No abstract

Adjunctive dexamethasone reduces mortality from tuberculous meningitis (TBM) but not disability, which is associated with brain infarction. We hypothesised that aspirin prevents TBM-related brain infarction through its anti-thrombotic, anti-inflammatory, and pro-resolution properties. We conducted a randomised controlled trial in HIV-uninfected adults with TBM of daily aspirin 81 mg or 1000 mg, or placebo, added to the first 60 days of anti-tuberculosis drugs and dexamethasone (NCT02237365). The primary safety endpoint was gastro-intestinal or cerebral bleeding by 60 days; the primary efficacy endpoint was new brain infarction confirmed by magnetic resonance imaging or death by 60 days. Secondary endpoints included 8-month survival and neuro-disability; the number of grade 3 and 4 and serious adverse events; and cerebrospinal fluid (CSF) inflammatory lipid mediator profiles. 41 participants were randomised to placebo, 39 to aspirin 81 mg/day, and 40 to aspirin 1000 mg/day between October 2014 and May 2016. TBM was proven microbiologically in 92/120 (76.7%) and baseline brain imaging revealed ≥1 infarct in 40/114 (35.1%) participants. The primary safety outcome occurred in 5/36 (13.9%) given placebo, and in 8/35 (22.9%) and 8/40 (20.0%) given 81 mg and 1000 mg aspirin, respectively (p=0.59). The primary efficacy outcome occurred in 11/38 (28.9%) given placebo, 8/36 (22.2%) given aspirin 81 mg, and 6/38 (15.8%) given 1000 mg aspirin (p=0.40). Planned subgroup analysis showed a significant interaction between aspirin treatment effect and diagnostic category (Pheterogeneity = 0.01) and suggested a potential reduction in new infarcts and deaths by day 60 in the aspirin treated participants with microbiologically confirmed TBM (11/32 (34.4%) events in placebo vs. 4/27 (14.8%) in aspirin 81 mg vs. 3/28 (10.7%) in aspirin 1000 mg; p=0.06). CSF analysis demonstrated aspirin dose-dependent inhibition of thromboxane A2 and upregulation of pro-resolving CSF protectins. The addition of aspirin to dexamethasone may improve outcomes from TBM and warrants investigation in a large phase 3 trial.

Dengue is a viral disease for which there is currently no therapeutic agent. We investigated the potential of lovastatin in the treatment of dengue. Lovastatin was safe and well tolerated, but did not demonstrate a therapeutic benefit.

Graphitic carbon nitride (g-C3N4) nanosheets were exfoliated from bulk g-C3N4 and utilized to improve the sensing performance of a pure graphene sensor for the first time. The role of hydrochloric acid treatment on the exfoliation result was carefully examined. The exfoliated products were characterized by X-ray diffraction (XRD) patterns, scanning electron microscopy (SEM), atomic force microscopy (AFM), and UV-Vis spectroscopy. The exfoliated g-C3N4 nanosheets exhibited a uniform thickness of about 3–5 nm and a lateral size of about 1–2 µm. A g-C3N4/graphene nanocomposite was prepared via a self-assembly process and was demonstrated to be a promising sensing material for detecting nitrogen dioxide gas at room temperature. The nanocomposite sensor exhibited better recovery as well as two-times the response compared to pure graphene sensor. The detailed sensing mechanism was then proposed.