Sulfur-mediated annulation of 1,2-phenylenediamines towards benzofuro- and benzothieno-quinoxalines.

We report a method for condensation between ortho-phenylenediamines and ortho-hydroxyacetophenones to afford benzofuroquinoxalines. The reactions proceeded in the presence of an elemental sulfur mediator, DABCO base, and DMSO solvent. Functionalities such as nitrile, ester, and halogen groups were compatible. The conditions could be applicable for the synthesis of benzothienoquinoxalines from ortho-chloroacetophenones.

Copper-catalyzed one-pot domino reactions via C-H bond activation: synthesis of 3-aroylquinolines from 2-aminobenzylalcohols and propiophenones under metal-organic framework catalysis.

A Cu2(OBA)2(BPY) metal-organic framework was utilized as a productive heterogeneous catalyst for the synthesis of 3-aroylquinolines via one-pot domino reactions of 2-aminobenzylalcohols with propiophenones. This Cu-MOF was considerably more active towards the one-pot domino reaction than a series of transition metal salts, as well as nano oxide and MOF-based catalysts. The MOF-based catalyst was reusable without a significant decline in catalytic efficiency. To the best of our knowledge, the transformation of 2-aminobenzylalcohols to 3-aroylquinolines was not previously reported in the literature, and this protocol would be complementary to previous strategies for the synthesis of these valuable heterocycles.

A Model for Osteonecrosis of the Jaw with Zoledronate Treatment following Repeated Major Trauma.

This study aims to develop a reproducible rat model for post-traumatic bisphosphonate-related osteonecrosis of the jaw (BRONJ). In our previous studies using dental extraction as an inducing factor, only 30%-60% of zoledronate-treated animals fulfilled the definition of clinical BRONJ. We modified the zoledronate regimen and introduced repeated surgical extraction to illicit quantifiable BRONJ in all animals. Eighty retired-breeder female Sprague-Dawley rats were divided between the treatment (i.v. zoledronate; 80 µg/kg/week for 13 weeks) and control (saline) groups. On week 13, the left mandibular first molar was surgically extracted, followed by the second molar a week later. Animals were euthanized at 1-week, 2-weeks, and 8-weeks following extraction. The occurrence and severity of BRONJ were scored in each animal based on gross and MicroCT analysis. Parameters of bone formation and osteoclast functions at the extraction site were compared between groups. All zoledronate-treated animals developed a severe case of BRONJ that fulfilled the clinical definition of the condition in humans. Osteoclast attachment continued to be defective eight weeks after stopping the treatment. There were no signs of kidney or liver toxicity. Our data confirmed that repeated surgical extraction (major trauma) by itself consistently precipitated massive bone necrosis in ZA-treated animals, eliminating the need to induce pre-existing infection or comorbidity. These results will be the basis for further studies examining the in-vivo pathogenesis and prevention of BRONJ.

Virological characterization of influenza H1N1pdm09 in Vietnam, 2010-2013.

OBJECTIVES: Influenza A/H1N1pdm09 virus was first detected in Vietnam on May 31, 2009, and continues to circulate in Vietnam as a seasonal influenza virus. This study has monitored genotypic and phenotypic changes in this group of viruses during 2010-2013 period. DESIGN AND SETTING: We sequenced hemagglutinin (HA) and neuraminidase (NA) genes from representative influenza A/H1N1pdm09 and compared with vaccine strain A/California/07/09 and other contemporary isolates from neighboring countries. Hemagglutination inhibition (HI) and neuraminidase inhibition (NAI) assays also were performed on these isolates. SAMPLE: Representative influenza A/H1N1pdm09 isolates (n = 61) from ILI and SARI surveillances in northern Vietnam between 2010 and 2013. MAIN OUTCOME MEASURES AND RESULTS: The HA and NA phylogenies revealed six and seven groups, respectively. Five isolates (8·2%) had substitutions G155E and N156K in the HA, which were associated with reduced HI titers by antiserum raised against the vaccine virus A/California/07/2009. One isolate from 2011 and one isolate from 2013 had a predicted H275Y substitution in the neuraminidase molecule, which was associated with reduced susceptibility to oseltamivir in a NAI assay. We also identified a D222N change in the HA of a virus isolated from a fatal case in 2013. CONCLUSIONS: Significant genotypic and phenotypic changes in A/ H1N1pdm09 influenza viruses were detected by the National Influenza Surveillance System (NISS) in Vietnam between 2010 and 2013 highlighting the value of this system to Vietnam and to the region. Sustained NISS and continued virological monitoring of seasonal influenza viruses are required for vaccine policy development in Vietnam. 3.