Shorter treatment for minimal tuberculosis (TB) in children (SHINE): A study protocol for a randomised controlled trial

BACKGROUND: Tuberculosis (TB) in children is frequently paucibacillary and non-severe forms of pulmonary TB are common. Evidence for tuberculosis treatment in children is largely extrapolated from adult studies. Trials in adults with smear-negative tuberculosis suggest that treatment can be effectively shortened from 6 to 4 months. New paediatric, fixed-dose combination anti-tuberculosis treatments have recently been introduced in many countries, making the implementation of World Health Organisation (WHO)-revised dosing recommendations feasible. The safety and efficacy of these higher drug doses has not been systematically assessed in large studies in children, and the pharmacokinetics across children representing the range of weights and ages should be confirmed. METHODS/DESIGN: SHINE is a multicentre, open-label, parallel-group, non-inferiority, randomised controlled, two-arm trial comparing a 4-month vs the standard 6-month regimen using revised WHO paediatric anti-tuberculosis drug doses. We aim to recruit 1200 African and Indian children aged below 16 years with non-severe TB, with or without HIV infection. The primary efficacy and safety endpoints are TB disease-free survival 72 weeks post randomisation and grade 3 or 4 adverse events. Nested pharmacokinetic studies will evaluate anti-tuberculosis drug concentrations, providing model-based predictions for optimal dosing, and measure antiretroviral exposures in order to describe the drug-drug interactions in a subset of HIV-infected children. Socioeconomic analyses will evaluate the cost-effectiveness of the intervention and social science studies will further explore the acceptability and palatability of these new paediatric drug formulations. DISCUSSION: Although recent trials of TB treatment-shortening in adults with sputum-positivity have not been successful, the question has never been addressed in children, who have mainly paucibacillary, non-severe smear-negative disease. SHINE should inform whether treatment-shortening of drug-susceptible TB in children, regardless of HIV status, is efficacious and safe. The trial will also fill existing gaps in knowledge on dosing and acceptability of new anti-tuberculosis formulations and commonly used HIV drugs in settings with a high burden of TB. A positive result from this trial could simplify and shorten treatment, improve adherence and be cost-saving for many children with TB. Recruitment to the SHINE trial begun in July 2016; results are expected in 2020

Homozygous staggerer (sg/sg) mice display improved insulin sensitivity and enhanced glucose uptake in skeletal muscle

Homozygous staggerer (sg/sg) mice, which have decreased and dysfunctional Ror alpha (also known as Rora) expression in all tissues, display a lean and dyslipidaemic phenotype. They are also resistant to (high fat) diet-induced obesity. We explored whether retinoic acid receptor-related orphan receptor (ROR) alpha action in skeletal muscle was involved in the regulation of glucose metabolism

Potential therapeutic applications of microbial surface-activecompounds

Numerous investigations of microbial surface-active compounds or biosurfactants over the past two decades have led to the discovery of many interesting physicochemical and biological properties including antimicrobial, anti-biofilm and therapeutic among many other pharmaceutical and medical applications. Microbial control and inhibition strategies involving the use of antibiotics are becoming continually challenged due to the emergence of resistant strains mostly embedded within biofilm formations that are difficult to eradicate. Different aspects of antimicrobial and anti-biofilm control are becoming issues of increasing importance in clinical, hygiene, therapeutic and other applications. Biosurfactants research has resulted in increasing interest into their ability to inhibit microbial activity and disperse microbial biofilms in addition to being mostly nontoxic and stable at extremes conditions. Some biosurfactants are now in use in clinical, food and environmental fields, whilst others remain under investigation and development. The dispersal properties of biosurfactants have been shown to rival that of conventional inhibitory agents against bacterial, fungal and yeast biofilms as well as viral membrane structures. This presents them as potential candidates for future uses in new generations of antimicrobial agents or as adjuvants to other antibiotics and use as preservatives for microbial suppression and eradication strategies

Bioflocculation of high-ash Indian coals using Paenibacillus polymyxa

Most Indian coals have high ash content of the order of 25-35%. High ash in the coal not only reduces the thermal value of coal but also leads to production of fly ash, which is a major environmental problem. Cleaning with gravity concentration techniques is ineffective and more efficient techniques need to be developed. In recent times, bioflocculation as an alternative preparation method has been reported for a number of mineral systems including high-sulfur coals. In this paper, bioflocculation of high-ash Indian coals has been studied using Paenibacillus polymyxa for two coal samples. A quartz sample was used for comparison purposes. Zeta-potential measurements showed that coal samples and the bacterium were negatively charged over most of the pH range with a point-of-zero-charge (PZC) around pH 2-3 Surface free energy, determined through contact angle measurements, showed that the coal samples were hydrophobic while the bacterium was hydrophilic. Among the coal samples, the coal with the lower ash content exhibited greater hydrophobicity. Adhesion tests revealed that adhesion took place in about 25 min and that maximum adhesion occurred around pH 2. Similarly, flocculation tests showed that the bacterium flocculated coal effectively and efficiently with the best results around pH 2. More than 90% of the coal flocculated in about a minute in the presence of the bacterium while compared to about 20-30% in the absence of the bacterium. Flocculation of quartz was retarded under the same conditions, indicating that it is dispersed. Ash analysis of the flocculated portion showed a decrease in ash by 60% thereby suggesting that selective flocculation of coal is possible

The effect of nature of raw coal on the adhesion of bacteria to coal surface

The surface properties of coal and solution pH play a major role in determining the adhesion of microorganisms. In this study, three Indian coal samples with different compositions have been used and the adhesion of the bacterium Bacillus polymyxa to these coals has been investigated. It was found that due to the high ash content of coal, the zeta-potential was negative over most of the pH range which is close to the values exhibited by pure quartz as well as B. polymyxa. Similarly, the surface free energy components of coal (derived from contact angle measurements) showed that the electron-donor component increased with ash content. Adhesion experiments revealed that maximum adhesion of the bacterium B. polymyxa occurred on to the coal samples around the point-of-zero-charge of the coal and the bacterium i.e. about pH 2. Further, adhesion was found to be dependent on the ash content and the surface free energy of the coals. (C) 2002 Published by Elsevier Science Ltd

Role of interfacial phenomena in determining adsorption of Bacillus polymyxa onto hematite and quartz

Utility of microorganisms as surface modifiers in flotation and flocculation has generated great interest in recent times. The surface properties of the minerals and the microorganisms such as zeta-potential ($\zeta$-potential) and hydrophobicity play a major role in determining adsorption of the microorganisms to the minerals and hence the efficiency of flocculation and flotation. These properties are also dependent on the solution conditions such as pH and ionic strength. In the present investigation, the role of ionic strength and pH in determining the surface properties and hence adsorption of the bacterium Bacillus polymyxa to hematite and quartz has been studied in detail. Results indicate that increasing the ionic strength changes the $\zeta$-potential of hematite and the bacterium without changing the point-of-zero-charge (PZC). Contact angle measurements showed that hematite was the most hydrophobic when compared with both quartz and the bacterium. Adsorption tests demonstrated that conditioning time, pH and ionic strength are all important in controlling adsorption of B. polymyxa on to both quartz and hematite. Adsorption of bacteria on to hematite was more compared with quartz. Flocculation tests demonstrated that in the presence of bacteria and electrolyte, hematite settled very rapidly in the pH range of 2–8. However, quartz settled much slower under the same indicating that the quartz particles are being dispersed. Thus selective flocculation of hematite can be used effectively in separating hematite from quartz. Interaction energies calculated using the extended DLVO theory were found to be in good agreement with the adsorption and flocculation tests

The utility of Bacillus subtilis as a bioflocculant for fine coal

The application of Bacillus subtilis as a flocculant for fine coal has been reported here. Zeta-potential measurements showed that both the coal and bacteria had similar surface charge as a function of pH. Surface free energy calculations showed that the coal was hydrophobic while the bacterium was hydrophilic. The adhesion of the bacteria to coal and subsequent settling was studied in detail. Adhesion of bacteria to coal surface and subsequent settling of coal was found to be quick. Both adhesion and settling were found to be independent of pH, which makes the process very attractive for field applications. The presence of an electrolyte along with the bacterium was found to not only enhance adhesion of bacteria, but also produce a clear supernatant. Further, the settled fraction was more compact than with bacteria alone. Interaction energy calculations using the extended DLVO theory showed that the electrical forces along with the acid-base interaction energy play a dominant role in the lower pH range. Above pH 7, the acid-base interaction energy is the predominant attractive force and is sufficient enough to overcome the repulsive forces due to electrical charges to brine about adhesion and thus settling of fine coal. With increase in electrolyte concentration, the change in total interaction energy with pH is minimal which probably leads to better adhesion and hence settling. (C) 2003 Elsevier Science B.V. All rights reserved

Removal of As(V) by adsorption onto mixed rare earth oxides

Arsenic pollution of water is a major problem faced worldwide. Arsenic is a suspected carcinogen in human beings and is harmful to other living beings. In the present study, a novel adsorbent was used to remove arsenate [As(V)] from synthetic solutions. The adsorbent, which is a mixture of rare earth oxides, was found to adsorb As(V) rapidly and effectively. The effect of various parameters such as contact time, initial concentration, pH, and adsorbent dose on adsorption efficiency was investigated. More than 90% of the adsorption occurred within the first 10 min and the kinetic rate constant was found to be about 3.5 mg min(-1). Adsorption efficiency was found to be dependent on the initial As(V) concentration, and the adsorption behavior followed the Langmuir adsorption model. The optimum pH was found to be 6.5. The presence of other ions such as nitrate, phosphate, sulphate, and silicate decreased the adsorption of As(V) by about 20-30%. The adsorbed As(V) could be desorbed easily by washing the adsorbent with pH 12 solution. This study demonstrates the applicability of naturally occurring rare earth oxides as selective adsorbents for As(V) from solutions