In Vitro and In Vivo Antibacterial Activities of a Novel Quinolone Compound, OPS-2071, against Clostridioides difficile.

OPS-2071 is a novel quinolone antibacterial agent characterized by low oral absorption that reduces the risk of adverse events typical of fluoroquinolone class antibiotics. The in vitro and in vivo antibacterial activities of OPS-2071 against Clostridioides difficile were evaluated in comparison to vancomycin and fidaxomicin. OPS-2071 exhibited potent antibacterial activity against 54 clinically isolated C. difficile strains with a MIC of 0.125 µg/ml (MIC50) and 0.5 µg/ml (MIC90), making it more active than vancomycin on a concentration basis (MIC50, 2 µg/ml; MIC90, 4 µg/ml) and comparable to fidaxomicin (MIC50, 0.063 µg/ml; MIC90, 8 µg/ml). OPS-2071 showed equally potent antibacterial activity against both hypervirulent and nonhypervirulent strains, while a significant difference in susceptibility to fidaxomicin was observed. Spontaneous resistance to OPS-2071 and vancomycin was not observed; however, resistance to fidaxomicin was observed at 4× MIC. The mutant prevention concentration of OPS-2071 was 16-fold lower than those of fidaxomicin and vancomycin, and the postantibiotic effect of OPS-2071 was longer than those of fidaxomicin and vancomycin. Also, OPS-2071 showed low systemic exposure, with OPS-2071 having 2.9% oral bioavailability at 1 mg/kg in rats. Furthermore, OPS-2071 showed significant in vivo efficacy at 0.0313 mg/kg/day (50% effective doses), 39.0-fold and 52.1-fold lower than those of vancomycin and fidaxomicin, respectively, in a hamster model of C. difficile infection. OPS-2071 has the potential to become a new therapeutic option for treating C. difficile infection.

Nutrition leadership training in North-East Asia: an IUNS initiative in conjunction with nutrition societies in the region.

Food for humans is one of the most important of all global issues. It is a critical determinant of planetary and individual health, of economic development, of how sustainable energy and water supplies are, and its security a powerful determinant of peace or conflict. Those who assume leadership for the integrity of food and health systems have great responsibility. The IUNS (International Union of Nutritional Sciences), regional and national nutrition science and food technology organizations have concern about the leadership capacity available and required in what are rapidly changing and increasingly demanding circumstances. These include persistent poverty and hunger, climate change which threatens the sustainability of food production and fragile financial systems which are making food less affordable for many. North East Asia (NEA) is a major region for its population size, its economic wealth and disparities, its food production, its life expectancies among the best and its global reach. In 2008, for those of Chinese ancestry and of wider Asian origin, Nutrition Leadership training has been conducted in Hangzhou, Shanghai, Seoul and Taiwan (Hsinchu and Zhunan). Ninety prospective young leaders participated in all. Several successful early career Asian nutrition scientists and professionals served as role models. Senior colleagues acted as mentors for groups of 2 or 3. With mentors, the concept of leadership has been examined, careers and roles explored, knowledge and skills honed for a different future, and plans made to network in mutual support. Early feedback indicates that new opportunities have been created and seized.

Generation of synthetic equivalents of benzdiynes from benzobisoxadisiloles.

Linear and angular benzobisoxadisiloles 14 and 16 can serve as the precursors for stepwise generations of the syntetic equivalents of 1,4- and 1,3-benzdiynes. Benzynes generated were trapped as [4+2] cycloaddition products. Two identical or different rings can be fused to the benzdiyne equivalents. Highly substituted arenes were obtained by removing the oxygen bridges from the furan adducts. The synthesis of naphthoxadisilole 28, which can serve as the precursor of 2,3-naphthyne, is also described.