TB Treatment Delays in Odisha,India: Is It Expected Even after These Many Years of RNTCP Implementation?

Background

In India, the Revised National TB Control Programme (RNTCP) envisages initiation of TB treatment within seven days of diagnosis among smear-positive patients. After nearly two decades of RNTCP implementation, treatment delays are usually not expected.

Objectives

To determine the proportion of sputum smear-positive TB patients who were initiated on treatment after seven days and their associated risk factors.

Methods

The study was conducted in Cuttack and Rayagada districts of Odisha. It was a retrospective cohort study that involves review of TB treatment registers and laboratory registers for 2013.

Results

Among 1,800 pulmonary TB (PTB) patients, 1,074 (60%) had been initiated on treatment within seven days of diagnosis, 721 (40%) had been initiated on treatment more than seven days, and 354 (20%) had delays of more than 15 days. The mean duration between TB diagnosis and treatment initiation was 21 days with a range of 8–207 days (median = 14 days). Odds of treatment delay of more than seven days were 4.9 times (95% confidence interval [CI] 3.3-6.6) among those who had been previously treated, 6.2 times (95% CI 1.3-29.7) among those infected with HIV, and 1.8 times (95% CI 1.1-2.9) among those diagnosed outside district DMC.

Conclusion

Delay in initiation of TB treatment occurred in majority of the smear-positive patients. The RNTCP should focus on core areas of providing quality TB services with time-tested strategies. To have real-time monitoring mechanisms for diagnosed smear-positive TB patients is expected to be the way forward.     

Stereochemistry–activity relationship of orally active tetralin S1P agonist prodrugs

Modifying FTY720, an immunosuppressant modulator, led to a new series of well phosphorylated tetralin analogs as potent S1P1 receptor agonists. The stereochemistry effect of tetralin ring was probed, and (?)-(R)-2-amino-2-((S)-6-octyl-1,2,3,4-tetrahydronaphthalen-2-yl)propan-1-ol was identified as a good SphK2 substrate and potent S1P1 agonist with good oral bioavailability.     

Synthesis of alkyne derivatives of a novel triazolopyrazine as A(2A) adenosine receptor antagonists

A novel [1,2,4]triazolo[1,5-a]pyrazine core was synthesized and coupled with terminal acetylenes. The structure-activity relationship of the alkynes from this novel template was studied for their in vitro and in vivo adenosine A(2A) receptor antagonism. Selected compounds from this series were shown to have potent in vitro and in vivo activities against adenosine A(2A) receptor. Compound 12, in particular, was found to be orally active at 3mg/kg in both a mouse catalepsy model and a 6-hydroxydopamine-lesioned rat model.     

Comet Assay measurements: a perspective

The Comet Assay or single cell gel electrophoresis assay is one of the very widely used assays to microscopically detect DNA damage at the level of a single cell. The determination of damage is carried out either through visual scoring of cells (after classification into different categories on the basis of tail length and shape) or by using different commercially available or public domain software (which automatically recognise the extent of damage). In this assay, the shape, size and amount of DNA within the ‘comet’ play important roles in the determination of the level of damage. The use of a software in particular also provides a range of different parameters, many of which might not be relevant in determining the extent of DNA damage. As a large number of factors could influence the shape, size, identification and determination of induced damage, which includes the scoring criteria, staining techniques, selection of parameters (whilst using the software packages) and appearance of ‘hedgehog’ or ‘clouds’, this article aims (a) to provide an overview of evolution of measurements of DNA damage using the Comet Assay and (b) to summarise and critically analyse the advantages and disadvantages of different approaches currently being adopted whilst using this assay. It is suggested that judicious selection of different parameters, staining methods along with inter-laboratory validation and harmonisation of methodologies will further help in making this assay more robust and widely acceptable for scientific as well as regulatory studies.     

Heterologous signals allow efficient targeting of a nuclear-encoded fusion protein to plastids and endoplasmic reticulum in diverse plant species

Approximately 30% of plant nuclear genes appear to encode proteins targeted to the plastids or endoplasmic reticulum (ER). The signals that direct proteins into these compartments are diverse in sequence, but, on the basis of a limited number of tests in heterologous systems, they appear to be functionally conserved across species. To further test the generality of this conclusion, we tested the ability of two plastid transit peptides and an ER signal peptide to target green fluorescent protein (GFP) in 12 crops, including three monocots (barley, sugarcane, wheat) and nine dicots ( Arabidopsis , broccoli, cabbage, carrot, cauliflower, lettuce, radish, tobacco, turnip). In all species, transient assays following microprojectile bombardment or vacuum infiltration using Agrobacterium showed that the plastid transit peptides from tomato DCL (defective chloroplast and leaves) and tobacco RbcS [ribulose bisphosphate carboxylase (Rubisco) small subunit] genes were effective in targeting GFP to the leaf plastids. GFP engineered as a fusion to the N-terminal ER signal peptide from Arabidopsis basic chitinase and a C-terminal HDEL signal for protein retention in the ER was accumulated in the ER of all species. The results in tobacco were confirmed in stably transformed cells. These signal sequences should be useful to direct proteins to the plastid stroma or ER lumen in diverse plant species of biotechnological interest for the accumulation of particular recombinant proteins or for the modification of particular metabolic streams.     

Robust clustering analysis for the management of self-monitoring distributed systems

We present a decentralized algorithm for online clustering analysis used for anomaly detection in self-monitoring distributed systems. In particular, we demonstrate the monitoring of a network of printing devices that can perform the analysis without the use of external computing resources (i.e. in-network analysis). We also show how to ensure the robustness of the algorithm, in terms of anomaly detection accuracy, in the face of failures of the network infrastructure on which the algorithm runs. Further, we evaluate the tradeoff in terms of overhead necessary for ensuring this robustness and present a method to reduce this overhead while maintaining the detection accuracy of the algorithm.

Early Exposure to Ethylene Modifies Shoot Development and Increases Sucrose Accumulation Rate in Sugarcane

Sugarcane varieties (Saccharum spp. hybrids) that accumulate high levels of sucrose at the start of the harvest season are of considerable commercial interest. Our understanding of the factors that contribute to early sucrose accumulation in these varieties is limited. In this study we used the plant hormone ethylene to investigate the relationship between growth and early sucrose accumulation in sugarcane. The sugarcane variety KQ228 was exposed to a low concentration of the ethylene-forming compound 2-chloroethylphosphonic acid (CEPA) for a prolonged duration commencing from shoot emergence. The changes in sucrose accumulation and plant growth were investigated. Results from two glasshouse experiments revealed that the CEPA-treated plants accumulated a significantly higher amount of sucrose in their primary culm 2 and 3½ months post-germination. The treated plants had taller primary culms with many smaller internodes, smaller leaves, and a higher photosynthetic rate. Despite producing smaller internodes, treated culms were comparable in fresh weight and volume to the controls due to the compensating effect of faster internode formation. We identified three factors that may have contributed to the early accumulation of more sucrose in the treated culm: (1) the specific leaf area of young leaves was greater indicating efficient diversion of photoassimilate to sink tissue, (2) internode formation was initiated earlier, and (3) internodes continued to form at a faster rate. Consequently, a greater proportion of the internodes in the treated sugarcane matured earlier and began filling with sucrose sooner. The higher reducing sugar level in the apical region of the culm probably contributed to faster internode development. This coincided with elevated vacuolar and cell wall acid invertase gene expression that increased sucrose turnover in the vacuole and increased apoplastic uptake of reducing sugars. These findings extend our understanding of how some sugarcane varieties can naturally accumulate a high level of sucrose early in the season.