Urban-Rural Disparity of Generics Prescription in Taiwan: The Example of Dihydropyridine Derivatives

The aim of the current study was to investigate the urban-rural disparity of prescribing generics, which were usually cheaper than branded drugs, within the universal health insurance system in Taiwan. Data sources were the cohort datasets of National Health Insurance Research Database with claims data in 2010. The generic prescribing ratios of dihydropyridine (DHP) derivatives (the proportion of DHP prescribed as generics to all prescribed DHP) of medical facilities were examined against the urbanization levels of the clinic location. Among the total 21,606,914 defined daily doses of DHP, 35.7% belonged to generics. The aggregate generic prescribing ratio rose from 6.7% at academic medical centers to 15.3% at regional hospitals, 29.4% at community hospital, and 66.1% at physician clinics. Among physician clinics, the generic prescribing ratio in urban areas was 63.9 ± 41.0% (mean ± standard deviation), lower than that in suburban (69.6 ± 38.7%) and in rural (74.1% ± 35.3%). After adjusting the related factors in the linear regression model, generic prescribing ratios of suburban and rural clinics were significantly higher than those of urban clinics (β=0.043 and 0.077; P=0.024 and 0.008, resp.). The generic prescribing ratio of the most popular antihypertensive agents at a clinic was reversely associated with the urbanization level

Mechanism for controlling the monomer-dimer conversion of SARS coronavirus main protease

[[incitationindex]]SCI[[booktype]]紙

Ultrasound sonication with microbubbles disrupts blood vessels and enhances tumor treatments of anticancer nanodrug

Ultrasound (US) sonication with microbubbles (MBs) has the potential to disrupt blood vessels and enhance the delivery of drugs into the sonicated tissues. In this study, mouse ear tumors were employed to investigate the therapeutic effects of US, MBs, and pegylated liposomal doxorubicin (PLD) on tumors. Tumors started to receive treatments when they grew up to about 15 mm3 (early stage) with injection of PLD 10 mg/kg, or up to 50 mm3 (medium stage) with PLD 6 (or 4) mg/kg. Experiments included the control, PLD alone, PLD + MBs + US, US alone, and MBs + US groups. The procedure for the PLD + MBs + US group was that PLD was injected first, MB (SonoVue) injection followed, and then US was immediately sonicated on the tumor. The results showed that: (1) US sonication with MBs was always able to produce a further hindrance to tumor growth for both early and medium-stage tumors; (2) for the medium-stage tumors, 6 mg/kg PLD alone was able to inhibit their growth, while it did not work for 4 mg/kg PLD alone; (3) with the application of MBs + US, 4 mg/kg PLD was able to inhibit the growth of medium-stage tumors; (4) for early stage tumors after the first treatment with a high dose of PLD alone (10 mg/kg), the tumor size still increased for several days and then decreased (a biphasic pattern); (5) MBs + US alone was able to hinder the growth of early stage tumors, but unable to hinder that of medium stage tumors. The results of histological examinations and blood perfusion measurements indicated that the application of MBs + US disrupts the tumor blood vessels and enhances the delivery of PLD into tumors to significantly inhibit tumor growth

Mechanism for controlling the monomer–dimer conversion of SARS coronavirus main protease

[[abstract]]The Severe acute respiratory syndrome coronavirus (SARS-CoV) main protease (Mpro) cleaves two virion polyproteins (pp1a and pp1ab); this essential process represents an attractive target for the development of anti-SARS drugs. The functional unit of Mpro is a homodimer and each subunit contains a His41/Cys145 catalytic dyad. Large amounts of biochemical and structural information are available on Mpro; nevertheless, the mechanism by which monomeric Mpro is converted into a dimer during maturation still remains poorly understood. Previous studies have suggested that a C-terminal residue, Arg298, interacts with Ser123 of the other monomer in the dimer, and mutation of Arg298 results in a monomeric structure with a collapsed substrate-binding pocket. Interestingly, the R298A mutant of Mpro shows a reversible substrate-induced dimerization that is essential for catalysis. Here, the conformational change that occurs during substrate-induced dimerization is delineated by X-ray crystallography. A dimer with a mutual orientation of the monomers that differs from that of the wild-type protease is present in the asymmetric unit. The presence of a complete substrate-binding pocket and oxyanion hole in both protomers suggests that they are both catalytically active, while the two domain IIIs show minor reorganization. This structural information offers valuable insights into the molecular mechanism associated with substrate-induced dimerization and has important implications with respect to the maturation of the enzyme.[[notice]]補正完畢[[incitationindex]]SCI[[booktype]]電子

Momentum space imaging of Cooper pairing in a half-Dirac-gas topological superconductor (a helical 2D topological superconductor)

Superconductivity in Dirac electrons has recently been proposed as a new platform between novel concepts in high-energy and condensed matter physics. It has been proposed that supersymmetry and exotic quasiparticles, both of which remain elusive in particle physics, may be realized as emergent particles in superconducting Dirac electron systems. Using artificially fabricated topological insulator-superconductor heterostructures, we present direct spectroscopic evidence for the existence of Cooper pairing in a half Dirac gas 2D topological superconductor. Our studies reveal that superconductivity in a helical Dirac gas is distinctly different from that of in an ordinary two-dimensional superconductor while considering the spin degrees of freedom of electrons. We further show that the pairing of Dirac electrons can be suppressed by time-reversal symmetry breaking impurities removing the distinction. Our demonstration and momentum-space imaging of Cooper pairing in a half Dirac gas and its magnetic behavior taken together serve as a critically important 2D topological superconductor platform for future testing of novel fundamental physics predictions such as emergent supersymmetry and quantum criticality in topological systems.Comment: Submitted June'14; Accepted to NaturePhysics, to appear AOP (2014