Outcome of Tuberculosis Treatment in Patients with Diabetes Mellitus Treated in the Revised National Tuberculosis Control Programme in Malappuram District,Kerala, India

Settings

Kerala State, India has reported the greatest dual burden of Tuberculosis (TB) and Diabetes Mellitus (DM). Malappuram district in Kerala has monitored and recorded DM status and its control from 2010 under Revised National Tuberculosis Control Program (RNTCP).

Objectives

To assess, under programme conditions, comprehensiveness of recording DM status among TB cases and the TB treatment outcomes among DM patients (disaggregated by glycemic control) and compare with-non DM patients.

Design

This retrospective record review included 3,116TB patients from April 2010 to September 2011.DM was defined as per international guidelines and TB treatment outcomes were categorized as favourable(cured and treatment completed) and unfavourable(death, default, failure and transfer out). Relative Risk (RR) and 95% confidence intervals(CI) were calculated to assess the risk of unfavourable outcomes.

Results

DM status was recorded in 90% of TB cases and 667 (24%) had DM. 17% of DM patients and 23% of patients with unknown DM status had unfavourable outcomes but this difference was not statistically significant. Unadjusted RR for poor glycemic control or unknown control status for unfavourable outcome were (2.00; 95% CI 0.97–4.13) and (2.14; 95% CI 1.11–4.13).

Conclusion

This study could not confirm an adverse association between DM or its control during treatment and the course of response to TB treatment.DM screening in TB cases and recording of DM care needs to be improved to enable more conclusive evidence.     

Virulence factors and<Emphasis Type="Italic">in Vitro</Emphasis> adherence of<Emphasis Type="Italic">Enterococcus</Emphasis> strains to urinary catheters

The ability to adhere in vitro to urinary catheters and the presence of enterococcal virulence factors was determined in 30 Enterococcus urinary isolates (12 E. faecalis, 12 E. faecium, 3 E. casseliflavus, 3 E. gallinarum). Silicone, siliconized latex and polyvinyl chloride (PVC) were examined by sonication quantitative culture technique and scanning electron microscope. As compared to E. faecalis and E. faecium, E. casseliflavus and E. gallinarum displayed lower adhesion to all synthetic materials. All the tests performed showed higher adherence of all tested strains to siliconized latex and silicone than to PVC. Biofilmforming ability was observed in 5 E. faecalis but in none of the remaining strains. The gene coding enterococcal surface protein (Esp) was detected in 7 E. faecalis and 6 E. faecium strains. Gelatinase was found in 1 E. faecalis, 2 E. faecium and hemolysins were found in 6 E. faecalis and 1 E. faecium strains. All E. casseliflavus and E. gallinarum strainswere negative for these traits. Hydrophobic type of cell surface (measured by its affinity for n-hexadecane) was shown in a few isolates. Bacterial adherence was not significantly associated with the above pathogenic factors.     

Formulation and evaluation of ketorolac tromethamine-loaded albumin microspheres for potential intramuscular administration

The objective of this work was to prepare and evaluate ketorolac tromethamine-loaded albumin microspheres using a factorial design. Albumin microspheres were prepared by emulsion cross-linking method. Selected formulations were characterized for their entrapment efficiency, particle size, surface morphology, and release behavior. Analysis of variance (ANOVA) for entrapment efficiency indicated that entrapment efficiency is best fitted to a response surface linear model. From the statistical analysis it was observed that as the drug:polymer (D∶P) ratio and volume of glutaraldehyde increased, there was a significant increase in the encapsulation efficiency. Scanning electron microscopy of the microspheres revealed a spherical, nonporous and uniform appearance, with a smooth surface. Based on the entrapment efficiency and physical appearance, 9 formulations were selected for release study. The maximum particle size observed was below 40 μm. The release pattern was biphasic, characterized by an initial burst effect followed by a slow release. All selected microspheres, except those having less polymer proportion (D∶P ratio is 1∶1), exhibited a prolonged release for almost 24 hours. On comparingr ² values for Higuchi and Peppas kinetic models, different batches of microspheres showed Fickian, non-Fickian, and diffusion kinetics. The release mechanism was regulated by D∶P ratio and amount of cross-linking agent. From the experimental data obtained with respect to particle size and extent of drug relaase, it could be concluded that the prepared microspheres are useful for once-a-day intramuscular administration of ketorolac tromethamine. Published: February 23, 2007     

Analysis of optimal phenotypic space using elementary modes as applied to Corynebacterium glutamicum

Background  

Quantification of the metabolic network of an organism offers insights into possible ways of developing mutant strain for better productivity of an extracellular metabolite. The first step in this quantification is the enumeration of stoichiometries of all reactions occurring in a metabolic network. The structural details of the network in combination with experimentally observed accumulation rates of external metabolites can yield flux distribution at steady state. One such methodology for quantification is the use of elementary modes, which are minimal set of enzymes connecting external metabolites. Here, we have used a linear objective function subject to elementary modes as constraint to determine the fluxes in the metabolic network of Corynebacterium glutamicum. The feasible phenotypic space was evaluated at various combinations of oxygen and ammonia uptake rates.     

A simulation model of <Emphasis Type="Italic">Escherichia coli</Emphasis> osmoregulatory switch using E-CELL system

Background  

Bacterial signal transduction mechanism referred to as a "two component regulatory systems" contributes to the overall adaptability of the bacteria by regulating the gene expression. Osmoregulation is one of the well-studied two component regulatory systems comprising of the sensor, EnvZ and the cognate response regulator, OmpR, which together control the expression of OmpC and OmpF porins in response to the osmolyte concentration.     

A steady state analysis indicates that negative feedback regulation of PTP1B by Akt elicits bistability in insulin-stimulated GLUT4 translocation

Background  

The phenomenon of switch-like response to graded input signal is the theme involved in various signaling pathways in living systems. Positive feedback loops or double negative feedback loops embedded with nonlinearity exhibit these switch-like bistable responses. Such feedback regulations exist in insulin signaling pathway as well.     

Quantification of the glycogen cascade system: the ultrasensitive responses of liver glycogen synthase and muscle phosphorylase are due to distinctive regulatory designs

Background

Signaling pathways include intricate networks of reversible covalent modification cycles. Such multicyclic enzyme cascades amplify the input stimulus, cause integration of multiple signals and exhibit sensitive output responses. Regulation of glycogen synthase and phosphorylase by reversible covalent modification cycles exemplifies signal transduction by enzyme cascades. Although this system for regulating glycogen synthesis and breakdown appears similar in all tissues, subtle differences have been identified. For example, phosphatase-1, a dephosphorylating enzyme of the system, is regulated quite differently in muscle and liver. Do these small differences in regulatory architecture affect the overall performance of the glycogen cascade in a specific tissue? We address this question by analyzing the regulatory structure of the glycogen cascade system in liver and muscle cells at steady state.

Results

The glycogen cascade system in liver and muscle cells was analyzed at steady state and the results were compared with literature data. We found that the cascade system exhibits highly sensitive switch-like responses to changes in cyclic AMP concentration and the outputs are surprisingly different in the two tissues. In muscle, glycogen phosphorylase is more sensitive than glycogen synthase to cyclic AMP, while the opposite is observed in liver. Furthermore, when the liver undergoes a transition from starved to fed-state, the futile cycle of simultaneous glycogen synthesis and degradation switches to reciprocal regulation. Under such a transition, different proportions of active glycogen synthase and phosphorylase can coexist due to the varying inhibition of glycogen-synthase phosphatase by active phosphorylase.

Conclusion

The highly sensitive responses of glycogen synthase in liver and phosphorylase in muscle to primary stimuli can be attributed to distinctive regulatory designs in the glycogen cascade system. The different sensitivities of these two enzymes may exemplify the adaptive strategies employed by liver and muscle cells to meet specific cellular demands.

     

Detailed protein sequence alignment based on Spectral Similarity Score (SSS)

Background  

The chemical property and biological function of a protein is a direct consequence of its primary structure. Several algorithms have been developed which determine alignment and similarity of primary protein sequences. However, character based similarity cannot provide insight into the structural aspects of a protein. We present a method based on spectral similarity to compare subsequences of amino acids that behave similarly but are not aligned well by considering amino acids as mere characters. This approach finds a similarity score between sequences based on any given attribute, like hydrophobicity of amino acids, on the basis of spectral information after partial conversion to the frequency domain.     

Possible rheumatoid arthritis subtypes in terms of rheumatoid factor,depression, diagnostic delay and emotional expression: an exploratory case-control study

Introduction

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathology of rheumatoid arthritis (RA), particularly as vulnerable personality types are exposed to chronic stress. Emotions are powerful modulators of stress responses. However, little is known about whether patients with RA process emotions differently to matched controls. In this study we: 1) assessed whether the trait emotional intelligence (trait EI) scores of patients with RA differ from healthy controls at the facet level; 2) explored any subgroups in RA, in terms of trait EI and common risk factors.

Methods

A total of 637 patients with RA were compared to 496 controls on the trait EI Questionnaire (TEIQue). RA subgroups were explored in terms of trait EI, rheumatoid factor status (RF+/-), depression and time from onset of symptoms until diagnosis (diagnostic delay).

Results

The RA group rated themselves lower on Adaptability, Stress-management, Emotion management, Self-esteem, Sociability, Assertiveness, Impulsiveness and Well-being, and higher on Empathy and Relationships than healthy controls. The RF- subtype reported more time with depression (25.2 vs. 11.3 months), a longer diagnostic delay (3.0 vs. 1.7 years), and greater emotional expression (5.15 vs. 4.72), than the RF+ subtype. These differences were significant at the P <0.05 level, but not following strict Bonferroni corrections and should therefore be treated as indicative only. RF- patients with a longer diagnostic delay reported depression lasting three times longer (42.7 months), when compared to three other subtypes (11.0 to 12.7 months).

Conclusions

RA patients and controls differ in their emotion-related personality traits, as operationalized by trait EI. These differences may make people with RA more susceptible to chronic stress and HPA-axis dysregulation. RA may be a highly heterogeneous illness where at least two subtypes may be characterized by personality, psychiatric and immunological differences. RF- status, as well as diagnostic delay and emotional expression, may predict future risk of depression. Research on the causes of RA could benefit from a systems science approach.