The economic burden of TB faced by patients and affected families in Papua New Guinea.

BACKGROUND The costs associated with TB disease can be catastrophic for patients, affecting health and socioeconomic outcomes. Papua New Guinea (PNG) is a high TB burden country and the costs associated with TB are unknown.METHODS We undertook a national survey of TB patients to determine the magnitude of costs associated with TB in PNG, the proportion of households with catastrophic costs and cost drivers. We used a cluster sampling approach and recruited TB patients from health facilities. Descriptive statistics were used to analyse the costs and cost drivers and multivariate logistic regression to determine factors associated with catastrophic costs.RESULTS We interviewed 1,000 TB patients; 19 (1.9%) of them had multidrug-resistant TB (MDR-TB). Costs due to TB were attributable to income loss (64.4%), non-medical (29.9%) and medical (5.7%) expenses. Catastrophic costs were experienced by 33.9% (95% CI 31.0-36.9) of households and were associated with MDR-TB (aOR 4.47, 95% CI 1.21-16.50), hospitalization (aOR 3.94, 95% CI 2.69-5.77), being in the poorest (aOR 3.52, 95% CI 2.43-5.10) or middle wealth tertiles (aOR 1.51, 95% CI 1.03-2.21) or being employed (aOR 2.02, 95% CI 1.43-2.89).CONCLUSION The costs due to TB disease were catastrophic for one third of TB-affected households in PNG. Current support measures could be continued, while new cost mitigation interventions may be considered where needed.

Extracellular matrix compression temporally regulates microvascular angiogenesis.

Mechanical cues influence tissue regeneration, and although vasculature is known to be mechanically sensitive, little is known about the effects of bulk extracellular matrix deformation on the nascent vessel networks found in healing tissues. Previously, we found that dynamic matrix compression in vivo potently regulated revascularization during bone tissue regeneration; however, whether matrix deformations directly regulate angiogenesis remained unknown. Here, we demonstrated that load initiation time, magnitude, and mode all regulate microvascular growth, as well as upstream angiogenic and mechanotransduction signaling pathways. Immediate load initiation inhibited angiogenesis and expression of early sprout tip cell selection genes, while delayed loading enhanced microvascular network formation and upstream signaling pathways. This research provides foundational understanding of how extracellular matrix mechanics regulate angiogenesis and has critical implications for clinical translation of new regenerative medicine therapies and physical rehabilitation strategies designed to enhance revascularization during tissue regeneration.

Selection of specific endophytic bacterial genotypes by plants in response to soil contamination.

Plant-bacterial combinations can increase contaminant degradation in the rhizosphere, but the role played by indigenous root-associated bacteria during plant growth in contaminated soils is unclear. The purpose of this study was to determine if plants had the ability to selectively enhance the prevalence of endophytes containing pollutant catabolic genes in unrelated environments contaminated with different pollutants. At petroleum hydrocarbon contaminated sites, two genes encoding hydrocarbon degradation, alkane monooxygenase (alkB) and naphthalene dioxygenase (ndoB), were two and four times more prevalent in bacteria extracted from the root interior (endophytic) than from the bulk soil and sediment, respectively. In field sites contaminated with nitroaromatics, two genes encoding nitrotoluene degradation, 2-nitrotoluene reductase (ntdAa) and nitrotoluene monooxygenase (ntnM), were 7 to 14 times more prevalent in endophytic bacteria. The addition of petroleum to sediment doubled the prevalence of ndoB-positive endophytes in Scirpus pungens, indicating that the numbers of endophytes containing catabolic genotypes were dependent on the presence and concentration of contaminants. Similarly, the numbers of alkB- or ndoB-positive endophytes in Festuca arundinacea were correlated with the concentration of creosote in the soil but not with the numbers of alkB- or ndoB-positive bacteria in the bulk soil. Our results indicate that the enrichment of catabolic genotypes in the root interior is both plant and contaminant dependent.

NMR structural studies of human cystatin C dimers and monomers.

Human cystatin C undergoes dimerization before unfolding. Dimerization leads to a complete loss of its activity as a cysteine proteinase inhibitor. A similar process of dimerization has been observed in cells, and may be related to the amyloid formation seen for the L68Q variant of the protein. Dimerization is barrier controlled, and no dimer/monomer interconversion can be observed at physiological conditions. As a consequence, very stable, "trapped" dimers can be easily separated from monomers. A study of the structural aspects of cystatin C dimer formation was undertaken using NMR spectroscopy. The monomer/dimer model was verified by (pulse field gradient NMR) self-diffusion molecular mass measurements. Complete backbone resonance assignments and secondary structure determination were obtained for the monomer using data from triple resonance experiments performed on 13C/15N doubly labeled protein. A marked similarity of the cystatin C secondary structure to that of chicken cystatin was observed. Using uniformly and amino-acid-specific 15N-enriched protein, backbone NH signals were assigned for cystatin C in its dimeric state. Comparison of 1H -15N correlation NMR spectra of the monomer and dimer shows that the three-dimensional structure remains unchanged in the dimer and that only local perturbations occur. These are localized to the amino acid residues comprising the cysteine proteinase binding site. Such a mode of dimerization readily explains the complete loss of the inhibitory activity in the dimer. The NMR results also demonstrate that the dimer is symmetric.

A scanning electron microscopic study of rabbit ligaments under strain.

For the purpose of determining the critical strain level for ligaments submitted to mechanical stimulation, rabbit medial collateral ligaments (MCLs) were subjected to different predetermined strain levels and then examined by scanning electron microscopy (SEM). Below 10% strain no evidence of disruption of the collagenous entities has been found. At about 10% strain, the ligaments were still intact macroscopically but SEM revealed numerous broken thin collagen fibers. At 20% strain, ruptures of thick collagen fibers bundles (5 to 10 mu in diameter) were found. These findings suggest that when using mechanical stimulation of ligaments, care must be taken to not exceed 10% strain level.

Enhancement of metabolic coronary vasodilatation by nicotinic acid or amide.

Cardiostimulation produced by noradrenaline, glucagon, or tachycardia on the isolated perfused rat heart produced a metabolic coronary dilatation that was potentiated by nicotinic acid or its amide [NIC; 0.05-1.0 mM] without affecting the cardiostimulation. Reactive hyperaemia to brief coronary occlusion was unaffected by NIC, thus confirming that its vasodilator mechanism is of a different nature than that leading to metabolic coronary dilatation. It is suggested that NIC may be of significance as an adjuvant in the treatment of certain types of coronary insufficiencies.