Association between Health Systems Performance and Treatment Outcomes in Patients Co-Infected with MDR-TB and HIV in KwaZulu-Natal,South Africa: Implications for TB Programmes

Objective

To improve the treatment of MDR-TB and HIV co-infected patients, we investigated the relationship between health system performance and patient treatment outcomes at 4 decentralised MDR-TB sites.

Methods

In this mixed methods case study which included prospective comparative data, we measured health system performance using a framework of domains comprising key health service components. Using Pearson Product Moment Correlation coefficients we quantified the direction and magnitude of the association between health system performance and MDR-TB treatment outcomes. Qualitative data from participant observation and interviews analysed using systematic text condensation (STC) complemented our quantitative findings.

Findings

We found significant differences in treatment outcomes across the sites with successful outcomes varying from 72% at Site 1 to 52% at Site 4 (p<0.01). Health systems performance scores also varied considerably across the sites. Our findings suggest there is a correlation between treatment outcomes and overall health system performance which is significant (r = 0.99, p<0.01), with Site 1 having the highest number of successful treatment outcomes and the highest health system performance. Although the ‘integration’ domain, which measured integration of MDR-TB services into existing services appeared to have the strongest association with successful treatment outcomes (r = 0.99, p<0.01), qualitative data indicated that the ‘context’ domain influenced the other domains.

Conclusion

We suggest that there is an association between treatment outcomes and health system performance. The chance of treatment success is greater if decentralised MDR-TB services are integrated into existing services. To optimise successful treatment outcomes, regular monitoring and support are needed at a district, facility and individual level to ensure the local context is supportive of new programmes and implementation is according to guidelines.     

The mutation rates of di-, tri- and tetranucleotide repeats in Drosophila melanogaster

In a recent study, we reported that the combined average mutation rate of 10 di-, 6 tri-, and 8 tetranucleotide repeats in Drosophila melanogaster was 6.3 x 10(-6) mutations per locus per generation, a rate substantially below that of microsatellite repeat units in mammals studied to date (range = 10(-2)-10(-5) per locus per generation). To obtain a more precise estimate of mutation rate for dinucleotide repeat motifs alone, we assayed 39 new dinucleotide repeat microsatellite loci in the mutation accumulation lines from our earlier study. Our estimate of mutation rate for a total of 49 dinucleotide repeats is 9.3 x 10(-6) per locus per generation, only slightly higher than the estimate from our earlier study. We also estimated the relative difference in microsatellite mutation rate among di-, tri-, and tetranucleotide repeats in the genome of D. melanogaster using a method based on population variation, and we found that tri- and tetranucleotide repeats mutate at rates 6.4 and 8.4 times slower than that of dinucleotide repeats, respectively. The slower mutation rates of tri- and tetranucleotide repeats appear to be associated with a relatively short repeat unit length of these repeat motifs in the genome of D. melanogaster. A positive correlation between repeat unit length and allelic variation suggests that mutation rate increases as the repeat unit lengths of microsatellites increase.      

Viscosity of chromatin solutions increases with increasing ionic strength

Increasing the ionic strength of rat liver chromatin solutions above 0.4 M causes increasing viscosity. This indicates transformation of the compact chromatin molecules to more elongated forms. In the range of 0.4–0.5 M ionic strength histone H1 is dissociating continuously from the chromatin and the quaternary structure chromatin unravels. At ionic strength higher than 0.5 M the viscosities of chromatin solutions are furthermore increasing due to structural deformation. Near 0.7 M ionic strength the core histones H2A and H2B begin to dissociate from the chromatin, and the opening of the nucleosome cores leads to increasing elongation of the chromatin molecules.     

Lifetime development of behavioural phenotype in the house mouse (<Emphasis Type="Italic">Mus musculus</Emphasis>)

With each trajectory taken during the ontogeny of an individual, the number of optional behavioural phenotypes that can be expressed across its life span is reduced. The initial range of phenotypic plasticity is largely determined by the genetic material/composition of the gametes whereas interacting with the given environment shapes individuals to adapt to/cope with specific demands. In mammalian species, the phenotype is shaped as the foetus grows, depending on the environment in the uterus, which in turn depends on the outer environment the mother experiences during pregnancy. After birth, a complex interaction between innate constitution and environmental conditions shapes individual lifetime trajectories, bringing about a wide range of diversity among individual subjects.In laboratory mice inbreeding has been systematically induced in order to reduce the genetic variability between experimental subjects. In addition, within most laboratories conducting behavioural phenotyping with mice, breeding and housing conditions are highly standardised. Despite such standardisation efforts a considerable amount of variability persists in the behaviour of mice. There is good evidence that phenotypic variation is not merely random but might involve individual specific behavioural patterns consistent over time. In order to understand the mechanisms and the possible adaptive value of the maintenance of individuality we review the emergence of behavioural phenotypes over the course of the life of (laboratory) mice. We present a literature review summarizing developmental stages of behavioural development of mice along with three illustrative case studies. We conclude that the accumulation of environmental differences and experiences lead to a “mouse individuality” that becomes increasingly stable over the lifetime.     

Microfingerprints of proteins through labeling acetylation of their proteolytic peptides

Microgram amounts of proteins applied to polyacrylamide gel electrophoresis were subjected to a fingerprinting procedure using a combined proteolysis-acetylation method with the aid of ¹⁴C-labeled acetic anhydride of high specific activity. After staining, gel slices were partially dried and were resoaked in a solution of a protease. After elution and acetylation, the resulting peptides were resolved in fingerprints on cellulose thin-layer chromatography plates and subjected to autoradiography with or without sensitization. Yields, completeness of fingerprinting, and possible artefacts were investigated.