Oil-in-water emulsion lotion providing controlled release using 2-methacryloyloxyethyl phosphorylcholine n-butyl methacrylate copolymer as emulsifier

AbstractLotion is a useful vehicle for active ingredients used to treat skin disease because it can be applied to the scalp, can cover large areas of skin, and it is easy to spread due to low viscosity. An emulsion lotion (EL) containing 2-methacryloyloxyethyl phosphorylcholine n-butyl methacrylate copolymer (PMB) as an emulsifier that provides controlled-release was developed. Diphenhydramine (DPH) was used as a model drug. Formulation with 5% DPH, 5% soybean oil, and 4% PMB in water was emulsified using a high-pressure homogenizer. Polysorbate 80 (TO) was used instead of PMB for comparison. They were applied in vitro to Yucatan micropig intact or stripped skin at a practical dose (2μL/cm2). For stripped skin, penetration of DPH from 4% PMB EL was slower than that from 1% TO EL; results for intact skin were similar. The same phenomenon was observed with application to rabbit skin in vivo. When 4% PMB EL dried on the skin, it made a thin film matrix incorporating the oil phase, which controlled the release of DPH. The release rate could be controlled by the ratio of oil phase to PMB. The EL with PMB shows promise as a vehicle for long-acting treatment of skin diseases

The Japanese space gravitational wave antenna; DECIGO

DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future Japanese space gravitational wave antenna. DECIGO is expected to open a new window of observation for gravitational wave astronomy especially between 0.1 Hz and 10 Hz, revealing various mysteries of the universe such as dark energy, formation mechanism of supermassive black holes, and inflation of the universe. The pre-conceptual design of DECIGO consists of three drag-free spacecraft, whose relative displacements are measured by a differential Fabry– Perot Michelson interferometer. We plan to launch two missions, DECIGO pathfinder and pre- DECIGO first and finally DECIGO in 2024

Sequential therapies after atezolizumab plus bevacizumab or lenvatinib first-line treatments in hepatocellular carcinoma patients

Introduction: The aim of this retrospective proof-of-concept study was to compare different second-line treatments for patients with hepatocellular carcinoma and progressive disease (PD) after first-line lenvatinib or atezolizumab plus bevacizumab.Materials and methods: A total of 1381 patients had PD at first-line therapy. 917 patients received lenvatinib as first-line treatment, and 464 patients atezolizumab plus bevacizumab as first-line.Results: 49.6% of PD patients received a second-line therapy without any statistical difference in overall survival (OS) between lenvatinib (20.6 months) and atezolizumab plus bev-acizumab first-line (15.7 months; p = 0.12; hazard ratio [HR] = 0.80). After lenvatinib first-line, there wasn't any statistical difference between second-line therapy subgroups (p = 0.27; sorafenib HR: 1; immunotherapy HR: 0.69; other therapies HR: 0.85). Patients who under-went trans-arterial chemo-embolization (TACE) had a significative longer OS than patients who received sorafenib (24.7 versus 15.8 months, p < 0.01; HR = 0.64). After atezolizumab plus bevacizumab first-line, there was a statistical difference between second-line therapy subgroups (p < 0.01; sorafenib HR: 1; lenvatinib HR: 0.50; cabozantinib HR: 1.29; other therapies HR: 0.54). Patients who received lenvatinib (17.0 months) and those who under-went TACE (15.9 months) had a significative longer OS than patients treated with sorafenib (14.2 months; respectively, p = 0.01; HR = 0.45, and p < 0.05; HR = 0.46).Conclusion: Approximately half of patients receiving first-line lenvatinib or atezolizumab plus bevacizumab access second-line treatment. Our data suggest that in patients progressed to atezolizumab plus bevacizumab, the systemic therapy able to achieve the longest survival is lenvatinib, while in patients progressed to lenvatinib, the systemic therapy able to achieve the longest survival is immunotherapy

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Intramural hematoma appearing as a new lesion after coronary stenting

Case study - A 51-year-old man with hypertension and hyperlipidemia presented with exertional chest pain and underwent a stress echocardiogram that showed anterior and lateral ischemia

First Experiment of Spin Contrast Variation Small-Angle Neutron Scattering on the iMATERIA Instrument at J-PARC

Recently, we have developed a novel dynamic nuclear polarization (DNP) apparatus with a magnetic field of 7 T and a sample temperature of 1 K. High proton spin polarizations from −84% to 76%, for TEMPO doped polystyrene samples, have been demonstrated. This DNP apparatus satisfies the simultaneous requirement for quick and easy sample exchange and high DNP performance. On the iMATERIA (BL20) instrument at J-PARC, the first beam experiment using this DNP apparatus has been performed. For this experiment, the beamline was equipped with a supermirror polarizer. The stray magnetic field due to the superconducting magnet for DNP was also evaluated. The stray magnetic field plays an important role for in maintaining the neutron polarization during the transportation from the polarizer to the sample. The small-angle neutron scattering (SANS) profiles of silica-filled rubber under dynamically polarized conditions are presented. By applying our new analytical approach for SANS coherent scattering intensity, neutron polarization (PN) as a function of neutron wavelength was determined. Consequently, for the neutron wavelength, range from 4 Å to 10 Å, |PN| was sufficient for DNP-SANS studies