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.     

Comparative study of perturbations of peripheral markers in different stressors in rats

Stress has been implicated in the etiopathogenesis of several diseases. In the present study, the effects of acute (AS), chronic (CS), and chronic unpredictable stress (CUS) were studied on the ulcer index, adrenal gland mass, and biochemical and hormonal changes in rats. The stress was provided in the form of immobilization-immobilization for 150 min, once only, and for 10 consecutive days in CS and CUS. In CUS, animals received variable unpredictable stressors. Immediately after stress, animals were decapitated, blood was collected, and plasma was separated for the estimation of plasma glucose, triglyceride, cholesterol, creatine kinase (CK), corticosterone, and insulin. The adrenal gland and stomach were also dissected for mass and ulcer scoring, respectively. AS significantly increased the ulcer index, plasma glucose, CK, corticosterone, and insulin. CS and CUS significantly increased the ulcer index, adrenal gland mass, and corticosterone. In CS, a significant decrease in plasma triglyceride and cholesterol levels was found, but in CUS only cholesterol was decreased significantly. High CK activity and hyperglycemia maintain the energy demands of metabolism, and elevated corticosterone desensitizes the insulin receptor in AS. In CS and CUS, prolonged elevation of corticosterone shifts metabolism to utilization of lipids as a secondary substrate by gluconeogenesis. From our experiment, it is clear that AS causes maximum activation of energy metabolism, which becomes specific after habituation in prolonged CS. These biochemical manipulations in the body by using different types of stressors are good markers that can be of great use to understand, target, and manage stress-induced etiologies.     

Biologically synthesized fluorescent CdS NPs encapsulated by PHB

Here an attempt was made to biologically synthesize fluorescent cadmium sulfide nanoparticles and to immobilize the synthesized nanoparticles in PHB nanoparticles. The present study uses Brevibacterium casei SRKP2 as a potential producer for the green synthesis of CdS nanoparticles. Biologically synthesized nanoparticles were characterized and confirmed using electron microscopy and XRD. The size distribution of the nanoparticles was found to be 10-30 nm followed by which the consequence of time, growth of the organism, pH, concentration of CdCl(2) and Na(2)S on the synthesis of nanoparticles were checked. Enhanced synthesis and fluorescence emission of CdS nanoparticles were achieved at pH 9. The synthesized CdS NPs were immobilized with PHB and were characterized. The fluorescent intensity of the CdS nanoparticles remained unaffected even after immobilization within PHB nanoparticles.     

Effects of linoleic acid on capping,lectin mediated mitogenesis,surface antigen expression,and fluorescent polarization in lymphocytes and BHK cells

The incubation of linoleic acid with cells causes profound effects on membrane associated phenomenon. Using the fluorescent probe diphenyl hexatriene (DPH) to monitor lipid changes in the microenvironment of the cell surface, we find that linoleic acid reduces the polarization values (P) in mouse lymphocytes and BHK cells. Measurements on lipids extracted from the cells grown in linoleic acid produce similar results. We also find in the mouse lymphocyte that capping of Ig is inhibited and con A stimulated mitogenesis is unaffected. In contrast to the latter effect, LPS and PHA stimulated mitogenesis is inhibited and in the rat lymph node, con A stimulated mitogenesis, greatly enhanced. We also show that linoleic acid alters the binding of antibodies to the cell surface of EL-4 lymphoma cells. These observations suggest that linoleic acid alters cellular function by interfering with protein/lipid interactions within the surface membrane.     

Real-Time Analysis and Visualization for Single-Molecule Based Super-Resolution Microscopy

Accurate multidimensional localization of isolated fluorescent emitters is a time consuming process in single-molecule based super-resolution microscopy. We demonstrate a functional method for real-time reconstruction with automatic feedback control, without compromising the localization accuracy. Compatible with high frame rates of EM-CCD cameras, it relies on a wavelet segmentation algorithm, together with a mix of CPU/GPU implementation. A combination with Gaussian fitting allows direct access to 3D localization. Automatic feedback control ensures optimal molecule density throughout the acquisition process. With this method, we significantly improve the efficiency and feasibility of localization-based super-resolution microscopy.     

Unexpected equivalent potency of a constrained chromene enantiomeric pair rationalized by co-crystal structures in complex with estrogen receptor alpha

Despite tremendous progress made in the understanding of the ERα signaling pathway and the approval of many therapeutic agents, ER+?breast cancer continues to be a leading cause of cancer death in women. We set out to discover compounds with a dual mechanism of action in which they not only compete with estradiol for binding with ERα, but also can induce the degradation of the ERα protein itself. We were attracted to the constrained chromenes containing a tetracyclic benzopyranobenzoxepine scaffold, which were reported as potent selective estrogen receptor modulators (SERMs). Incorporation of a fluoromethyl azetidine side chain yielded highly potent and efficacious selective estrogen receptor degraders (SERDs), such as 16aa and surprisingly, also its enantiomeric pair 16ab. Co-crystal structures of the enantiomeric pair 16aa and 16ab in complex with ERα revealed default (mimics the A-D rings of endogenous ligand estradiol) and core-flipped binding modes, rationalizing the equivalent potency observed for these enantiomers in the ERα degradation and MCF-7 anti-proliferation assays.     

Skimmed Milk-Based Encapsulation for Enhanced Stability and Viability of Lactobacillus gastricus BTM 7 Under Simulated Gastrointestinal Conditions

Probiotics and Antimicrobial Proteins - The present study investigated skimmed milk and alginate-based encapsulation for protection of a probiotic strain, Lactobacillus gastricus BTM7 during...