HD patients. Methods: We conducted a cross-sectional study of 152 HD patients in our affiliated hospital. We investigated PAD history and patient characteristics and quantified plasma S100A12 levels in all participants. Results: HD patients with PAD (n = 26; 21.9 [13.6–33.4] ng/ml) showed significantly higher plasma S100A12 levels than HD patients without PAD (n = 126; 11.8 [7.5–17.6]ng/ml; p Conclusion: These results suggest that plasma S100A12 levels are strongly associated with PAD prevalence in ESRD patients undergoing HD

Protocol for a prospective multicentre registry cohort study on suicide attempters given the assertive case management intervention after admission to an emergency department in Japan: post-ACTION-J Study (PACS)

Introduction Suicide attempt is the most important risk factor for later suicide. A randomised-controlled, multicentre trial of postsuicide attempt case management for the prevention of further suicide attempts in Japan, named ACTION-J, has established effective interventions for prevention of suicide reattempts. The ACTION-J assertive case management intervention programme was adopted by the Japanese Ministry of Health, Labour and Welfare in 2016, when medical fees were revised. This nationwide programme is provided to patients who attempt suicide and who are admitted to emergency departments in Japan.The aim of the present study is to examine the current implementation status of the ACTION-J programme. The present study also aims to clarify which patients’ and hospitals’ factors affect the implementation of the programme.Methods and analysis This is a prospective, multicentre, patient registry cohort study. Participants will be suicide attempters admitted to the emergency departments of medical facilities with both psychiatry and emergency departments. The assertive case management programme will be delivered to participants by a case manager for up to 24 weeks, based on psychiatric diagnoses, social risks and patient needs. The core feature of the programme is to encourage patients to participate in psychiatric treatment.The primary outcome will be the proportion of patients still participating in the case management intervention at 24 weeks after registration. The secondary outcomes will include measures of the fidelity of the case management intervention. The fidelity will be evaluated using a fidelity assessment manual developed by the study group.Ethics and dissemination This observational study has been approved by the ethics board of Sapporo Medical University. Enrolment began in October 2016 and will continue until December 2018. Dissemination plans include presentations at scientific conferences and scientific publications

Transition from Positive to Neutral in Mutation Fixation along with Continuing Rising Fitness in Thermal Adaptive Evolution

It remains to be determined experimentally whether increasing fitness is related to positive selection, while stationary fitness is related to neutral evolution. Long-term laboratory evolution in Escherichia coli was performed under conditions of thermal stress under defined laboratory conditions. The complete cell growth data showed common continuous fitness recovery to every 2°C or 4°C stepwise temperature upshift, finally resulting in an evolved E. coli strain with an improved upper temperature limit as high as 45.9°C after 523 days of serial transfer, equivalent to 7,560 generations, in minimal medium. Two-phase fitness dynamics, a rapid growth recovery phase followed by a gradual increasing growth phase, was clearly observed at diverse temperatures throughout the entire evolutionary process. Whole-genome sequence analysis revealed the transition from positive to neutral in mutation fixation, accompanied with a considerable escalation of spontaneous substitution rate in the late fitness recovery phase. It suggested that continually increasing fitness not always resulted in the reduction of genetic diversity due to the sequential takeovers by fit mutants, but caused the accumulation of a considerable number of mutations that facilitated the neutral evolution

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Comparative anatomic and electron microscopic study of specific granules of heart atrial muscle

Specific granules of heart atrial muscle obtained from mammals (mouse, rat, rabbit, dog, pig, ox and monkey), aves (chicken), reptiles (Geoclemmys), amphibia (Rana), pisces (carp, goldfish and shark) and cyclostomata (Entosphenus) were investigated by electron microscope and the following results were obtained. The mean diameter of the specific granules was large in rat (315 nm) and mouse (283 nm), medium in rabbit (260 nm) and pig (210 nm) and small in dog and ox (170 nm) and monkey (175 nm) among mammals. The core of these granules was electron-translucent in rat and mouse and electron-dense in rabbit. The atria of rat and mouse had a large number of granules while that of monkey showed a fairly large number of granules. The dog showed a small number of granules and the granules of ungulate (pig and ox) were sparse. Granules in vertebrates other than mammals were relatively smaller than in mammals. The mean diameter was 144 nm in chicken, 175 nm in Geoclemmys, 150 nm in Rana and carp and 168 nm in Entosphenus. The atria of Geoclemmys and Rana had a large number of granules while that of Entosphenus also had a fairly large number of granules. Shark only showed a small number of granules and the granules of chicken, carp and goldfish were sparse. Electron microscopic study of specific granules in rat heart atrial muscle showed that there were two types of granules. One (Type I) had a homogenous and electron-dense core and the other (Type II) was electron-translucent and consisted of small granular materials. Both were enclosed by a limiting membrane. Type II were distributed near the Golgi apparatus present at the perinuclear area of the muscle cell while Type I were widely distributed in sarcoplasm at the perinuclear area, between myofibrils and beneath the cell membrane of the cell. From the results, the process of the formation, maturation and release of specific granules of heart atrial muscle was discussed

Comparative anatomic and electron microscopic study of specific granules of heart atrial muscle

Specific granules of heart atrial muscle obtained from mammals (mouse, rat, rabbit, dog, pig, ox and monkey), aves (chicken), reptiles (Geoclemmys), amphibia (Rana), pisces (carp, goldfish and shark) and cyclostomata (Entosphenus) were investigated by electron microscope and the following results were obtained. The mean diameter of the specific granules was large in rat (315 nm) and mouse (283 nm), medium in rabbit (260 nm) and pig (210 nm) and small in dog and ox (170 nm) and monkey (175 nm) among mammals. The core of these granules was electron-translucent in rat and mouse and electron-dense in rabbit. The atria of rat and mouse had a large number of granules while that of monkey showed a fairly large number of granules. The dog showed a small number of granules and the granules of ungulate (pig and ox) were sparse. Granules in vertebrates other than mammals were relatively smaller than in mammals. The mean diameter was 144 nm in chicken, 175 nm in Geoclemmys, 150 nm in Rana and carp and 168 nm in Entosphenus. The atria of Geoclemmys and Rana had a large number of granules while that of Entosphenus also had a fairly large number of granules. Shark only showed a small number of granules and the granules of chicken, carp and goldfish were sparse. Electron microscopic study of specific granules in rat heart atrial muscle showed that there were two types of granules. One (Type I) had a homogenous and electron-dense core and the other (Type II) was electron-translucent and consisted of small granular materials. Both were enclosed by a limiting membrane. Type II were distributed near the Golgi apparatus present at the perinuclear area of the muscle cell while Type I were widely distributed in sarcoplasm at the perinuclear area, between myofibrils and beneath the cell membrane of the cell. From the results, the process of the formation, maturation and release of specific granules of heart atrial muscle was discussed