Hearing the Voice of Medical Students Worldwide

The Student Forum, a new section of PLoS Medicine, is a space where medical students from across the world can exchange ideas about the critical issues affecting health and health care from their unique perspectiv

Tailored second line therapy in asthmatic children with the arginine-16 genotype

The arginine-16 beta-2 receptor genotype confers increased susceptibility to exacerbations in asthmatic children taking regular long acting beta-2 agonists. We therefore evaluated using montelukast as an alternative to salmeterol as tailored second line asthma controller therapy in children expressing this susceptible genotype. 62 persistent asthmatic children with the homozygous arginine-16 genotype were randomized to receive salmeterol 50ug bid or montelukast 5/10mg od as add on to inhaled fluticasone for 1 year. School absences (the primary outcome) were reduced with montelukast arm compared to salmeterol: difference in score = 0.40 (95%CI 0.07-0.87) p=0.005. Albuterol use was also reduced with montelukast compared with salmeterol: difference in score = 0.47 (95%CI 0.16-0.79) p<0.0001. Greater improvements occurred in both symptom and quality of life scores with montelukast vs salmeterol, while there was no difference in FEV1. Montelukast may be suitable as tailored second line controller therapy instead of salmeterol in asthmatic children expressing the susceptible arginine-16 genotype - moving towards a personalised medicine approach to management

Measuring human rights abuse from access to information requests

Existing measures of human rights abuses are often only available at the country-year level. Several more fine-grained measures exhibit spatio-temporal inaccuracies or reporting biases due to the primary sources upon which they rely. To address these challenges, and to increase the diversity of available human rights measures more generally, this study provides the first quantitative effort to measure human rights abuses from textual records of citizen-government interactions. Using a dataset encompassing over 1.5 million access-to-information (ATI) requests made to the Mexican federal government from June 2003 onward, supervised classification is used to identify the subset of these requests that pertain to human rights abuses of various types. The results from this supervised machine learning exercise are validated against (i) gold standard ATI requests pertaining to past human rights abuses in Mexico and (ii) several accepted external measures of sub-national and sub-annual human rights abuses. In doing so, we demonstrate that the measurement of human rights abuses from citizen-submitted ATI request texts can provide measures of human rights abuse that exhibit both high validity and notable spatio-temporal specificity, relative to existent human rights datasets and variables

Biotransformation of fluorophenyl pyridine carboxylic acids by the model fungus Cunninghamella elegans

1. Fluorine plays a key role in the design of new drugs and recent FDA approvals included two fluorinated drugs, tedizolid phosphate and vorapaxar, both of which contain the fluorophenyl pyridyl moiety. 2. To investigate the likely phase-I (oxidative) metabolic fate of this group, various fluorinated phenyl pyridine carboxylic acids were incubated with the fungus Cunninghamella elegans, which is an established model of mammalian drug metabolism. 3. 19F NMR spectroscopy established the degree of biotransformation, which varied depending on the position of fluorine substitution, and gas chromatography–mass spectrometry (GC–MS) identified alcohols and hydroxylated carboxylic acids as metabolites. The hydroxylated metabolites were further structurally characterised by nuclear magnetic resonance spectroscopy (NMR), which demonstrated that hydroxylation occurred on the 4′ position; fluorine in that position blocked the hydroxylation. 4. The fluorophenyl pyridine carboxylic acids were not biotransformed by rat liver microsomes and this was a consequence of inhibitory action, and thus, the fungal model was crucial in obtaining metabolites to establish the mechanism of catabolism

Increased yields and simplified purification with a second-generation cobalt catalyst for the oxidative formation of trans-THF rings.

The synthesis of a second-generation cobalt catalyst for the formation of trans-THF products via the Mukaiyama aerobic oxidative cyclization is reported. Two procedures have been developed with the new water-soluble catalyst that give superior yields and greatly simplify purification compared to the previous catalysts

Oxidative cyclization of tertiary pentenol derivatives forming 2,5,5-trisubstituted THF rings and the total synthesis of cyclocapitelline

The synthesis of 2,5,5-trisubstituted tetrahydrofuran rings was accomplished via the Mukaiyama aerobic oxidative cyclization of tertiary 5-pentenols employing the Co(nmp)2catalyst. A variety of THFs were formed in moderate to good yield and diastereoselectivity. The method developed herein was successfully applied to an enantioselective total synthesis of cyclocapitelline