Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration. NCT02958709

Microbial eukaryotes in an arctic under-ice spring bloom north of Svalbard

Microbial eukaryotes can play prominent roles in the Arctic marine ecosystem, but their diversity and variability is not well known in the ice-covered ecosystems. We determined the community composition of microbial eukaryotes in an Arctic under-ice spring bloom north of Svalbard using metabarcoding of DNA and RNA from the hypervariable V4 region of 18S nrDNA. At the two stations studied, the photosynthetic biomass was dominated by protists >3 μm and was concentrated in the upper 70–80 m, above the thermocline and halocline. Hierarchical cluster analyses as well as ordination analyses showed a distinct clustering of the microbial eukaryote communities according to a combination of water mass and local environmental characteristics. While samples collected in the surface mixed layer differed distinctly between the two sites, the deeper communities collected in Atlantic Water were fairly similar despite being geographically distant. The differentiation of the microbial eukaryote communities of the upper mixed water was probably driven by local development and advection, while the lack of such differentiation in the communities of Atlantic Water reflects the homogenizing effect of water currents on microbial communities

An exploration of physiological, medicinal and safety aspects of Guduchi (Tinospora cordifolia): A complete Ayurvedic and modern review

Introduction: Tinospora cordifolia commonly known as “Amrita” or “Guduchi” is an important drug of Indian systems of medicine (ISM) and used in medicines since times immemorial. Guduchi is a Sanskrit word which means that ‘which protects body from diseases’. Another name for this herb is ‘Amrita’, which refers to the heavenly elixir according to Hindu mythology. The drug is well known Indian bitter and prescribed in fevers, diabetes, dyspepsia, jaundice, urinary problems, skin diseases and chronic diarrhoea and dysentery. It has been also indicated useful in the treatment of heart diseases, leprosy, helminthiasis and rheumatoid arthritis. It is an important drug and is used in form of different preparations like Satva, Ghrita, Tail, Swarasa etc. Material &amp; Methods: For this review article Charaka Samhita, Sushruta Samhita, Ashtanga Hridaya, Ashtanga Sangraha, Bhavprakash Nighantu, Raj Nighantu, Dhanvantari Nighantu, Shaligrama Nighantu, Priya Nighantu, Kaiydev Nighantu, Madanpal Nighantu, Shodhal Nighantu, internet and modern medical literature have been reviewed. Result: The Tinospora cordifolia plant had been appreciated to having high levels for medicinal, therapeutical, curative, healing and relieving nature. Discussion: Guduchi has high therapeutic potential by its anti-toxic, anti-inflammatory, anti-pyretic and anti-oxidant properties. There is also no evidence that Guduchi has any toxic content or side effects, which proves its safety aspect as well. Conclusion: The therapeutic and safety aspects studies reported in the present review confirm the medicinal properties of herb Tinospora cordifolia (Giloy) in preventing various diseases or abnormalities by increasing immunity naturally in human bodies